Frequency and Quality of Exposure to Adaptive Cruise Control and Impact on Trust, Workload, and Mental Models.
Advanced Driver Assistance Systems (ADAS) support drivers with some driving tasks. However, drivers may lack appropriate knowledge about ADAS resulting in inadequate mental models. This may result in drivers misusing ADAS, or mistrusting the technologies, especially after encountering edge-case events (situations beyond the capability of an ADAS where the system may malfunction or fail) and may also adversely affect driver workload. Literature suggests mental models could be improved through exposure to ADAS-related driving situations, especially those related to ADAS capabilities and limitations. The objective of this study was to examine the impact of frequency and quality of exposure on drivers' understanding of Adaptive Cruise Control (ACC), their trust, and their workload after driving with ACC. Sixteen novice ACC users were recruited for this longitudinal driving simulator study. Drivers were randomly assigned to one of two groups - the 'Regular Exposure' group encountering 'routine' edge-case events, and the 'Enhanced Exposure' group encountering 'routine' and 'rare' events. Each participant undertook four different simulator sessions, each separated by about a week. Each session comprised a simulator drive featuring five edge-case scenarios. The study followed a mixed-subject design, with exposure frequency as the within-subject variable, and quality of exposure (defined by two groups) as the between-subject variable. Surveys measured drivers' trust, workload, and mental models. The results from the analyses using linear regression models revealed that drivers' mental models about ACC improve with frequency of exposure to ACC and associated edge-case driving situations. This was more the case for drivers who experienced 'rare' ACC edge cases. The findings also indicate that for those who encountered 'rare' edge cases, workload was higher and trust was lower than those who did not. These findings are significant since they underline the importance of experience and familiarity with ADAS for safe operation. While these findings indicate that drivers benefit from increased exposure to ACC and edge cases in terms of appropriate use of ADAS, and ultimately promise crash reductions and injury prevention, a challenge remains regarding how to provide drivers with appropriate exposure in a safe manner.


Effect of pH and imidazole on protein C purification from Cohn fraction IV-1 by IMAC.
Cohn Fraction IV-1 (CFIV-1) is a by-product (often discarded) of a plasma fractionation process. It retains 90% of Protein C (PC) of plasma but contains several coagulants structurally homologous to PC. Of these coagulants, Factor II (FII) has the longest half-life (12 times of PC) and largest quantity (9 times of PC) in CFIV-1. Current purification process for PC is by immunoaffinity chromatography using monoclonal antibodies, which is very expensive. Immobilized metal affinity chromatography (IMAC) is an inexpensive process that uses metal ions to adsorb proteins via their surface histidines. Affinity of PC to the metal ions in IMAC is higher than that of FII because PC has 15 surface histidines and FII has 5. Two important factors in an IMAC process are pH and imidazole concentration. PH controls protonation of histidine, and imidazole, a histidine analog, competitively reacts with metal ions. The effects of pH and imidazole on adsorption and elution of PC and FII during IMAC process were studied. The effect of pH on PC and FII adsorption was similar within the range of 6.0 and 8.0. At concentrations below 15 mM imidazole, little PC or FII eluted. At 15 and 20 mM imidazole 2.5% of PC was eluted, while 20-30% of FII was eluted.


Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation.
The role of infection in the pathomechanism of obliterative bronchiolitis (OB) after human lung transplantation is controversial. In a rat lung transplantation model, we analyzed the effect of viral [rat cytomegalovirus (RCMV)] and bacterial infection [Listeria monocytogenes (LM)] on the development of chronic allograft rejection. Fisher rats underwent single left lung transplantation with allografts from Lewis rats. Postoperatively, animals were infected with either RCMV or LM, or served as noninfected controls. Animals were killed on day 120 and both lungs were evaluated histopathologically for chronic airway and chronic vascular rejection. Infection with RCMV produced a significant increase in the incidence of chronic airway rejection (66.7% vs. 20%), compared with noninfected long-term surviving animals. In rats with bacterial infection (LM) a similar increase of chronic airway changes as in viral infection (50% vs. 20%) was observed. Chronic rejection of allografts infected with either RCMV or LM was associated with significantly enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelium. More infiltrating leukocytes (CD18, CD11a, CD44) and ED1-positive macrophages were found in allografts of infected animals. In this experimental model of chronic airway rejection in long-term surviving rats, not only viral but also bacterial infection resulted in enhanced development of chronic airway and vascular rejection. These results support our hypothesis that infectious complications have a substantial influence on the development of OB in human lung allografts.


The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets: A Report from the 23rd Annual Harvard Nutrition Obesity Symposium.
Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.


Mother-child relation in human schistosomiasis mansoni : skin test and cord blood reactivity to schistosomal antigens.
Reaction to schistosomal antigen was studied in children born to mothers infected with Schistosoma mansoni. Values of immediate (15 min) skin reactions were more elevated and values of delayed (24 h) skin reactions were significantly higher in children born to infected mothers than in children born to uninfected mothers. The macrophage migration inhibition test, done on cord blood cells, was positive to schistosomal antigen in 40% of children born to infected mothers and negative in all children born to uninfected mothers. These results suggest prenatal sensitization to schistosomal antigen in children born to mothers infected with S. mansoni.


Interventions for decreasing the risk of recurrent IgA nephropathy: A systematic review and meta-analysis.
Recurrent IgA nephropathy (rIgAN) is an important cause of kidney allograft loss. Till now, no proven strategies have been confirmed to prevent/decrease the rIgAN. Here, a systematic review and meta-analysis were performed on the available interventions impacting rIgAN. PubMed, Embase, Web of sciences, ProQuest, and Cochrane library databases along with Google Scholar were searched for articles evaluating the rIgAN after kidney transplantation (up to 23 February 2023). The main inclusion criteria were kidney transplantation because of primary IgAN and articles studying the rate of the rIgAN based on different therapeutic interventions to find their effects on the disease recurrence. Based on our criteria, 11 papers were included in this systematic review, two of which pleased the criteria for the meta-analysis. Meta-analysis showed that the risk of the rIgAN in the steroid-free group was 3.33 times more than that of the steroid-receiving group (Pooled Hazard Ratio = 3.33, 95% CI 0.60 to18.33, Z-value = 1.38, p-value = 0.16). Steroid-free therapy increases the risk of rIgAN in kidney transplant recipients with primary IgAN. High-quality trials with large sample sizes studies are needed to confirm the impact of the steroids on decreasing the rate of the rIgAN.


Magnesium deficiency anemia in the rat fetus.
Magnesium-deficient fetuses exhibited malformations (44%), anemia, and edema. Maternal plasma magnesium levels at day 21 of pregnancy reflected the level of dietary magnesium (2.43 +/- 0.09 mg Mg/100 ml, control; 0.74 +/- 0.02 mg Mg/100 ml, deficient). Plasma magnesium levels of deficient fetuses showed similar decreases although all fetal magnesium values at term were hihger than maternal values from the same group (3.29 +/- 0.22 mg Mg/100 ml, control; 1.78 +/- 0.07 mg Mg/100 ml, deficient). Magnesium deficiency did not appear to affect the maternal blood parameters. However, when fetal blood was examined, all of the parameters measured were altered in magnesum-deficient fetuses (Table 2). No abnormalities in hemoglobin bands or plasma proteins were seen between any groups by electrophoresis. Measurement of total protein contents showed no differences between maternal blood protein contents, but total plasma protein from magnesium-deficient fetuses was significantly lower than controls (2.00 +/- 0.14 versus 2.62 +/- 0.13 g/100 ml), thus establishing a factor in fetal edema production. Morphologic data showed that in magnesium-deficient fetuses, fetal erythropoiesis was significantly greater in liver, adrenal glands, and spleen than in controls and that maturation was normoblastic. Stained and unstained peripheral blood smears of magnesium-deficient fetuses showed and obvious macrocytosis and at least 50% of the red cells stained abnormally, exhibiting pale areas. Erythrocytic morphology seen in fetal magnesium deficiency is consistent with inadequate filling of the cell by hemoglobin as suggested by Cohlan et al. (5), a probable cause of membrane collapse. The inadequate filling of magnesium-deficient red blood cells (RBC) with hemoglobin might be explained by a reduction in hemoglobin synthesis which is consistent with the reduced mean corpuscular hemoglobin (MCH) and MCH concentration (MCHC) of the deficient fetal red cells. The role of magnesium in protein synthesis is also compatible with a reduction in hemoglobin synthesis, yet may not completely explain the abnormalities and resultant shortened lifespan of the red cells.


The circadian clock and inflammation: A new insight.
The circadian clock is a complex cellular mechanism that controls a series of physiological processes, including inflammation. It can directly interact physically with the components of the key inflammatory pathway. Similarly, inflammation can also lead to circadian rhythm disorders, which may further amplify the inflammatory response and aggravate tissue damage. This review offers a structured overview that focusses on the core proteins of the circadian clock and their interactions with inflammatory players, and provides a potential mechanism for the pathological rhythms observed under inflammatory conditions.


Nanotechnology in the agri-food sector: Consumer perceptions.
The purpose of this work was to evaluate Spanish consumers' opinions on using nanotechnology in food processing and packaging. For this purpose, a literature review was carried out in the main research database to determine the most widespread uses of nanotechnology in the food industry and the most promising developments. Of all the nanotechnology uses in food, five areas of application were identified: developing new ingredients or additives, formulating new antimicrobial systems, and designing new processing methods, sensors and packaging with nanostructured materials. Subsequently, a consumers' opinion study was carried out by means of a survey, in which the opinions and purchase intention of a representative product of all five categories were evaluated, as well as the neophobia level to new food technologies. All the products obtained positive evaluations, and the applications in which nanotechnology did not form part of food were generally better valued than those in which it did form part. The respondents had a medium neophobia level, with an average score of 4.59 (out of 7 points), being consumers with more knowledge about new technologies the least neophobic and those who gave products higher scores. This study provides relevant information for using nanotechnology in the food processing and packaging sector.


Reactive coagulation induced by plasmin in patients treated with recombinant tissue-type plasminogen activator.
We and others have demonstrated that administration of thrombolytic agents causes the generation of thrombosis-promoting agents. At present, we have studied whether formation in vivo of excessive amounts of plasmin is responsible for the activation of coagulation in patients treated with recombinant tissue-type plasminogen activator. Modified crossed immunoelectrophoresis was used for determination of the plasminogen-binding form of alpha 2-antiplasmin. Enzyme-linked immunosorbent assay methods were used for determination of hemostatic reaction products. The association between the generation of hemostatic reaction products and the exhaustion of the plasminogen-binding form of alpha 2-antiplasmin (PB alpha 2AP) was studied in 21 patients with acute myocardial infarction and 11 patients with unstable angina pectoris who were given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA). We observed in all patients a fall in blood concentrations of PB alpha 2AP (P < 0.01) after 2.25 hours of treatment and, simultaneously, a significant increase in fibrin degradation products (P < 0.01), D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin fragment 1 + 2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01). When we evaluated individual data, we observed high concentrations of the reaction products when the PB alpha 2AP concentration after 2.25 hours of treatment was lower than 25% of the pretreatment values. Also, we observed highly significant associations between the increase in the plasma concentrations of fibrin degradation products and thrombin-antithrombin III complexes (rs = 0.72; P < 0.01), the increase in plasma concentrations of fibrin degradation products and prothrombin fragment 1 + 2 (rs = 0.63; P < 0.01), the increase in plasma concentrations of D-dimer and thrombin-antithrombin III complexes (rs = 0.78; P < 0.01), and the increase in plasma concentrations of D-dimer and prothrombin fragment 1 + 2 (rs = 0.79; P < 0.01). Generation of excessive amounts of plasmin is the main factor in producing the procoagulant response in patients who receive thrombolytic therapy with rt-PA, and intravenous heparin does not abolish this response. Plasmin inhibitors might be used in relation to thrombolytic therapy as indirect "antithrombotics."


Carcinosarcoma, an atypical subset of gallbladder malignancies.
Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor. The patient was a woman in her 70s. Abdominal sonography revealed that the gallbladder lumen was half-filled by a large mass (maximum diameter, 68 mm) showing heterogeneous echogenicity slightly higher than that of bile. However, despite the large size of the mass, gallbladder shape was well-preserved. Considering the findings on computed tomography, cholecystectomy was performed under a diagnosis of gallbladder malignancy. Pathological examination revealed two types of malignant histology: a sarcomatous element of malignant spindle cells and a carcinomatous element of adenocarcinoma tissue. Foci of malignant cartilage and bone areas were also found sporadically. Accompanied by immunohistochemical examination, the mass was diagnosed as carcinosarcoma. The present case showed somewhat different imaging findings from those of ordinary gallbladder carcinoma. Carcinosarcoma should be considered when a well-preserved shape of the gallbladder is recognized along with protrusion of a large heterogeneously echogenic mass into and filling the gallbladder lumen.


Nano-magnetic particles as multifunctional microreactor for deep desulfurization.
Oxidation of dibenzothiophene with hydrogen peroxide using a recyclable amphiphilic catalyst has been studied. The catalyst was synthesized by surfacely covering magnetic silica nanospheres (MSN) with the complexes between 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (AEM) and phosphotungstic acid (PTA). The morphology and components of the composite material were characterized by TEM, EDX, XPS, FT-IR, and VSM, respectively. The effects of several factors on desulfurization reactivity were systematically investigated. The results showed that the composite nanospheres have core/shell structure with the properties of amphiphilicity and superparamagnetism. The composite nanospheres have high catalytic activity in the oxidation of dibenzothiophene to corresponding sulfones by hydrogen peroxide under mild reaction conditions. The sulfur level could be lowered from 487 ppm to less than 0.8 ppm under optimal conditions. Additionally, the amphiphilic catalyst and the oxidized product could be simultaneously separated from medium by external magnetism, and the recovered composite material could be recycled for three times with almost constant activity.


Appalachian versus non-Appalachian U.S. traffic fatalities, 2008-2010.
Although myriad health disparities exist in Appalachia, limited research has examined traffic fatalities in the region. This study compared traffic fatality rates in Appalachia and the non-Appalachian United States. Fatality Analysis Reporting System and Census data from 2008 through 2010 were used to calculate traffic fatality rates. Poisson models were used to estimate unadjusted (rate ratio [RR]) and adjusted rate ratios, controlling for age, gender, and county-specific population density levels. The Appalachian traffic fatality rate was 45% (95% confidence interval [CI], 1.42-1.47) higher than the non-Appalachian rate. Although only 29% of fatalities occur in rural counties in non-Appalachia versus 48% in Appalachia, rates in rural counties were similar (RR, 0.97; 95% CI, 0.95-1.00). However, the rate for urban, Appalachian counties was 42% (95% CI, 1.38-1.45) higher than among urban, non-Appalachian counties. Appalachian rates were higher for passenger vehicle drivers, motorcyclists, and all terrain vehicle riders, regardless of rurality, as well as for passenger vehicle passengers overall and for urban counties. Conversely, Appalachia experienced lower rates among pedestrians and bicyclists, regardless of rurality. Disparities in traffic fatality rates exist in Appalachia. Although elevated rates are partially explained by the proportion of residents living in rural settings, overall rates in urban Appalachia were consistently higher than in urban non-Appalachia.


Physiologically inspired culture medium prolongs the lifetime and insulin sensitivity of human hepatocytes in micropatterned co-cultures.
Given significant species-specific differences in liver functions, cultures of primary human hepatocytes (PHHs) are useful for assessing drug metabolism and to mitigate the risk of drug-induced hepatotoxicity in humans. While significant advances have been made to keep PHHs highly functional for 2-4 weeks in vitro, especially upon co-culture with both liver- and non-liver-derived non-parenchymal cells (NPCs), the functional lifespan of PHHs is 200-400 days in vivo. Therefore, it is desirable to determine culture conditions that can further prolong PHHs functions in vitro for modeling chronic drug exposure, disease pathogenesis, and to provide flexibility to the end-user for staggering drug incubations across multiple culture batches. Most PHH culture platforms utilize supraphysiologic levels of glucose and insulin and bovine-derived serum when including NPCs, which can alter PHH functions. Therefore, here we developed a culture medium containing physiologic levels of glucose (5 mM), insulin (500 pM), and human serum (10 % v/v) and tested its effects on micropatterned co-cultures (MPCCs) in which PHHs are organized onto collagen domains of empirically optimized dimensions and surrounded by 3T3-J2 murine fibroblasts that express liver-like molecules and induce higher PHH functions than liver-derived NPCs. Our physiologically-inspired culture medium allowed better retention of PHH morphology, polarity, and functions (albumin and urea, cytochrome-P450 activities, and sensitivity to insulin-mediated inhibition of gluconeogenesis) for up to 10 weeks relative to the traditional medium. Finally, PHHs in the physiologic medium displayed clinically-relevant responses to prototypical drugs for hepatoxicity and cytochrome-P450 induction. Ultimately, our physiologic culture medium could find broader utility for the continued development of PHH-NPC co-cultures for drug development, investigating the effects of patient-derived sera on PHH functions and disease phenotypes, and for use in cell-based therapies.


Lateral lumbosacral fracture dislocation: a case report.
A case of lateral fracture dislocation of the fifth lumbar vertebra on the sacrum successfully treated by open reduction is described. The literature of this injury is reviewed.


Occurence of subtelomeric rearrangements in the genome of the microsporidian parasite Encephalitozoon cuniculi, as revealed by a new fingerprinting procedure based on two-dimensional pulsed field gel electrophoresis.
In Microsporidia, mitochondria-lacking eukaryotic intracellular parasites, genomic comparisons were so far based on molecular karyotyping. The mammal-infecting species Encephalitozoon cuniculi is characterized by a very low haploid genome size (approximately 2.8 Mbp) and rather high karyotype variability. Recently, we developed a two-dimensional pulsed field gel electrophoresis (2-D PFGE) fingerprinting technique useful for constructing a restriction map fo the genome of a mouse E. cuniculi isolate (karyotype variant A). The so-called karyotype and restriction display 2-D PFGE (KARD-PFGE) protocol involved 1-D chromosome separation, digestion with a rare cutter, Klenow radiolabeling of genomic DNA and 2-D separation of restriction fragments followed by autoradiography. In order to assess its suitability for detecting polymorphic loci in E. cuniculi, we applied KARD-PFGE with either BssHII or Mlul digestion to genome analysis of two rabbit isolates representative of two different karyotype variants (A and C). The 2-D spot pattern of the rabbit isolate variant A is identical to the reference mouse isolate but differs greatly from the rabbit isolate variant C. Chromosomal restriction fragment length polymorphisms (RFLPs) provide strong evidence for homologous chromosomes and frequent DNA rearrangements within subtelomeric regions just upstream of the dispersed rDNA units closely associated with each chromosomal end.


Calibrating a thermometer for Earth's interior over time.
New high-pressure, high-temperature experiments refine our ability to trace the thermal evolution of the Earth's interior using the geological record of intermittent, large-volume volcanic episodes.


Influence of prazosin on cardiac reflex function.
Prazosin administration significantly decreased arterial blood pressure without affecting heart rate in pentobarbital-anesthetized dogs. Wile pressor and reflex bradycardic responses to angiotensin II were not altered by prazosin, reflex tachycardia produced produced by histamine and acetylcholine were significantly attenuated by prazosin. The failure of prazosin administration to cause an increase in heart rate may be due to the ability of the agent to inhibit reflex tachycardic responses to depressor stimuli, the mechanism of whcih needs to be further investigated.


Pancreatic mucinous cystadenoma doubly complicated by acute pancreatitis and retroperitoneal rupture.
Mucinous cystadenomas are the most frequent cystic benign tumors of the pancreas. They are characterized by a malignant potential. Acute pancreatitis is their most common complication. This manuscript reports a unique complication of mucinous cystadenomas of the pancreas: retroperitoneal rupture associated to acute pancreatitis. After resuscitation, the patient underwent surgery. A cystic mass of the pancreas tail with retroperitoneal rupture was found. Splenopancreatectomy was performed. Outcomes were straightforward. After 3 years of follow-up, no signs of recurrence are highlighted.


Extracorporeal shock wave lithotripsy monotherapy: experience with piezoelectric second generation lithotriptor in 642 patients.
Extracorporeal shock wave lithotripsy monotherapy was performed in 642 patients for 1 year with an EDAP-LT01 piezoelectric lithotriptor. Of 642 patients 398 completed extracorporeal shock wave lithotripsy treatment and 244 still are undergoing multiple extracorporeal shock wave lithotripsy sessions. The 398 patients had renal (64.6 per cent) or ureteral (35.4 per cent) stones 0.6 to 4.8 cm. in diameter (mean 1.4 cm.). No general or regional anesthesia was required except in 7 children. Among 398 patients who completed extracorporeal shock wave lithotripsy the rate free of stones was 73.4 per cent and the rate of clinically insignificant residual fragments was 12.8 per cent. The success rate (rate free of calculi plus that of clinically insignificant renal fragments) ranged from 95.6 per cent for stones 0.6 to 1.0 cm. in diameter to 52.6 per cent for stones larger than 3.0 cm. (mean 86.2 per cent). The number of treatment sessions in 343 patients with successful results increased in accordance with the stone size, with an average of 1.6 sessions. Double-J* stents were placed in 7 patients and ureteral catheterization was performed in 11 as post-extracorporeal shock wave lithotripsy adjunctive measures. The steinstrasse phenomenon was noted in 14 patients, of whom only 1 required Double-J stenting. There were no significant complications. Therefore, extracorporeal shock wave lithotripsy monotherapy with the piezoelectric lithotriptor is considered to be a safe and efficient outpatient procedure for the initial treatment of urinary stones regardless of stone sizes.


How Early in Life do Transgender Adults Begin to Experience Gender Dysphoria? Why This Matters for Patients, Providers, and for Our Healthcare System.
The age at which transgender women (TW) and men (TM) first experience gender dysphoria (GD) has not been reported in a U.S. population of adults seeking genital gender-affirming surgery (gGAS). Because gender is an innate part of identity, we hypothesized that untreated GD would be a part of individuals' earliest memories. Understanding GD onset can help guide providers with when and how to focus care to patients not yet identified as "transgender AIM: (i) Determine the age at which transgender adults seeking gGAS first experience GD (ii) Determine the number of life-years that transgender adults spend living with untreated GD METHODS: During initial consultation for gGAS, we asked patients the earliest age at which they experienced GD and the age at which they had their earliest episodic memory. We also queried history of anxiety, depression, and suicide attempt. Patients self-reported their earliest recollections of experiencing GD, earliest memories in general, and history of anxiety, depression, and suicide attempt. Data from 155 TW (mean age 41.3; SD 16.3) and 55 TM (mean age 35.4; SD 10.8) were collected. Most patients (TM: 78%; TW: 73%) reported experiencing GD for the first time between ages 3 and 7 years. For TM the mean age of onset was 6.17 years; for TW it was 6.71 years. A total of 81% of TW and 80% of TM described their first recollection of GD as one of their earliest memories. Mean years of persistent GD before the start of gender transition were 22.9 (TM) and 27.1 (TW). Rates of depression, anxiety, and suicide ideation decreased following gender transition. Our findings suggest that GD typically manifests in early childhood and persists untreated for many years before individuals commence gender transition. Diagnosis and early management during childhood and adolescence can improve quality of life and survival. Zaliznyak M, Yuan N, Bresee C, et al. How Early in Life do Transgender Adults Begin to Experience Gender Dysphoria? Why This Matters for Patients, Providers, and for Our Healthcare System. Sex Med 2021;9:100448.


Centerband-only-detection-of-exchange (31)P nuclear magnetic resonance and phospholipid lateral diffusion: theory, simulation and experiment.
Centerband-only-detection-of-exchange (CODEX) (31)P NMR lateral diffusion measurements were performed on dimyristoylphosphatidylcholine (DMPC) assembled into large unilamellar spherical vesicles. Optimization of sample and NMR acquisition conditions provided significant sensitivity enhancements relative to an earlier first report (Q. Saleem, A. Lai, H. Morales, and P. M. Macdonald, Chem. Phys. Lipids, 2012, 165, 721). An analytical description was developed that permitted the extraction of lateral diffusion coefficients from CODEX data, based on a Gaussian-diffusion-on-a-sphere model (A. Ghosh, J. Samuel, and S. Sinha, Europhys. Lett., 2012, 98, 30003-p1) as relevant to CODEX (31)P NMR measurements on a population of spherical unilamellar phospholipid bilayer vesicles displaying a distribution of vesicle radii.


Concordance between patient- and physician-reported Myasthenia Gravis Activities of Daily Living (MG-ADL) scores.
Myasthenia gravis (MG) is a neuromuscular disease characterized by abnormal skeletal muscle fatiguability. The MG Activities of Daily Living (MG-ADL) scale assesses eight symptoms and is often used as primary endpoint in MG clinical trials where it is completed by neurologists. However, in observational studies, patients frequently complete the MG-ADL scale independently of their neurologist. In this study we aimed to assess the concordance between self- and physician-reported MG-ADL scores. An international observational study was conducted among adult patients with MG scheduled for a routine visit or who entered the hospital via emergency services. Consenting patients and physicians completed the MG-ADL. Concordance between assessments was calculated using Gwet's agreement coefficient (Gwet's AC) for the MG-ADL individual items and the intraclass correlation coefficient (ICC) for the MG-ADL total score. Data were collected from 137 patients (63% female; mean age, 57.7 years). Physicians assessed the patient's symptoms as slightly more severe (8.1 vs 7.5 MG-ADL total score, respectively), corresponding to a difference of 0.6 on a range from 0 to 24. The ICC for the MG-ADL total score between the patient and the physician assessment was 0.94 (95% confidence interval, 0.89 to 0.95), showing excellent concordance. Gwet's AC showed substantial to almost perfect agreement for all items, except eyelid droop, for which the agreement was moderate. Our results demonstrate that patients and neurologists have a concordant assessment of the patient's MG symptoms when using the MG-ADL scale. This evidence supports patient self-administration of the MG-ADL in clinical practice and research.


Influence of stingless bee genus (Scaptotrigona and Melipona) on the mineral content, physicochemical and microbiological properties of honey.
Stingless bees, important pollinating insects in the tropics, produce honey whose unique quality features differentiate their origin. The feasibility of multivariate data analysis for quality discrimination of stingless bee honey from different genera (Melipona bicolor, quadrifasciata, marginata and Scaptotrigona bipunctata) by mineral content, physicochemical and microbiological properties were investigated. The principal component analysis explained 72.12% of the total variance of the data, and the separation into two main groups in a scatter plot was observed. Group 2 was formed by Scaptotrigona genus, that showed the highest values of pH, ash, and soluble solids. Potassium was the most abundant mineral followed by calcium and sodium for both groups quantified by inductively coupled plasma optical emission spectrometry. This honey has higher acidity and moisture than Apis mellifera honey. Microbiological analyses showed that total aerobic mesophiles ranged between 2.00 and 4.77 log CFU/g. Salmonella spp. was not detected, while the mould and yeast content was above the maximum allowed under the Apis mellifera honey legislation. The evaluated honey samples presented the lactic acid bacteria, which are considered a benefit. The multivariate statistical analysis was efficient in discriminate stingless bee honey, contributing to approaches that can be used for standardization and regulation.


TLR agonists that induce IFN-beta abrogate resident macrophage suppression of T cells.
Resident tissue macrophages (Mφs) continually survey the microenvironment, ingesting Ags and presenting them on their surface for recognition by T cells. Because these Ags can be either host cell- or pathogen-derived, Mφs must be able to distinguish whether a particular Ag should provoke an immune response or be tolerated. However, the mechanisms that determine whether Mφs promote or inhibit T cell activation are not well understood. To investigate this, we first determined the mechanism by which murine resident peritoneal Mφs suppress in vitro T cell proliferation in the absence of pathogens and then explored the effects of different pathogen-derived molecules on Mφ immunosuppression. Our results suggest that, in response to IFN-γ, which is secreted by TCR-activated T cells, resident peritoneal Mφs acquire immunosuppressive properties that are mediated by NO. However, pretreatment of Mφs with LPS or dsRNA, but not CpG or peptidoglycan, eliminates their suppressive properties, in part via the induction of autocrine-acting IFN-β. These results suggest TLR agonists that activate TRIF, and consequently induce IFN-β, but not those that exclusively signal through MyD88, abrogate the immunosuppressive properties of Mφs, and thus promote T cell expansion and elimination of invading microorganisms.


Acquired Hearing Loss in Children.
Hearing loss is the most common congenital sensory impairment. According to National Health and Nutrition Examination Survey data from 2001 to 2008, 20.3% of subjects aged greater than or equal to 12 had unilateral or bilateral hearing loss. The World Health Organization notes that, worldwide, there are 360 million people with disabling hearing loss, with 50% preventable. Although many hearing losses are acquired, many others are manifestations of preexisting conditions. The purpose of a pediatric hearing evaluation is to identify the degree and type of hearing loss and etiology and to outline a comprehensive strategy that supports language and social development and communication.


Cross-species molecular dissection across alcohol behavioral domains.
This review summarizes the proceedings of a symposium presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference held in Volterra, Italy on May 9-12, 2017. Psychiatric diseases, including alcohol-use disorders (AUDs), are influenced through complex interactions of genes, neurobiological pathways, and environmental influences. A better understanding of the common neurobiological mechanisms underlying an AUD necessitates an integrative approach, involving a systematic assessment of diverse species and phenotype measures. As part of the World Congress on Stress and Alcoholism, this symposium provided a detailed account of current strategies to identify mechanisms underlying the development and progression of AUDs. Dr. Sean Farris discussed the integration and organization of transcriptome and postmortem human brain data to identify brain regional- and cell type-specific differences related to excessive alcohol consumption that are conserved across species. Dr. Brien Riley presented the results of a genome-wide association study of DSM-IV alcohol dependence; although replication of genetic associations with alcohol phenotypes in humans remains challenging, model organism studies show that COL6A3, KLF12, and RYR3 affect behavioral responses to ethanol, and provide substantial evidence for their role in human alcohol-related traits. Dr. Rob Williams expanded upon the systematic characterization of extensive genetic-genomic resources for quantifying and clarifying phenotypes across species that are relevant to precision medicine in human disease. The symposium concluded with Dr. Robert Hitzemann's description of transcriptome studies in a mouse model selectively bred for high alcohol ("binge-like") consumption and a non-human primate model of long-term alcohol consumption. Together, the different components of this session provided an overview of systems-based approaches that are pioneering the experimental prioritization and validation of novel genes and gene networks linked with a range of behavioral phenotypes associated with stress and AUDs.


Hearing impaired families: the social ecology of hearing loss.
The services available to parents of children with hearing losses, and the options concerning the modes of communication and the educational programs for their children, have significant effects on family relations and the family's understanding of hearing impairment and deafness. This is particularly true in rural areas of British Columbia, Canada, where the range of programs is limited. This paper examines the programs available, parents' understandings of their options, the decisions they make, and the impact on the family of the selection and availability of programs.


Phosphate flame retardants and novel brominated flame retardants in home-produced eggs from an e-waste recycling region in China.
Phosphate flame retardants (PFRs) and novel brominated flame retardants (NBFRs) (2-ethylhexyl-2,3,4,5-tetrabromo-benzoate (EH-TBB) and bis-(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (BEH-TEBP)) were measured in free-range chicken eggs from three e-waste recycling sites and a negative control site located in Guangdong province, Southern China. BEH-TEBP, tris-(chloroethyl)-phosphate (TCEP), tris-(chloropropyl)-phosphate (∑TCPP, two isomers) and tris-(1,3-dichloroisopropyl)-phosphate (TDCIPP) were detected in more than 50% of eggs samples with low concentrations. The median values of BEH-TEBP and total PFRs were 0.17-0.46 ng/g ww (wet weight) and 1.62-2.59 ng/g ww in eggs from the e-waste sites, respectively. The results indicate that EH-TBB, BEH-TEBP and PFRs are less persistent and bioaccumulative than polybrominated diphenyl ethers (PBDEs) in chicken eggs, and possibly also in other bio-matrices. Triphenyl phosphate (TPHP) were identified in albumen with higher frequencies, but at similar concentrations compared to yolk, while BEH-TEBP was mainly detected in yolk. The estimated daily intake (EDI) of BEH-TEBP and total PFRs from consumption of chicken eggs ranged from 0.03 to 0.09 and 0.32-0.52 ng/kg bw/day for adults, and 0.20-0.54 and 1.89-3.02 ng/kg bw/day for children in e-waste sites, respectively. Indoor dust ingestion seems to be a more important pathway for the intake of these FRs, while egg consumption is probably a more important exposure pathway for PBDEs.


Gel-based methods in redox proteomics.
The key to understanding the full significance of oxidants in health and disease is the development of tools and methods that allow the study of proteins that sense and transduce changes in cellular redox. Oxidant-reactive deprotonated thiols commonly operate as redox sensors in proteins and a variety of methods have been developed that allow us to monitor their oxidative modification. This outline review specifically focuses on gel-based methods used to detect, quantify and identify protein thiol oxidative modifications. The techniques we discuss fall into one of two broad categories. Firstly, methods that allow oxidation of thiols in specific proteins or the global cellular pool to be monitored are discussed. These typically utilise thiol-labelling reagents that add a reporter moiety (e.g. affinity tag, fluorophore, chromophore), in which loss of labelling signifies oxidation. Secondly, we outline methods that allow specific thiol oxidation states of proteins (e.g. S-sulfenylation, S-nitrosylation, S-thionylation and interprotein disulfide bond formation) to be investigated. A variety of different gel-based methods for identifying thiol proteins that are sensitive to oxidative modifications have been developed. These methods can aid the detection and quantification of thiol redox state, as well as identifying the sensor protein. By understanding how cellular redox is sensed and transduced to a functional effect by protein thiol redox sensors, this will help us better appreciate the role of oxidants in health and disease. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.


Mycobacterium abscessus cellulitis and multifocal abscesses of the breasts in a transsexual from illicit intramammary injections of silicone.
We report the case of a 29-year-old transsexual who developed Mycobacterium abscessus infection after receiving intramammary liquid silicone injections in the nonphysician office setting. Our patient represents 1 of 14 confirmed and 11 suspected cases in New York City of M abscessus infection after illicit cosmetic procedures. As injectable cosmetic procedures are becoming increasingly popular, dermatologists should be aware of both the common and unusual complications. Furthermore, all physicians should be alerted to the current cluster of M abscessus infections after injections for cosmetic purposes by nonmedical practitioners in New York City.


Azo dye decolorization assisted by chemical and biogenic sulfide.
The effectiveness of chemical and biogenic sulfide in decolorizing three sulfonated azo dyes and the robustness of a sulfate-reducing process for simultaneous decolorization and sulfate removal were evaluated. The results demonstrated that decolorization of azo dyes assisted by chemical sulfide and anthraquinone-2,6-disulfonate (AQDS) was effective. In the absence of AQDS, biogenic sulfide was more efficient than chemical sulfide for decolorizing the azo dyes. The performance of sulfate-reducing bacteria in attached-growth sequencing batch reactors suggested the absence of competition between the studied azo dyes and the sulfate-reducing process for the reducing equivalents. Additionally, the presence of chemical reduction by-products had an almost negligible effect on the sulfate removal rate, which was nearly constant (94%) after azo dye injection.


The PHAR-QA Project: Competency Framework for Pharmacy Practice-First Steps, the Results of the European Network Delphi Round 1.
PHAR-QA, funded by the European Commission, is producing a framework of competences for pharmacy practice. The framework is in line with the EU directive on sectoral professions and takes into account the diversity of the pharmacy profession and the on-going changes in healthcare systems (with an increasingly important role for pharmacists), and in the pharmaceutical industry. PHAR-QA is asking academia, students and practicing pharmacists to rank competences required for practice. The results show that competences in the areas of "drug interactions", "need for drug treatment" and "provision of information and service" were ranked highest whereas those in the areas of "ability to design and conduct research" and "development and production of medicines" were ranked lower. For the latter two categories, industrial pharmacists ranked them higher than did the other five groups.


Batch and dynamic sorption of Ni(II) ions by activated carbon based on a native lignocellulosic precursor.
Vinal-derived Activated Carbon (VAC) developed by phosphoric acid activation of sawdust from Prosopis ruscifolia native wood was tested for the adsorption of Ni(II) ions from dilute solutions in both batch and dynamic modes, comparing it with a Commercial Activated Carbon (CAC). Batch experiments were performed to determine adsorption kinetics and equilibrium isotherms for both carbons. It was possible to remove near 6.55 mg Ni g(-1) VAC and 7.65 mg Ni g(-1) CAC after 5 h and 10 h contact time, respectively. A pseudo second order equation fitted well with the kinetics of the process, and Langmuir adsorption model was used to adjust the experimental results concerning the adsorption isotherm. The parameters obtained indicate a stronger interaction between sorbent and sorbate for VAC (K = 26.56 L mmol(-1)) than for CAC (K = 19.54 L mmol(-1)). Continuous experiments were performed in a fixed-bed column packed with the investigated carbons, evaluating the influence of operational parameters such as flow rate, bed height and feed concentration on the breakthrough curves obtained. The breakthrough occurred more slowly for low concentrations of the metal ion in the feed, low flow rates and high bed height. The breakthrough curves were properly represented by Hall's model for both carbon types. Regeneration of the vinal activated carbon in column was tested, obtaining the same breakthrough curve in a new cycle of use. Finally, vinal-derived activated carbon can effectively be used to treat wastewater having until 30 ppm Ni(II).


A modified algorithm for choosing the most appropriate intraoperative pacemaker mode for patients with permanent pacemaker in non-cardiac surgery.
To avoid the risk of R-on-T incident and the unnecessary decrease of cardiac output, we devised an algorithm consisting of six steps for choosing the most appropriate intraoperative pacemaker (PM) mode, which is modified from Heart Rhythm Society and the American Society of Anesthesiologists expert consensus statement. Following this algorithm, we reviewed previous operations at our hospital to evaluate the appropriateness of the choices. Six of 78 cases (7.7%) were unfit to the algorithm because of an inappropriate mode change. The PM mode was changed preoperatively in four patients, even though the surgical site was under the umbilicus. In one case of the two other cases, the PM mode was changed from AAI to VOO. This case could not be avoided by the previous algorithm of the expert clinical statements. In another case, the anesthesiologist did not change PM mode even though the patient underwent parotidectomy and his heart rate depended on PM. Prospective research on this algorithm could clarify its usefulness in the future. Moreover, discussions about this algorithm could help develop this field of study and improve the intraoperative management of PMs.


Use of tartaric acid resistance of beta-glucuronidase for the characterization of cancer cells in pleural effusions.
Tartaric acid was shown to have an inhibiting effect on beta-glucuronidase staining in mesothelial cells and macrophages but not in malignant cells in pleural effusions. Staining for beta-glucuronidase with tartaric acid inhibition is thus suggested for the differentiation of cancer cells from mesothelial cells and macrophages in effusions.


Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes.
JC virus is a neurotropic virus that causes the demyelinating disease progressive multifocal leukoencephalopathy in humans. In order to understand the neurotropic nature of this virus, we examined the binding of nuclear proteins to the viral regulatory region. A close association of nuclear factor-1 (NF-1) and Jun protein binding sites was found. These binding sites were either adjacent or overlapped each other. Depending on the order of binding, there was some interference of binding of the NF-1 protein by Jun even at a non-Jun binding site. This suggests that there may be a direct interaction between these proteins. Examination of the regulatory region of a number of genes expressed in the central and peripheral nervous systems revealed that many of these genes apparently have adjacent NF-1 and activator protein binding sites immediately upstream from the mRNA start site. Since it had been demonstrated that nuclear proteins from brain and non-brain cells could interact with these sites, it is probable that the NF-1- and Jun-related proteins which interact at these sites are involved in the basal activity of these genes. It appears that adjacent binding sites for NF-1 and Jun immediately upstream from the mRNA start site may be a characteristic of many genes expressed in the nervous system.


Performance evaluation of two SARS-CoV-2 IgG/IgM rapid tests (Covid-Presto and NG-Test) and one IgG automated immunoassay (Abbott).
The aim of this study was to assess the analytical performances, sensitivity and specificity, of two rapid tests (Covid- Presto® test rapid Covid-19 IgG/IgM and NG-Test® IgM-IgG COVID-19) and one automated immunoassay (Abbott SARS-CoV-2 IgG) for detecting anti- SARS-CoV-2 antibodies. This study was performed with: (i) a positive panel constituted of 88 SARS-CoV-2 specimens collected from patients with a positive SARS-CoV-2 RT-PCR, and (ii) a negative panel of 120 serum samples, all collected before November 2019, including 64 samples with a cross-reactivity panel. Sensitivity of Covid-Presto® test for IgM and IgG was 78.4% and 92.0%, respectively. Sensitivity of NG-Test® for IgM and IgG was 96.6% and 94.9%, respectively. Sensitivity of Abbott IgG assay was 96.5% showing an excellent agreement with the two rapid tests (κ = 0.947 and κ = 0.936 for NGTest ® and Covid-Presto® test, respectively). An excellent agreement was also observed between the two rapid tests (κ = 0.937). Specificity for IgM was 100% and 86.5% for Covid-Presto® test and NG-Test®, respectively. Specificity for IgG was 92.0%, 94.9% and 96.5% for Covid-Presto®, NGTest ®, and Abbott, respectively. Most of the false positive results observed with NG-Test® resulted from samples containing malarial antibodies. In conclusion, performances of these 2 rapid tests are very good and comparable to those obtained with automated immunoassay, except for IgM specificity with the NG-Test®. Thus, isolated IgM should be cautiously interpreted due to the possible false-positive reactions with this test. Finally, before their large use, the rapid tests must be reliably evaluated with adequate and large panel including early seroconversion and possible cross-reactive samples.


Exact peak compression factor in linear gradient elution. I. Theory.
The only existing expression for the peak compression factor in linear gradient elution chromatography assumes that the linear-solvent-strength model (LSSM) applies to the retention of the compound studied, that the column efficiency is independent of the mobile phase composition, and that, during gradient elution, the relative retention factor of a compound inside its band varies linearly with the distance from the band center. Because the retention factors of many analytes in reversed-phase liquid chromatography do not rigorously follow the LSSM, we extend the theoretical approach of Poppe et al. to the prediction of peak compression factors in linear gradient elution chromatography for any retention model, when column efficiency varies with the mobile phase composition. Only the contribution of the chromatographic column to the peak compression was taken into account, the contribution of the dwell volume being neglected. A second restriction is the linearity of the relative retention factor as a function of the position along the band width inside the column. These constraints could be the sources for the difference observed between experimental and theoretical values of peak compression factors. When the retention factor varies steeply with the mobile phase composition, such as with proteins or large peptides in RP-HPLC, it is found that the thermodynamic compression term, which tends to sharpen the peak, is coupled with the column dispersion term, which tends to broaden the peak. This coupling term acts as an apparent dispersion term, contributing to broaden the peak. This result is consistent with the measurements of peak compression factors found in the literature.


Patterns of rod proliferation in deep-sea fish retinae.
In a sample of 37 species of deep-sea fish species from the sea floor of the Porcupine Seabight and the Gobal spur (North Atlantic) we investigated the overall structure of the retina with special respect for the organization of rods, their length and their arrangement in multiple banks. Using an immunocytochemical marker for cell proliferation (PCNA) we studied the mechanisms of rod proliferation, and, by means of serial section reconstruction followed their integration into the existing population of rods. Furthermore, in three different species we have observed growth related changes in retinal thickness, rod density and proliferation activity. We found evidence for two different principles for the organization of rods in these deep-sea fish retinae. In the first group of species represented by Nematonurus armatus and Coryphaenoides guentheri we found rods to be rather short (20-30 microns) and arranged in three and more banks. In these species rod proliferation occurred in a single band of cells immediately vitread of the external limiting membrane, thus showing a high degree of spatial and temporal order. In these species, young rods are inserted just sclerad of the external limiting membrane and the older outer segments pushed away from the incoming light towards the back of the eye. This may be linked to a progressive loss of function of the older rods and might represent an alternative mechanism to the disk shedding in other vertebrates. In the second population (e.g. Conocara macroptera, Alepocephalus agassizii) we observed considerably longer rod outer segments (60-80 microns) forming no more than two layers. These retinae had rod precursors arranged in disseminated clusters throughout the outer nuclear layer indicating the lack of clear spatio-temporal order in mitotic activity along with a more statistical pattern of integration of the newly formed outer segments. In our sample of species both populations were of about equal size suggesting that the two mechanisms are equally effective and may have arisen independently.


Prediction of RNA-binding amino acids from protein and RNA sequences.
Many learning approaches to predicting RNA-binding residues in a protein sequence construct a non-redundant training dataset based on the sequence similarity. The sequence similarity-based method either takes a whole sequence or discards it for a training dataset. However, similar sequences or even identical sequences can have different interaction sites depending on their interaction partners, and this information is lost when the sequences are removed. Furthermore, a training dataset constructed by the sequence similarity-based method may contain redundant data when the remaining sequence contains similar subsequences within the sequence. In addition to the problem with the training dataset, most approaches do not consider the interacting partner (i.e., RNA) of a protein when they predict RNA-binding amino acids. Thus, they always predict the same RNA-binding sites for a given protein sequence even if the protein binds to different RNA molecules. We developed a feature vector-based method that removes data redundancy for a non-redundant training dataset. The feature vector-based method constructed a larger training dataset than the standard sequence similarity-based method, yet the dataset contained no redundant data. We identified effective features of protein and RNA (the interaction propensity of amino acid triplets, global features of the protein sequence, and RNA feature) for predicting RNA-binding residues. Using the method and features, we built a support vector machine (SVM) model that predicted RNA-binding residues in a protein sequence. Our SVM model showed an accuracy of 84.2%, an F-measure of 76.1%, and a correlation coefficient of 0.41 with 5-fold cross validation on a non-redundant dataset from 3,149 protein-RNA interacting pairs. In an independent test dataset that does not include the 3,149 pairs and were not used in training the SVM model, it achieved an accuracy of 90.3%, an F-measure of 72.8%, and a correlation coefficient of 0.24. Comparison with other methods on the same datasets demonstrated that our model was better than the others. The feature vector-based redundancy reduction method is powerful for constructing a non-redundant training dataset for a learning model since it generates a larger dataset with non-redundant data than the standard sequence similarity-based method. Including the features of both RNA and protein sequences in a feature vector results in better performance than using the protein features only when predicting the RNA-binding residues in a protein sequence.


Derivatives of ColE1 cer show altered topological specificity in site-specific recombination.
ColE1 contains a 250-bp sequence (cer) which is required in cis for the conversion of plasmid dimers to monomers. Recombination between cer and parB (a dimer resolution site from plasmid CloDF13) occurs in vivo at low frequency. The properties of the resulting hybrid sites have been studied. The type I hybrid closely resembles wild-type cer. It supports intramolecular recombination and requires the products of the chromosomal xerA, xerB and xerC genes together with the 250-bp site. In contrast, the type II hybrid (although differing from type I by only 2 bp) functions independently of the topological relationship of the participating sites, supporting both inter- and intramolecular recombination. Furthermore, recombination between type II sites is independent of the products of the xerA and xerB genes and requires a site of less than 50 bp.


Two-fold transmission reach enhancement enabled by transmitter-side digital backpropagation and optical frequency comb-derived information carriers.
We demonstrate a two-fold reach extension of 16 GBaud 16-Quadrature Amplitude Modulation (QAM) wavelength division multiplexed (WDM) system based on erbium doped fiber amplifier (EDFA)-only amplified standard and single mode fiber -based link. The result is enabled by transmitter-side digital backpropagation and frequency referenced carriers drawn from a parametric comb.


Mosses in biotechnology.
Biotechnological exploitation of mosses has several aspects, for example, the use of moss extracts or the whole plant for diverse industrial applications as well as their employment as production platforms for valuable metabolites or pharmaceutical proteins, especially using the genetically and developmentally best-characterised model moss Physcomitrella patens. Whole moss plants, in particular peat mosses (Sphagnum spec.), are useful for environmental approaches, biomonitoring of environmental pollution and CO2-neutral 'farming' on rewetted bogs to combat climate change. In addition, the lifestyle of mosses suggests the evolution of genes necessary to cope with biotic and abiotic stress situations, which could be applied to crop plants, and their structural features bear an inspiring potential for biomimetics approaches.


Optimal positive end-expiratory pressure (PEEP) settings in differential lung ventilation during simultaneous unilateral pneumothorax and laparoscopy: an experimental study in pigs.
A combined thoraco-laparoscopic technique for esophageal resection is technically possible, but it requires special attention to ventilation. The positive insufflation pressure normally used in laparoscopy will, when communication between thorax and abdomen is established, create a pneumothorax. We performed an experimental study of differential lung ventilation with different levels of positive end-expiratory pressure (PEEP) settings during thoraco-laparoscopy in anesthetized pigs. Positive pressure insufflation of carbon dioxide (CO2) resulted in elevated pulmonary capillary wedge pressure, hypercarbia, and respiratory acidosis. Hypoxemia, however, developed only at lower settings of PEEP. Heart rate, mean arterial pressure, and cardiac output remained relatively stable. Pneumopleuroperitoneum under positive CO2 insufflation pressure had adverse effects on blood gases. Hypercarbia, respiratory acidosis, and hypoxemia were early manifestations that occurred even in the presence of hemodynamic stability. The application of PEEP equal to or above CO2 insufflation pressure improved blood gases; in particular, the hypoxia could be avoided. No beneficial effects of differential lung ventilation were documented.


The effects of electronic nicotine vapor on voluntary alcohol consumption in female and male C57BL/6 J mice.
Alcohol drinking and nicotine vaping often co-occur and dependence on both substances is common. However, the impact of nicotine vaping on alcohol consumption is not fully understood. We examined the effects of nicotine vaping on ethanol drinking in female and male C57BL/6 J mice using an electronic nicotine delivery system and intermittent access two-bottle choice (IA-2BC) drinking. Mice were exposed to electronic nicotine vapor (3%) or propylene glycol/vegetable glycerol (PG/VG) control for 3 h sessions daily for 4 weeks and voluntary alcohol consumption was monitored. Nicotine vapor exposure was stopped and voluntary alcohol drinking was measured for a 2 week abstinence period. We also examined the effects of alcohol and nicotine on locomotion, temperature, and nicotine metabolism. Following acute nicotine vapor exposure, alcohol drinking was increased in males but not in females. Thermoregulation was disrupted following nicotine vapor exposure and voluntary drinking. Male and female mice displayed increased locomotor activity immediately following chronic nicotine vapor exposure, and an anxiolytic effect was seen in males. In nicotine vapor abstinence, female mice displayed increased alcohol consumption. Locomotor activity and anxiolytic effects remained elevated in male but not female mice. Female mice displayed higher levels of serum nicotine and hydroxycotinine, suggesting impaired metabolism following chronic drinking and nicotine vapor exposure. Collectively, these results suggest that while both male and female ethanol-drinking mice experience the stimulatory effects of nicotine vapor, only in males is there a parallel increase in ethanol drinking and only females display impairments in nicotine metabolism after drinking.


Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium.
Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.


Clinical development of IDH1 inhibitors for cancer therapy.
Isocitrate dehydrogenase 1 (IDH1) has been investigated as a promising therapeutic target in select cancers with a mutated version of the enzyme (mtIDH1). With only one phase III trial published to date and two indications approved for routine clinical use by the FDA, we reviewed the entire clinical trial portfolio to broadly understand mtIDH1 inhibitor activity in patients. We queried PubMed.gov and ClinicalTrials.gov to identify published and ongoing clinical trials related to IDH1 and cancer. Progression-free survival (PFS), overall survival (OS), 2-hydroxyglutarate levels, and adverse events were summarized. To date, ten clinical trials investigating mtIDH1 inhibitors among patients with diverse malignancies (cholangiocarcinoma, acute myeloid leukemia, chondrosarcoma, glioma) have been published. Almost every trial (80%) has investigated ivosidenib. In multiple phase I trials, ivosidenib treatment resulted in promising radiographic and biochemical responses with improved survival outcomes (relative to historic data) among patients with both solid and hematologic mtIDH1 malignancies. Among patients enrolled in a phase III trial with advanced cholangiocarcinoma, ivosidenib resulted in a PFS rate of 32% at 6 months, as compared to 0% with placebo. There was a 5.2 month increase in OS with ivosidenib relative to placebo, after considering crossover. The treatment-specific grade ≥3 adverse event rate of ivosidenib was 2%-26% among all patients, and was just 3.6% among 284 patients who had a solid tumor across four trials. Although <1% of malignancies harbor IDH1 mutations, small molecule mtIDH1 inhibitors, namely ivosidenib, appear to be biologically active and well tolerated in patients with solid and hematologic mtIDH1 malignancies.


Two distinct azobenzenearsonate-specific helper T-cell subpopulations mediate different forms of T-B cooperation.
Popliteal lymph node T cells from mice footpad-primed with azobenzenearsonate (ABA)-protein conjugates were able to help the anti-trinitrophenyl (TNP) and anti-ABA plaque-forming cell (PFC) responses of normal syngeneic spleen cells cultured in vitro with TNP-ABA-keyhole limpet haemocyanin. Enrichment in ABA-specific helper cells was obtained by positive selection of ABA-primed T cells on ABA-pulsed syngeneic macrophages. The ABA-specific T cells induced by ABA-protein priming are able to help the anti-TNP PFC response of normal B cells through recognition of the ABA determinant either unlinked to TNP (ABA and TNP separately presented to T and B cells) or linked to TNP (ABA and TNP presented as moieties of the same molecule). These two mechanisms of T-B cooperation are mediated by two different ABA-specific helper T-cell subpopulations, which can be distinguished by their different radiosensitivities: the former mechanism is mediated by radioresistant T cells, whereas the latter is mediated by radiosensitive T cells. Both helper T-cell subpopulations bind the ABA-pulsed syngeneic macrophages, demonstrating the presence of ABA-specific receptors on both cell types.


The effect of clofibrate feeding on the NADP-linked dehydrogenases activity in rat tissue.
Administration of clofibrate to the rat increased several fold the activity of malic enzyme in the liver. Clofibrate treatment resulted also in an increased activity of the hepatic hexose monophosphate shunt dehydrogenases but was without effect on NADP-linked isocitrate dehydrogenase. The increased activity of malic enzyme in the liver resulting from the administration of clofibrate was inhibited by ethionine and puromycin, which suggests that de novo synthesis of the enzyme protein did occur as the result of the drug action. In contrast to the liver malic enzyme, the enzyme activity in kidney cortex increased only two-fold, whereas in the heart and skeletal muscle the activity was not affected by clofibrate administration.


Suppression of the frequencies of sister chromatid exchanges in Bloom's syndrome fibroblasts by co-cultivation with Chinese hamster cells.
The effect of co-cultivation of Bloom's syndrome fibroblasts with Chinese hamster ovary cells (CHO) on the incidence of sister chromatid exchanges (SCEs) was studied. The results show that suppression of the frequency of SCEs in Bloom's syndrome cells occurs only if cell to cell contact is present with CHO cells, without any effect on the SCE frequency in the latter. It is suggested that possible genetic heterogeneity between different Bloom's syndrome patients can be studied using the method of co-cultivation.


Trisomy 18 syndrome with incomplete Cantrell syndrome.
The pentalogy of Cantrell was first described in 1958 by Cantrell and coworkers, who reported five cases in which they described a pentad of findings including a midline supraumbilical thoracoabdominal wall defect, a defect of the Lower sternum, abnormalities of the diaphragmatic pericardium and the anterior diaphragm, and congenital cardiac anomalies. Trisomy 18 has an incidence of about 0.3 per 1000 newborns. We present a case of trisomy 18 with incomplete Cantrell syndrome. The patient presented with hypogenesis of the corpus callosum, vermian-cerebellar hypoplasia (Dandy-Walker variant), ventricular septal defect, dextrocardia, patent ductus arteriosus, a defect of the lower sternum, a midline supraumbilical abdominal wall defect with omphalocele, congenital left posterior diaphragmatic hernia (Bochdalek hernia), micrognathia, low-set and malformed ears, rocker-bottom feet, dorsiflexed hallux, hypoplastic nails, short neck, and wrist deformity. Trisomy 18 syndrome was unusually combined with the pentalogy of Cantrell. We present this case because of its rarity and high risk of mortality.


Coronary arteriographic findings in cocaine abuse-induced myocardial infarction.
A 31-year-old black man was admitted with an acute anterior myocardial infarction 20 minutes after IV cocaine abuse. Cardiac catheterization showed a totally occluded left anterior descending artery. Intracoronary and intravenous streptokinase resulted in thrombolysis: repeat angiography showed a normal anterior descending.


Sex Differences in the Relationship Between Arterial Stiffness and Cognitive Function in Older Adults.
To examine potential sex differences in the relationship between arterial stiffness and global cognitive function and executive functions. Baseline data from 80 older adults were included from two randomized controlled trials (NCT02669394 and NCT02737878). Arterial stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV). Cognitive function assessment included global cognition (Mini-Mental State Examination [MMSE]) and executive functions (set shifting [Trail Making Test Part B minus A], inhibition [Stroop Test], and working memory [Verbal Digit Span Backwards Test]). Separate statistical models were constructed to assess the effect of cf-PWV on each cognitive outcome for females and males. Each statistical model controlled for Framingham cardiovascular disease risk score and education. Higher cf-PWV was associated with impaired MMSE performance in males (β = -0.48; p = 0.018), but not females (p ≥ 0.389). For executive processes, higher cf-PWV was associated with impaired Trail Making Test Part B minus A (β = 0.56; p = 0.005) and Stroop Test (β = 0.59; p = 0.004) in males, but not in females (ps ≥ 0.108). cf-PWV was not significantly associated with Verbal Digit Span Forward minus Backward Test in males or females (ps ≥ 0.108). Arterial stiffness is more strongly associated with cognitive impairment in males than females. These results further elucidate the interplay between vascular health and cognitive function by providing support for sex-specific mechanisms.


Re-thinking the online distance instruction based on students' feedback.
During the covid-19 pandemic, schools at all levels were often closed and online distance instruction (ODI) was applied. The main objective of this research was to discover the main didactic features of online distance instruction; and based on the collected data to define didactic recommendations towards improving the quality of the process. Five hypotheses were set that evaluated students' opinions in the areas of teachers' support for learners within ODI, types of sources exploited within ODI, means used for practising and fixing new knowledge within ODI, assessment of learners' performance within ODI, and students' feedback on ODI. In total, 272 respondents from upper secondary and higher education institutions participated in the research. Each respondent described the process of online distance instruction in two courses they selected of 64: (1) in a course that they appreciated, liked, enjoyed, and considered efficient from the point of view of their learning; (2) in a course that caused them discomfort in learning, as it was conducted in a way that did not suit them, and their learning did not bring the expected learning outcomes. Data were collected via a questionnaire; Chí-square test, adjusted residuals, and t test for comparison of means were calculated. Before the research started, teachers were trained in online distance instruction. Therefore, we expected that they will be competent in designing online distance courses and the courses will follow didactic principles. The results discovered significant differences in the frequency of occurrence of observed features in courses that received positive feedback compared to those having negative evaluation. However, some exceptions were detected.


Antinociceptive properties of oxymorphazole in the mouse.
Oxymorphazole (17-methyl-6,7-dehydro-3,14-dihydroxy-4,5 alpha-epoxy-6,7:3',4'-pyrazolomorphinan), a hydrophilic opioid, given intracerebroventricularly (2.5-50 nmol) or intrathecally (0.3-5 nmol) dose-dependently produced tail-flick inhibition in male CD-1 mice. However, oxymorphazole given subcutaneously even at high doses (10-80 mg/kg) produced weak tail-flick inhibition. Oxymorphazole given intraperitoneally (0.1 to 10 mg/kg) dose-dependently inhibited abdominal constriction response induced by intraperitoneally injection of 0.6% acetic acid. Oxymorphazole given intracerebroventricularly (25 nmol) or intrathecally (5 nmol) induced tail-flick inhibition was blocked by pretreatment with the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Orn-Thr-Pen-Thr-NH2, but not kappa-opioid receptor antagonist nor-binaltrophimine. The delta-opioid receptor antagonist, naltrindole, blocked the tail-flick inhibition induced by oxymorphazole given intrathecally but not intracerebroventricularly. The inhibition of the abdominal constriction response by oxymorphazole given intraperitoneally was blocked by intraperitoneally pretreatment with naloxone, but not naltrindole or nor-binaltrophimine. Thus, oxymorphazole given systemically produces antinociception only with the abdominal constriction test, but not the tail-flick test, suggesting that it produces the antinociception at the peripheral sites when administered systemically. The oxymorphazole-induced antinociception is mainly mediated by the stimulation of mu-opioid receptors when given either centrally or systemically and also the delta-opioid receptors when given intrathecally. The lack of central antinociceptive effect of oxymorphazole given systemically may have interesting clinical implications.


The demise of Archbishop Wolf Dietrich--A historical note on a fatal status epilepticus documented at Salzburg in 1617.
Wolf Dietrich of Raitenau (WD) ruled the archiepiscopal Salzburg from March 2nd 1587 to December 17th 1611. He was condemned by his successor Archbishop Markus Sittikus of Hohenems to spend his last years imprisoned at the Fortress Hohensalzburg, where he died on January 16th 1617. This historical note describes the causes of his death. The original Latin handwriting, including the detailed medical history and the autopsy of the Archbishop's body performed by his personal physician, was analyzed in conjunction with historical handwritings provided by St. Peter's Abbey, Salzburg handwriting assigned to Markus Sittikus. Wolf Dietrich of Raitenau had his first well-documented left hemispheric stroke in winter 1604/05. He had palsy of his right arm, was unable to write, and, therefore, used a stamp instead of his signature until October 1605. After another stroke, right hemispheric in origin with persisting palsy of his left arm ["leva corporis pars iam pridem simili ex apoplectico assultu in paralysin resoluta"], he developed symptomatic epilepsy with recurring seizures ["epileptico insultu quo etiam alias correptus est"]. On January 15th 1617, he suffered from a secondarily generalized convulsive status epilepticus ["toto corpore convellitur epileptico insultu"] with stertorous breathing and distortion of his face ["spuma stertore insigni faciei perversione"] and was unconscious for 8h. He recovered from coma and showed dysphagia, buccofacial apraxia ["abolitam diglutiendi facultatem"], reversible speech disturbance ["accisa etiam verba loqui"], and left-sided hemiplegia ["leva corporis pars… immobilis prorsus est reddita"]. The following day, he had speech disturbances, and he died at noon. His autopsy showed large but intact liver ["hepar magnum sanum"] and heart ["cor magnum in quo lapsus nullus"]. There was intrapulmonal mucus ["pituita imbutus"], and part of the lungs adhered to its pleura. He had five kidney stones and a partly cirrhotic spleen. The cause of his death was assumed to be intracerebral ["causa mortis in capite requienda fuisset"]. The terminal suffering of Wolf Dietrich of Raitenau is the first witnessed case report on a fatal status epilepticus in Salzburg. Most likely, he suffered from vascular epilepsy due to a right hemispheric stroke, leading to status epilepticus with left-sided Todd's palsy and speech disturbances. An acute symptomatic etiology of this disease cannot be ruled out, as for religious reasons, the Archbishop's brain was not autopsied. Meticulous medical reporting including autopsy was already available in Salzburg in 1617, and the symptomatic etiology of epilepsy was diagnosed correctly. This article is part of a Special Issue entitled "Status Epilepticus".


Individual differences in radial maze performance and locomotor activity in the meadow vole, Microtus pennsylvanicus.
Individual differences in the radial maze performance and locomotor activity of wild-caught and first-generation laboratory-born meadow voles are described. Based on their patterns of response in an eight-arm radial maze the essentially wild voles fell into three behavioral categories: 1) strict algorithmic (i.e., they systematically chose the next adjacent arm to their previous choice); 2) nonalgorithmic (i.e., they ran the maze without any consistent or definable pattern); and 3) nonrunners (i.e., nonperformers of the task who remained relatively immobile in the arms of the maze). The algorithmic and nonalgorithmic voles further differed in their responses to an interference manipulation of the radial maze task. Algorithmic individuals displayed a marked performance deficit, while the nonalgorithmic individuals showed minimal disruption to a 1-min delay interruption of the maze task. Measurements of several aspects of locomotor activity using the automated Digiscan activity monitoring system revealed that the algorithmic individuals also displayed significantly greater levels of activity than the nonalgorithmic or nonrunners, with no significant difference in activity between the latter two groups. These findings suggest that the algorithmic voles were relatively inflexible in their behavior, while the nonalgorithmic individuals were more flexible in their maze performance and likely in their use of spatial and nonspatial information. These individual differences in laboratory measures of learning behavior and locomotor activity in meadow voles are consistent with the polymorphism that is proposed to occur in the wild.


Peptides in the cerebrospinal fluid of neuropsychiatric patients: an approach to central nervous system peptide function.
This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.


Nanocarriers to Enhance the Accumulation of Vitamin K1 into the Skin.
Vitamin K1 (VK1) is a molecule abundant in some species of leaf vegetables with beneficial effects in humans following administration on the skin. This work investigates the possibility to use formulations based on lipid vesicles, namely liposomes, transfersomes and ethosomes, suitable to be administered on the skin by nebulization and alternative to fat semisolid preparations present on the market. Lipid vesicles encapsulating VK1 were prepared and characterized. Ex-vivo experiments on Franz cells were carried out to study the VK1 accumulation/permeation in/through the skin. Vesicles interaction with the skin was investigated by confocal laser scanning microscopy (CLSM) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. All developed carriers were stable following long-term storage and were not altered following nebulization. In ex-vivo experiments, vesicles with the highest deformability index, namely transfersomes and ethosomes, led to an enhanced VK1 accumulation/permeation into/through the skin. Interestingly, the nebulization of the vesicles led to a further increase of VK1 accumulation into the skin. In conclusion, to achieve a local effect of VK1 on the skin, the topical nebulization of VK1-containing transfersomes could offer a good compromise between a high VK1 penetration into the skin and a limited permeation through it.


Environmental transport in the Oil Shale Risk Analysis.
The Oil Shale Risk Analysis differs from similar efforts in coal and nuclear energy in that the industry is not yet developed to a commercial scale. Many assumptions are necessary to predict the future oil shale industry pollutants, the environmental transport of these pollutants, and subsequent human health and environmental effects. The environmental transport analysis in the Oil Shale Risk Analysis is used as an example of applying assumptions to the best available data to predict potential environmental effects of a future commercial industry. The analysis provides information to aid in formulating and managing a program of environmental research focused on reducing uncertainties in critical areas.


Azathioprine and acute pancreatitis: studies with an isolated perfused canine pancreas.
Recent controlled clinical trials have documented the development of acute pancreatitis in 5% of patients receiving azathioprine for Crohn's disease, by far the highest incidence of drug-induced pancreatitis recorded to date. In an effort to evaluate the effects of azathioprine on the pancreas, the isolated ex vivo perfused canine pancreas model was used. No significant changes in gross appearance, weight, or serum amylase occurred in azathioprine-treated glands compared to controls. Azathioprine administration, however, resulted in a significant increase in secretory volume (two fold) and bicarbonate output (two fold), and a profound depression of trypsin output compared to controls. These preliminary studies demonstrate that azathioprine has marked effect on pancreatic function in this model.


New robust subtilisins from halotolerant and halophilic Bacillaceae.
The aim of the present study was the characterisation of three true subtilisins and one phylogenetically intermediate subtilisin from halotolerant and halophilic microorganisms. Considering the currently growing enzyme market for efficient and novel biocatalysts, data mining is a promising source for novel, as yet uncharacterised enzymes, especially from halophilic or halotolerant Bacillaceae, which offer great potential to meet industrial needs. Both halophilic bacteria Pontibacillus marinus DSM 16465T and Alkalibacillus haloalkaliphilus DSM 5271T and both halotolerant bacteria Metabacillus indicus DSM 16189 and Litchfieldia alkalitelluris DSM 16976T served as a source for the four new subtilisins SPPM, SPAH, SPMI and SPLA. The protease genes were cloned and expressed in Bacillus subtilis DB104. Purification to apparent homogeneity was achieved by ethanol precipitation, desalting and ion-exchange chromatography. Enzyme activity could be observed between pH 5.0-12.0 with an optimum for SPPM, SPMI and SPLA around pH 9.0 and for SPAH at pH 10.0. The optimal temperature for SPMI and SPLA was 70 °C and for SPPM and SPAH 55 °C and 50 °C, respectively. All proteases showed high stability towards 5% (w/v) SDS and were active even at NaCl concentrations of 5 M. The four proteases demonstrate potential for future biotechnological applications. KEY POINTS: • Halophilic and halotolerant Bacillaceae are a valuable source of new subtilisins. • Four new subtilisins were biochemically characterised in detail. • The four proteases show potential for future biotechnological applications.


[Rare pulmonary mycoses in patients with hematologic diseases].
Patients with hematology disease in post-chemotherapy medullary aplasia are susceptible to life-threatening bronchopulmonary mycoses, especially aspergillosis. Other less common pulmonary mycoses are also observed. We report 4 cases due to Penicillium purpurogenum, Acromonium strictum and Scedosporium apiospermum (n = 2) infections. These unusual fungi appear to be emerging as pathogens in this population. They have common ubiquitous, opportunistic and low pathogenicity characteristics in immunocompetent subjects. The major risk factor is neutropenia. Isolating one of these fungi in an immunodepressed patient modifies management protocols since certain unusual fungi such as Scedosporium are resistant to amphotericin B.


ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway.
A disintegrin and metalloproteinase-17 (ADAM17) is a member of the metalloproteinase superfamily and involved in the cleavage of ectodomain of many transmembrane proteins. ADAM17 is overexpressed in a variety of human tumors, which is associated with tumor development and progression. In the present study, we sought to investigate the expression and function of ADAM17 in hypoxia-treated hepatocellular carcinoma (HCC) cells. Western blot analysis was used to measure the expression of ADAM17 in HCC cell lines (Hep3B and HepG2 cells). Annexin V/PI double staining was performed to analyze the effects of ADAM17 on hypoxia-mediated cisplatin resistance. ADAM17 expression was upregulated by hypoxia treatment in HCC cells at both mRNA and protein levels. Overexpression of ADAM17 reduced cisplatin-induced apoptosis in HCC cells, accompanies by less cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Forced expression of ADAM17 enhanced the phosphorylation of epidermal growth factor receptor (EGFR) and Akt without affecting the expression of total EGFR and Akt. Pretreatment with EGFR inhibitor AG1478 or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 rescued ADAM17-mediated cisplatin resistance of HCC cells. ADAM17 silencing attenuated hypoxia-induced cisplatin resistance and enhanced the accumulation of cleaved caspase-3 and PARP. Western blot analysis showed that overexpression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor, upregulated the expression of ADAM17 and HIF-1α silencing downregulated the expression of ADAM17 in hypoxia-treated HCC cells, indicating the regulation of ADAM17 by HIF-1α. Taken together, our results indicated that ADAM17 is upregulated by hypoxia and contributes to hypoxia-induced cisplatin resistance via EGFR/PI3K/Akt pathway.


On-line solid phase extraction using organic-inorganic hybrid monolithic columns for the determination of trace β-lactam antibiotics in milk and water samples.
A rapid and simple method with on-line solid phase extraction (SPE) has been developed for the simultaneous determination of beta-lactam antibiotics (BLAs) (amoxicillin, cephradine, and cefazolin sodium) in aquatic environment and milk. The epoxy-based organic-inorganic hybrid monolithic column was used as SPE sorbent to simultaneously monitor three analytes. The morphology of monolithic column and pressure drop across the columns were characterized. Excellent permeability and high selectivity were obtained. The linear range of the standard curve was from 2.0 to 500 ng/mL (r(2)≥0.999). Precision for inter- and intra-day assay showed acceptable results for quantitative assay with relative standard deviation (RSD) less than 11%. The accuracy and recovery were found to be within the range of 93-103% and 83-105%. The results indicated that the prepared monolithic column could provide excellent reproducibility and implied that the prepared monolith was feasible to be used as an on-line SPE sorbent material.


Cell cycle effects and cellular pharmacology of 5-aza-2'-deoxycytidine.
The cytotoxic action of 5-aza-2'-deoxycytidine (5-AZA-CdR) in synchronized cells and logarithmic- and plateau-phase cultures of EMT6 murine tumor cells was investigated. 5-AZA-CdR produced a greater cell kill of S phase cells than of cells in G1 phase. Cells in the logarithmic phase of growth were more sensitive to the cytotoxic effects of 5-AZA-CdR than cells in the plateau phase of growth. These results indicate that 5-AZA-CdR produces a preferential kill of cells in the S phase of the cell cycle. 5-AZA-CdR did not block the cell cycle progression of cells into S phase. The survival curve of EMT6 cells exposed to 5-AZA-CdR suggests that the cytotoxic action of this analogue is not self-limiting. The mutagenic activity of 5-AZA-CdR was investigated using induction of 6-thioguanine resistance in Chinese hamster ovary cells. 5-AZA-CdR was not a detectable mutagen in this assay system.


A national survey of Neurology Vice Chairs For Education.
A growing number of Neurology Departments have appointed a Neurology Vice Chair for Education (NVCE), yet the roles and responsibilities of an NVCE have not been previously described in the literature. A group of current NVCEs developed a survey that was sent to all NVCEs in the US via a secure, anonymous survey. Questions included roles and responsibilities, sources of support, metrics to determine success, faculty development, basic demographics and education scholarship engagement. Response rate was 27 of 45 NVCEs (60%). Among the respondents, 70% have been in the role 5 years or less and the NVCE role existed for 5 years or less in 60% of departments. Eighteen percent were provided with a written job description, and 63% never received any job description. Most common responsibilities included overseeing student (78%), resident (78%), and fellowship (74%) education, participation in education section of an annual report (67%) and oversight of education scholarship (59%). Fifty-two percent reported no specific funding for the NVCE role. Most were prior program directors (59%), male (61%) and White (85%). The NVCE role is new, and few have written job descriptions or specific funding for the role. They oversee education across the continuum of learners in their departments, communicate the education mission in an annual report and oversee educational scholarship. Most were not formally trained for the role and previously served in other education leadership roles. These data will be useful to programs in creating job descriptions and goals for the NVCE role.


[Construction of a non-viral vector H1s-EGFc and a preliminary study on its function].
To construct a non-viral vector for targeting cancer gene therapy. The coding sequence of H1s-EGFc was inserted into the expression vectors of Pichia pastoris, and the fusion protein was expressed in secretary way. H1s-EGFc was purified by anion exchange chromatography and size exclusion chromatography. H1s-EGFc fusion protein and "killing gene" expression recombinant pKG plasmid DNA were dissolved in serum-free RPMI-1640 culture to produce H1s-EGFc/pKG complex. HeLa cells, an epidermal growth factor receptor (EGFR) highly expressing cell line, and Jurkat cells, an EGFR non-expressing cell line, were cultured and transfected with H1s-EGFc/pKG complex of different concentrations. Trypan blue staining was used to calculate the number of live cells and the killing rate of H1s-EGFc/pKG. H1s-EGFc fusion protein was constructed and expressed with a purity of over 90%. When the concentrations of H1s-EGFc/pKG complex were 3 microg/ml, 6 microg/ml, and 9 microg/ml respectively the killing rates were 30.6%, 36.2%, and 58.1% respectively. The fusion protein H1s-EGFc binds functional gene efficiently and targets it into specific cells. It can be used as non-viral vector in target cancer gene therapy.


The association of vitamin D with bone microarchitecture, muscle strength, and mobility performance in older women in long-term care.
Osteoporosis and sarcopenia are prevalent in older adults. Trabecular bone score (TBS) is a novel method to evaluate bone microarchitecture, whereas grip strength and gait speed are simple methods to assess muscle strength and function. Few studies have linked the relationship between vitamin D levels (25OHD) with TBS, grip strength, and gait speed in healthy community dwelling adults. We sought to investigate this relationship in older women with osteoporosis and multiple comorbid conditions residing in long-term care (LTC) facilities. We analyzed baseline 25OHD, spine TBS, grip strength, and gait speed in 246 women with osteoporosis who were residents of LTC and enrolled in a randomized controlled clinical trial. On average, participants were 81.6 years old and had a BMI of 26.8 kg/m2. The correlation (r) of 25OHD with spine TBS, grip strength, and gait speed were (r = 0.15; p = 0.0208), (r = - 0.05; p = 0.4686), and (r = 0.19; p = 0.0041), respectively. Each 5 ng/dl increase in 25OHD was associated with an increase of 0.006 in spine TBS and 0.014 m/s in gait speed. After adjusting for covariates, each 5 ng/dl increase in 25OHD was associated with an increase of 0.004 in spine TBS (p = 0.0599) and 0.012 m/s in gait speed (p = 0.0144). In older women residing in LTC facilities, 25OHD was associated with spine TBS and gait speed. The strengths of the associations suggest there may be other factors with a more prominent role in bone microarchitecture, muscle strength, and physical function in this population. Our study found in older women who are residents of long-term care facilities, vitamin D level is associated with bone microarchitecture and mobility performance.