The potential of residues of furfural and biogas as calcareous soil amendments for corn seed production.
Intensive corn seed production in Northwest of China produced large amounts of furfural residues, which represents higher treatment cost and environmental issue. The broad calcareous soils in the Northwest of China exhibit low organic matter content and high pH, which led to lower fertility and lower productivity. Recycling furfural residues as soil organic and nutrient amendment might be a promising agricultural practice to calcareous soils. A 3-year field study was conducted to evaluate the effects of furfural as a soil amendment on corn seed production on calcareous soil with compared to biogas residues. Soil physical-chemical properties, soil enzyme activities, and soil heavy metal concentrations were assessed in the last year after the last application. Corn yield was determined in each year. Furfural residue amendments significantly decreased soil pH and soil bulk density. Furfural residues combined with commercial fertilizers resulted in the greater cumulative on soil organic matter, total phosphorus, available phosphorus, available potassium, and cation exchange capacity than that of biogas residue. Simultaneously, urease, invertase, catalase, and alkaline phosphatase increased even at the higher furfural application rates. Maize seed yield increased even with lower furfural residue application rates. Furfural residues resulted in lower Zn concentration and higher Cd concentration than that of biogas residues. Amendment of furfural residues led to higher soil electrical conductivity (EC) than that of biogas residues. The addition of furfural residues to maize seed production may be considered to be a good strategy for recycling the waste, converting it into a potential resource as organic amendment in arid and semi-arid calcareous soils, and may help to reduce the use of mineral chemical fertilizers in these soils. However, the impact of its application on soil health needs to be established in long-term basis.


Stability and instability of a neuron network with excitatory and inhibitory small-world connections.
This study considers a delayed neural network with excitatory and inhibitory shortcuts. The global stability of the trivial equilibrium is investigated based on Lyapunov's direct method and the delay-dependent criteria are obtained. It is shown that both the excitatory and inhibitory shortcuts decrease the stability interval, but a time delay can be employed as a global stabilizer. In addition, we analyze the bounds of the eigenvalues of the adjacent matrix using matrix perturbation theory and then obtain the generalized sufficient conditions for local stability. The possibility of small inhibitory shortcuts is helpful for maintaining stability. The mechanisms of instability, bifurcation modes, and chaos are also investigated. Compared with methods based on mean-field theory, the proposed method can guarantee the stability of the system in most cases with random events. The proposed method is effective for cases where excitatory and inhibitory shortcuts exist simultaneously in the network.


A new therapy for refractory partial epilepsy: current shunt.
A large number of epileptic patients suffer from refractory epilepsy, despite optimal treatment; thus these patients require new therapeutic approaches. Focal seizure activity is typically initiated in a fixed and localized region, which subsequently spreads to neighboring regions or more distant areas. At the initial onset of a seizure, the epileptic discharge will generate a relatively high voltage in seizure focus, and the discharge subsequently spreads to other relatively low-voltage regions. However, it is unknown whether seizure can be controlled through current shunt using a conduction microelectrode to conduct the epileptic discharge with a relatively high voltage in the seizure focus outside the brain. The current therapies for epilepsy, including drugs, resective surgery and neuromodulation, focus on inhibiting abnormal excessive or synchronous neuronal activity to control seizures; thus, the basic mechanism underlying these therapies is "inhibition". In contrast, we proposed a "conduction" mechanism, whereby a current shunt with conduction electrode is used to control seizures. To our knowledge, this therapeutic strategy has not been previously reported, and we propose that this approach might be an alternative choice for the treatment of refractory partial epilepsy in the future.


Radiocarbon Production Events and their Potential Relationship with the Schwabe Cycle.
Extreme cosmic radiation events occurred in the years 774/5 and 993/4 CE, as revealed by anomalies in the concentration of radiocarbon in known-age tree-rings. Most hypotheses point towards intense solar storms as the cause for these events, although little direct experimental support for this claim has thus far come to light. In this study, we perform very high-precision accelerator mass spectrometry (AMS) measurements on dendrochronological tree-rings spanning the years of the events of interest, as well as the Carrington Event of 1859 CE, which is recognized as an extreme solar storm even though it did not generate an anomalous radiocarbon signature. Our data, comprising 169 new and previously published measurements, appear to delineate the modulation of radiocarbon production due to the Schwabe (11-year) solar cycle. Moreover, they suggest that all three events occurred around the maximum of the solar cycle, adding experimental support for a common solar origin.


Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam.
Oral Transmucosal ketamine (lollipop) has been shown to be an effective, harmless preoperative medication for children. However, its efficacy was not compared with commonly used premedication drugs. We, therefore, compared the efficacy of oral transmucosal ketamine with oral midazolam for premedication in children. Fifty-five children (2-6 years of age) were randomized to receive orally either a lollipop containing 50 mg of ketamine (the group K; n = 27) or syrup containing 0.5 mg.kg(-1) of midazolam (the group M; n = 28) before minor surgery. A five points-sedation score (1 = asleep to 5 = agitated; scores 2 and 3 were defined as 'effective') on arrival in the operating room and a three points-acceptance score of separation from the parents and a three points-mask cooperation score at induction of anesthesia (1 = easy to 3 = markedly resistant; score 3 was defined as 'poor') were used. Sedation scores in group K were significantly higher than those in group M (P = 0.012), and the incidence of 'effective' in sedation was significantly lower in group K than in group M (P = 0.036). The incidence of 'poor' at separation from the parents and for mask cooperation was significantly higher in group K than in group M (P = 0.017, P = 0.019, respectively). These results indicate that a relatively low dose of oral transmucosal ketamine premedication provides no benefits over oral midazolam in children.


A comprehensive update of ICET-A Network on COVID-19 in thalassemias: what we know and where we stand.
A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among β-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations.


Physicochemical characterization and solubility analysis of thalidomide and its N-alkyl analogs.
The present study was primarily aimed at exploring the feasibility of improving percutaneous delivery via chemical manipulation of the thalidomide molecule to form analogs with improved physicochemical properties. N-Alkyl analogs were synthesized with the belief that these would be suitably hydrophobic and far less crystalline than the reference compound. This article presents their physicochemical properties. Thalidomide and three of its N-alkyl analogs were synthesized. Identification and levels of purity (>96%) were assured through element analysis, fast atom-bombardment mass spectrometry, nuclear magnetic resonance spectroscopy, and high-performance liquid chromatography. N-Octanol/water partition coefficients were determined at pH 6.4. Solubilities in water and a series of n-alkanols were obtained. Best-fit solubility parameters were determined from the solubilities of the respective compounds in London solvents and were also calculated from respective hexane solubilities. melting points and heats of fusion. Methylation of the thalidomide molecule at its acidic nitrogen led to an aqueous solubility about 6-fold higher than thalidomide but, because the alkyl chain length was further extended from methyl to pentyl. aqueous solubilities decreased essentially exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increased solubility in nonpolar media. The log partition coefficient increased linearly with increasing alkyl chain length and the solubility parameters declined systematically through this series. By adding a methyl group to the thalidomide structure, the melting point dropped by more than 100 degrees C. Adding to the alkyl chain length led to further, more modest decreases. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. Alkylation of the thalidomide molecule resulted in compounds with physicochemical properties that appear to be markedly better suited for percutaneous delivery.


Systemic amyloidosis and the gastrointestinal tract.
Systemic amyloidosis is caused by a variety of different diseases and frequently involves the gastrointestinal tract. Each type of amyloid affects the gastrointestinal tract differently. This article reviews the unique pathogenesis, pattern of gastrointestinal disposition, diagnosis, and treatment of the five systemic amyloidoses, and discusses the gastrointestinal diseases that cause systemic amyloidosis: inflammatory bowel disease and familial Mediterranean fever.


What happened to health labour markets during COVID-19? Insights from the analysis of cross-sectional survey data on the perceptions of medical doctors in Brazil.
To examine physicians' perceptions of changing employment opportunities in Brazil, and gain an insight into labour markets in low/middle-income countries (LMICs) during the pandemic. Descriptive and inferential analysis of a quantitative dataset from a representative cross-sectional survey of physicians of two Brazilian states. São Paulo and Maranhão states in Brazil. Representative sample of 1183 physicians. We estimated prevalence and 95% CIs for physicians' perceptions of changes in demand and supply of doctors, as well as changes in prices of medical services for facilities of practice in the two states, stratified by public, private and dual-practice physicians. Most doctors reported increased job opportunities in the public sector (54.9%, 95% CI 52.0% to 57.7%), particularly in Maranhão state (65.0%, 95% CI 60.9% to 68.9%). For the private sector, increased opportunities were reported only in large private hospitals (46.7%, 95% CI 43.9% to 49.6%) but not in smaller clinics. We recorded perceptions of slight increases in availability of doctors in Maranhão, particularly in the public sector (51.4%, 95% CI 43.2% to 59.5%). Younger doctors recounted increased vacancies in the public sector (64%, 95% CI 58.1% to 68.1%), older doctors only in walk-in clinics in Maranhão (47.5%, 95% CI 39.9% to 55.1%). Those working directly with patients with COVID-19 saw opportunities in public hospitals (65%, 95% CI 62.3% to 68.4%) and in large private ones (55%, 95% CI 51.8% to 59.1%). Our findings hint that health labour markets in LMICs may not necessarily shrink during epidemics, and that impacts will depend on the balance of public and private services in national health systems.


Psychiatric morbidity among physically injured Syrian refugees in Turkey.
To the best of our knowledge, the mental health status of physically injured Syrian refugees has not yet been investigated. The aim of this study was to examine the prevalence of psychiatric morbidity among physically injured Syrian refugees in Turkey receiving treatment at the main rehabilitation centre near the Syrian border. This is a cross sectional study. Information was collected from consenting injured Syrian refugees at Dar-el-Shefa'a Hospital in Reyhanlı (Turkey) during a one week period in December 2012 and another one week period in August 2013. A clinical psychiatric interview was conducted to determine a diagnosis according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-TR. A total of 40 refugees consented and completed a clinical psychiatric interview. All refugees in this study did not have a significant past psychiatric history. The most prevalent current diagnosis was major depressive disorder (22.5%), adjustment disorder (20%), and post-traumatic stress disorder (15%). Five (12.5%) patients had no evidence of a psychiatric disorder. The prevalence of psychiatric morbidity among injured Syrian refugees in our study was extremely high. This may help guide the treatment and management of this select population. This study had a low number of participants. The method of assessment was not standardized with a validated tool. This study may help guide the treatment and management of this select population, both in neighbouring countries and as resettled refugees in Western host countries.


Hippocampal EEG responses induced by carbachol and atropine infusions into the septum and the hippocampus in the urethane-anaesthetized rat.
Infusion of 1 microgram of carbachol, a potent cholinergic agonist, into the lateral septum of the urethane-anaesthetized rat systematically caused the induction of clear-cut hippocampal theta (theta). However, infusion of an equivalent amount of the drug into the hippocampus, close to the recording electrode, failed to induce theta in 50% of the animals and produced a mixture of theta waves and desynchronized activity, resulting in atypical EEG patterns, in the remaining subjects. Both carbachol EEG effects were blocked by intraseptal infusion of the antimuscarinic agent, atropine. Our data demonstrate that muscarinic receptors in the septum are predominant sites for cholinergic agonist-antagonist action capable of generating or suppressing hippocampal theta in the rat. They also indicate that intraseptal cholinergic mechanisms play an important role in the initiation and generation of this rhythm.


Investigation of the apoptotic pathway induced by benzimidazole-oxindole conjugates against human breast cancer cells MCF-7.
In our previous studies, benzimidazole-oxindole conjugates were synthesized and evaluated by National Cancer Institute (NCI) for their cytotoxic activity and the new molecules like 5c and 5p were considered as potential leads. These conjugates arrested the cell cycle at G2/M phase and inhibited tubulin polymerization. These observations prompted us to investigate the apoptotic mechanism induced by these lead molecules against human breast cancer cells (MCF-7). Studies like measurement of mitochondrial membrane potential (ΔΨm), generation of reactive oxygen species (ROS) and Annexin V-FITC assay revealed that these compounds induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cells. It was further confirmed by western blot analysis of pro apoptotic protein Bax, anti apoptotic protein Bcl-2, cytochrome c release, caspase-9 activity and cleavage of PARP.


New interacting partners of the F-box protein Ufo1 of yeast.
The yeast F-box protein Ufo1 recruits proteins for ubiquitylation by the SCF ubiquitin ligase complex preparing them for proteasomal degradation. Ufo1 has a role in maintenance of genome stability; its substrates include Ho endonuclease and Rad30 polymerase of error-prone DNA repair. Ufo1 is an unusual F-box protein, as it has three ubiquitin interacting motifs (UIMs). Deletion of the genomic UIMs is lethal; ectopic expression of UFO1 Delta UIMs extends protein half-life and arrests the cell cycle. A whole-genome study employing a TAP tag fused to the C-terminal UIMs did not identify Ufo1-interacting proteins. Here we therefore used stabilized N-terminally tagged Ufo1 Delta UIM as a strategy to identify Ufo1-interacting proteins by mass spectroscopy. We identified proteins that function in transcription, and an indirect interaction with Hsp70 molecular chaperones via the Skp1 adaptor; we also show that Ufo1 interacts with the 19S regulatory particle of the proteasome. Thus, our data augment the current network of known Ufo1 interacting proteins. We show directly that the UIMs are crucial for Ufo1 ubiquitylation in vivo, indicating that they facilitate turnover of SCF Ufo1 complexes. This allows recycling of the core subunits of the SCF complex and cell cycle progression.


Effect of ethanol on hepatic oxygenation: evidence of hepatic hypoxia.
The effects of low (1 g/kg body wt) and high doses (4 g/kg body wt) of ethanol on hepatic oxygenation in rats was investigated employing an in vivo microscopic and spectrophotometric system and also a micro oxygen electrode. The low dose of ethanol increased sinusoidal blood hemoglobin oxygenation (ISO2) at periportal regions in the liver lobule. The high dose of ethanol increased ISO2 at periportal regions, but decreased ISO2 at pericentral regions. The low dose of ethanol increased hepatic surface tissue PO2, but the high dose decreased this PO2. From these data it is concluded that the increase of hepatic blood flow, after administration of a low dose of ethanol, compensated for the increase of oxygen demand in hepatocytes but that administration of a high dose of ethanol reduced hepatic tissue oxygenation via an imbalance between delivery and demand of oxygen in pericentral regions of the liver lobule, resulting in local hypoxia in surface hepatic tissue.


Determination of cobalt in low-alloy steels using laser-induced breakdown spectroscopy combined with laser-induced fluorescence.
Cobalt element plays an important role for the properties of magnetism and thermology in steels. In this work, laser-induced breakdown spectroscopy combined with laser-induced fluorescence (LIBS-LIF) was studied to selectively enhance the intensities of Co lines. Two states of Co atoms were resonantly excited by a wavelength-tunable laser. LIBS-LIF with ground-state atom excitation (LIBS-LIFG) and LIBS-LIF with excited-state atom excitation (LIBS-LIFE) were compared. The results show that LIBS-LIFG has analytical performance with LoD of 0.82μg/g, R(2) of 0.982, RMSECV of 86μg/g, and RE of 9.27%, which are much better than conventional LIBS and LIBS-LIFE. This work provided LIBS-LIFG as a capable approach for determining trace Co element in the steel industry.


SCH 23390 blocks D-1 and D-2 dopamine receptors in rat neostriatum in vitro.
The agonistic and antagonistic effects of the new compound SCH 23390 were tested in functional model systems for the D-1 dopamine receptor and for the D-2 dopamine receptor in vitro. In superfused rat neostriatal slices the increase in the efflux of cyclic AMP was used as a parameter for D-1 receptor stimulation. D-2 receptor stimulation was measured as the decrease in the K+-evoked release of [3H]-acetylcholine. SCH 23390 had no agonistic activity in these two models. SCH 23390 was a potent antagonist of the stimulating effect of dopamine in the D-1 receptor model (apparent pA2 = 7.28). SCH 23390 also antagonized the effect of the D-2 receptor agonist LY 141865 in the D-2 receptor model (apparent pA2 = 6.34). This D-2 receptor antagonism proved to be of a competitive nature.


Interaction of hydroxyapatite and protein-coated hydroxyapatite with Streptococcus mutans and Streptococcus sanguis.
The present study showed that S. mutans and S. sanguis behaved like negatively-charged particles in their interaction with hydroxyapatite in vitro. Phosphate in the system inhibited bacterial uptake by apatite, whereas calcium increased the uptake. A layer of acidic protein inhibited the uptake of bacteria by hydroxyapatite. The opposite was true when a basic protein was first adsorbed to the apatite. A saliva film on the apatite decreased the uptake of bacteria, supporting the view that acidic proteins are selectively adsorbed by hydroxyapatite from saliva. The results indicate clearly that electrostatic forces may be involved in bacterial interaction with tooth surface.


Anorexia and hypothalamic degeneration.
Anorexia, meaning poor appetite, occurs in many human conditions, for example, anorexia nervosa, cachexia, and failure to thrive in infants. A key player in the regulation of appetite/food intake in general, as well as conditions of anorexia, is the hypothalamus, in particular, the AGRP/NPY and POMC/CART neurons in the arcuate nucleus. In this chapter, we review the hypothalamic aberrances seen in the anorectic anx/anx mouse. This mouse displays deviations in neuropeptidergic/-transmitter systems, including selective hypothalamic degeneration and inflammation that have been associated with mitochondrial dysfunction. In addition, we discuss data from other animal models, as well as clinical data relating hypothalamic inflammation/degeneration, neurogenesis, and mitochondrial dysfunction to conditions of disturbed regulation of food intake.


Chemical carcinogen alteration of SV40 virus induced transformation of normal human cell populations in vitro.
The frequency of simian papovirus 40 (SV40) induced transformation of human cells was enhanced after pretreatment with either napthylamine-2,N-methyl-N'-nitrosoguanidine (MNNG), N-acetyl-2-fluorenylacetamide (N-Ac-AAF), benzo[a]pyrene (BP), aflatoxin B1, propane sultone (PS), beta-propiolactone, 4-nitroquinoline oxide (4-NQO), methylmethane sulfonate (MMS) or diethyl nitrosamine (DEN). Posttreatment with 4-NQO, MMS, MNNG or DEN inhibited transformation; while posttreatment with either aflatoxin B1, beta-propiolactone or napthylamine-2 did not alter transformation similar to the action of N-Ac-AAF and BP. All carcinogens that altered transformation after pretreatment damaged cellular DNA. Pretreatment or posttreatment with carcinogens 3-methylcholanthrene (3-MCA) or 7,12-dimethylbenzanthrene (7,12-DMBA), that did not damage cellular DNA also did not enhance transformation. Moreover, pre- or posttreatment with other weak or non-carcinogens that did not damage cellular DNA did not alter virus induced transformation. All foci formed in the co-carcinogen treated cultures whether the carcinogen inhibited or enhanced transformation were virus directed. While a similar pattern of response existed for carcinogens that either enhance or inhibit transformation, each of the carcinogens that enhanced or inhibited foci formation damaged cellular DNA. Moreover, those carcinogens that enhanced focus formation, compared to the carcinogens that inhibited focus formation, exhibited similar DNA damage profiles.


Repolarizing K+ currents ITO1 and IKs are larger in right than left canine ventricular midmyocardium.
The ventricular action potential exhibits regional heterogeneity in configuration and duration (APD). Across the left ventricular (LV) free wall, this is explained by differences in repolarizing K+ currents. However, the ionic basis of electrical nonuniformity in the right ventricle (RV) versus the LV is poorly investigated. We examined transient outward (ITO1), delayed (IKs and IKr), and inward rectifier K+ currents (IK1) in relation to action potential characteristics of RV and LV midmyocardial (M) cells of the same adult canine hearts. Single RV and LV M cells were used for microelectrode recordings and whole-cell voltage clamping. Action potentials showed deeper notches, shorter APDs at 50% and 95% of repolarization, and less prolongation on slowing of the pacing rate in RV than LV. ITO1 density was significantly larger in RV than LV, whereas steady-state inactivation and rate of recovery were similar. IKs tail currents, measured at -25 mV and insensitive to almokalant (2 micromol/L), were considerably larger in RV than LV. IKr, measured as almokalant-sensitive tail currents at -50 mV, and IK1 were not different in the 2 ventricles. Differences in K+ currents may well explain the interventricular heterogeneity of action potentials in M layers of the canine heart. These results contribute to a further phenotyping of the ventricular action potential under physiological conditions.


Comparative Study of ZnO-and-TiO2-Nanoparticles-Functionalized Polyvinyl Alcohol/Chitosan Bionanocomposites for Multifunctional Biomedical Applications.
This study aimed to synthesize chitosan/polyvinyl alcohol (CS/PVA)-based zinc oxide (ZnO) and titanium dioxide (TiO2) hybrid bionanocomposites (BNCs) and observe their comparative accomplishment against the skin cancer cell line, A431, and antioxidant potential. CS was blended with PVA to form polymeric films reinforced with the immobilization of ZnO and TiO2 nanoparticles (NPs), separately. The optimization of the BNCs was done via physicochemical studies, viz. moisture content, swelling ratio, and contact angle measurements. The free radical scavenging activity was observed for 1,1-diphenyl-2-picryl-hydrazyl, and the antibacterial assay against the Escherichia coli strain showed a higher zone of inhibition. Furthermore, the anticancer activity of the synthesized BNCs was revealed against the skin cancer cell line A431 under varying concentrations of 50, 100, 150, 200, and 300 μg/mL. The anticancer study revealed a high percent of cancerous cell inhibition (70%) in ZnO BNCs as compared to (61%) TiO2 BNCs in a dose-dependent manner.


Assessment of residents' loss of interest in academic careers and identification of correctable factors.
To quantify interest in an academic career at the dermatology resident and residency applicant level. Cross-sectional survey. Dermatology residents attending a basic science course and residency applicants applying to a single residency program. Self-reported level of interest in an academic dermatology career, reasons for losing interest in academics, and area of desired primary academic contribution. One hundred nine of 230 dermatology applicants and 130 of 190 dermatology residents completed the survey. Seventy-nine applicants (72.5%) and 48 residents (36.9%) were interested in an academic career. Thirty-three of 47 residents (70.2%) and 63 of 79 applicants (79.8%) interested in an academic career hoped to make their primary academic contribution as teacher-clinicians, while only 7 residents (14.9%) and 15 applicants (19.0%) planned to primarily contribute through basic or clinical research. Thirty-eight resident respondents (29.2%) reported losing interest in academics for the following primary reasons: bureaucracy, 24 (63.2%); salary differential/financial issues, 20 (52.6%); lack of effective mentorship, role model, or professional guidance, 19 (50.0%); and location or practice environment, 10 (26.3%). Many residents report losing interest in pursuing a career in academic dermatology. Many reasons for this are not easy to correct. However, half of those residents primarily lose interest because of a lack of mentors, role models, and career guidance. Methods to improve this perception and experience should be sought. Strategies should also be developed to cultivate future teacher-clinicians, where most of the interest lies.


COVID-19 update: the first 6 months of the pandemic.
The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.


Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia.
We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene. The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34(+)cells/μl in peripheral blood. The gene expression profile was more prominent in CML CD34(+) cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34(+) cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34(+) cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML. The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34(+) cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects.


Influence of the conformational state on the isoelectric points of rat brain synaptosomes, mitochondria and mitoplasts.
The isoelectric points of rat brain synaptosomes, mitochondria and mitoplasts have been determined by using different charged two-phase systems containing dextran and poly(ethylene glycol). The cross-partition diagrams of these organelles show isoelectric points at pH 4.1, 4.5 and 4.7, respectively. The influence of the conformational state of mitochondrial membranes upon their partition in two-phase systems has been studied. Shrunk mitoplasts showed a large change in their partition behavior as reflected by an increased affinity for the lower dextran phase, while shrinkage of mitochondria did not affect their partition. Shrunk mitoplasts showed the same isoelectric point of pH 4.7 as swollen mitoplasts, which indicates that no charge changes occurred on the outer side of the inner mitochondrial membrane during shrinkage of mitoplasts.


Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia: A matched cohort study.
An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB). Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population. Within a year, 278 of 15,669 SAB patients and 2570 of 156,690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE. SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB.


Accuracy of computed tomography: magnetic resonance imaging image fusion using a phantom for skull base surgery.
The aim of this study is to assess the positional accuracy of image fusions of the skull base region using different magnetic resonance imaging (MRI) and computed tomography (CT) image pairs. An image set of 3D fast imaging employing steady-state acquisition-C (FIESTA-C) was used as the base image set. Image fusions were performed using an image set with different fields of view (FOVs): one with different matrix size, one with a different sequence of 3D spoiled gradient recalled acquisition, and one with different modality (CT), using a phantom including multi columnar objects. Position of columns at the center, and 4 and 8 cm from the center were measured. The displacements between the base image set and fused image set were measured. For slices with different z-positions, the displacement of the 8-cm column was assessed. For 20 clinical MRI cases, the distance between the dorsum sellae and the cranial nerves was measured. No significant differences were found between the different FOVs or image sequences. However, with the different matrix sizes and modalities, significant displacements were observed, although they were all within 0.5 mm. Similar displacements were observed in the slices at different z-positions. All cranial nerves were located within 40 mm of the dorsum sellae. The displacements following image fusion were within approximately 0.5 mm, even at 8 cm from the center. This suggests that the region where the cranial nerves are located, within 40 mm of the dorsum sellae, had no risk of positional error following image fusion.


Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model.
Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis arising during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Therefore, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. Besides, CD4+ T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (ASCs-CM) in vitro. We detected the ratio of Th2%/Th1%. Results showed that the retention rate was higher in 104 group, while even lower in 108 group with significantly increased inflammation and fibrosis than control group at week 12 in vivo. There was no significance between control group and 106 group. Also, 108 group increased the infiltration of M2 macrophages, CD4+ T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by ASCs-transwell group was higher than ASCs-CM group and showed concentration-dependent. Accordingly, high concentrations of ASCs in adipose tissue can promote Th1-Th2 shifting, and excessive Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. Also, we found ASCs promoted Th1-Th2 shifting in vitro.


The management of hiatal hernia: an update on diagnosis and treatment.
Hiatal hernia (HH) occurs quite frequently in the general population and is characterized by a wide range of non-specific symptoms, most of them related to gastroesophageal reflux disease. Treatment can be challenging at times, depending on the existence of complications. The most recent guideline regarding the management of hiatal hernia was released by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) in the year 2013. This review aims to present the most recent updates on the diagnosis and management of hiatal hernia for clinical practitioners. The PubMed database was screened for publications using the terms: "hiatal hernia", "paraesophageal hernia", "management", "treatment", "hiatal repair". A literature review of contemporary and latest studies was completed. The studies that we looked into include prospective, randomized trials, systematic reviews, clinical reviews and original articles. The information was compiled in narrative review format. This narrative review presents new data on the diagnosis and management of hiatal hernia. While the diagnostic pathway has remained virtually unchanged, new data have come to light regarding the surgical treatment of hiatal hernia. We present the imaging methods used for its diagnosis, as well as the medical and surgical treatment currently available. In the last five years, there has been vast research in the field of hiatal hernia management, especially regarding the surgical treatment. However, unanswered questions still remain and solid updates on the guidelines have yet to be formulated. To address this, more randomized studies need to be done on subsets of patients, stratified by age, gender, symptoms and comorbidities.


Driveline dressings used in heartmate patients and local complications: A retrospective cohort.
Patients with long-term ventricular assist devices (VAD) are predisposed to infection, bleeding, and pressure injuries at the insertion of the driveline. There is no consensus on a driveline dressing protocol. Chlorhexidine is often used to clean the driveline exit site and has been associated with lower rates of infection. For driveline coverage, bacteriostatic agents and transparent film have shown good results, but are costly. The same issue was associated with anchorage devices. The purpose of this study was to evaluate the types of dressings used in the driveline of patients using HeartMate (HM) and to describe the incidence density of local complications (infection, bleeding, and pressure injury) within 30 days postoperatively. A retrospective cohort study was conducted and included 22 patients admitted to the Intensive Care Unit after implantation of HM II and III in a Brazilian private hospital. Several types of dressings were used in the drivelines. There were 22 different types of dressings. Dressing type 6 (Chlorhexidine, Excilon, Gauze and IV3000) were the most used (45.4%). Subjects using the Flexi-Trak anchoring device had a higher rate of local bleeding (50.0%) and those who used the Hollister device had more infection (61.1%) and pressure injury associated with a medical device (11.1%), compared to others. Infection was the primary complication (45.4%), followed by local bleeding (27.7%). Despite the high variability of products used in the driveline of patients using HeartMate, the dressing made with chlorhexidine, silver-impregnated absorbent foam and transparent film, and the use of anchoring devices was the most frequently used. Infection was the most common complication.


Reversible impairment of glucose-induced insulin secretion in SHR/N-cp rats. Genetic model of type II diabetes.
The SHR/N-cp rat is a new genetically obese model for non-insulin-dependent diabetes mellitus. Expression of the diabetes is enhanced by a high-sucrose (54%) diet. After 4 wk on the diet, the cp/cp rats weigh significantly more than their +/? controls, have postprandial hyperglycemia (greater than 400 mg/dl), and are hyperinsulinemic, with immunoreactive insulin (IRI) levels 10- to 20-fold greater than controls. Total pancreatic IRI tends to be increased 1.6-fold in the cp/cp rats (although not significantly). There is no increase in pancreatic proinsulin content as a percent of total IRI. Studies of in vitro pancreatic function were carried out with the isolated nonrecirculating perfused pancreas method. The cp/cp rats (n = 10) showed impaired or absent IRI responses to 16.5 mM glucose, whereas +/? rats (n = 9) responded with classic biphasic curves. Comparison of insulin secreted in 20 min revealed a greater than 53% decrease in IRI secretion in cp/cp rats (P less than .05). A paradoxical hypersecretion of IRI at glucose concentrations of 0-2.7 mM was noted in cp/cp but not lean rats, i.e., 1.8 +/- 0.2 mU/min IRI in cp/cp rats vs. 0.04 +/- 0.007 mU/min in +/? rats. Perfusion of pancreases for 45 min with buffers containing no glucose resulted in restoration of a normal biphasic IRI response to 16.5 mM glucose in the cp/cp rats, whereas response in the lean rats was markedly reduced. Brisk IRI responses to 10 mM arginine in buffers with no glucose also occurred in cp/cp but not +/? rats. Glucagon secretion was relatively suppressed in the cp/cp rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Concussion.
We have observed the effects of concussion on nonanesthetized rats and humans. We believe the phenomenon in both to be identical. There are four obvious stages to concussion and the recovery therefrom: fourth stage--visceral (respiratory) and somatic immobility; third stage--return of irregular visceral (respiratory) mobility with continuing somatic immobility; second stage--normal visceral mobility with impaired somatic mobility; and first stage--normal somatic mobility with impaired performance. Zero stage is complete normality. Our method of testing detects no lingering or permanent change after a single concussion. This proves only that we must continue with open minds on the question, "Does concussion always leave permanent brain damage?"


Echogenicity of the Common Carotid Artery Intima-Media Complex in Stroke.
The grey-scale median of the common carotid artery intima-media complex (IM-GSM) characterizes arterial wall composition, and a low IM-GSM is associated with increased cardiovascular mortality in the elderly. We aimed to determine differences in the IM-GSM between a cohort with cerebrovascular disease and a healthy cohort. Eighty-two healthy individuals (control group: 63.2 ± 8.7 y) and 96 patients with either stroke or transient ischemic attacks (CRVD group: 68.6 ± 9.8 y) were studied. Common carotid artery intima-media thickness and IM-GSM obtained by ultrasound were analyzed using semi-automated edge-detection software. The IM-GSM was significantly lower in the CRVD group than in the control group (106 ± 24 vs. 124 ± 27 au, p < 0.001). The IM-GSM was similar for the infarct and non-infarct sides in CRVD. In the pooled cohort of all participants, the lower the quartile of IM-GSM, the greater were the carotid artery intima-media thickness and carotid artery remodeling. These results suggest the presence of an altered atherosclerotic phenotype in the intima-media complex of CRVD patients that can be detected by ultrasound.


π-Extended Diaza[7]helicenes by Hybridization of Naphthalene Diimides and Hexa-peri-hexabenzocoronenes.
The synthesis of an unprecedented, π-extended hexabenzocorene (HBC)-based diaza[7]helicene is presented. The target compound was synthesized by an ortho-fusion of two naphthalene diimide (NDI) units to a HBC-skeleton. A combination of Diels-Alder and Scholl-type oxidation reactions involving a symmetric di-NDI-tolane precursor were crucial for the very selective formation of the helical superstructure via a hexaphenyl-benzene (HPB) derivative. The formation of the diaza[7]helicene moiety in the final Scholl oxidation is favoured, affording the symmetric π-extended helicene as the major product as a pair of enantiomers. The separation of the enantiomers was successfully accomplished by HPLC involving a chiral stationary phase. The absolute configuration of the enantiomers was assigned by comparison of circular dichroism spectra with quantum mechanical calculations.


Efficacy and safety of metformin and sodium-glucose co-transporter-2 inhibitors in adults with type1 diabetes: A systematic review and network meta-analysis.
To compare the efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and metformin in adults with type1 diabetes mellitus (T1DM). Randomized clinical trials until February 2019, designed to assess the efficacy and safety of SGLT2 inhibitors/metformin in adults with T1DM, were searched on PubMed, EMBASE, the Cochrane Library, and Web of Science. Safety and efficacy data were synthesized using Bayesian network meta-analyses. Twenty eligible studies with 5868 participants were included in network meta-analysis. SGLT2 inhibitors provided greater reductions in HbA1c than placebo (weighted mean difference [WMD] -0.40; 95% confidence interval [CI] -0.47, -0.32) and metformin (WMD: -0.32; 95%CI: -0.47, -0.14). Both SGLT2 inhibitors and metformin promoted greater reductions in body weight than placebo. SGLT2 inhibitors caused greater reductions in body weight than metformin (WMD: -1.54; 95%CI: -2.93, -0.09). Both SGLT2 inhibitors and metformin provided greater reductions in total insulin dose than placebo, while no difference between metformin and SGLT2 inhibitors was found. No difference in severe hypoglycemia was found between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for diabetic ketoacidosis (DKA) than metformin/placebo. SGLT2 inhibitors provided greater reductions in HbA1c and body weight than metformin/placebo. Both SGLT2 inhibitors and metformin induced greater reductions in total insulin dosage than placebo, with no significant differences observed between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for DKA than metformin/placebo.


Torque placed by dentists on prefabricated threaded posts.
Thirty-one dentists were tested relative to the optimal and maximum amount of torque they could deliver to posts in teeth. The mean for the optimal amount of torque was 15.55 ounce-inches, and the mean for the maximum amount of torque was 35.29 ounce-inches. Female dentists showed a statistically significantly lower mean difference of 24.5 ounce-inches on the maximum torque test.


Binding of leukaemic blasts to various subpopulations of lymphokine-activated killer cells.
Conjugate formation by natural killer (NK)-resistant and NK-sensitive leukaemic cell lines with fresh and IL-2-stimulated (lymphokine-activated killer, LAK) peripheral blood lymphocytes (PBL) was studied by a flow cytofluorometry method with double staining. A significant difference in binding of NK-resistant T-cell lymphoma (HuT 78) and NK-sensitive myeloid (K562) blasts to fresh PBL was observed (P < 0.01). Activation of lymphocytes with IL-2 resulted in a significant increase of binding and killing of both K562 and HuT 78. However, in the case of blasts from NK-resistant cell line Daudi a similar conjugate formation with fresh PBL and LAK effectors was observed, despite a significant increase in killing. Various subpopulations of LAK effectors (CD3, CD16 and CD56 positive) displayed similar binding activity towards myeloid (K562) and lymphoid (Raji) blasts, which shows that conjugate formation occurs not only with NK-cell-derived, but also with T-cell-derived LAK cells. The blocking of CD71 antigen (transferrin receptor) on K562 blasts inhibited binding of cytotoxic lymphocytes, which was mostly due to the blocking of binding of CD56+ subpopulation. Our results indicate that the resistance of leukaemic blasts to cell-mediated cytotoxicity may depend on different (and probably several) steps of this process.


Patient-specific ventricular beat classification without patient-specific expert knowledge: a transfer learning approach.
We present an adaptive binary classification algorithm, based on transductive transfer learning. We illustrate the method in the context of electrocardiogram (ECG) analysis. Knowledge gained from a population of patients is automatically adapted to patients' records to accurately detect ectopic beats. On patients from the MIT-BIH Arrhythmia Database, we achieve a median sensitivity of 94.59% and positive predictive value of 96.24%, for the binary classification task of separating premature ventricular contractions (PVCs), a type of ectopic beat, from non-PVCs.


How to make your research jump off the page: Co-creation to broaden public engagement in medical research.
Nina Finley and co-authors discuss public involvement in planning and reporting medical research.


Outpatient breast-conserving surgery for breast cancer: Use of local and intravenous anesthesia and/or sedation may reduce recurrence and improve survival.
The use of general anesthesia (GA) with inhalational anesthetics for breast cancer surgery may be associated with breast cancer recurrence and increased mortality due to the immunosuppressive effects of these drugs. Less-immunosuppressive anesthetic techniques may reduce breast cancer recurrence. We evaluated the feasibility, safety, and efficacy of outpatient breast-conserving surgery (BCS) for breast cancer in a breast clinic in terms of the anesthetic technique used, complications occurring, recurrence, and survival. Methods: The sample comprised 456 consecutive patients with stage 0-III breast cancer who underwent BCS/axillary lymph node (ALN) management using local and intravenous anesthesia and/or sedation between May 2008 and January 2020. Most patients received adjuvant chemotherapy and/or endocrine therapy and radiotherapy after surgery. Patient outcomes were evaluated retrospectively. Results: All patients recovered and were discharged after resting for 3-4 h postoperatively. No procedure-related severe complication or death occurred. Sixty-four complications (14.0%) were observed: 14 wound infections, 17 hematomas, and 33 axillary lymphoceles. The median follow-up period was 2259 days (range, 9-4190 days), during which disease recurrence was observed in 25 (5.4%) patients. The overall survival and breast cancer-specific survival rates were 92.3% and 94.7%, respectively. Conclusions: Outpatient surgery for breast cancer involving BCS and ALN management under local and intravenous anesthesia and/or sedation can be performed safely, without serious complication or death. Less-immunosuppressive anesthetic techniques with spontaneous breathing may reduce the recurrence of breast cancer and improve survival relative to GA.


Vmac: a novel protein associated with vimentin-type intermediate filament in podocytes of rat kidney.
Vimentin-type intermediate filaments (IFs) play an important role in cytoskeletal organization and cell morphology. We identified here a novel protein associated with vimentin-type IFs and named it vimentin-type IF-associated coiled-coil protein (Vmac). Vmac consists of 171 amino acids with a calculated Mr of 18,844 and has a coiled-coil domain in its N-terminal region and the PDZ-binding tetrapeptide consensus motif in its C-terminal region. Northern blotting showed that the Vmac mRNA was expressed in many rat tissues examined but most abundantly expressed in the kidney. Immunofluorescence microscopy revealed that Vmac was highly concentrated at podocytes of renal glomeruli. Podocytes are highly specialized epithelial cells characterized by a large cell body and numerous foot processes, and express vimentin-type IFs that are distributed in the cell body and the major processes. Immunoelectron microscopy revealed that Vmac was associated with vimentin-type IFs of podocytes. These results indicate that Vmac is a novel protein associated with vimentin-type IF in podocytes of rat kidney.


Unusual arterial thrombotic events in Covid-19 patients.
COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.


Spinocerebellar Ataxia type 17 presenting with progressive myoclonic epilepsy.
•SCA17 should be included in the differential diagnoses of PMEs.•SCA17 is characterized by cerebellar features, myoclonic epilepsy, cognitive decline, psychiatric features, and chorea.•Subtle clinical signs like chorea can provide additional diagnostic clues to SCA17(HDL4), a Huntington disease phenocopy.


A novel anticancer pharmacological agent targeting mitochondrial complex I.
Targeting metabolic reprogramming has proven successful in oncology, but this field requires better identification of drugs that inhibit mitochondrial metabolism in cancer cells. Recent work from Dr Wolf's group reveals that the primary target of the antitumor compound SMIP004-7 is mitochondrial complex I (NDUFS2 subunit), inhibition of which promotes anticancer immune surveillance.


Towards establishing human body-on-a-chip systems.
Body-on-a-chip (BoC) platforms are established from multiple organs-on-chips (OoCs) to recapitulate the interactions between different tissues. Recently, Vunjak-Novakovic and colleagues reported the creation of a BoC system comprising four fluidically linked OoCs. Herein, the major innovations in their BoC system are discussed, followed by our future perspectives on enhancing the physiological relevance and scalability of BoCs for applications in studying disease mechanisms, testing potential therapeutics, and developing personalized medicine.


HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part I. HSV-1 structure, replication and pathogenesis.
The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological alterations associated with the disease, on the biological characteristics of the target tissue, and on the development of safe vectors and expression systems to achieve efficient, targeted and regulated, therapeutic gene expression. The herpes simplex virus type 1 (HSV-1) virion is one of the most efficient of all current gene transfer vehicles with regard to nuclear gene delivery in central nervous system-derived cells including brain tumors. HSV-1-related research over the past decades has provided excellent insight into the structure and function of this virus, which, in turn, facilitated the design of innovative vector systems. Here, we review aspects of HSV-1 structure, replication and pathogenesis, which are relevant for the engineering of HSV-1-based vectors.


Catheter-related septic thrombophlebitis of the superior vena cava involving the atrial septum: a case report.
Intravascular catheters provide necessary vascular access, for intravenous therapy, blood sampling and pressure monitoring. However, their use is often associated with serious local and systemic complications including local site infection, intravascular catheter-related bloodstream infections, septic thrombophlebitis, and endocarditis. We present a case of a 72 year old postoperative patient presented with persistent fever. Transthoracic and transesophageal echocardiograms demonstrated a lesion in the superior vena cava, protruding into the right atrium and infiltrating the atrial septum. Candida albicans grew in blood cultures as well as in the subclavian catheter tip culture. Anti-fungal and antithrombotic therapy was initiated. After 2 weeks treatment the lesion was diminished. Transthoracic and transesophageal echocardiography has been proved efficient and cost-effective in guiding therapy in cases of catheter related infections. In the presented case the lesions in vena cava and the involvement of the endocardium were early identified by echocardiography. Moreover, a follow-up echocardiogram confirmed the efficiency of the therapeutic approach.


Whole body MRI with Diffusion Weighted Imaging versus 18F-fluorodeoxyglucose-PET/CT in the staging of lymphomas.
To assess the diagnostic performance of Whole Body (WB)-MRI in comparison with 18F-Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) in lymphoma staging and to assess whether quantitative metabolic parameters from 18F-FDG-PET/CT and Apparent Diffusion Coefficient (ADC) values are related. We prospectively enrolled patients with a histologically proven primary nodal lymphoma to undergo 18F-FDG-PET/CT and WB-MRI, both performed within 15 days one from the other, either before starting treatment (baseline) or during treatment (interim). Positive and negative predictive values of WB-MRI for the identification of nodal and extra-nodal disease were measured. The agreement between WB-MRI and 18F-FDG-PET/CT for the identification of lesions and staging was assessed through Cohen's coefficient k and observed agreement. Quantitative parameters of nodal lesions derived from 18F-FDG-PET/CT and WB-MRI (ADC) were measured and the Pearson or Spearman correlation coefficient was used to assess the correlation between them. The specified level of significance was p ≤ 0.05. Among the 91 identified patients, 8 refused to participate and 22 met exclusion criteria, thus images from 61 patients (37 men, mean age 30.7 years) were evaluated. The agreement between 18F-FDG-PET/CT and WB-MRI for the identification of nodal and extra-nodal lesions was 0.95 (95% CI 0.92 to 0.98) and 1.00 (95% CI NA), respectively; for staging it was 1.00 (95% CI NA). A strong negative correlation was found between ADCmean and SUVmean of nodal lesions in patients evaluated at baseline (Spearman coefficient rs = - 0.61, p = 0.001). WB-MRI has a good diagnostic performance for staging of patients with lymphoma in comparison with 18F-FDG-PET/CT and is a promising technique for the quantitative assessment of disease burden in these patients.


Immunogenic cell death in anticancer chemotherapy and its impact on clinical studies.
The traditional view holds that apoptosis is non-immunogenic and does not induce an inflammatory response. However, recent studies have suggested that certain chemotherapeutic drugs that induce tumor cell apoptosis can induce immunogenic cell death (ICD) in cancer cells. This process is characterized by not only up-regulation of a series of signaling molecules in cancer cells, including expose of calreticulin (CRT), secretion of adenosine triphosphate (ATP) and release of high mobility group box 1 (HMGB1). In this review, we summarize recent progress in identifying and classifying ICD inducers; concepts and molecular mechanisms of ICD; and the impact and potential applications of ICD in clinical studies. We also discuss the contributions of ICD inducers in combination with other anticancer drugs in clinical applications.


Prevalence on beef carcasses of Mycobacterium avium subsp. paratuberculosis DNA.
Fifty samples were collected from each of skinned and dressed carcasses, from each of culled beef breeding cows and fed beef cattle <18 months old at two beef packing plants A and B, and from culled dairy cows at a packing plant C. The 450 samples were collected by swabbing an area of about 1000 cm2 in the anal region of each carcass. DNA extracted from each swab was tested for the IS900 and F57 sequences of the Mycobacterium avium subsp. paratuberculosis (MAP) genome by two stage, nested polymerase chain reaction (PCR) procedures. An internal amplification control (IAC) was detected in 45 or more of each group of 50 DNA preparations. IS900 and F57 were detected in some IAC-positive preparations from all and all but one of the groups of carcasses, respectively. Of the IAC-positive preparations in each group, between 6 and 54% were positive for IS900, and between 4 and 20% were positive for F57. When preparations were tested by single stage, quantitative PCR procedures, IS900 was detected in two samples but F57 was detected in none. The MAP DNA on carcasses was probably derived from small numbers of MAP from the environment that contaminated the animals' hides.


Understanding and Optimizing Group Dynamics in Case-Based Collaborative Learning.
Teamwork skills are recognized as a core competency of physicians. To more effectively prepare trainees for the demands of their future work, medical educators are increasingly turning to group-based instructional formats. We employ case-based collaborative learning (CBCL) - a format which requires daily in-class discussion and collaboration in assigned small groups. While students overwhelmingly embraced CBCL as stimulating and thought-provoking, some students reported that social dynamics among group members adversely impacted their experience. Using mixed methods, we demonstrate that a short intervention that asked students to discuss how they can best learn together improved small group dynamics, and promoted psychological safety among peers. Importantly, no specific instruction in team work was required, students overall had a clear understanding how they could improve, but they did not know how to start this conversation with each other. To promote team learning, we propose that educators emphasize students' accountability to their peers' learning in addition to their own, and devote some time in class for teams to reflect and discuss how to improve learning with each other. Our observations are of interest to anyone frequently relying on group work without peer assessment or formal feedback on group performance.


[Calibration of oxygen meters and determination of the curve for hemoglobin dissociation by kinetics of oxygenation and deoxygenation of the blood].
A method to determine optical oxygenometers calibration and hemoglobin--oxygen equilibrium curve for the undamaged blood is described. This method does not require the oxygen equilibrium between the blood plasma and erythrocyte cytoplasm and uses only readings of the oxygenometer calibrated.


Basic concept of development and practical application of animal models for human diseases.
The "humanized mouse" is a mouse harboring functioning human tissues used as in vivo human models for both physiological and pathological conditions. The NOD/Shi-scid IL2rgamma(null) (NOG) mouse, an excellent immunodeficient mouse used as the basis for the humanized mouse, requires strict genetic and environmental control for production and use in experiments. Genetic control using marker-assisted selection is described. In addition, NOG mice are easily affected by microbiological and proximate environmental factors, which can cause severe damage to the mice in some cases. Therefore, rigorous microbiological and environmental controls are necessary to ensure reproducibility of experimental results. At the end of this chapter, future aspects of the application of "humanized mice" based on novel super-immunodeficient mice such as NOG mice and Rag2(null) IL2rgamma(null) mice in biomedical research and testing are briefly reviewed.


Empathy in Japanese paramedicine students: A cross-sectional study.
Empathy is an important characteristic for healthcare students and professionals that may improve the quality of healthcare interactions. Empathy has predominantly been studied within medicine, but also among various allied health personnel. Within paramedicine, empathy has previously been examined internationally, but not within Japan. This study used a descriptive, cross-sectional methodology which aimed to examine self-reported empathy in Japanese paramedic students using the Jefferson Scale of Empathy, and compare results with similar international cohorts. Empathy levels in the Japanese cohort were higher among females compared to males. In addition, there was a decrease in empathy with each subsequent year of the paramedic program, and a general decrease as age increased. This contrasts with comparable Australian cohorts which demonstrate no significant change in empathy levels during the undergraduate program. Empathy levels measured in the Japanese paramedic cohort were generally lower than for Australian cohorts. The reasons for the differences are unclear at present and thus further research in this area is required to fully determine and describe the contributing factors.


Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia.
In many tissues, stem cell (SC) proliferation is dynamically adjusted to regenerative needs. How SCs adapt their metabolism to meet the demands of proliferation and how changes in such adaptive mechanisms contribute to age-related dysfunction remain poorly understood. Here, we identify mitochondrial Ca2+ uptake as a central coordinator of SC metabolism. Live imaging of genetically encoded metabolite sensors in intestinal SCs (ISCs) of Drosophila reveals that mitochondrial Ca2+ uptake transiently adapts electron transport chain flux to match energetic demand upon proliferative activation. This tight metabolic adaptation is lost in ISCs of old flies, as declines in mitochondrial Ca2+ uptake promote a "Warburg-like" metabolic reprogramming toward aerobic glycolysis. This switch mimics metabolic reprogramming by the oncogene RasV12 and enhances ISC hyperplasia. Our data identify a critical mechanism for metabolic adaptation of tissue SCs and reveal how its decline sets aging SCs on a metabolic trajectory reminiscent of that seen upon oncogenic transformation.


MRI volume of the medial frontal cortex predicts financial capacity in patients with mild Alzheimer's disease.
Persons with mild Alzheimer's disease (AD) have significant deficits in financial abilities. This study examined the relationship between brain structure volumes, cognition, and financial capacity in patients with mild AD. Sixteen mild AD patients and 16 older adult comparisons completed the Financial Capacity Instrument (FCI), a psychometric measure of financial abilities, and also underwent magnetic resonance imaging (MRI) to obtain volumes of the bilateral hippocampi, angular gyri, precunei, and medial and dorsolateral frontal cortices. Mild AD patients performed significantly below comparisons on the FCI and had significantly smaller hippocampi. Among mild AD patients, FCI performance was moderately correlated with frontal (medial and dorsolateral frontal cortex) and posterior (angular gyri and precunei) cortical volumes. Stepwise regression demonstrated that medial frontal cortex volume predicted FCI score. The relationship between medial frontal cortex volume and overall FCI score was partially mediated by two measures of simple attention (DRS Attention, DRS Construction). The findings suggest that medial frontal cortex atrophy and associated declines in simple attention play an increasingly important role in declining financial skills in patients with mild AD.


Comparative proteomic analysis of maize (Zea mays L.) seedlings under rice black-streaked dwarf virus infection.
Maize rough dwarf disease (MRDD) is a severe disease that has been occurring frequently in southern China and many other Asian countries. MRDD is caused by the infection of Rice black streaked dwarf virus (RBSDV) and leads to significant economic losses in maize production. To well understand the destructive effects of RBSDV infection on maize growth, comparative proteomic analyses of maize seedlings under RBSDV infection was performed using an integrated approach involving LC-MS/MS and Tandem Mass Tag (TMT) labeling. In total, 7615 maize proteins, 6319 of which were quantified. A total of 116 differentially accumulated proteins (DAPs) were identified, including 35 up- and 81 down-regulated proteins under the RBSDV infection. Enrichment analysis showed that the DAPs were most strongly associated with cyanoamino acid metabolism, protein processing in ER, and ribosome-related pathways. Two sulfur metabolism-related proteins were significantly reduced, indicating that sulfur may participate in the resistance against RBSDV infection. Furthermore, 15 DAPs involved in six metabolic pathways were identified in maize under the RBSDV infection. Our data revealed that the responses of maize to RBSDV infection were controlled by various metabolic pathways.


Coexpression of hyperactivated AKT1 with additional genes activated in leukemia drives hematopoietic progenitor cells to cell cycle block and apoptosis.
The phosphatidylinositol 3-kinase/AKT pathway is an integral component of signaling involved in the development of many cancers, including myeloid leukemias such as chronic myeloid leukemia and acute myeloid leukemia (AML). Increased AKT1 activity is frequently seen in AML patients, providing leukemic cells with growth and survival promoting signals. An important aspect of AKT1 function is its involvement in cellular metabolism and energy production. Under some circumstances, strong activation of AKT1 increases oxidative stress, which can cause apoptosis when cells progressively build up excess free radicals. This has been described in hematopoietic cells overexpressing activated AKT1; however, whether this is true in cells coexpressing other genetic events involved in leukemia is not known. This prompted us to investigate the effect of constitutively active AKT1 (myristoylated AKT1) in hematopoietic progenitor cells expressing constitutively active signal transducer and activator of transcription 5, Fms-related tyrosine kinase 3-internal tandem duplication, or antiapoptotic B-cell lymphoma 2. Surprisingly, myristoylated AKT1 was incompatible with proliferation driven by both signal transducer and activator of transcription 5 and Fms-related tyrosine kinase 3-internal tandem duplication, which triggered cell cycle block and apoptosis. Moreover, transplantable cells of B-cell lymphoma 2-transgenic mice were impaired in their engraftment ability to recipient mice when expressing hyperactivated AKT1. This was linked to AKT1-mediated proapoptotic functions and not to impairment in homing to the bone marrow. Although cells expressing hyperactivated AKT1 displayed higher levels of reactive oxygen species both in vitro and in vivo, the addition of the antioxidant N-acetyl-L-cysteine significantly reduced apoptosis. Taken together, the results indicate that constitutive AKT1 activity is incompatible with growth- and survival-promoting ability of other activated genes in AML.


The role of the EAP in the identification and treatment of substance abuse.
Employee Assistance Programs (EAPs) are cost-effective strategies for employers to contain the substantial direct and indirect costs of substance abuse in the workplace. EAPs offer prevention, early detection, assessment of referral, and after-care programs to help stem the enormous costs of substance abuse in the workplace. Most effective employer substance abuse programs integrate drug-testing and EAP services to ensure a well coordinated, cost-effective program.


The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: glial-neuronal metabolic interactions.
Recently, a new experimental model of epilepsy was introduced by the authors [Neurochem. Int. 40 (2002) 413]. This model combines pentylenetetrazole (PTZ)-kindling in senescence-accelerated mice P8 (SAMP8), a genetic model of aging. Since imbalance of glutamate and GABA is a major cause of seizures, the study of glial-neuronal interactions is of primary importance. Nuclear magnetic resonance spectroscopy (NMRS) is an excellent tool for metabolic studies. Thus, we examined whether NMRS when combined with administration of [1-13C]glucose and [1,2-13C]acetate might give valuable insights into neurotransmitter metabolism in this new model of epilepsy and aging. The 2- and 8-month-old SAMP8 were kindled with PTZ alone, received PTZ and phenobarbital (PB), or served as controls. In older animals, PTZ-kindling decreased labeling in glutamate C-4 from [1-13C]glucose, whereas, in the younger mice, labeling in glutamine C-4 was decreased both from [1-13C]glucose and [1,2-13C]acetate. It could be concluded that PTZ-kindling affected astrocytes in younger and glutamatergic neurons in older animals. In the presence of PTZ, phenobarbital decreased labeling of most metabolites in all cell types, except GABAergic neurons, from both labeled precursors in the younger animals. However, in older animals only GABAergic neurons were affected by phenobarbital as indicated by an increase in GABA labeling.


Hemodynamic responses to asphyxia in spontaneously breathing newborn term and premature lamb.
The comparative effects of asphyxia were studied in spontaneously breathing premature and full term newborn lambs. The premature lambs exhibited significantly higher baseline blood flow to several organs. Asphyxia induced similar changes in regional organ blood flow in preterm and term newborn lambs. Regional differences were found in baseline brain blood flow with an increase from cephalad to caudad. Asphyxia resulted in preferential increases in blood flow to the lower brain structures (cerebellum, medulla, midbrain, and spinal cord). Blood flow to most organs returned to baseline 140 min after recovery from asphyxia.


The Perception of Risk of Heart Disease Scale: development and psychometric analysis.
Perception of risk of getting heart disease is an important predictor of individuals' engagement in a healthy lifestyle. This study describes the development and testing of the Perception of Risk of Heart Disease Scale (PRHDS). The 20-item instrument was tested in successive steps with 295 individuals for internal consistency, test-retest reliability, and construct validity. The three subscales of dread risk, risk, and unknown risk had internal consistency values ranging from .68 to .80. The total scale alpha was .80. Evidence of the instrument's stability over time was supported by subscale test-retest reliabilities ranging from .61 to .76. Construct validity was documented with a positive correlation between PRHDS and the Health Promotion Lifestyle Profile II (r = .20 to .39). Further psychometric testing of the PRHDS in a larger sample with a heterogeneous cultural background is recommended.


A molecular dynamics study of cell-penetrating peptide transportan-10 (TP10): Binding, folding and insertion to transmembrane state in zwitterionic membrane.
Transportan 10 (TP10) is a 21-residue, cationic, α-helical cell-penetrating peptide that can be used as a delivery vector for various bioactive molecules. Based on recent confocal microscopy studies, it is believed that TP10 can translocate across neutral lipid membrane passively, possibly as a monomer, without the formation of permanent pore. Here, we performed extensive molecular dynamics (MD) simulations of TP10W (Y3W variant of TP10) to find the microscopic details of binding, folding and insertion of TP10W to transmembrane state in POPC bilayer. Binding study with CHARMM36 force field showed that TP10W initially binds to the membrane surface in unstructured configuration, but it spontaneously folds into α-helical conformation under the lipid head groups. Further insertion of TP10W, changing from a surface bound state to a vertically oriented transmembrane state, was investigated via umbrella simulations. The resulting free energy profile shows a relatively small barrier between two states, suggesting a possible translocation pathway as a monomer. In fact, unbiased simulation of transmembrane TP10W revealed how a charged Lys side chain can move from one leaflet to the other without a significant free energy cost. Finally, we compared the results of TP10W simulations with those of point mutated variants (TP10W-K12A18 and TP10W-K19L) to understand the effect of charge distribution on the peptide. It was observed that such a conservative mutation can cause noticeable changes in the conformations of both surface bound and transmembrane states. The results of present study will be discussed in relation to the experimentally observed activities of TP10W against neutral membrane.


Utilization of energy nutrients by cerebellar slices.
We performed an ontogenetic study about the utilization of glycine, glutamine, beta-hydroxybutyrate and glycerol as energy nutrients by rat cerebellum slices. Production of CO2 from glycerol and glutamine increased with the animals' age and glutamine was the most used nutrient for CO2 production. In adult age, glutamine oxidation to CO2 was 15 to 35 times higher than all other nutrients studied. CO2 production from glycine decreased markedly with age and 10 day-old rats showed an oxidation 7.5 times higher than that of adult rats. At fetal age and at 10 postnatal days, glycine oxidation to CO2 was only 2 times lower than glutamine oxidation to CO2. Lipid synthesis from beta-hydroxybutyrate was highest in adult rats. We did not observe any difference in the utilization of beta-hydroxybutyrate between slices of cerebral cortex and cerebellum at the ages of 10 days and adult. The main nutrients used for lipid synthesis were glycerol and beta-hydroxybutyrate.


Abiotic redox reactions in hydrothermal mixing zones: Decreased energy availability for the subsurface biosphere.
Subseafloor mixing of high-temperature hot-spring fluids with cold seawater creates intermediate-temperature diffuse fluids that are replete with potential chemical energy. This energy can be harnessed by a chemosynthetic biosphere that permeates hydrothermal regions on Earth. Shifts in the abundance of redox-reactive species in diffuse fluids are often interpreted to reflect the direct influence of subseafloor microbial activity on fluid geochemical budgets. Here, we examine hydrothermal fluids venting at 44 to 149 °C at the Piccard hydrothermal field that span the canonical 122 °C limit to life, and thus provide a rare opportunity to study the transition between habitable and uninhabitable environments. In contrast with previous studies, we show that hydrocarbons are contributed by biomass pyrolysis, while abiotic sulfate (SO42-) reduction produces large depletions in H2 The latter process consumes energy that could otherwise support key metabolic strategies employed by the subseafloor biosphere. Available Gibbs free energy is reduced by 71 to 86% across the habitable temperature range for both hydrogenotrophic SO42- reduction to hydrogen sulfide (H2S) and carbon dioxide (CO2) reduction to methane (CH4). The abiotic H2 sink we identify has implications for the productivity of subseafloor microbial ecosystems and is an important process to consider within models of H2 production and consumption in young oceanic crust.


Finding Time for Fiction.
With growing advances in psychiatric care come growing amounts of knowledge to be read by psychiatry trainees. This essay presents one resident's experience putting aside some of the official psychiatric literature during residency in favor of more fiction, and his self-perceived growth because of that. Fiction, in the author's perspective, can make us all better psychiatrists.


Water storage compromises walking endurance in an active forager: evidence of a trade-off between osmoregulation and locomotor performance.
Trade-offs between locomotor performance and load-carrying in animals are well-established and often result from requisite life processes including reproduction and feeding. Osmoregulation, another necessary process, may involve storage of fluid in the urinary bladder of some species. The purpose of this study was to determine whether storage of urine in the urinary bladder reduces walking endurance in an actively foraging lizard. The results of our paired-design study indicate that the volume of fluid stored in the urinary bladder (36.5+/-1.6 ml) contributed a significant load (9.2% of body mass) to the lizards. This load resulted in a disproportionate 24.5+/-2.8% decrement in walking endurance. Specifically, Gila monsters walked at a fixed pace for a significantly shorter duration when the urinary bladder contained fluid (26+/-2.0 min) compared to when the bladder was empty (34.3+/-2.3 min). Since fluid stored in the bladder contributes to osmoregulation in this species, our results indicate the presence of a trade-off between osmoregulation and endurance in Gila monsters. Bearing other loads (e.g., a clutch or meal) influences the evolution of life-history traits and foraging strategy; thus the negative effect of fluid storage on endurance may also have evolutionary implications.


Idiotypes of anti-phosphocholine antibodies: structural correlates.
Phosphocholine-specific antibodies in mice are composed of three families of antibodies, the T15, the M603 and the M511, which are constructed by combinatorial association of a VH4 H chain and one of three different L chains, VK22, VK8 and VK24, respectively. Antiidiotypic antisera can be generated which (1) recognize all members of a family, i. e. anti-T15 IdX, anti-M603 IdX and anti-M511 IdX, (2) distinguish between members of a family, e. g. A/J anti-T15, or (3) recognize determinants on only a single anti-PC antibody. Consideration of protein sequences and L-chain polymorphisms and analysis of chain recombination experiments among Id-positive and -negative antibodies revealed that IdX are determined by the L chain. A similar approach demonstrated that the Id determinant defined by the A/J anti-T15 is dependent upon the L chain and the D region of the H chain.


Estimation of sleep problems among pregnant women during COVID-19 pandemic: a systematic review and meta-analysis.
To estimate the sleep problems among pregnant women during the COVID-19 pandemic. English, peer-reviewed, observational studies published between December 2019 and July 2021 which assessed and reported sleep problem prevalence using a valid and reliable measure were included. Scopus, Medline/PubMed Central, ProQuest, ISI Web of Knowledge and Embase. The Newcastle-Ottawa Scale checklist. Prevalence of sleep problems was synthesised using STATA software V.14 using a random effects model. To assess moderator analysis, meta-regression was carried out. Funnel plot and Egger's test were used to assess publication bias. Meta-trim was used to correct probable publication bias. The jackknife method was used for sensitivity analysis. A total of seven cross-sectional studies with 2808 participants from four countries were included. The pooled estimated prevalence of sleep problems was 56% (95% CI 23% to 88%, I2=99.81%, Tau2=0.19). Due to the probability of publication bias, the fill-and-trim method was used to correct the estimated pooled measure, which imputed four studies. The corrected results based on this method showed that pooled prevalence of sleep problems was 13% (95% CI 0% to 45%; p<0.001). Based on meta-regression, age was the only significant predictor of prevalence of sleep problems among pregnant women. All studies were cross-sectional absence of assessment of sleep problems prior to COVID-19, and the outcomes of the pregnancies among those with and without sleep problems in a consistent manner are among the limitation of the current review. Pregnant women have experienced significant declines in sleep quality when faced with the COVID-19 pandemic. The short-term and long-term implications of such alterations in sleep on gestational and offspring outcomes are unclear and warrant further studies. CRD42020181644.


Patterns of early visual field loss in open-angle glaucoma.
We examined two groups of patients with primary open-angle glaucoma with distinctly different patterns of early visual field loss using two visual field indices: mean defect and loss variance. Patients were selected on the basis of visual field criteria only. Eight patients were selected for diffuse depression of the differential light sensitivity without localized scotomas (mean defect greater than 3.0 decibels, loss variance less than 10.0 decibels). Seven patients were selected for localized scotomas without diffuse depression of the differential light sensitivity (mean defect less than or equal to 3.0 decibels, loss variance greater than or equal to 20.0 decibels). Patients with diffuse depression manifested intraocular pressures that were higher (mean peak pressure +/- S.E.M., 27.6 +/- 1.2 mm Hg) than those with localized defects (22.4 +/- 1.4 mm Hg). The optic disk rim area of the localized loss group (mean +/- S.E.M., 1.02 +/- 0.15 mm2) was significantly smaller (P less than .05) than the disk rim area of the diffuse loss group (1.33 +/- 0.07 mm2). This difference was largely because of thinner temporal disk rims in the localized loss group. Different patterns of visual field loss may be caused by different mechanisms of glaucomatous optic nerve damage.


Characterization of a highly pathogenic H5N1 avian influenza virus isolated from ducks in Eastern China in 2011.
This study describes the characterization of seven H5N1 avian influenza viruses from domestic ducks in Eastern China in 2011. Phylogenetic analysis showed these viruses were closely related to an H5N1 virus circulating in wild birds in Hong Kong. Some characteristics of these viruses were similar to those of an H5N1 strain that circulated in China and Vietnam (2003-2004). The virulence of three isolates was examined in chickens and mice, and they were found to be highly pathogenic in chickens but showed low pathogenicity in mice. These results suggest that continued H5N1 surveillance in poultry should be used as an early warning system for avian influenza outbreaks.


Blood parasites in northern goshawk (Accipiter gentilis) with an emphasis to Leucocytozoon toddi.
Haemosporidians and trypanosomes of the northern goshawk (Accipiter gentilis) population in the Czech Republic were studied by morphological and molecular methods. Despite the wide distribution of these medium-large birds of prey, virtually nothing is known about their blood parasites. During a 5-year period, altogether 88 nestlings and 15 adults were screened for haemosporidians and trypanosomes by microscopic examination of blood smears and by nested PCR. Both methods revealed consistently higher prevalence of blood protists in adults, Leucocytozoon (80.0 % in adults vs. 13.6 % in nestlings), Haemoproteus (60.0 vs. 2.3 %), Plasmodium (6.7 vs. 0 %), and Trypanosoma (60.0 vs. 2.3 %). Altogether, five haemosporidian lineages were detected by cytochrome b sequencing. Two broadly distributed and host nonspecific lineages, Plasmodium (TURDUS1) and Leucocytozoon (BT2), were detected only sporadically, while three newly described northern goshawk host-specific Leucocytozoon lineages (ACGE01-03) represent the absolute majority of the haemosporidians identified by molecular methods. Our findings support evidences that in falconiform birds the Leucocytozoon toddi group is formed by several host-specific clusters, with Leucocytozoon buteonis in buzzards and Leucocytozoon mathisi in hawks. Between-year comparisons revealed that the infection status of adults remained predominantly unchanged and individuals stayed uninfected or possessed the same parasite lineages; however, two gains and one loss of blood parasite taxa were also recorded.


As in other countries, the situation of nurses in training has changed in Austria during the COVID 19 pandemic. Therefore, the aim of this survey was to show the challenges faced by nurses in training during the COVID 19 pandemic in order to help shape a better future for nursing students. All nursing students in Austria were invited to take part in an electronic survey between November 26, 2020 and March 1, 2021. The questionnaire contained nine quantitative and two open questions. 610 nursing students participated. 39.6% had a negative view of the nursing profession in times of the pandemic. There were reports of increased physical and psychological stress during their time on the wards. The results of this survey provide an overview of the situation of nurses in training during the COVID 19 pandemic. It became clear that the conditions for students in nursing have to be improved and requirements such as pay and better working conditions implemented.


Immunologic studies in patients with chyluria.
Patients with chyluria, postoperative chylothorax, or surgical thoracic duct drainage are depleted of lymphocytes, IgA, and C3 as a result of the loss of lymphatic cellular and humoral elements, but the specific defects have not been well characterized. Therefore, we investigated the immunologic status of three patients with longstanding chyluria who were lymphopenic but did not have evidence of opportunistic infections. All patients had normal levels of immunoglobulins except for a moderate decrease in the IgA fraction, a normal antibody response to viral agents, and a normal hypersensitivity response to at least one of six recall antigens. Their complement levels were essentially normal. All were leukopenic because of decreased numbers of circulating lymphocytes. Two had depressed relative and absolute numbers of OKT4 (helper/inducer) T cells and normal or increased relative numbers of OKT8 (cytotoxic/suppressor) T cells, resulting in a marked reversal of the OKT4 to OKT8 ratio. The third was severely depleted of both OKT4 and OKT8 cells. The response of their peripheral blood mononuclear cells to mitogen stimulation was reduced, but they all had normal or increased absolute and relative numbers of natural killer (NK) cells as defined by HNK-1 or OKM-1. Their NK activity was less than that of normal controls unless stimulated by interferon, suggesting that many of the NK cells were immature. Normal delayed hypersensitivity, reduced but effective mitogen stimulation, and a normal NK response after interferon may be factors that protect these patients against opportunistic infections and neoplasms.


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Maize (Zea mays) cell cultures were used for the production of zearalenone-4-β-D-glucopyranoside as standard compound. Wheat samples were extracted with acetonitrile: water, applied to a florisil column and eluted with methanol:ethyl acetate. For determination and quantification of zearalenone-4-β-D-glucopyranoside and zearalenone a LC-MS method was developed. A concentration of 10 μg/kg zearalenone-4-β-D-glucopyranoside and zearalenone was detectable. The recovery rates were calculated to be 69% and 89% at a concentration level of 100 μg/kg for zearalenone-4-β-D-glucopyranoside and zearalenone, respectively.24 Bavarian wheat samples from harvest 1999 were analyzed. Zearalenone was present in 22 out of 24 field samples, the levels ranged from 11-860 μg/kg. Zearalenone-4-β-D-glucopyranoside was found in 10 out of the zearalenone positive samples (42%) at levels ranging from 17 to 104 μg/kg. The amounts of zearalenone-4-β-D-glucopyranoside were correlated to those of zearalenone (r2=0,86; b=0,10).


The novel acute phase protein, IHRP, inhibits actin polymerization and phagocytosis of polymorphonuclear cells.
In the present study, the involvement of the binding of IHRP (inter-alpha-trypsin inhibitor family heavy chain-related protein) and actin in phagocyte activity was investigated. The actin polymerization and the phagocytic activity of the polymorphonuclear (PMN) cells were studied in the presence of IHRP. IHRP inhibited the polymerization of actin and the phagocytic activity of the PMN cells. 1) IHRP may bind to actin released from the damaged cells and suppress its toxic action by preventing the formation of actin fibril. 2) IHRP may bind to cell surface actin on PMN cells and inhibit their phagocytic activities. 3) From these results, IHRP may act as an anti-inflammatory protein.


Staphylococcus aureus septicemia mimicking fulminant Rocky Mountain spotted fever.
Septicemia due to Staphylococcus aureus can be a difficult diagnosis to make early in its presentation. This report illustrates a case that mimicked fulminant Rocky Mountain spotted fever in a patient with no other medical problems that might predispose her to the development of staphylococcal sepsis. Epidemiology, cerebrospinal fluid characteristics, and early biopsy of skin lesions are emphasized as important factors leading to early diagnosis and definitive treatment.


The gastrointestinal absorption of drugs in man: a review of current concepts and methods of investigation.
The various mechanisms which have been advanced to explain drug absorption are critically reviewed and the limitations of current theories are discussed. Various techniques for investigating drug absorption and transit through the gut are presented, and the results obtained with metoprolol are briefly considered to illustrate the potential of some of these methods.


Mitigating the adverse effects of Aflatoxin B1 in LMH, IPEC-J2 and 3D4/21 cells by a novel integrated agent.
This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B1 (AFB1)-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC30) of AFB1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB1 (IC30) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB1-induced inflammatory response by decreasing IL-1β, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1β in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB1 in the three cells, suggesting that AFB1-induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB1-induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling.


Oral and maxillofacial reconstruction in a cat using wire and acrylic.
A 15-month-old DSH cat was presented with facial deformity secondary to multiple oral and maxillofacial fractures after being struck by an automobile. Multiple wires and dental acrylics were used for fracture repair.


In vitro radical scavenging activity of two Columbian Magnoliaceae.
The recent interest in the conservation of the tropical forest is due, at least in part, to the potential economic and health benefits that can be exploited from several plants. This report shows the in vitro antioxidant activity of some fractions isolated from leaves of two Columbian Magnoliaceae, Talauma hernandezii G. Lozano-C and Dugandiodendron yarumalense Lozano. The activity was determined using the radical monocation 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS.+) and the stable free radical 2-2-diphenyl-1-picrylhydrazyl (DPPH.), as part of general biological screening of these plants. The antioxidant capacity obtained from fractions was similar to those of alpha-tocopherol, tert-butylated hydroxyanisole (BHA), and ascorbic acid. The most active scavenger extract was the fraction 7 (TAA = 48.6 mmol Trolox/kg extract and IC50 < or = 0.01 kg extract/mmol DPPH); and the least active was the fraction 1 (TAA = 11.23 mmol Trolox/kg extract and IC50 = 0.21 kg extract/mmol DPPH) all of them isolated from D. yarumalense. These results suggest that these plants can be attractive as source of antioxidant compounds with the ability to reduce radicals like ATBS and DPPH.


Immunocytochemical localization of angiotensinogen in the fetal and neonatal rat brain.
The aim of this study was to define the temporal appearance and regional distribution of angiotensinogen in the fetal and neonatal rat brain. This was done by immunocytochemical localization of angiotensinogen in brains from embryonic day 16 to postnatal day 12. Immunostaining was first observed on embryonic day 18, and persisted to postnatal day 2, in the choroid plexus and ependymal cells lining the third ventricle. This initial expression of angiotensinogen at embryonic day 18 was followed at postnatal day 20 by a rapid progression of angiotensinogen staining appearing in astrocytes in the paraventricular nucleus, medial preoptic area, ventromedial and arcuate hypothalamic nuclei; these areas showed the highest astrocyte staining intensity in the brain. This was followed sequentially by staining in areas of the thalamus, midbrain, forebrain and brainstem. In general, neuroglial staining was higher in regions proximal to the cerebral ventricles and cerebral aqueduct. Neuronal angiotensinogen was observed at day postnatal day 0 and later. The most consistent immunopositive areas were in the forebrain and thalamus; in particular, the hippocampus, anterior and posterior cingulate cortex, basal and lateral amygdala, the caudate-putamen, globus pallidus, lateral septum, medial habenular nuclei and lateral thalamic nuclei. Most of the immunopositive cells in the hypothalamus and brainstem were astrocytes, while those in the cortex were almost exclusively neurons. Staining in thalamic regions was both neuronal and neuroglial. From the intensity of staining and cell density, it was determined that a rapid increase in angiotensinogen occurs between embryonic day 20 and postnatal day 0, followed by further, smaller increases postnatally. In conclusion, this study has shown that angiotensinogen, the protein from which angiotensin II is generated, is present in the rat fetal brain. The timing of its appearance supports the establishment of a renin-angiotensin system by late gestation. Its predominance in fetal hypothalamic nuclei and in thalamic, cerebellar and cortical neurons suggests major roles in prenatal fluid and electrolyte balance, in sensorimotor development and in brain maturation.