Vagal nerve stimulation releases vasoactive intestinal peptide which significantly increases coronary artery blood flow.
To determine the effects of vasoactive intestinal peptide (VIP), released endogenously from cardiac vagal nerves, on coronary artery blood flow (CBF). We determined the effects of vagal nerve stimulation (VNS) at frequencies of 10, 15, 20, and 30 Hz on left circumflex coronary artery (LCx) blood flow. The increases in CBF during VNS were compared with the increases in CBF produced by exogenous VIP and also nitroglycerin (NTG). In 18 anesthetized open chest mongrel dogs, we blocked the muscarinic and beta-adrenergic receptors with atropine and propranolol. We controlled heart rate and aortic pressure by right atrial pacing and an arterial reservoir. CBF was measured in the LCx with a Doppler flow probe. A 25 gauge catheter was placed in the proximal LCx to inject the VIP receptor antagonist [4Cl-D-Phe6Leu17]VIP, VIP, NTG, or vehicle. CBF, aortic and ventricular pressures, ventricular contractility (+dp/dt(max)) and relaxation (-dp/dt(min)) and the EKG were measured. VNS (0.5 ms, 20 V, 5 min.) at 20 Hz maximally increased CBF by 62 +/- 14% at 5 min from 71 +/- 10 to 115 +/- 19 ml/min (p < 0.01). VNS at 10, 15, and 30 Hz increased CBF by 6 +/- 1%, 24 +/- 5%, and 24 +/- 7%, respectively (all p < 0.05 vs control). Following 20 Hz VNS, CBF returned toward the baseline over 30 min. Aortic and left ventricular (LV) pressures, LV +dp/dt(max) and LV-dp/dt(min) did not significantly change. After the direct administration of [4Cl-D-Phe6Leu17]VIP into the LCx, VNS increased CBF by only 10 +/- 4% (p = NS). Exogenous VIP, in doses of 9.0 x 10(-11) to 2.1 x 10(-9) mol, increased CBF by 106 +/- 17% to 169 +/- 17% (all p < 0.01 vs control). NTG, in doses of 2.2 x 10(-8) to 1.7 x 10(-7) mol, increased CBF by 101 +/- 15% to 169 +/- 20% (all p < 0.01 vs control). These increases in CBF persisted during the 1 to 2 min injection period and returned to the baseline within 5 min. Neither VIP nor NTG significantly changed the heart rate, aortic or LV pressures, LV +dp/dt(max) or LV -dp/dt(min). VNS at 20 Hz, exogenous VIP, 9.0 x 10(-11) mol, and exogenous NTG, 2.2 x 10(-8) to 4.4 x 10(-8) mol, produced equivalent increases in CBF by analysis of variance determination. The present experiments suggest that VNS releases VIP which directly dilates coronary arteries and significantly increases coronary artery blood flow.


Termites of a South African savanna : III. Comparative attack on toilet roll baits in subhabitats.
Cellulose toilet roll baits were exposed in three different subhabitats at Nylsvley Reserve, northern Transvaal, and respective attacks by up to eight species of termites are described and illustrated. In broad-leaved savanna attack was principally by Microcerotermes, a slow feeder that attacked rolls throughout the year, finding about half the rolls exposed each season. In Acacia savanna attack was largely by Microtermes, a fast feeder active only at wetter times of year. In open, grassy areas there was relatively little attack, except sporadically by Macrotermes which consumed whole rolls within a day or two. Bush-fires delayed initial attack on rolls, perhaps because reduced surface litter gave less protection to soil. The amount of each roll eaten during the trials is shown in histograms; it was consistently greater in Acacia than in broad-leaved savanna. The soil-feeding termites Aganotermes and Promirotermes were attracted during the wet season to the undersides of rolls, perhaps as a source of organic-rich soil (or possibly of water).


Modulation of purine synthesis and phosphoribosylpyrophosphate content in human fibroblasts at different population doublings.
Human diploid fibroblasts of embryonic origin which display the limited lifespan phenomenon, respond to purine base deprivation with a large accumulation of phosphoribosylpyrophosphate when studied at early population doubling levels. This suggests that the purine salvage enzymes are the main consumers of phosphoribosylpyrophosphate in such cells. There is a strong positive correlation between the rate of de novo purine synthesis and the phosphoribosylpyrophosphate content, consistent with its role in the first and rate-limiting reaction of de novo purine synthesis. With increasing population doublings, the cells become less responsive to purine base deprivation; the phosphoribosylpyrophosphate does not increase significantly and a lower rate of de novo purine synthesis is observed. As the rate of cell replication decreases with serial passages, it becomes apparent that such cells appropriately adjust the concentration of phosphoribosylpyrophosphate, thereby controlling the rate of purine synthesis according to their needs for cellular growth.


Partial recovery of cisplatin-induced hearing loss in the albino guinea pig in relation to cisplatin dose.
The objective of the present study was to further characterize cochlear recovery after cisplatin damage. We equipped albino guinea pigs with permanent round window electrodes. Cisplatin was injected i.p. on a daily basis at either 1.5 or 2.0 mg/kg/day. Treatment was stopped when the criterion of > or =40 dB loss in the compound action potential iso-response level at 8 kHz had occurred. Either shortly (1-3 days) or long (4 weeks or more) after this stop, the endocochlear potential (EP) was measured and all animals were sacrificed for histology. At a cisplatin dose of 2.0 mg/kg/day, the time needed to reach the criterion hearing loss varied from 5 to 11 days. With 1.5 mg/kg/day this period lasted longer, the cumulative dose being the first-order predictor. The cochlear potentials gradually recovered in the first 2 weeks after treatment. At the lower frequencies, recovery was often complete. At the higher frequencies complete recovery was never seen. EP was depressed when measured just after treatment but had normal values long after. Basal outer hair cell (OHC) loss was found for both the short and the long post-treatment period. Thus, loss and recovery of cochlear potentials can for a large part be explained by loss and recovery of the EP. Recovery is limited by permanent OHC loss.


Membrane properties and synaptic potentials in rat sympathetic preganglionic neurons studied in horizontal spinal cord slices in vitro.
Intracellular recordings were made from neurons in the intermediolateral column and adjacent white matter in horizontal slices of upper thoracic spinal cord from rats aged 21-28 days. Membrane properties were studied in the presence of picrotoxin (100 microM) to block ongoing inhibitory synaptic potentials. 37 neurons were identified as sympathetic preganglionic neurons (SPNs) by their electrical behaviour, anatomical location and/or morphology. SPNs had resting potentials of -57 +/- 2 mV and input resistances of 254 +/- 31 M omega (n = 14). Following a hyperpolarising voltage step, a transient outward current was activated which had a time constant of decay of approx. 400 ms. The inflection in the repolarising phase of the action potential and the following prolonged AHP were both abolished by Cd2+ (50 microM). The current underlying the AHP had two components with kinetic properties similar to the two calcium-activated potassium conductances, gKCa1, and gKCa2, characterized in other autonomic neurons. Noradrenaline (10-100 microM) caused a small depolarization and blocked the calcium component of the action potential suppressing the AHP. This revealed an afterdepolarization (ADP) with an underlying inward current with a decay time constant of approx. 150 ms. All effects of noradrenaline were blocked by phentolamine (10 microM). Graded stimulation of the lateral funiculus 0.5-1 mm rostral to the recording site evoked in all cells monosynaptic fast excitatory synaptic potentials (fEPSPs) which were graded in amplitude. fEPSPs decayed with a time constant identical to the cell input time constant and were reduced in amplitude by CNQX (10-20 microM). In 7 cells, higher stimulus voltages elicited slow EPSPs with a time to peak of 1.1 +/- 0.1 s and a half decay of 2.8 +/- 0.3 s (n = 7) which were not reduced by alpha-adrenoceptor antagonists. The AHP was not blocked when the action potential was initiated during the slow EPSP. We conclude that excitatory bulbospinal inputs to SPNs involve at least one fast transmitter which is likely to be glutamate and one slow transmitter which is not noradrenaline.


Optimized design and synthesis of a cell-permeable biarsenical cyanine probe for imaging tagged cytosolic bacterial proteins.
To optimize cellular delivery and specific labeling of tagged cytosolic proteins by biarsenical fluorescent probes built around a cyanine dye (Cy3) scaffold, we have systematically varied the polarity of the N-alkyl chain (i.e., 4-5 methylene groups appended by a sulfonate or methoxy ester moiety) and arsenic capping reagent (ethanedithiol versus benzenedithiol). Optimal live-cell labeling and visualization of tagged cytosolic proteins is reported using an ethanedithiol capping reagent with the uncharged methoxy ester functionalized N-alkyl chains. These measurements demonstrate the general utility of this new class of photostable and highly fluorescent biarsenical probes based on the cyanine dye scaffold for in vivo labeling of tagged cellular proteins for live cell imaging measurements of protein dynamics.


Microstructure and fracture toughness of hot-rolling biomedical degradable ZKX500 magnesium bone plates.
In this study, the microstructure and fracture toughness of ZKX500 magnesium alloy under different processing were investigated. The results show that the as-extruded (FH) consists of coarsen and fine grains with higher residual stress. The fracture toughness and crack propagation are significantly distinct along different directions. By contrast, the rolled specimen (FRH) shows an equiaxed grain structure and precipitation dispersion in the matrix. After hot-rolling and heat treatment, less texture effect affected on the fracture toughness and rupture energy absorption. These renders the higher attractive on the rolled ZKX500 magnesium alloy in the applications of orthopedic bone plates.


Prophylactic use of antimicrobial agents in adult patients.
Prophylactic antimicrobial agents are recommended for prevention of a variety of conditions, including tuberculosis, endocarditis, rheumatic fever, recurrent cellulitis and lymphangitis in patients with lymphedema, meningococcal meningitis, bite wounds, and herpes virus infections. In addition, prophylactic antimicrobial agents have proved effective in certain surgical procedures such as a variety of abdominal operations, hysterectomy, and head and neck operations for cancer. Except for oral bowel preparations, administration of antimicrobial agents for prophylaxis should be limited, in general, to the perioperative time period. Doses given more than an hour before or 3 hours after a surgical procedure have not been shown to increase effectiveness, and such an approach increases the cost and the probability of toxicity and superinfection. Investigation of antimicrobial prophylaxis necessitates adequate evaluation of potential advantages and disadvantages in prospective double-blind fashion.


Autophagic lipid metabolism sustains mTORC1 activity in TSC-deficient neural stem cells.
Although mTORC1 negatively regulates autophagy in cultured cells, how autophagy impacts mTORC1 signaling, in particular in vivo, is less clear. Here we show that autophagy supports mTORC1 hyperactivation in NSCs lacking Tsc1, thereby promoting defects in NSC maintenance, differentiation, tumourigenesis, and the formation of the neurodevelopmental lesion of Tuberous Sclerosis Complex (TSC). Analysing mice that lack Tsc1 and the essential autophagy gene Fip200 in NSCs we find that TSC-deficient cells require autophagy to maintain mTORC1 hyperactivation under energy stress conditions, likely to provide lipids via lipophagy to serve as an alternative energy source for OXPHOS. In vivo, inhibition of lipophagy or its downstream catabolic pathway reverses defective phenotypes caused by Tsc1-null NSCs and reduces tumorigenesis in mouse models. These results reveal a cooperative function of selective autophagy in coupling energy availability with TSC pathogenesis and suggest a potential new therapeutic strategy to treat TSC patients.


Adverse Events and Resource Use Before and After Treat-to-Target in Rheumatoid Arthritis: A Post Hoc Analysis of a Randomized Controlled Trial.
Treat-to-target (TTT) is an accepted paradigm for care of patients with rheumatoid arthritis (RA). Because TTT can be associated with more medication switches, concerns arise regarding whether implementing TTT may increase adverse events and/or resource use. The aim of this study was to examine adverse events and resource use during the preintervention and intervention periods of the TTT intervention trial. We used data from 6 practices enrolled in an 18-month cluster-randomized controlled trial to compare adverse events and resource use before (months 1-9) and during (months 10-18) a TTT intervention. The outcomes of interest, adverse events and resource use, were based on medical record review of all rheumatology visits for RA patients before and during the intervention. We examined records for 321 patients before the intervention and 315 during the intervention. An adverse event was recorded in 10.2% of visits before the intervention and 8.8% of visits during the intervention (P = 0.41). Biologic disease-modifying antirheumatic drugs were taken by 53.6% of patients before the intervention and 49.8% of patients during the intervention (P = 0.73). Rheumatology visits were more frequent before the intervention (mean ± SD 4.0 ± 1.4) than during the intervention (mean ± SD 3.6 ± 1.2; P = 0.02). More visits were accompanied by monitoring laboratory tests before the intervention (90.0%) compared with during the intervention (52.7%; P < 0.001). A greater percentage of visits before the intervention included diagnostic imaging (15.4%) versus during the intervention (8.9%; P < 0.001). We observed similar rates of adverse events before and during the implementation of TTT for RA. Rheumatology visits, use of laboratory monitoring, and diagnostic imaging did not increase during the TTT intervention.


Label-free, real-time interaction and adsorption analysis 1: surface plasmon resonance.
A key requirement for the development of proteins for use in nanotechnology is an understanding of how individual proteins bind to other molecules as they assemble into larger structures. The introduction of labels to enable the detection of biomolecules brings the inherent risk that the labels themselves will influence the nature of biomolecular interactions. Thus, there is a need for label-free interaction and adsorption analysis. In this and the following chapter, two biosensor techniques are reviewed: surface plasmon resonance (SPR) and the quartz crystal microbalance (QCM). Both allow real-time analysis of biomolecular interactions and both are label-free. The first of these, SPR, is an optical technique that is highly sensitive to the changes in refractive index that occur with protein (or other molecule) accumulation near an illuminated gold surface. Unlike QCM ( Chapter 18 ) SPR is not affected by the water that may be associated with the adsorbed layer nor by conformational changes in the adsorbed species. SPR thus provides unique information about the interaction of a protein with its binding partners.


The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease.
Fecal calprotectin (FC) is elevated in patients with inflammatory bowel disease (IBD). Studies evaluating FC during the initial investigation of children with suspected IBD have been limited, especially with regard to their small patient groups. We aimed to evaluate the diagnostic accuracy of FC in a large regional cohort of children undergoing full upper and lower endoscopy for suspected IBD, comparing FC with six common blood parameters. Using a retrospective case-control design all FC measurements carried out between 2005 and 2010 in children <18 years old were obtained. All IBD and non-IBD patients who had a FC measurement available before full endoscopic evaluation for suspected bowel inflammation were examined. FC was measured using the PhiCal Test. Multivariate analyzes and receiver operating characteristic curve generation were used to derive significance. A total of 190 patients (91 IBD and 99 non-IBD controls) met the inclusion criteria. Median FC at diagnosis for the IBD group was 1,265 μg/g (interquartile range (IQR) 734-2,024 μg/g), compared with 65 μg/g (IQR 20-235 μg/g) in controls (P<0.001). FC levels did not vary significantly between patients with Crohn's disease, ulcerative colitis, and IBD unclassified and were not influenced by age or disease location. FC was found to be far superior to commonly utilized blood parameters such as C-reactive protein and white cell count (both P<0.01), with an area under the curve of 0.93 (95% confidence interval 0.89-0.97). This study demonstrates that FC is an invaluable tool in determining those children who may require endoscopy for suspected IBD, and elevated values should prompt further investigation.


Transannular Enantioselective (3 + 2) Cycloaddition of Cycloalkenone Hydrazones under Brønsted Acid Catalysis.
Hydrazones derived from cycloalkenones undergo an enantioselective transannular formal (3 + 2) cycloaddition catalyzed by a chiral phosphoric acid. The reaction provides high yields and excellent stereocontrol in the formation of complex adducts with one or two α-tertiary amine moieties at the ring fusion, and these can be converted into very versatile stereodefined decalin- or octahydro-1H-indene-derived 1,3-diamines through simple reductive N-N cleavage.


Comparison of tumor neovasculature-targeted paramagnetic nanoliposomes for MRI in mice xenograft models.
Neovasculature imaging is a promising approach for tumor diagnosis. We constructed tumor neovasculature targeted paramagnetic nanoliposomes with RGD10, F56, and K237 peptides, which can bind to Integrin αvβ3 and VEGFR-1, VEGFR-2, respectively, and compared their potential value as MRI contrast agents for detecting small tumors in animal models. Peptide-Ahx-palmitic acid conjugate was synthesized using Fmoc solid-phase synthesis chemistry. Targeted paramagnetic nanoliposomes were prepared by the thin film dispersion-sonication method. The tumor signal enhancements of liposome particles were evaluated by MRI in a xenograft mice model. The apparent affinity constants of RGD10, K237, and F56 peptides binding to their cell receptors were 9.15 × 10(7), 6.01 × 10(7), and 3.85 × 10(7) mol/L, respectively. RGD10 and K237 targeted paramagnetic nanoliposomes have shown much greater tumor-specific MRI signal enhancement in xenograft of the nude mice compared to F56 targeted paramagnetic nanoliposome. Tumor signal enhancement rate (SER %) increased 2.21 ± 0.09 and 1.82 ± 0.05 fold, respectively, for RGD10 and K237 compared to non-targeted control in T1 weighted MR image. RGD10 and K237 targeted paramagnetic nanoliposomes can be developed as potential tumor-specific MRI contrast agents and are helpful for tumor detection.


Structural model of the Plasmodium CDK, Pfmrk, a novel target for malaria therapeutics.
Malaria, with 300-500 million clinical cases resulting in 1-3 million fatalities a year, is one of the most deadly tropical diseases. As current antimalarial therapeutics become increasingly ineffective due to parasitic resistance, there exists an urgent need to develop and pursue new therapeutic strategies. Recent genome sequencing and molecular cloning projects have identified several enzymes from Plasmodium (P.) falciparum that may represent novel drug targets, including a family of proteins that are homologous to the mammalian cyclin-dependent kinases (CDKs). CDKs are essential for the control of the mammalian cell cycle and, based on the conservation of the CDKs across species, the plasmodial CDKs are expected to play a crucial role in parasitic growth. Here we present a 3D structural model of Pfmrk, a putative human CDK activating kinase (CAK) homolog in P. falciparum. Notable features of the present structural model include: (1) parameterization of the Mg2+ hexacoordination system using ab initio quantum chemical calculations to accurately represent the ATP-kinase interaction; and (2) comparison between the docking scores and measured binding affinities for a series of oxindole-based Pfmrk inhibitors of known activity. Detailed analysis of inhibitor-Pfmrk binding interactions enabled us to identify specific residues (viz. Met66, Met75, Met91, Met94 and Phe143) within the Pfmrk binding pocket that may play an important role in inhibitor binding affinity and selectivity. The availability of this Pfmrk structural model, together with insights gained from analysis of ligand-receptor interactions, should promote the rational design of potent and selective Pfmrk inhibitors as antimalarial therapeutics.


Breba Fruits Characterization from Four Varieties (Ficus carica L.) with Important Commercial Interest in Spain.
Although most of the published articles generalize with the fruit of the fig tree (Ficus carica L.), the differentiation between fig and breba is increasingly common in the bibliography. In this regard, keep in mind that the fig tree generally produces two crops a year, the parthenocarpic breba, also called as early fig, and the main non-parthenocarpic crop, the fig proper. In this study, four brebas varieties ('Colar', 'SuperFig1', 'Cuello de Dama Negro' and 'San Antonio') were selected in order to identify compositional, nutritional, and chemical diversity. These varieties were chosen for their commercial relevance in Spain. Color (internal and external), fruit and peel weight, size, pH, total soluble solids (TSS), titratable acidity (TA), maturity index (MI), sugar, and organic content were determined for all the breba fruits samples. In addition, polyphenolic profile, amino acids, and volatile aromatic compounds were also identified. The varieties 'Colar' and 'SuperFig1' showed the highest fruit weight and size, while 'Cuello de Dama Negro' presented the higher pulp yield. The higher organic acid and sugar contents were determined for 'SuperFig1' and 'Cuello de Dama Negro', respectively. Although in low concentrations, the phenolic compound quercetin 3-(6-O-acetyl-beta-glucoside) and the amino acid tyrosine were only detected in the ''Cuello de Dama Negra' and 'SuperFig1' fruits, respectively. Of the eighty volatile aromatic compounds identified, only eight were common in four varieties. An important knowledge gap was identified in relation to the characterization of the two Ficus carica L. crops, that is, the differentiation and specification in the literature when working with brebas and/or figs.


Synthesis of deoxynivalenol-glucosides and their characterization using a QTrap LC-MS/MS.
Deoxynivalenol (DON)-glucosides were successfully synthesized in a two-step reaction from 1-β-Bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-α-D-gluco-pyranose and 3-Acetyl-DON or 15-Acetyl-DON. After purification of the reaction products, the mycotoxin conjugates were for the first time characterized by means of a triple quadrupole mass spectrometer in combination with a linear ion trap. Due to different fragmentation behaviour it was also possible to distinguish between the two glucosides.


Allergen disrupts amygdala-respiration coupling.
Allergic asthma affects both the respiratory function and central nervous system. Communication between the amygdala and respiratory control system is critical for regulating breathing function. To date, no study provides the effect of allergic inflammation on amygdala-respiration coupling. Here, we simultaneously recorded respiration and local field potentials of the amygdala during awake immobility in a rat model of allergic asthma. A decreased synchrony was found between amygdala and respiration in asthmatic rats. Allergen also reduced the modulatory effect of the respiration phase on amygdala power at delta, theta and gamma2 (80-120 Hz) frequencies. Moreover, in the animal model of allergic asthma, delta and theta oscillations strongly coordinate local gamma2 activity in the amygdala. These findings suggest that allergen can induce brain alterations and therefore shed light on future works to address how disruption of amygdala-respiration coupling contributes to respiratory dysfunction in allergic asthma.


A Rare Case of Tibioperoneal Arterial Trunk Entrapment Caused by a Fibular Osteochondroma.
Osteochondromas or exostoses are the most common benign tumors of the bones, which appear during the growth period. The involvement of lower extremities is common, particularly in metaphyseal structures of the femur and humerus and around the knee joint. However, the incidence of the development of the tumor at the proximal fibula is rare. The most common signs and symptoms of the disease are pain, pulsatile mass, limb swelling, neurologic sequelae, bursa formation with subsequent bursitis, and impairment of the developmental growth. Vascular complications are rare, yet osteochondromas can cause catastrophic arterial complications threatening the life of the patient if they occur and can include vessel perforation and thrombosis, arterial thromboembolic events, and pseudoaneurysm formation. We report a case of a 24-year-old male patient presenting with tibioperoneal arterial trunk entrapment caused by a massive osteochondroma derived from the proximal fibula. A combined vascular-orthopedic approach was initiated with the excision of the tumor, in which the neurovascular structures (tibial nerve, popliteal artery and vein, anterior tibial artery, and tibioperoneal trunk) were carefully recognized and protected. The postoperative course of the patient was uneventful. High clinical suspicion of a vascular complication should be raised by physicians when investigating a young patient with a suspected osseous tumor in the popliteal fossa and symptomatology of concurrent peripheral arterial disease. Prompt surgical management is crucial for the salvage of the affected limb in cases of arterial involvement. Furthermore, quick surgical exposure of the mass and regular postoperative follow-up check minimizes the risk of irreparable impairments and tumor recurrence.


Arbuscular mycorrhizal fungi promote lead immobilization by increasing the polysaccharide content within pectin and inducing cell wall peroxidase activity.
The mechanism by which arbuscular mycorrhizal (AM) fungi immobilize lead (Pb) within the cell wall is unclear. Therefore, the aim of this study was to investigate the mechanism by which AM fungi immobilize Pb within the cell wall by measuring the Pb content in the cell wall, the polysaccharide and the uronic acid contents of different cell wall fractions, and the activity of cell wall peroxidase. Mycorrhizal-associated Medicago truncatula had higher shoot and root biomass than nonmycorrhizal-associated M. truncatula. AM inoculation increased the content of Pb in the cell wall under Pb stress. The polysaccharide content in the pectin and hemicellulose fractions were increased by AM inoculation with or without Pb stress. In AM-associated roots, the cell wall peroxidase activity increased in response to Pb stress. However, Pb stress did not affect the cell wall peroxidase activity in non-AM-associated roots. Correlation analysis suggested that MtPrx05 and MtPrx10 may participate in polysaccharide cross-linking and cell wall stiffening. The Pb stress resistance mechanism of AM-associated roots may involve cell wall stiffening. Taken together, the results show that AM inoculation may improve host plant growth and increase Pb immobilization in the cell wall by increasing the polysaccharide content within pectin and hemicellulose and by inducing cell wall peroxidase activity. Both the polysaccharide composition and cell wall peroxidase have important contributions to the resistance of mycorrhizal-associated plants.


Sonochemical decomposition of noble metal oxides and sonochemical alloying of gold-silver systems.
Recently, environmental problems, such as global warming, have become more severe; thus, there is a requirement to implement sustainable development goals in materials processing. In this study, we investigated a low-cost and environmentally-friendly sonochemical process for the synthesis of metal nanoparticles with large specific surface areas and catalysis effects. Au2O3 hydrate and Ag2O were reduced to Au and Ag, respectively, at room temperature in a short time when irradiated with ultrasound in ethanol. Furthermore, when a mixed powder of Au2O3 hydrate and Ag2O was irradiated in ethanol, Au-Ag alloys were obtained in only 10 min. This fast and environmentally friendly alloying technique, known as sonochemical alloying, is promising for alloy syntheses.


Vulnerability to ventricular fibrillation in patients with clinically manifest ventricular tachycardia.
Ventricular vulnerability may be assessed by measuring the threshold current for the induction of ventricular fibrillation (VF). This technique has been widely utilized in animal experimentation and has been safely applied in a small number of clinical studies. We measured the VF threshold (VFT), using the single stimulus technique in 10 patients with coronary artery disease just prior to the institution of cardiopulmonary bypass. There were no adverse effects of VFT measurement. Three patients had nonsustained ventricular tachycardia (VT) on 24-hour ambulatory monitoring and had VFTs of 10, 14, and 16 mA. In this group VF was induced without any preceding repetitive ventricular responses. Seven patients had no repetitive forms on ambulatory monitoring. Their VFTs ranged from 30 to greater than 40 mA (mean greater than 37). Repetitive extrasystoles were regularly observed in this group at current intensities which ranged from 53% to 80% of the VFT. Thus patients with manifest VT appear to have an enhanced vulnerability to VF. Single or multiple responses were not observed in these patients but appeared to be present in patients with coronary disease and no demonstrable rhythm disorder.


Hypothesis-driven physical examination curriculum.
Medical students traditionally learn physical examination skills as a rote list of manoeuvres. Alternatives like hypothesis-driven physical examination (HDPE) may promote students' understanding of the contribution of physical examination to diagnostic reasoning. We sought to determine whether first-year medical students can effectively learn to perform a physical examination using an HDPE approach, and then tailor the examination to specific clinical scenarios. Medical students traditionally learn physical examination skills as a rote list of manoeuvres CONTEXT: First-year medical students at the University of Minnesota were taught both traditional and HDPE approaches during a required 17-week clinical skills course in their first semester. The end-of-course evaluation assessed HDPE skills: students were assigned one of two cardiopulmonary cases. Each case included two diagnostic hypotheses. During an interaction with a standardised patient, students were asked to select physical examination manoeuvres in order to make a final diagnosis. Items were weighted and selection order was recorded. First-year students with minimal pathophysiology performed well. All students selected the correct diagnosis. Importantly, students varied the order when selecting examination manoeuvres depending on the diagnoses under consideration, demonstrating early clinical decision-making skills. An early introduction to HDPE may reinforce physical examination skills for hypothesis generation and testing, and can foster early clinical decision-making skills. This has important implications for further research in physical examination instruction.


Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship.
Incubation of hippocampal slices with different concentrations of creatine (0.5, 1, 10, 25 mM) results in a dose-dependent increase in intracellular phosphocreatine (PCr). Electrophysiological evidence suggests that this effect can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation. In this paper we show that incubation of brain slices with varying doses of creatine increases intracellular phosphocreatine and delays anoxic depolarization (AD) in a dose-dependent way. Specifically, addition to the incubation medium of 1 mM creatine significantly increased AD latency during hypoxia and prevented irreversible neuronal damage. Adding 0.5 mM creatine had no significant effect. Higher concentrations of creatine (up to 25 mM) did not provide any better protection. Our data also suggest a linear correlation between intracellular PCr and AD latency. These data report neural protection by exogenous creatine at concentrations lower than those usually reported in the literature.


Prevalence and molecular characterization of Cryptosporidium spp. in dairy cattle in Central Inner Mongolia, Northern China.
Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.


In vivo visual evaluation of nanoparticle transfer in a three-species terrestrial food chain.
Nanoparticles (NPs) are increasingly being used, and they present the risk of being introduced into food webs. Numerous studies have been conducted to evaluate the toxicological effects of NPs in the aquatic and freshwater environments and their transfer to upper-level trophic organisms. However, information on the transfer and consequent effects of NPs on soil invertebrates is still limited. In this study, we assessed the transfer of quantum dots (QDs) through a three-species terrestrial food chain that consisted of the yeast Saccharomyces cerevisiae, the collembolan Folsomia candida, and the pill bug Armadillidium vulgare, as well as their biodistribution in vital organs using fluorescence analytical techniques. To visualize QD incorporation and biodistribution in F. candida, longitudinal and transversal sections were observed after short-term (3 d) and long-term (12 d) feeding with QD-treated yeast. QDs were located only in the intestine of F. candida and excreted within 1-2 d. QDs were also transferred to the pill bug by feeding, and remained in its intestine. This study showed the transfer of NPs through a model terrestrial food chain and indicated the potential hazards of released NPs for organisms at different trophic levels.


Whole genome sequencing: a considered approach to clinical implementation.
The recent entry of "whole" exome/"whole" genome sequencing into limited clinical practice has led to a progression of the availability of genome-scale testing beyond deletion/duplication copy number arrays. This unit provides a considered approach to the implementation of such testing in routine clinical practice. Specifically, we will highlight the challenges in patient selection and consent, and the technical issues surrounding test interpretation and reporting. The unit will then provide practical solutions that allow for genome-wide sequencing to be implemented in current clinical practice.


The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer.
Breast cancer, the most frequent cancer in women, is characterized by pathological changes to the microbiome of breast tissue, the tumor, the gut, and the urinary tract. Changes to the microbiome are determined by the stage, grade, origin (NST/lobular), and receptor status of the tumor. This year is the 50th anniversary of when Hill and colleagues first showed that changes to the gut microbiome can support breast cancer growth, namely that the oncobiome can reactivate excreted estrogens. The currently available human and murine data suggest that oncobiosis is not a cause of breast cancer, but can support its growth. Furthermore, preexisting dysbiosis and the predisposition to cancer are transplantable. The breast's and breast cancer's inherent microbiome and the gut microbiome promote breast cancer growth by reactivating estrogens, rearranging cancer cell metabolism, bringing about a more inflammatory microenvironment, and reducing the number of tumor-infiltrating lymphocytes. Furthermore, the gut microbiome can produce cytostatic metabolites, the production of which decreases or blunts breast cancer. The role of oncobiosis in the urinary tract is largely uncharted. Oncobiosis in breast cancer supports invasion, metastasis, and recurrence by supporting cellular movement, epithelial-to-mesenchymal transition, cancer stem cell function, and diapedesis. Finally, the oncobiome can modify the pharmacokinetics of chemotherapeutic drugs. The microbiome provides novel leverage on breast cancer that should be exploited for better management of the disease.


Effect of revealing authors' conflicts of interests in peer review: randomized controlled trial.
To assess the effect of disclosing authors' conflict of interest declarations to peer reviewers at a medical journal. Randomized controlled trial. Manuscript review process at the Annals of Emergency Medicine. PARTICIPANTS: Reviewers (n=838) who reviewed manuscripts submitted between 2 June 2014 and 23 January 2018 inclusive (n=1480 manuscripts). Reviewers were randomized to either receive (treatment) or not receive (control) authors' full International Committee of Medical Journal Editors format conflict of interest disclosures before reviewing manuscripts. Reviewers rated the manuscripts as usual on eight quality ratings and were then surveyed to obtain "counterfactual scores"-that is, the scores they believed they would have given had they been assigned to the opposite arm-as well as attitudes toward conflicts of interest. Overall quality score that reviewers assigned to the manuscript on submitting their review (1 to 5 scale). Secondary outcomes were scores the reviewers submitted for the seven more specific quality ratings and counterfactual scores elicited in the follow-up survey. Providing authors' conflict of interest disclosures did not affect reviewers' mean ratings of manuscript quality (Mcontrol=2.70 (SD 1.11) out of 5; Mtreatment=2.74 (1.13) out of 5; mean difference 0.04, 95% confidence interval -0.05 to 0.14), even for manuscripts with disclosed conflicts (Mcontrol= 2.85 (1.12) out of 5; Mtreatment=2.96 (1.16) out of 5; mean difference 0.11, -0.05 to 0.26). Similarly, no effect of the treatment was seen on any of the other seven quality ratings that the reviewers assigned. Reviewers acknowledged conflicts of interest as an important matter and believed that they could correct for them when they were disclosed. However, their counterfactual scores did not differ from actual scores (Mactual=2.69; Mcounterfactual=2.67; difference in means 0.02, 0.01 to 0.02). When conflicts were reported, a comparison of different source types (for example, government, for-profit corporation) found no difference in effect. Current ethical standards require disclosure of conflicts of interest for all scientific reports. As currently implemented, this practice had no effect on any quality ratings of real manuscripts being evaluated for publication by real peer reviewers.


Sensitivity and specificity of single-fibre EMG in the diagnosis of ocular myasthenia varies accordingly to clinical presentation.
Single-fibre electromyography (SF-EMG) is considered as the most sensitive test for the diagnosis of MG. However, previous studies had limitations, such as a retrospective design, non-consecutive sampling, incorporation bias or were performed in small or mixed populations. Our aims were to determine the diagnostic sensitivity and specificity of SF-EMG of the orbicularis oculi in OMG and the utility of this test in relation to patients' clinical presentation. We studied 232 consecutive patients referred to the SF-EMG laboratory for a suspected OMG. Stimulated SF-EMG was performed on the orbicularis oculi muscle. OMG was diagnosed in 165 cases and other disorders (OD) in 67. SF-EMG showed a sensitivity of 0.79 (95% CI 0.73-0.85) and a specificity of 0.80 (95% CI 0.71-0.90). False negative results were associated with mild symptoms and with isolated diplopia. Comparison of the diagnostic yield among patients with different clinical presentations showed a similar diagnostic accuracy of SF-EMG in patients with ptosis and in patients with ptosis and diplopia, significantly higher than in patients with isolated diplopia (P < 0.0001). Twenty-two patients with OMG presenting with isolated ptosis or diplopia, who initially tested negative, were re-tested in relation to a worsening of their symptoms showing a positivisation in 91% of cases. SF-EMG on the orbicularis oculi muscle is very sensitive in patients with ptosis. In contrast, in patients with isolated diplopia SF-EMG does not exclude OMG. Therefore, the interpretation of the results of the test should take into account the patients' clinical presentation.


Pain and Hand Function.
Pain is a unique somatosensory perception that can dramatically affect our ability to function. It is also a necessary perception, without which we would do irreparable damage to ourselves. In this article, the authors assess the impact of pain on function of the hand. Pain can be categorized into acute pain, chronic pain, and neuropathic pain. Hand function and objective measurements of hand function are analyzed as well as the impact of different types of pain on each of these areas.


Spin Circuit Model for 2D Channels with Spin-Orbit Coupling.
In this paper we present a general theory for an arbitrary 2D channel with "spin momentum locking" due to spin-orbit coupling. It is based on a semiclassical model that classifies all the channel electronic states into four groups based on the sign of the z-component of the spin (up (U), down (D)) and the sign of the x-component of the velocity (+, -). This could be viewed as an extension of the standard spin diffusion model which uses two separate electrochemical potentials for U and D states. Our model uses four: U+, D+, U-, and D-. We use this formulation to develop an equivalent spin circuit that is also benchmarked against a full non-equilibrium Green's function (NEGF) model. The circuit representation can be used to interpret experiments and estimate important quantities of interest like the charge to spin conversion ratio or the maximum spin current that can be extracted. The model should be applicable to topological insulator surface states with parallel channels as well as to other layered structures with interfacial spin-orbit coupling.


Prolonged ELS test with the marine flatfish sole (Solea solea) shows delayed toxic effects of previous exposure to PCB 126.
The effect of the dioxin-like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) on the early development of the marine flatfish sole (Solea solea) was tested in a newly developed early life stage (ELS) test that includes the metamorphosis of the symmetric larvae into an asymmetrical flatfish. Early life stages of sole were exposed to a concentration series of PCB 126 in seawater until 4, 8, 10 and 15 days post fertilisation (dpf). Subsequently the development of the larvae was registered under further unexposed conditions. The LC50s at the start of the free-feeding stage (12 dpf) ranged between 39 and 83 ng PCB 126/l depending on exposure duration. After the fish had completed the metamorphosis, the LC50 values ranged between 1.7 and 3.7 ng PCB 126/l for the groups exposed for 4, 8 and 10 dpf, respectively. Thus exposure for only 4 days, covering only the egg stage, was sufficient to cause adverse effects during a critical developmental phase two weeks later. The internal dosages of these larvae, determined by means of an in vitro gene reporter assay as dioxin-equivalent values (TEQ), revealed a LD50 of 1ng TEQ/g lipid, which is within the same order of magnitude as TEQ levels found in fish from highly polluted areas. This study indicates that ELS fish tests that are terminated shortly after the fish becomes free-feeding, underestimate the toxic potential of compounds with low acute toxicity such as PCBs. Our prolonged ELS with this native marine flatfish suggests that reproductive success of fish populations at contaminated sites can be affected by persistent compounds that are accumulated by the female fish and passed on to the eggs.


Histiocytic necrotizing lymphadenitis (Kikuchi's disease): cytologic diagnosis by fine-needle biopsy.
A cytologic diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi's lymphadenitis) was made in a 14-yr-old female with cervical lymphadenopathy, fever, neutropenia, and hepatosplenomegaly. A predominance of reticulum cells, foamy macrophages, and karyorrhectic debris are clues to the diagnosis in the fine-needle biopsy smears. Subsequent histology confirmed the diagnosis of Kikuchi's lymphadenitis. The differential diagnoses are discussed including malignant lymphoma, which was excluded by morphology as well as flow cytometry and polymerase chain reaction (PCR) studies.


Recommendation of treatment strategy for postpancreatectomy hemorrhage: Lessons from a single-center experience in 35 patients.
Postpancreatectomy hemorrhage (PPH) is a life-threatening complication of pancreatic surgery. The shift from surgical to radiological intervention was recently reported in retrospective cohort studies, but it has remained controversial as to which emergent intervention provides optimal management. All 553 patients who underwent standard pancreatic resection at Kobe University Hospital between January 2003 and December 2013 were included. Patient data and complication data were identified from a prospective database. The overall incidence of PPH was 6% (35 of 553 patients). Ten patients underwent endoscopic intervention or observation monitoring, or suffered hemorrhagic sudden death. Among the remaining 25 PPH patients, primary surgical intervention was successful in the 6 hemodynamically unstable PPH patients. Primary radiological intervention could successfully stop the bleeding in 15 of the 17 patients with late-PPH. Nine patients who had bleeding from the hepatic artery after pancreaticoduodenectomy were rescued by endovascular embolization of the artery-trunk. The in-hospital mortality of PPH was 20% (7 of 35). Four of the 5 PPH patients who died following any intervention eventually died due to the other complications associated with prolonged pancreatic fistula. The leading treatment has been radiological intervention. Endovascular embolization of the hepatic artery-trunk can be securely performed only if blood flow to the liver by an alternate route is confirmed. To reduce mortality of PPH patients, it is necessary to prevent other complications associated with pancreatic fistula following hemostasis. Proactive surgical intervention such as abscess drainage or remnant pancreatectomy is a key consideration.


Sensitivity of fitness to macroparameter changes: an analysis of survivorship and individual growth in sea urchin life histories.
An analysis for an age-structured demography was conducted to explore the sensitivity of fitness to individual parameters of a growth equation (Brody-Bertalanffy) and a survivorship function (Weibull). Initial parameters were selected to simulate populations of sea urchins and include northern and southern populations of the temperate sea urchin Strongylocentrotus purpuratus and tropical species such as Diadema antillarum. Results of the analysis are intuitively reasonable. Regardless of whether a population is increasing or decreasing, there would always be an increase in fitness associated with increases of: 1) the growth-rate constant, 2) maximum gonad size, 3) maximum lifespan, 4) the shape parameter of the Weibull function; and, decreases of 1) the age at first reproduction and 2) the ratio of number of recruits/spawn weight. If trade-offs are possible then improved survival characteristics and increased lifespan would be favored in declining populations. In general, relative sensitivity is dependent upon which parameter is varied in the simulations. The analysis shows which changes of parameters would bring about the greatest change in fitness but can not show trade-offs or design constraints. An example of trade-off in urchin life history is the relationship between the growth-rate constant, K and maximum lifespan, ω. A doubling of lifespan is associated with a halving of K.


Detection of an amphiphilic biosample in a paper microchannel based on length.
We developed a simple method to achieve semiquantitative detection of an amphiphilic biosample through measuring the length of flow on a microfluidic analytical device (μPAD) based on paper. When an amphiphilic sample was dripped into a straight microchannel defined with a printed wax barrier (hydrophobic) on filter paper (hydrophilic), the length of flow was affected by the reciprocal effect between the sample, the filter-paper channel and the wax barrier. The flow length decreased with increasing concentration of an amphiphilic sample because of adsorption of the sample on the hydrophobic barrier. Measurement of the flow length enabled a determination of the concentration of the amphiphilic sample. The several tested samples included surfactants (Tween 20 and Triton X-100), oligonucleotides (DNA), bovine serum albumin (BSA), human albumin, nitrite, glucose and low-density lipoprotein (LDL). The results show that the measurement of the flow length determined directly the concentration of an amphiphilic sample, whereas a non-amphiphilic sample was not amenable to this method. The proposed method features the advantages of small cost, simplicity, convenience, directness, rapidity (<5 min) and requirement of only a small volume (5 μL) of sample, with prospective applications in developing areas and sites near patients for testing at a point of care (POCT).


Enhanced biogas production from municipal solid waste via co-digestion with sewage sludge and metabolic pathway analysis.
The present study intends to evaluate the potential of co-digestion for utilizing Organic fraction of Municipal Solid Waste (OFMSW) and sewage sludge (SS) for enhanced biogas production. Metagenomic analysis was performed to identify the dominant bacteria, archaea and fungi, changes in their communities with time and their functional roles during the course of anaerobic digestion (AD). The cumulative biogas yield of 586.2 mL biogas/gVS with the highest methane concentration of 69.5% was observed under an optimum ratio of OFMSW:SS (40:60 w/w). Bacteria and fungi were found to be majorly involved in hydrolysis and initial stages of AD. Probably, the most common archaea Methanosarsina sp. primarily followed the acetoclastic pathway. The hydrogenotrophic pathway was less followed as indicated by the reduction in abundance of syntrophic acetate oxidizers. An adequate understanding of microbial communities is important to manipulate and inoculate the specific microbial consortia to maximize CH4 production through AD.


Teacher and observer views on student-teacher relationships: convergence across kindergarten and relations with student engagement.
Most studies regarding the role of teacher-child relationships for children's early school adjustment use only teacher ratings of relationship quality. The current study examines (a) the agreement between teacher and observer ratings, (b) whether similar patterns of relations with behavioral engagement are obtained across informants, and (c) which informant matters the most in the prediction of engagement. Teacher and observer ratings of teacher-child closeness, conflict, and dependency were gathered for a sample of 148 kindergartners and their teachers at three measurement occasions. Teacher and observer reports converged to a moderate degree but only when considering multiple occasions and ruling out occasion-specific variance. Although some relations with behavioral engagement were similar, only teacher ratings had unique, added value in this prediction.


High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication.
Fluorescent in situ hybridization (FISH) is a powerful, direct and sensitive technique with a wide resolution range that enables the simultaneous study of multiple targets, labelled in different colours. Spreading techniques, denoted here as 'Fiber-FISH', increase FISH-resolution to the DNA fiber, using decondensed nuclear DNA as hybridization target. FISH could be a powerful analytical tool for thorough physical examination of yeast artificial chromosomes (YACs) which are often chimaeric or contain internal deletions. However, with one exception restricted to meiotic yeast chromosomes, FISH has not been used successfully on yeast/YAC DNA. We have developed a fast and simple method that can be applied routinely for compositional and structural analysis of cosmid and YAC DNA in yeast. It enables precise localization and ordering of clones, resolves overlaps and distances and gives a detailed picture of the integrity and colinearity of both probe and target. The combination of high resolution, signal abundance and short yeast cell cycle allows direct visualization of replicating DNA fibers. In a 400 kb region of the human dystrophin gene, we identified two replication origins, demonstrating that human DNA cloned in yeast is capable of initiating its own replication.


Central somatosensory conduction time and short latency somatosensory evoked potentials in post-traumatic coma.
Short latency evoked potentials (SEPs) were elicited by stimulation of the median nerve at the wrist and recorded simultaneously from the neck and the contralateral scalp in 44 comatose patients with signs of brain stem impairment due to head injury. Thirty-four patients were studied in acute coma on day 1 or 2 after brain injury. Twenty-three patients were studied in prolonged coma during days 3-12 after trauma. Six patients were examined in brain death. Brain stem involvement was divided clinically and by CT scan into secondary lesions due to supratentorial mass displacement and primary lesions due to direct violence to the brain stem. The central somatosensory conduction time (CCT) was measured by subtracting the peak latency of the major response from the neck (N14) from that of the primary scalp response (N20). The amplitude ratios (ARs) N20/N14 were calculated for each trace. Further asymmetries and absence of SEP over one or both hemispheres were noted. In cases in coma due to supratentorial lesions CCT and AR were close to normal in patients with good outcome. CCT increased and AR decreased with the worsening of outcome both in acute and prolonged coma. Asymmetries of SEPs indicated moderate or severe final disability. Patients with absent SEPs over one or both hemispheres due to supratentorial lesions died or survived severely disabled (1 case). In patients suffering from primary brain stem dysfunction, confirmed by a normal or slightly abnormal CT scan, prolonged CCT, asymmetric but also absent SEPs were also found in patients with good outcome both in acute and prolonged coma. AR was generally low in these cases. Early appearance of SEPs or early recovery of initially distorted SEPs and decrease of CCT in prolonged coma or during recovery was a favourable prognostic sign. Therefore even absent or severely distorted SEPs should be interpreted cautiously in patients who may suffer from primary brain stem involvement. Scalp SEPs were totally absent in patients with brain death.


Muse cells: ushering in a new era of stem cell-based therapy for stroke.
Stem cell-based regenerative therapies have recently become promising and advanced for treating stroke. Mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) have received the most attention for treating stroke because of the outstanding paracrine function of MSCs and the three-germ-layer differentiation ability of iPSCs. However, the unsatisfactory homing ability, differentiation, integration, and survival time in vivo limit the effectiveness of MSCs in regenerative medicine. The inherent tumorigenic property of iPSCs renders complete differentiation necessary before transplantation, which is complicated and expensive and affects the consistency among cell batches. Multilineage differentiating stress-enduring (Muse) cells are natural pluripotent stem cells in the connective tissues of nearly every organ and thus are considered nontumorigenic. A single Muse cell can differentiate into all three-germ-layer, preferentially migrate to damaged sites after transplantation, survive in hostile environments, and spontaneously differentiate into tissue-compatible cells, all of which can compensate for the shortcomings of MSCs and iPSCs. This review summarizes the recent progress in understanding the biological properties of Muse cells and highlights the differences between Muse cells and other types of stem cells. Finally, we summarized the current research progress on the application of Muse cells on stroke and challenges from bench to bedside.


Carbon nanobelts with zigzag and armchair edge and interlocked carbon nanobelts for chirality.
This paper presents a theoretical study on the optical properties of carbon nanobelts with zigzag and armchair edges, as well as interlocked carbon nanobelts for chirality. The results demonstrate that two photon absorption (TPA) and electronic circular dichroism (ECD) techniques can effectively differentiate carbon nanoribbons with different boundaries, revealing their relationship and distinguishing features. The findings from this research contribute to a better comprehension of carbon nanoribbons, mechanically interlocked molecules, and chirality.


Starting an Emergency Radiology Division: Scheduling and Staffing, Compensation, and Equity and Parity.
Establishing an emergency radiology division in a practice that has long-standing patterns of operational routines comes with both challenges and opportunities. In this article, considerations around scheduling and staffing, compensation, and equity and parity are provided with supporting literature references. Furthermore, a panel of experts having established, grown and managed emergency radiology divisions in North America and Europe share their experiences through a question and answer format.


Frailty Predicts Loss of Independence After Liver Surgery.
Loss of independence (LOI) is a significant concern in patients undergoing liver surgery. Although the risks of morbidity and mortality have been well studied, there is a dearth of data regarding the risk of LOI. Therefore, this study aimed to assess predictors of LOI after liver surgery. This study utilized the National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2018 from a retrospective cohort study of patients undergoing liver resections. LOI was defined as the change from preoperative functional independence to the postoperative discharge requirement in a post-care facility. Frailty was defined using the modified frailty index-5 (mFI-5). A total of 22,463 patients underwent hepatectomy via the NSQIP during the study period. In total, 22,067 participants were included in the analysis. A total of 4.7% of patients had LOI after surgery and were discharged to a rehabilitation center or nursing facility. mFI-1 was an independent predictor of LOI (OR:2.2 [1.9-4.3]). However, the odds for LOI were higher (OR:5.1[2.5-8.2]) in patients with mFI ≥ 2. LOI is an important outcome of liver surgery. Frailty is a predictor of LOI and should be used as a guide to inform patients about the potential outcomes.


Autoantibody against oxidized low-density lipoproteins may be enhanced by cigarette smoking.
A total of 59 healthy male subjects (32 smokers and 27 nonsmokers) who had no reported systemic disease and did not take alcohol and vitamin supplementation were included. The levels of autoantibody to oxidized low-density lipoproteins (ox-LDL) in smokers and age-matched nonsmokers were compared. The plasma levels of antioxidants that can affect the formation of ox-LDL were also measured, and correlation analyses between anti ox-LDL IgG and plasma antioxidants, controlling for age and body mass index (BMI), were performed. Plasma alpha-tocopherol and uric acid concentrations of nonsmokers (2.78+/-1.09 microg/mg total lipid and 6.96+/-1.69 mg/dl, respectively) were significantly higher than those of smokers (1.68+/-0.48 microg/mg total lipid and 6.15+/-1.14 mg/dl, respectively) (P<0.05). Although plasma ascorbate and retinol levels were not significantly different between smokers and nonsmokers, smokers older than 45 years old had significantly lower plasma ascorbate levels (0.32+/-0.17 mg/dl) than age-matched nonsmokers (0. 53+/-0.14 mg/dl) (P=0.036). Higher level of plasma anti ox-LDL IgG was noted in the group of smokers compared with nonsmokers (515+/-409 mU/ml vs. 407+/-268 mU/ml, respectively) under the statistic method of Chi-Square test (P=0.049). A significant negative correlation was found between plasma anti ox-LDL IgG and alpha-tocopherol in the combined population as well as in the smoker group (r=-0.26, p=0.047; r=-0.48, p=0.006; respectively). However, there was no correlation between plasma anti ox-LDL IgG and the levels of other antioxidants. These results suggest that reduced concentrations of alpha-tocopherol are associated with cigarette smoking. The significantly negative correlation between plasma anti ox-LDL IgG and alpha-tocopherol in the entire study population as well as in the smoker group suggests that plasma alpha-tocopherol may be partially effective if not totally at protecting LDL from oxidative damage caused by cigarette smoking and dietary supplementation with alpha-tocopherol may provide a protective effect against LDL oxidation, especially in smokers.


General anxiety symptoms after acute lung injury: predictors and correlates.
Acute lung injury (ALI) is common in the intensive care unit (ICU), typically requiring life support ventilation. Survivors often experience anxiety after hospital discharge. We evaluated general anxiety symptoms 3 months after ALI for: (1) associations with patient characteristics and ICU variables, and (2) cross-sectional associations with physical function and quality of life (QOL). General anxiety was assessed as part of a prospective cohort study recruiting patients from 13 ICUs at four hospitals in Baltimore, MD using the Hospital Anxiety and Depression Scale--Anxiety Subscale (HAD-A), with associations evaluated using multivariable linear and logistic regression models. Of 152 patients, 38% had a positive screening test for general anxiety (HAD-A≥8). Pre-ICU body mass index and psychiatric comorbidity were associated with general anxiety (OR, 95% confidence interval (CI): 1.06 (1.00, 1.13) and 3.59 (1.25, 10.30), respectively). No ICU-related variables were associated with general anxiety. General anxiety was associated with the number of instrumental ADL dependencies (Spearman's rho=0.22; p=0.004) and worse overall QOL as measured by EQ-5D visual analog scale (VAS) (rho=-0.34; p<0.001) and utility score (rho=-0.30; p<0.001), and by the SF-36 mental health domain (rho=-0.70; p<0.001) and Mental Component Summary score (rho=-0.73; p<0.001). Many patients have substantial general anxiety symptoms 3 months after ALI. General anxiety was associated with patient characteristics and impaired physical function and quality of life. Early identification and treatment of general anxiety may enhance physical and emotional function in patients surviving critical illnesses.


Repair of congenitally malformed mitral valve in children.
We report our experience with 30 children under 15 years of age treated surgically for congenital mitral valve disease from March 1972 to July 1986. Valve reconstruction was possible in 26 patients (87%), whereas in four the valve was replaced with a mechanical prosthesis. Five patients died in the hospital (16.6%), four after conservative operations and one after mitral valve replacement. There was only one late death in a child in chronic congestive heart failure. Three patients, treated conservatively, required valve replacement 2, 22, and 24 months, respectively, after the operation. Follow-up data reveal that 22 of 24 patients are asymptomatic 5 months to 15 years after operation. Two-dimensional echocardiographic studies were performed in 19 patients treated conservatively, 17 of whom are asymptomatic. Eleven of them have no signs of mitral regurgitation or stenosis, six show only mild mitral incompetence, and two have moderate mitral regurgitation or stenosis. Peak pulmonary artery pressure is within normal limits in all. Our results indicate that mitral valve reconstructive procedures for congenital valve dysplasia may be effective and reliable in children despite the frequent severity of valve malformation. Although no major prosthesis-related complications were observed in the present series, we believe that mitral valve repair should always be attempted in the pediatric population to avoid the drawbacks of the currently available prostheses.


Engendering health disparities.
How is gender implicated in our exploration of health disparities in Canada? Set against the backdrop of federal government policy, this review paper examines the ways in which gender intersects with other health determinants to produce disparate health outcomes. An overview of salient issues including the impact of gender roles, environmental exposures, gender violence, workplace hazards, economic disparities, the costs of poverty, social marginalization and racism, aging, health conditions, interactions with health services, and health behaviours are considered. This review suggests health is detrimentally affected by gender roles and statuses as they intersect with economic disparities, cultural, sexual, physical and historical marginalization as well as the strains of domestic and paid labour. These conditions result in an unfair health burden borne in particular by women whose access to health determinants is--in various degrees--limited. While progress has certainly been made on some fronts, the persistence of health disparities among diverse populations of women and men suggests a postponement of the vision of a just society with health for all that was articulated in the Federal Plan on Gender Equality. Commitment, creativity and collaboration from stakeholders ranging from various levels of government, communities, academics, non-governmental agencies and health professionals will be required to reduce and eliminate health disparities between and among all members of our society.


The mosaic of the uncrossed retinal projection in the superior colliculus of the cat.
The uncrossed retinocollicular projection in the cat was labeled by axonal transport of horseradish peroxidase from the eye and visualized in tangential sections through the superior colliculus. The terminals of this pathway are distributed in clusters and form a mosaic pattern rather than stripes in the superficial collicular layers. It is suggested that the periodicity of this pattern relates to the smallest receptive field diameters across the visual field.


Flavanols and vascular health: molecular mechanisms to build evidence-based recommendations.
Observational studies as well as public awareness and ancient medicine identify tea, wine and cocoa as healthy foods. Further compilations of epidemiological data reinforce the healthy properties of the grape, tea and cocoa derived foods and drinks made from, especially when considering cardiovascular disease, some cancers and other inflammation-related pathologies. Flavanols have emerged as bioactives responsible for such health effects, and flavanol-rich foods have been used in clinical studies. Results of these studies show a major participation of flavanols in mechanisms positively affecting endpoints of cardiovascular disease, i.e. hypertension and vascular function. In line, based on the chemistry (bioavailability and molecular structure of flavanol and target entities) several physiological mechanisms have been described backing the epidemiological and clinical studies. In summary, the discussion for defining evidence-based recommendations for flavanols is based on: a) the extensive research done and the positive results obtained support the incorporation of flavanol-rich foods as part of a healthy diet, this is a cost-effective action to ameliorate silent undesirable conditions as it is chronic inflammation; b) the fact that cardiovascular health seems especially sensitive to the beneficial effects of flavanols: based on clinical and mechanistic studies showing that certain flavanols, favor NO production; and c) the increasing technical possibilities to evaluate flavanols in foods and biological samples. Supported by UBACyT 20020120100177, CONICET PIP-20110100752, and ANPCyT PICT 2012/0765.


Human carcinoma-associated precursor antigens of the NM blood group system.
Blood group NM specificities occur in healthy, benign and carcinomatous breast glands and those of the gastrointestinal (G.I.) tract, but the precursors in their biosynthesis, T (Thomsen-Friedenreich) and Tn, are found in adenocarcinomata and not in benign or healthy tissues. T- and Tn-antigenic specificities are thus human carcinoma-associated. All humans possess anti-T and anti-Tn antibodies. Patients with breast or G.I. tract carcinoma show statistically significant alteration of anti-T titer levels when compared to patients with benign disease and to healthy controls. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vitro and in vivo. Most striking was the delayed-type hypersensitivity reaction, which was positive in over 90% of ductal breast carcinoma patients tested and negative in all presumably healthy individuals. T antigen is readily prepared from healthy human red blood cells in uncontaminated form, and free of HL-A and Au antigens. T antigen and anti-T antibodies may be useful in combating some human adenocarcinomata.


Induction of p21WAF1 expression protects HT29 colon cancer cells from apoptosis induced by cryoinjury.
Cryotherapy is a method of in situ destruction of tumors by freeze/thaw mechanisms. Cancer cells located in the peripheral zone of the tumor undergoing cryotherapy can die by apoptosis. We hypothesized that p21WAF1 is involved in the mediation of cryotherapy-induced apoptosis. HT29 cells grown on a plate were subjected to -10 degrees C and returned to 37 degrees C for various periods of time. Cells were analyzed by flow cytometry, Western blot, and reverse transcriptase-polymerase chain reaction for determining cell-cycle distribution, p21WAF1 protein expression, and messenger RNA levels, respectively. The p21WAF1 expression in nude mouse tumor xenografts after cryotherapy was examined by immunofluorescence staining. A series of the p21WAF1 promoter cloned into a luciferase reporter vector were transfected into HT29 cells for identifying the response element to cryoinjury. Antisense oligodeoxynucleotide (ODN) was applied to examine the effect of p21WAF1 expression on cryotherapy-induced apoptosis. Both protein and messenger RNA of p21WAF1 were induced by cryoinjury in cultured cells and tumor xenografts. Deletion analysis of the p21WAF1 promoter revealed that a region from -121 to -95 base pairs was responsible for the activation and that this activation was p53 independent. HT29 cells arrested at the G1 phase after cryoinjury. The cryotherapy-induced apoptotic rate in HT29 cells was increased in the presence of antisense p21WAF1 ODN in comparison to the random ODN. Induction of p21WAF1 increases tumor cell survival and may result in recurrences at treated sites after cryotherapy. Combining antisense ODN targeted against p21WAF1 and cryotherapy may improve clinical outcomes in the treatment of colorectal cancer.


Imaging of Altered Mental Status.
Neuroimaging is an invaluable diagnostic tool for sorting through the vast array of etiologies that underlie altered mental status (AMS). Head computed tomography (CT) without contrast is the primary modality for evaluation of AMS and should be complemented by MR imaging in cases of negative CT but high clinical concern. Studies to maximize brain imaging efficiency and improve the yield of positive scans through the utilization of clinical and laboratory pre-scan diagnostics are ongoing. However, imaging remains the gold standard due to its rapidity with which certain diagnoses can be made or excluded.


Natural convection with variable fluid properties of couple stress fluid with Cattaneo-Christov model and enthalpy process.
The geometry under consideration for this flow problem, namely paraboloid surface is similar to aircraft and car bonnet, bullet shape, front shape of submarine, rockets and these types of are useful in manufacturing of formula F1 cars and airplanes. The flow of fluid over paraboloid surface has several applications in space science, industries, mechanical works and architecture. The aim of this study is to explore the Cattaneo-Christov heat and mass flux model in steady 2D couple stress fluid flow with variable thermo-physical characteristics near the parabolic surface. The effects of enthalpy and activation energy are also taken into consideration. The stretching in the layers of fluid is assumed at the surface of body. The problem is amended by using the law of conservation of momentum, energy and mass transfer. The non-linear governing partial differential equations are converted into ordinary differential equations by using self-similar form with similarity transformation. The resulting ODE's are numerically solved by bvp4c method. The conclusion indicates that the fluid moves quickly due to higher inputs of couples stress parameter and buoyancy parameter while the viscosity coefficient creates restriction in the fluid motion. The transference analysis of temperature and concentration enhances for higher impacts of thermal conduction and mass diffusivity coefficient. The thermal concentration relaxation parameters are the source of decline in the concentration and temperature of fluid. The heat transmission rate is maximum and mass transfer is minimum due to raising values of Dramkholer number. The impression of all parameters on different fields is listed in discussion section.


Microbial Concrete-a Sustainable Solution for Concrete Construction.
In the ever-increasing demand of construction and construction materials worldwide, concrete is the most extensively used material for construction purposes almost next to the water. Therefore, there is a dire need of clean, green and durable concrete. Recently, an environmentally friendly strategy has been employed to manufacture bio-concrete by the usage of microorganisms in the traditional concrete to enhance its durability and compressive strength. In this review, we discuss the role of microbes in influencing the various properties of concrete such as compressive strength, flexural strength and tensile strength by reducing the concrete porosity and diminishing water absorption. The mechanism of microbial-induced calcium carbonate precipitation (MICP) in the traditional concrete by the action of microbes which resulted in the formation of bio-concrete as an improved building material has also been discussed. Additionally, an in-depth comparative analysis of the performance of bio-concrete with the traditional concrete synthesized from various industrial wastes such as silica fume, rice husk ash and metakaolin in terms of different properties such as compressive strength, flexural strength and percentage water absorption has been presented. This review highlights the impact of usage of microbes in the conventional concrete to produce novel and eco-friendly bio-concrete in construction technology.


Reactive astrocytes in lesioned rat spinal cord: effect of neural transplants.
The astroglial reaction following a laceration-type surgical lesion of rat spinal cord is recognized by hypertrophy of astrocytes. This phenomenon can be readily demonstrated by enhanced immunoreactivity for glial fibrillary acidic protein (GFAP) and a recently discovered 30 kD protein (J1-31 antigen). The results reported in this article lead to the conclusion that the astroglial reaction is not influenced significantly by the transplantation of embryonic neocortical tissue to the cavity of a laceration-type lesion. These observations could be relevant to the assessment of strategies for treatment of spinal cord injury.


Complex sound analysis (frequency resolution, filtering and spectral integration) by single units of the inferior colliculus of the cat.
The central nucleus of the inferior colliculus (ICC) is a center of convergence of brainstem input and is critical for auditory information processing. Here, the analysis of complex sound spectra by single neurons in the ICC is investigated. Several measures of frequency resolution (excitatory/inhibitory tuning curves, effective bandwidths, critical ratio bands, critical bands derived using narrowband masking and two-tone separation paradigms) have been obtained from the responses of these neurons at sound pressure levels (SPL) up to 80 dB above the units' response thresholds (nearly 110 dB SPL). Among our results are the following: (1) Narrowband masking measures of critical bands from ICC neurons closely parallel behavioral measures using the same stimulus paradigm. (2) Frequency resolution power as measured by critical bandwidths varies little as a function of stimulus intensity. (3) Tuning curves of ICC neurons provide no simple basis for predicting the frequency filtering of the same neurons excited by complex sound spectra. (4) There is a frequency dependence of all measures of frequency resolution similar to that found in psychophysical determinations of critical bandwidths. That is, spatial frequency resolution in the cochlea is the origin for the resolution found in the ICC and in behavioral tests. (5) Lateral inhibition at the level of the ICC clearly plays a role in frequency resolution. (6) Frequency resolution is encoded by response rate changes of ICC neurons and is independent of tone response threshold, response latency, spontaneous activity, tone response type, binaural response type. It is concluded that spectral analysis of sound is established by processes, including lateral inhibition, independent of other basic response properties of neurons at the level of the ICC.


Effect of Dietary Fiber and Thermal Conditions on Rice Bran Wax-Based Structured Edible Oils.
In this work, extra-virgin olive oil (EVO)- and sunflower oil (SFO)-based oleogels were structured using rice bran wax (RBW) at 10% by weight (w/w). Bamboo fiber milled with 40 (BF40), 90 (BF90) and 150 (BF150) µm of average size was added as a structuring agent. The effect of fiber addition and cooling temperature (0, 4, and 25 °C) on thermal and structural parameters of achieved gels was assessed by rheological (both in rotational and oscillatory mode), texture, and differential scanning calorimetry tests. Oleogelation modified the rheological behavior of EVO and SFO, thus shifting from a Newtonian trend typical of oils to a pseudoplastic non-Newtonian behavior in gels. Moreover, oleogels behaved as solid-like systems with G' > G″, regardless of the applied condition. All samples exhibit a thermal-reversible behavior, even though the presence of hysteresis suggests a partial reduction in structural properties under stress. Decreasing in cooling temperature negatively contributed to network formation, despite being partially recovered by low-granulometry fiber addition. The latter dramatically improved either textural, rheological, or stability parameters of gels, as compared with only edible oil-based systems. Finally, wax/gel compatibility affected the crystallization enthalpy and final product stability (gel strength) due to different gelator-gelator and gelator-solvent interactions.


Identification of a developmentally regulated cysteine protease of Trypanosoma brucei.
Trypanosoma brucei undergoes dramatic metabolic changes during differentiation from the mammalian bloodstream form into the procyclic form of the insect midgut. Because modulation of protein degradation is likely to be important during this process we studied T. brucei for life cycle mediated proteolysis. We detected an increase in the activity of a 28 kDa protease as pleomorphic GUTat 3.1 trypanosomes differentiate in the mammalian bloodstream from long slenders into short stumpies. Short stumpy trypanosomes hydrolyse z-Phe-Arg-AMC 12 fold more actively than either long slenders or procyclics. The 28 kDa protease is activated by dithiothreitol and is inhibited by trans-epoxysuccinyl-L-leucyl-amido(4-guanidino) butane (E-64), indicating that it is a cysteine protease. The proteolytic activity of monomorphic ILTat 1.4 trypanosomes does not increase during mammalian parasitemia. If monomorphic ILTat 1.4 trypanosomes are induced to differentiate into short stumpies by exposure to difluoromethylornithine, however, the activity of the 28 kDa cysteine protease increases 8 fold. This suggests that polyamine depletion induces the 28 kDa cysteine protease and that its expression may be regulated by mechanism not previously described in protozoa.


A case report of inflammatory myofibroblastic tumor of cecum mimicking malignant wall thickening.
Inflammatory myofibroblastic tumors (IMT) are an uncommon mesenchymal solid tumor commonly documented in children and young adults (Kim et al., 2012 [1]). Cecum is a rare location of this entity, may simulating a malignant tumor process. A 71 year old patient was admitted for pain in the right iliac fossa with chronic constipation evolving for two months associated with weight loss. As a diagnosic step, an abdominal computed tomography (CT) scan was performed showing a thickening of the cecal wall. There was no regional or distant metastasis. During a colonoscopy, many biopsies have been returned to a non-specific chronic colitis; as a result, the IMT of the cecum was confirmed pathologically after ilio-coecal resection. IMT is difined as a solid mesenchymal tumor basically affects the soft parts as well as the visceral organs. The litterature show that frequent localisations are pulmonary and intra-orbital (Krzysztof Siemion et al., 23 February 2022); therefore, the cecal location is very rare may mimic a malignant tumor (Mauricio Gonzalez-Urquijo et al., January 20, 2020), It is worth recalling that the imaging outcomes are polymorphic and inconclusive; in addition, Surgical excision is the treatment of choice for IMT (Alireza Mirshemirani et al., Dec 2011) and the histopathology is still required for the final diagnosis. Radiologic features of IMT present a diagnostic challenge to the radiologist; also, mimic malignancy may lead to unnecessary investigations.


Acute antiinflammatory and gastric effects of the seleno-organic compound ebselen.
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a seleno-organic compound with glutathione peroxidase-like activity in vitro, was compared with indomethacin, BW 755C, and levamisole as an inhibitor of carrageenan- and CVF (cobra venom factor)-induced paw oedema in the rat. The antiinflammatory potency of ebselen against CVF-induced oedema (ED50 = 56 mg/kg p.o.) was similar to that of BW 755C, while indomethacin was weakly active in this model, and levamisole exerted stronger activity. In the carrageenan model, ebselen exhibited weak inhibitory potency, like BW 755C, while indomethacin markedly inhibited this inflammatory response, and levamisole was inactive. Unlike cyclooxygenase inhibitors, ebselen produced almost no gastric irritation in rats up to 316 mg/kg p.o. Moreover, ebselen inhibited significantly diclofenac-induced gastric intolerance at 31.6 and 316 mg/kg p.o. Thus, ebselen represents a new tool for antiinflammatory therapy.


Shame and severity of bulimic symptoms.
Initial research suggests that self-conscious affect such as shame may perpetuate bulimic symptoms among individuals suffering from bulimia nervosa (BN). This investigation reports findings from two studies that examine the relation of shame to bulimic symptoms. In the first study, the relation of shame to bulimic symptoms was examined among 137 female college undergraduates. Shame accounted for a significant portion of variance in bulimic symptoms after controlling for age, weight status, guilt, and depressed mood. A second study examined the severity of shame in 30 bulimic patients compared to 28 eating-disordered patients with subclinical symptoms. Although patients with more severe bulimic symptoms exhibited higher levels of shame, this relation was not independent of the shared relation with depression and guilt. Findings are discussed in terms of the role of shame in bulimic symptoms.


Effects of illicit drugs on structural and functional impairment of testis, endocrinal disorders, and molecular alterations of the semen.
Illicit drug use is growing among young people, which is one of the major problems in today's society that can be associated with many medical issues, including infertility. Amphetamines, cocaine, opioids, and marijuana are the most common and the most used illicit drugs worldwide. The purpose of this review was to collect as much literature as possible about the impact of illicit drugs on male fertility and summarize their valuable data. Original studies and reviews were collected by searching the keywords "illicit drugs (all kinds of that) and male infertility". The obtained information was also categorized based on the content of the "Infertility in the Male" book. Almost all studies suggested that taking all kinds of illicit drugs with the effects on different parts of the male reproductive system can result in subfertility or complete infertility in the consumers. Although the data in this field are not decisive and there are some confounding factors in human studies, it can be inferred that the use of any illicit drug with an effect on male sexual health reduces fertility potency. Therefore, it is recommended that couples, who are planning to conceive, avoid taking any illicit drugs before and during treatment.


Efficacy of dose-reduced lenalidomide in patients with refractory or recurrent multiple myeloma.
Introduction of lenalidomide has expanded the therapeutic options for refractory and recurrent multiple myeloma (MM) patients. However, the application of the approved doses may be difficult in some patients due to adverse effects. Therefore, we evaluated the efficacy and safety of lenalidomide in 10 patients with relapsed and refractory MM who received a reduced dose due to leukopenia (4), polyneuropathy (1), muscle cramps (1), thrombocytopenia (1), renal insufficiency (1), at the request of patient (1), as continuous therapy (1), either from the beginning (2) or during treatment (8). They received lenalidomide at a mean (median) daily dose of 14 (15) mg/d once a day (days 1-21 every 28 days) in combination with dexamethasone at a mean (median) dose of 17.6 (28) mg per day (4-40 mg) on days 1-4, 9-12 and 17-20. Mean (median) duration of treatment with lenalidomide was 15.1 (15) months. Partial response or better was reported in seven and minimal response or better was reported in eight patients. Mean (median) values for time-to-progression (TTP) and for progression-free survival (PFS) were 8.7 (4) months. Mean overall survival (OS) has not been reached, all patients are still alive. In conclusion, dose-reduced lenalidomide is an effective and well tolerated treatment for patients with recurrent or refractory MM who cannot tolerate full doses.


Continuous monitoring of ventilatory mechanics during one-lung ventilation.
The Ultima SV respiratory monitor can be used to monitor the intraoperative effects of the lateral decubitus position and one-lung ventilation on ventilatory mechanics. Eight patients with esophageal cancer who required one-lung ventilation for esophagectomy and reconstruction were enrolled in the study. We monitored pressure-volume or flow-rate-volume loops continuously throughout the operation. Respiratory parameters were evaluated closely during five conditions of ventilation: two-lung ventilation in the supine position, two-lung ventilation in the lateral decubitus position, dependent one-lung ventilation in the lateral decubitus position, nondependent one-lung ventilation in the lateral decubitus position, and dependent one-lung ventilation in the lateral decubitus position with the chest opened. Respiratory rate was controlled at 10 breaths/min, and tidal volume was kept constant (10 ml/kg) during surgery. Peak inspiratory pressure increased to 29.0 +/- 9.0 (mean +/- SD) cm H2O in the dependent one-lung in the lateral decubitus position with the chest opened (p < 0.01). Dynamic compliance decreased to 29.4 +/- 4.9 ml/cm H2O in the dependent one-lung in the lateral decubitus position with the chest opened (p < 0.01). The changing configuration of the loops also offered additional and instantaneous information during one-lung ventilation. One-lung ventilation caused several changes in the whole respiratory system (lung, thorax, and endotracheal tube). Continuous monitoring of flow-rate-volume or pressure-volume loops with in-line spirometry provided comprehensive information regarding parameters in one-lung ventilation.


Visualization of Ca2+ Filling Mechanisms upon Synaptic Inputs in the Endoplasmic Reticulum of Cerebellar Purkinje Cells.
The endoplasmic reticulum (ER) plays crucial roles in intracellular Ca(2+) signaling, serving as both a source and sink of Ca(2+), and regulating a variety of physiological and pathophysiological events in neurons in the brain. However, spatiotemporal Ca(2+) dynamics within the ER in central neurons remain to be characterized. In this study, we visualized synaptic activity-dependent ER Ca(2+) dynamics in mouse cerebellar Purkinje cells (PCs) using an ER-targeted genetically encoded Ca(2+) indicator, G-CEPIA1er. We used brief parallel fiber stimulation to induce a local decrease in the ER luminal Ca(2+) concentration ([Ca(2+)]ER) in dendrites and spines. In this experimental system, the recovery of [Ca(2+)]ER takes several seconds, and recovery half-time depends on the extent of ER Ca(2+) depletion. By combining imaging analysis and numerical simulation, we show that the intraluminal diffusion of Ca(2+), rather than Ca(2+) reuptake, is the dominant mechanism for the replenishment of the local [Ca(2+)]ER depletion immediately following the stimulation. In spines, the ER filled almost simultaneously with parent dendrites, suggesting that the ER within the spine neck does not represent a significant barrier to Ca(2+) diffusion. Furthermore, we found that repetitive climbing fiber stimulation, which induces cytosolic Ca(2+) spikes in PCs, cumulatively increased [Ca(2+)]ER. These results indicate that the neuronal ER functions both as an intracellular tunnel to redistribute stored Ca(2+) within the neurons, and as a leaky integrator of Ca(2+) spike-inducing synaptic inputs.


Discrimination of global-motion signal strength.
The ability of observers to discriminate differences in global-motion-signal strength (that is the proportion of coherently moving dots in a field of randomly moving dots) was determined for both first and second-order stimuli. Observers could accurately discriminate differences in signal intensity for all reference signal levels tested; 20-100%. A similar pattern of performance was obtained for both types of stimuli. The observed first-order signal-discrimination performance is compatible with the results of electrophysiological studies that have investigated the dependence of the firing rate of V5 cells (also called the middle temporal area) upon global-motion signal intensity.


Surgical treatment for recurrent cholangiocarcinoma: a single-center series.
The present study aims to assess the results obtained after surgical treatment of cholangiocarcinoma (CC) recurrences. We carried out a single-center retrospective study, including all patients with recurrence of CC. The primary outcome was patient survival after surgical treatment compared with chemotherapy or best supportive care. A multivariate analysis of variables affecting mortality after CC recurrence was performed. Eighteen patients were indicated surgery to treat CC recurrence. Severe postoperative complication rate was 27.8% with a 30-day mortality rate of 16.7%. Median survival after surgery was 15 months (range 0-50) with 1- and 3-year patient survival rates of 55.6% and 16.6%, respectively. Patient survival after surgery or CHT alone, was significantly better than receiving supportive care (p< 0.001). We found no significant difference in survival when comparing CHT alone and surgical treatment (p=0.113). Time to recurrence of <1 year, adjuvant CHT after resection of the primary tumor and undergoing surgery or CHT alone versus best supportive care were independent factors affecting mortality after CC recurrence in the multivariate analysis. Surgery or CHT alone improved patient survival after CC recurrence compared to best supportive care. Surgical treatment did not improve patient survival compared to CHT alone.


Occurrence of organochlorine pesticides in surface soils from college school yards of Xi'an, China.
In this study, surface soil samples from 14 representative college school yards in Xi'an, the capital city of Shaanxi province, China, were collected and analyzed for 21 organochlorine pesticides (OCPs). The total concentrations were in the ranges of 0.2-67.0 ng/g. HCHs and DDTs were the most dominant compounds among the 21 OCPs, and their concentrations ranged from 0.1-8.5 to 0.1-56.3 ng/g, respectively. Source identification analysis indicated that the residues of HCHs and DDTs were mostly due to historical use of these chemicals or from other source regions. The quality of all the Xi'an college school yard soils except sample XAUAT was classified as low pollution by OCPs according to the National Environmental Quality Standards for Soils of China (GB15618-1995).


Vector manometric study of the sphincter of Oddi in the dog: functional and morphological correlation.
The relationship between sphincter of Oddi pressure and the morphological structure of the sphincter was studied in eight dogs prepared with a duodenal cannula. Sphincter of Oddi manometry was performed in awake animals in three directions, ventral, left dorsal, and right dorsal, using a catheter with three radial side holes for recording at one level. The pressure in the ventral direction (26.6+/-1.06 mmHg) (mean+/-SEM) was significantly lower than that in the left and right dorsal directions (30.6+/-1.42 and 31.2+/-1.23 mmHg, respectively). This functional manometric difference in the three directions correlated closely with the morphological structure of the sphincter of Oddi; the sum of the thickness of the sphincter of Oddi muscle and duodenal proper muscle was greater on the dorsal than on the ventral side. To our knowledge, this is the first report of axial asymmetry in sphincter of Oddi pressure.


Digital subtraction carotid angiography and retinal arterial obstruction.
Thirty-one consecutive patients with retinal arterial obstruction were studied with digital subtraction angiography (DSA). Among the 29 patients in whom DSA was technically acceptable, 45% (13/29) demonstrated evidence of carotid stenosis or an atherosclerotic plaque ipsilateral to the eye with the retinal arterial obstruction. In 21% of cases (6/29 patients) the stenosis was 60% or greater. The incidences of carotid atherosclerosis were similar among the central and branch retinal arterial groups.


Lessons learned during the COVID-19 pandemic: a single institution radiology chief resident experience.
Coronavirus Disease 2019 (COVID-19) has posed incredible new challenges for radiology residency programs, including resident training under tenuous and uncertain conditions, barriers to communication, deployment-induced anxiety, and social isolation. Chief residents and program leadership play a critical role in guiding radiology residents through these unprecedented times. Best practices and creative approaches experienced in a single institution's residency program located in New York City are shared in an effort to encourage other programs struggling with similar obstacles to prioritize resident education and wellness.