The effect of hospital staff training on management of obstetrical patients referred by traditional birth attendants.
A hospital staff training program was conducted in Guatemala to improve outcomes for patients with obstetrical and neonatal complications. This study examines the effect of the training program on the subset of women referred to the hospital by traditional birth attendants (TBAs). The program's goals were to institute standards of care for obstetrical and neonatal patients as well as to improve relations between hospital staff and TBAs. The training program was evaluated by comparing changes in the number of referrals, patient satisfaction, patient management, as well as Apgar scores and perinatal mortality. Evaluations were based on 756 questionnaires administered to TBA referred mothers. There was a significant increase in the overall numbers of referred women as well as improvement in patient satisfaction and decreased waiting time between admission and treatment. Apgar scores and perinatal mortality also improved, but changes were not statistically significant.


OTO method for preservation of actin filaments in electron microscopy.
Osmium tetroxide, commonly used as a fixative in electron microscopy, can destroy actin filaments. Thiocarbohydrizide (TCH) is a bipolar substance that binds to the osmium. By sandwiching TCH between two phases of osmium treatment, tissue exposure to osmium could be minimized without destroying actin filaments. The contrast of osmophilic components of cells was also enhanced.


A study on Amygdalin's genotoxicological safety and modulatory activity in human peripheral lymphocytes in vitro.
Amygdalin (AMY), a plant secondary metabolite containing nitrile, is a major component of the seeds of Rosaceae family plants. It is known that this compound has many pharmacological activities such as cancer prevention, antipyretic, and cough suppressant. In this study, the genotoxic and modulatory effects of amygdalin were assessed by chromosomal aberration (CA), sister chromatid exchange (SCE), and cytokinesis-block micronucleus assay (CBMN) assays using human peripheral lymphocytes (HPLs) in the absence and presence of metabolic activator (S9 mix). Lymphocytes were exposed to various concentrations of amygdalin (0.86, 1.72, 3.43, 6.86, and 13.75 μg/mL) alone and in combination with mitomycin-C (MMC, 0.20 μg/mL) or cyclophosphamide (CP, 12 μg/mL). The mitotic index (MI), replication index (RI), cytokinesis-block proliferation index (CBPI), and cytostasis were also evaluated to determine cytotoxicity. Amygdalin alone did not exhibit genotoxic and cytotoxic effects at all the tested concentrations both in the absence and presence of the S9 mix. In contrast, amygdalin significantly reduced the frequencies of CA (especially at 48 h treatments), SCE, and MN (except 0.86 μg/mL in pre- and simultaneous treatment) induced by MMC in all the tested concentrations and treatment protocols. It has also considerably decreased CP-induced CA and SCE frequencies at all the concentrations (except 0.86 μg/mL) in simultaneous treatment. This study demonstrated that amygdalin alone was not genotoxic, on the contrary, it has revealed modulatory effects against chemotherapy agents that induced genomic damage in human lymphocytes, suggesting its chemopreventive potential.


Effect of the mitogenic lectin concanavalin A on the thermotropic behavior of glycosyl-free cationic lipids and their mixtures with zwitterionic lipids.
The effect of concanavalin A (Con A) on the thermotropic behavior of positively charged, glycosyl-free lipids and their mixtures with zwitterionic lipids was investigated by differential scanning calorimetry. The gel to liquid-crystal phase transition enthalpy of pure dipalmitoylcholine (DPC) was found to be significantly increased in the presence of Con A (delta H = 31.2 and 42.5 KJ mol-1 lipid in the presence and in absence of Con A, respectively). Addition of the lectin to DPC liposomes, furthermore, induces the appearance of a new phase transition centered at 320 K. These results are interpretable by a partial hydrophobic interdigitation of the lectin molecule into the liposomal bilayer. The effect of Con A on the phase behavior of three 2:1 mixtures of zwitterionic and of positively charged lipids was also investigated. Phase diagrams of the systems dipalmitoyl-phosphatidylcholine-dihydrosphingosine (DPPC-DHS), sphingomyelin-dipalmitoylcholine (SPM-DPC), and dimyristoylphosphatidylcholine-dipalmitoylcholine (DMPC-DPC) are presented. In lipid mixtures of limited miscibility (DPPC-DHS and SPM-DPC), Con A induces pronounced phase-separation effects. These effects are attributable to a direct hydrophobic interaction of the lectin with the liposomal bilayer and do not require the presence of specific receptor groups. The possible relationship between lectin-induced phase separations in the lipid matrix of biomembranes, and the observed changes in membrane permeability, membranal enzymatic activities, etc., is briefly discussed.


Tweaking the conjugation effects on a pair of new triazene compounds by targeted deprotonation: a spectroscopic and theoretical overview.
Triazene compounds (-NNN(H)-) exhibit versatility in biological, physical, and chemical applications. In their anionic form (-NNN-)(-), they can act as coordinating sites for metals, forming metallic complexes. In this study, two new isomeric triazene compounds with meta- and para-substituents in their neutral and anionic forms were investigated. A combination of detailed experimental spectroscopic characterization and computational chemistry analyses were employed. The new compounds, 1-(2-benzamide)-3-(3-nitrophenyl) triazene (m-TZN) and 1-(2-benzamide)-3-(4-nitrophenyl) triazene (p-TZN), were compared to 1,3-diphenyltriazene (dph-TZN) to understand the effects of functionalization and targeted triazene deprotonation. The anionic forms are stable, and our investigation suggests that these new compounds are suitable tridentate ligands that can act as chelating agents for metallic cations in stable complexes, similar to those found in vitamin B12. The absorption, vibrational, and electronic properties of the newly synthesized triazene compounds were extensively characterized using FT-IR/FT-Raman and UV-Vis spectroscopy. Their distinct molecular properties, intramolecular hydrogen bond effects, stability, and electronic transitions were investigated using the ORCA software. These analyses involved DFT and TD-DFT calculations at the ωB97X-D3/Def2-TZVP level of theory with THF CPCM implicit solvation to determine the molecular topology and electronic structure. The advanced STEOM-DLPNO-CCSD method for excited states was employed, enabling an in-depth analysis of ground and excited-state chemistry, accounting for precise electronic correlation and solvation effects. Explicit THF solvation was tested on the full TD-DFT ωB97X-D3/Def2-TZVP level and using ONIOM on the STEOM calculation. Reactivity was studied using Fukui functions, and action as chelating agents was investigated using GFN-xTB2 and DFT.


Distinctive visual tasks for characterizing mild cognitive impairment and dementia using oculomotor behavior.
One's eye movement (in response to visual tasks) provides a unique window into the cognitive processes and higher-order cognitive functions that become adversely affected in cases with cognitive decline, such as those mild cognitive impairment (MCI) and dementia. MCI is a transitional stage between normal aging and dementia. In the current work, we have focused on identifying visual tasks (such as horizontal and vertical Pro-saccade, Anti-saccade and Memory Guided Fixation tasks) that can differentiate individuals with MCI and dementia from their cognitively unimpaired healthy aging counterparts based on oculomotor Performance indices. In an attempt to identify the optimal combination of visual tasks that can be used to differentiate the participant groups, clustering was performed using the oculomotor Performance indices. Results of our study with a group of 60 cognitively unimpaired healthy aging individuals, a group with 60 individuals with MCI and a group with 60 individuals with dementia indicate that the horizontal and vertical Anti-saccade tasks provided the optimal combination that could differentiate individuals with MCI and dementia from their cognitively unimpaired healthy aging counterparts with clustering accuracy of ∼92% based on the saccade latencies. Also, the saccade latencies during both of these Anti-saccade tasks were found to strongly correlate with the Neuropsychological test scores. This suggests that the Anti-saccade tasks can hold promise in clinical practice for professionals working with individuals with MCI and dementia.


White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial.
Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia. To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60-77 years) from the general population. This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed. FA decreased, and cognition improved more in the intervention group compared to the control group (p < 0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group. The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.


The effect of the water activity of the milieu on rates of glucose uptake by the osmophilic yeasts Saccharomyces rouxii and Debaryomyces hansenii.
Rates of glucose uptake in baker's yeast and in the osmophilic yeasts D. hansenii and S. rouxii were investigated at different values of water activity of the milieu, as regulated either by glycerol or sodium chloride. In both cases, D. hansenii could maintain relatively higher rates of glucose uptake. At lower values of water activity, sodium chloride exerted an inhibitory effect on rates of glucose uptake by S. rouxii, while in the presence of glycerol, rates of glucose uptake shown by S. rouxii resembled those shown by D. hansenii. Rates of glucose uptake by baker's yeast were drastically affected at lower values of water activity in the presence of either solute. Lower values of water activity exerted a stimulatory effect on catalase activity of both S. rouxii and D. hansenii. However, activities of baker's yeast with regard to catalase and invertase were moderately affected under such conditions. Results presented may lead to the presumption that osmophilic yeasts, at least partly, have solved the problem of osmotic tolerance over nonosmotolerant strains by possessing a high capacity for maintaining higher rates of glucose uptake, in spite of the adverse external concentration of solute.


Basal and stress-activated hypothalamic pituitary adrenal axis function in postmenopausal women with overactive bladder.
The aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB. Postmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST). Baseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction. Preliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.


Low-Temperature Solution-Processed Soluble Polyimide Gate Dielectrics: From Molecular-Level Design to Electrically Stable and Flexible Organic Transistors.
Aromatic soluble polyimides (PIs) have been widely used in organic field-effect transistors (OFETs) as gate dielectric layers due to their promising features such as outstanding chemical resistance, thermal stability, low-temperature processability, and mechanical flexibility. However, the molecular structures of soluble PIs on the electrical characteristics of OFETs are not yet fully understood. In this work, the material, dielectric, and electrical properties are evaluated to systematically investigate the chemical structure effect of aromatic dianhydride and diamine monomers on the device performance. Four soluble PIs based on 4,4'-(Hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 5-(2,5-Dioxotetrahydrofuryl)-3-methyl-3-cyclohexene-1,2-dicarboxylic anhydride, in which the monomeric precursors contain different backbones, side groups, and linkages, were employed to compare the chemical structure impact. The dielectric properties, which significantly affect the charge transport and crystallinity of OSC thin films, clearly depended on the soluble PI types as well as the surface energy and the thermal stability. Furthermore, the electrical characteristic measurement and parameter extraction of OFETs based on TIPS-pentacene revealed that the 6FDA-based soluble PIs, which lead to high field-effect mobility, near-zero threshold electric field, and outstanding electrical stability under bias stress, are the most promising gate dielectric candidates. Finally, low-temperature solution-processed OFETs are successfully integrated with ultrathin flexible substrates, and they exhibit no significant electrical performance loss after mechanical flexibility tests. This work presents a step forward in the development of soluble PI gate dielectrics for flexible electronic devices with high device performance.


Point-of-care ultrasonography for the management of shoulder dislocation in ED.
Point-of-care ultrasonography (POCUS) is an easily available and noninvasive tool without radiation exposure that is also gaining a broad range of use in emergency departments. The aim of this study is to evaluate the value of POCUS in the diagnosis of shoulder dislocation by comparing with plain radiography. This prospective observational study with a convenience sampling was conducted in emergency departments of 2 hospitals. Patients older than 15 years with possible shoulder dislocation during the physical examination composed the study population. All the study patients underwent POCUS evaluation to detect a shoulder dislocation or fracture before radiography, and the POCUS procedure was also achieved after the reduction attempt. A total of 103 patients were enrolled in the study. The mean age of study subjects was 33.9±15 years, and 80.6% (n=83) of them were male. The sensitivity and specificity of POCUS in identifying dislocation were 100% (95% confidence interval [CI], 96%-100%) and 100% (95% CI, 48%-100%), respectively. POCUS also confirmed reduction in 93 of 94 patients with a specificity of 100% (95% CI, 96%-100%). POCUS has a sensitivity of 100% (95% CI, 63%-100%) for excluding a shoulder fracture but a specificity of 84.2% (95% CI, 75%-91%). Point-of-care ultrasonography is an effective tool to either rule in or rule out shoulder dislocation in the emergency setting. Furthermore, it is a robust sensitive tool for excluding fractures but with false-positive results.


The dominant influencing factors of desertification changes in the source region of Yellow River: Climate change or human activity?
Due to the combined effects of global warming and human activities, the ecological environment of the Yellow River source area has undergone profound changes and desertification has become increasingly prominent. In this study, an optimal desertification monitoring index based on feature space was proposed for the Yellow River source area, and constructed using Landsat images. Then, the spatial and temporal variation of desertification in the Yellow River source area and its driving mechanism were studied using Geodetector. The main conclusions are as follows: (1) The newly proposed feature space-based desertification monitoring index has good applicability in the study area. The best inversion accuracy of the point-to-point Albedo-NDVI feature space model was 88.4%. (2) Desertification in the eastern and southern regions of the Yellow River source area has a tendency to increase, while the desertification situation in the central region is relatively stable. (3) From 1995 to 2015, there was a significant improvement in desertification in the study area, as evidenced by a decrease in desertification intensity. (4) As the intensity of human disturbance increases, the influence of natural factors on desertification gradually diminishes. The interaction of natural and anthropogenic factors has greater explanatory power for desertification than that of individual natural or anthropogenic factors. The research results can be used as a reference for decision-making on desertification control in the Three-River Source Region.


The role of arterial smooth muscle in vasorelaxation.
The concept of endothelium-derived relaxing factor (EDRF) implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium in response to vasorelaxants such as acetylcholine (ACh) acts on the underlying vascular smooth muscle cells (VSMC) inducing vascular relaxation. The EDRF concept was derived from experiments on denuded blood vessel strips and, in frames of this concept, VSMC were regarded as passive recipients of NO from endothelial cells. However, it was later found that VSMC express NOS by themselves, but the principal question remained unanswered, is the NO generation by VSMC physiologically relevant? We hypothesized that the destruction of the vascular wall anatomical integrity by rubbing off the endothelial layer might increase vascular superoxides that, in turn, reduced the NO bioactivity as a relaxing factor. To test our hypothesis, we examined ACh-induced vasorelaxation under protection against oxidative stress and found that superoxide scavengers restored vasodilatory responses to ACh in endothelium-deprived blood vessels. These findings imply that VSMC can release NO in amounts sufficient to account for the vasorelaxatory response and challenge the concept of the obligatory role of endothelial cells in the relaxation of arterial smooth muscle.


Peripheral blood tumor cell load reflects the clinical activity of the disease in patients with carcinoma of the breast.
Peripheral blood was examined for the presence of tumor cells at multiple time points over a one-year period in 45 patients with a history of surgical resection of breast carcinoma. The number of circulating epithelial cells in 8 of 8 patients with clinically active disease concurred or preceded changes in the disease activity. In 12 of 37 patients with no evidence of disease epithelial cells were found at least at one time point at a frequency larger than the control group. One patient had a recurrence of the breast cancer 4 weeks after circulating epithelial cells were detected in the blood.


Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue.
Clinical use of adipose-derived stem cells (ASCs) for a variety of indications is rapidly expanding in medicine. Most commonly, ASCs are isolated at the point of care from lipoaspirate tissue as the stromal vascular fraction (SVF). The cells are immediately administered to the patient as an injection or used to enrich fat grafts. Isolation of ASCs from adipose tissue is a relatively simple process performed routinely in cell biology laboratories, but isolation at the point of care for immediate clinical administration requires special methodology to prevent contamination, ensure integrity of clinical research and comply with regulatory requirements. A lack of practical laboratory experience, regulatory uncertainty and a relative paucity of objective published data can make selection of the optimum separation method for specific indications a difficult task for the clinician and can discourage clinical adoption. In this paper, we discuss the processes which can be used to separate SVF cells from fat tissue. We compare the various mechanical and enzymatic methods. We discuss the practical considerations involved in selecting an appropriate method from a clinical perspective. Studies consistently show that breakdown of the extracellular matrix achieved with proteolytic enzymes affords significantly greater efficiency to the separation process. SVF isolated through mechanical methods is equally safe, less costly and less time consuming but the product contains a higher frequency of blood mononuclear cells and fewer progenitor cells. Mechanical methods can provide a low cost, rapid and simple alternative to enzymatic isolation methods, and are attractive when smaller quantities of ASCs are sufficient.


Estimation of kinetic parameter for the biotransformation of three-ring azaarenes by the phenanthrene-degrading strain Sphingomonas sp. LH128.
We examined the biotransformation of several azaarenes to get information on their rate of removal from contaminated soil by cometabolic degradation. Acridine, 9-methyl-acridine, phenanthridine, benzo[f]quinoline, and benzo[h]quinoline were found to be cometabolized by phenanthrene-degrading Sphingomonas sp. strain LH128. The transformation of acridine and benzo[h]quinoline was shown to be inhibited at relatively high concentrations (24.9 mg/L and 58.2 mg/L, respectively). Maximum biotransformation rates (Vmaxs), Michaelis-Menten half saturation constants (Kms), and biotransformation constants (k1s) were estimated for acridine, phenanthridine, and benzo[f]quinoline and ranged from 14.0 to 26.1 mg/g total protein/h for Vmax, 0.57 to 2.9 mg/L for Km, and 4.9 to 30.8 L/g total protein/h for k1. For 9-methyl-acridine only, a k1 of 0.6 L/g total protein/h was estimated and for benzo[h]quinoline, the highest biotransformation rate measured was 6.8 +/- 0.4 mg/g total protein/h. To our knowledge, this is the first effort to determine both Vmax and Km kinetic parameters describing the biotransformation of phenanthrene- and anthracene-analogue azaarenes. The results show that the rate of removal of azaarenes from contaminated soil will probably be rather high, although accumulation of metabolites can be expected.


Highly branched amylopectin binder for sulfur cathodes with enhanced performance and longevity.
The sulfur cathode of lithium-sulfur (Li-S) batteries suffers from inherent problems of insufficient mechanical strength and the dissolution of sulfur and polysulfides. Inspired by the extraordinarily resilient and strong binding force of the Great Wall binder, that is, the sticky rice mortar, we extracted highly branched amylopectin (HBA), the effective ingredient, as a low-cost, nontoxic and environmentally benign aqueous binder for the sulfur cathode. The HBA-based cells outperform the Li-S batteries based on the traditional polyvinyldene diflouride (PVDF) binder and a lowly branched polysaccharide binder. The improved electrochemical performance in the HBA-based cell could be attributed to two mechanisms. First, the branched structure of the HBA provides enhanced mechanical and adhesive properties, which allow for a robust electronic and ionic conductive framework to be maintained throughout the cathode after extended cycling. Second, the HBA shows enhanced polysulfide retention due to the polymer's abundant lone-pair rich hydroxyl groups and the formation of C─S bonds between the HBA and polysulfides prohibits the shuttle effect of polysulfides. The improved mechanical properties and polysulfide retention function of the HBA binder facilitate the HBA-based Li-S battery to deliver a long cycle life of 500 cycles at 2 C while only displaying a capacity fading of 0.104% per cycle.


Thermoresponsive polysaccharides with tunable thermoresponsive properties via functionalisation with alkylamide groups.
Polysaccharides have been used widely in many industries, from food technology and mining to cosmetics and biomedical applications. Over recent years there has been growing interest in the development of responsive polysaccharides with unique and switchable properties, particularly systems that display lower-critical solution temperatures (LCSTs). Therefore, in this study we aimed to investigate a novel strategy that would allow the conversion of non-responsive polysaccharides into thermoresponsive polysaccharides with tuneable LCSTs. Through the functionalisation of dextran with alkylamide groups (isopropyl amide, diethyl amide, piperidinyl and diisobutyl amide) using a carbodiimide coupling approach in conjunction with amic acid derivatives, we prepared a library of novel dextrans with various degrees of substitution (DS), which were characterised via nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The alkylamide-functionalised dextrans were found to have good solubility in aqueous solutions, with the exception of those having a high DS of large hydrophobic substituents. Determination of the thermoresponsive characteristics of the polymer solutions via UV-vis spectroscopy revealed that the LCST of the alkylamide-functionalised dextrans was highly dependent on the type of alkylamide group and the DS and could be tuned over a large range (5-35 °C). Above the LCST, all of the thermoresponsive alkylamide-functionalised dextrans formed colloidal dispersions with particles sizes ranging from 400 -600 nm, as determined by dynamic light scattering (DLS). In addition, the polymers were found to exhibit a fast and reversible phase transition in solution with narrow hysteresis (∼ 1-5 °C). Finally, the injectability and biocompatibility of the novel thermoresponsive dextrans was confirmed in vivo via subcutaneous and intracranial ventricle injections, with no local or systemic toxicity noted over a 14 d period. Overall, the alkylamide-functionalised dextrans display interesting thermoresponsive properties and trends that may make them useful in biomedical applications, such as drug-delivery.


Tricholemmoma of the eyelid.
Tricholemmoma is a benign cutaneous tumor that shows differentiation characteristic of the outer hair sheath. The usual site of occurrence is the face, including the nose and eyelid. Four cases of tricholemmoma involving the eyelid margin to a variable extent are presented and the clinical and pathologic findings are reviewed. In three of the four cases, a histopathologic misdiagnosis of squamous cell carcinoma was initially made. In one case, this resulted in a greater sacrifice of normal lid tissue than was necessary, although the reconstruction yielded a good result. In the subsequent cases, the entity of tricholemmoma was well appreciated before definitive oculoplastic surgery and the referring diagnosis of squamous cell carcinoma was refuted.


Advanced Diffusion of the Pediatric Brain and Spine.
This article discusses new diffusion-weighted imaging (DWI) sequences, diffusion tensor imaging (DTI), and fiber tractography (FT), as well as more advanced diffusion imaging in pediatric brain and spine. Underlying disorder and pathophysiology causing diffusion abnormalities are discussed. Multishot echo planar imaging (EPI) DWI and non-EPI DWI provide higher spatial resolution with less susceptibility artifact and distortion, which are replacing conventional single-shot EPI DWI. DTI and FT have established clinical significance in pediatric brain and spine. This article discusses advanced diffusion imaging, including diffusion kurtosis imaging, neurite orientation dispersion and density imaging, diffusion spectrum imaging, intravoxel incoherent motion, and oscillating-gradient spin-echo.


Premature senescence of mesothelial cells is associated with non-telomeric DNA damage.
Human peritoneal mesothelial cells (HPMCs) senesce in vitro after barely few population doublings. In this report, we show that senescence of HPMCs is associated with increased accumulation of gamma-H2A.X foci, which reveal DNA double-strand breaks. Of note, already early-passage cultures contain a considerable fraction (44+/-10%) of cells bearing gamma-H2A.X foci. The gamma-H2A.X foci localize predominantly to non-telomeric DNA, either in young or senescent cells. Moreover, HPMCs seem to have unusually short telomeres (approximately 3.5 kbp) despite the presence of active telomerase. These telomeres do not shorten during senescence, but the activity of telomerase decreases to undetectable levels. In addition, senescence of HPMCs is associated with mitochondrial dysfunction, as manifested by increased production of reactive oxygen species and reduced mitochondrial membrane potential. These results may indicate that premature senescence of HPMCs is largely related to oxidative stress-induced DNA damage in non-telomeric regions of the genome.


Protocol for assessing the healthspan of Caenorhabditis elegans after potential anti-aging drug treatment.
The nematode Caenorhabditis elegans has been developed as a valuable genetic model for research on aging and aging-related diseases. Here, we present a protocol for assessing the healthspan of C. elegans after treatment of a potential anti-aging drug. We describe steps for C. elegans synchronization, drug treatment, and lifespan determination from the survivorship curve. We also detail assessment of locomotory ability through body bend rate and measurement of lipofuscin fluorescence to quantify age pigment in the worm intestine. For complete details on the use and execution of this protocol, please refer to Xiao et al. (2022).1.


Annual glycemic variations and risk of cancer among Chinese patients with type 2 diabetes mellitus: A population-based cohort study in Shanghai.
Long-term glycemic variation in diabetes patients may have contributed to cancer incidence. In this study we aimed at the association between annual glycemic variation and the risk of cancer in Chinese patients with type 2 diabetes mellitus (T2DM). Subjects of this study were from an established population-based cohort of T2DM patients in Minhang District of Shanghai, China. Incident cancer were obtained from the Shanghai Cancer Registry. Glycemic variation was evaluated using the annual fasting glucose coefficient of variation (FG-CV), which was used as a time-dependent variable in a Cox regression model to estimate the associations with the cancer risk. Restricted cubic splines were used to explore potential non-linear associations. A total of 2,140 incident cancers (1100 men and 1040 women) were identified from the 46,202 diabetes patients during 12-year follow-up. The annual FG-CV remained significantly associated with an increased risk of cancer, even after adjusting for the annual mean FG level. A significant non-linear association was found in male T2DM patients, and a significant linear association in female patients. The positive association of the annual FG-CV with the risk of cancer in T2DM patients indicate the importance to stabilize the FG level.


Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones.
The somatic membrane of guinea-pig olfactory cortex neurones in vitro (23 degrees C) was voltage clamped by means of a single-micro-electrode sample-and-hold technique. In most cells the current-voltage (I-V) relationship showed inward (anomalous) rectification with increasing hyperpolarization beyond the resting potential (ca. -80 mV). Under current-clamp conditions a time-dependent 'sag' of the hyperpolarizing electrotonic potentials was observed following an initial overshoot. No depolarizing after-potential was seen on return to the resting potential. Inward rectification was activated between -100 and -110 mV (irrespective of pre-set resting potential) and increased the membrane input conductance by up to three-fold. The rectification was unaffected by tetrodotoxin or Cd2+. Under somatic voltage clamp, hyperpolarization beyond -110 mV activated a rapid inward relaxation fitted by a single exponential. The relaxation time constant (tau on) decreased e-fold for a 40 mV hyperpolarization. (Typical values: 28 ms at -110 mV declining to 13 ms at -140 mV; external K+ concentration 3 mM, 23 degrees C). More extreme hyperpolarizations evoked a slower 'inactivation' phase (tau = 40-60 ms). A transient outward-decaying 'tail' current reflecting deactivation of inward rectification was seen on stepping from -140 mV to more positive potentials. tau off became slower with hyperpolarization. The tail current disappeared at a potential close to the expected VK but was rarely inverted to an inward-decaying tail. It is proposed that the fast inward-rectifying current of olfactory neurones (If.i.r.) is a K+ current analogous to the anomalous K+ rectifier of marine egg and frog muscle membranes. The behaviour of the inward rectifier was dependent on external K+ concentration in accordance with the unique 'V--VK' dependence of classical anomalous rectification; however, of several agents tested (external Cs+, Ba2+, Rb+, Tl+ or tetraethylammonium), only Cs+ and Ba2+ blocked If.i.r. in a time- and voltage-dependent manner. The effect of tetraethylammonium resembled that of an increase in external K+. The possible contribution of the inward rectifier to the passive cell membrane properties is discussed.


Dismutation of hydroxylamine to ammonia and nitrite by a novel, membrane-bound enzyme from the cyanobacterium Phormidium uncinatum.
Extracts from ammonium-grown phototrophic cultures of Phormidium uncinatum exhibited a catalytic and stoichiometric formation of nitrite and ammonia from hydrogen peroxide and hydroxylamine. This reaction was due to a novel enzyme (referred to as hydroxylamine dismutase), which was bound to the heavier thylakoid membranes. The enzyme was solubilized from the membranes by detergent treatment and further purified by ion-exchange chromatography. On the basis of inhibitor studies, the involvement of metal ions and sulfhydryl groups in the characteristic reaction is suggested.


Calcium antagonists: Do they equally protect against kidney injury?
Calcium antagonists are a heterogeneous group of drugs that affect not only different channels but different parts of the same channel. These differences translate into different renal hemodynamic effects. This Commentary discusses the implications of these differences for surrogate markers of outcome.


[Experimental exacerbation of latent Q rickettsial infection].
The evidence of the prolonged persistence of Coxiella burnetii in experimental animals was obtained. Cyclophosphamide was shown to be capable of activating Q rickettsiosis in guinea pigs, and the period of the aggravation of this infection was found to be accompanied by a decrease in IgG concentration and a relative increase in IgM content.


Automated DNA sequencing and the analysis of the human genome.
The Human Genome Initiative is a complex, multifaceted, international effort to establish a massive data base of map and sequence information for humans and other organisms. The success of this initiative is dependent upon the development of new technologies for the analysis of genomes. In this paper, an overview of the Human Genome Initiative is presented, and the current status of efforts to automate large-scale DNA sequence analysis is reviewed.


Incidence of Healthcare-Associated Infections (HAIs) and the adherence to the HAIs' prevention strategies in a military hospital in Alkharj.
Healthcare-associated infections (HAI) are considered one of the most common adverse events in health care service provision. In order to prevent the occurrence of HAIs, it is important to implement several prevention strategies. This study aims to determine the incidence of healthcare-associated infections in a military hospital in Alkharj and the adherence to the HAIs' prevention strategies. This study included exporting data for all infected cases confirmed by the infection disease specialists in 2019. The data were collected from the reports that were written by infection control unit and infectious disease department. The rate of healthcare associated infections (HAIs) in 2019 was 0.43% of total patient admissions. The rate of central line associated bloodstream infections in 2019 was 1.15 per 1000 central line days. The rate of catheter associated urinary tract infections in 2019 was 1.00 per 1000 catheter days. The rate of ventilator associated pneumonia in 2019 was 2.11 per 1000 ventilator days and the rate of surgical site infections in 2019 was 0.41 %. The rate of overall healthcare-associated infections (HAI) was low. The compliance rate of health care workers to preventive measures that control HAIs was generally high but there was a need for more awareness particularly regarding personal protective equipment and hand hygiene. So it is important to attend more awareness activities and workshops particularly regarding personal protective equipment and hand hygiene. Furthermore, infection control unit and infectious disease department in the hospital should support the robust HAI prevention programs.


Regional white matter change in pre-symptomatic Huntington's disease: a diffusion tensor imaging study.
The pathology of Huntington's disease (HD) is characterized by diffuse brain atrophy, with the most substantial neuronal loss occurring in the caudate and putamen. Recent evidence suggests that there may be more widespread neuronal degeneration with significant involvement of extrastriate structures, including white matter. In this study of pre-symptomatic carriers of the HD genetic mutation, we have used diffusion tensor imaging to examine the integrity and organization of white matter in a group of individuals who previously demonstrated abnormalities in response to a functional magnetic resonance imaging paradigm. Our results indicate that, before the onset of manifest HD, there are regional decreases in fractional anisotropy, indicating early white matter disorganization.


Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study.
To assess the association between atrial fibrillation and flutter and use of bisphosphonates for osteoporosis among women. Population based case-control study, using medical databases from Denmark. Northern Denmark. 13 586 patients with atrial fibrillation and flutter and 68 054 population controls, all with complete hospital and prescription history. Adjusted relative risk of atrial fibrillation and flutter. 435 cases (3.2%) and 1958 population controls (2.9%) were current users of bisphosphonates for osteoporosis. Etidronate and alendronate were used with almost the same frequency among cases and controls. The adjusted relative risk of current use of bisphosphonates compared with non-use was 0.95 (95% confidence interval 0.84 to 1.07). New users had a relative risk of 0.75 (95% confidence interval 0.49 to 1.16), broadly similar to the estimate for continuing users (relative risk 0.96, 95% confidence interval 0.85 to 1.09). The relative risk estimates were independent of number of prescriptions and the position of the atrial fibrillation and flutter diagnosis in the discharge record, and were similar for inpatients and outpatients. No evidence was found that use of bisphosphonates increases the risk of atrial fibrillation and flutter.


Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening.
The purpose of this study it was to evaluate the frequency of Multiple Endocrine Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP-Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005-2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed.


Measurement and restoration of equality in length of the lower limbs in total hip replacement.
Alteration of the length of the lower limb was measured in 39 patients undergoing total hip replacement. Radiographs were taken in the erect posture prior to operation and 6 months postoperatively. The inequality of limb length was measured by the difference between the height of the vertices of the femoral heads and by the difference between the lowest points of the ischial tuberosities. The change of the length was measured intraoperatively as the difference observed between two reference points: one above the acetabulum and the other on the proximal femur. Good correlation was obtained between the change of the limb length made intraoperatively and the change in the limb length using the ischial tuberosities as reference points; no correlation was observed when the vertices of the femoral heads were the reference points. Inequality of limb length can be radiologically determined before and after total hip arthroplasty. Femoral and prosthetic heads are not good reference points for measurement. The difference in the height of the ischial tuberosities demonstrates inequality of limb functional length as it reflects the tilting of the pelvis.


Amyloid A fibril degrading activity in serum in liver disease--relation to serum acute phase and other protein levels.
Human serum contains amyloid A degrading activity. This activity is decreased in patients with reactive systemic amyloidosis. To study the specificity of this finding, we evaluated the effect of liver disease per se on the amyloid degrading activity in serum as well as its relation to serum amyloid A (SAA), the putative precursor of amyloid A fibrils, and other serum protein levels in alcoholic and non-alcoholic non-malignant liver diseases without signs of amyloidosis. The amyloid A-degrading activity was significantly decreased in liver cirrhosis. The lowest activity was seen in patients with advanced cirrhosis. There was a positive correlation between the degradative activity and indices of hepato-cellular synthetic function (serum albumin, r = 0.77; serum prealbumin, r = 0.65). Most of the patients with liver disease had a detectable SAA level; 77% had a level higher than 5 mg/l (compared to 12% among blood donors). However, the SAA increase was generally only slight, e.g. in alcoholic liver cirrhosis the median SAA level was 15 mg/l. The results show that liver dysfunction per se decreases amyloid A-degrading activity in serum. A reduced activity cannot therefore be regarded as specific for reactive amyloidosis. Since reactive amyloidosis is extremely rare in liver cirrhosis, it seems obvious that a reduced amyloid degrading activity alone, in the absence of a markedly elevated SAA level, does not predispose, at least in patients with liver disease, to amyloidosis.


Detection of budesonide in human urine after inhalation by liquid chromatography-mass spectrometry.
Budesonide, a corticosteroid frequently used in the treatment of asthma, is most often administered via inhalation. Its use in sports is allowed when medically necessary. A fast, sensitive and accurate LC-MS method was developed and validated for the quantification of budesonide and its major metabolite 16alpha-hydroxyprednisolone in urine samples after inhalation of a metered dose (Pulmicort-Turbohaler 200). Sample preparation consists of an alkaline liquid-liquid extraction with ethyl acetate. Analysis was performed using liquid chromatography-tandem mass spectrometry with electrospray ionization (ESI). The method was linear in the range of 5-100 and 0.5-10ng/mL for 16alpha-hydroxyprednisolone and budesonide, respectively. The limits of quantification were 5ng/ml for 16alpha-hydroxyprednisolone and 0.5ng/mL for budesonide. The accuracy ranged from 2.2 to 3.5% for 16alpha-hydroxyprednisolone and from 0.8 to 16.4% for budesonide. After administration of 200microg of budesonide to five healthy volunteers budesonide could not be detected in any urine sample whereas 16alpha-hydroxyprednisolone was detectable up to 12h post-administration.


Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride.
Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer.


Competing interests at the heart of equine sports medicine ethics: A scoping review and thematic analysis.
The ethics of using horses in sport is receiving increasing attention and media scrutiny. Sports medicine ethics is an important and well-established discipline within human medicine and biomedical ethics, which has, thus far, received little application to the equine veterinary field. The purpose of this scoping review was to explore the existing literature on equine sports medicine ethics, to understand the current concerns and issues, and to map areas for future research. Scoping review. Academic databases (PubMed, Web of Science, CAB abstracts) were searched to identify papers, published in English, between 2000 and 2022, that mentioned aspect(s) of the ethics of veterinary provision to the performance horse. Additionally, grey (including lay) literature was identified through global search engines to locate supplementary and opinion articles. Relevant data on article characteristics and ethical concerns were extracted and charted. Thematic analysis was employed to identify key issues. A literature source of 41 papers/articles was used; of which 35 were from veterinary sources, mostly veterinary journals and conference proceedings. Several themes were identified including: competing stakeholder interests; governing bodies, rules and regulations; provision of optimal veterinary care; confidentiality; and social licence for the veterinary profession. The most commonly mentioned specific ethical concern was the use of medication in performance horses. In this scoping review, we have not sought to critically analyse the ethical arguments within the included literature, but rather to collate them so that an overview of ethical concerns can be established. Further consideration is required as to how the veterinary profession and sporting governing bodies can support individual veterinary surgeons to strive for the highest levels of professional conduct in equine sports medicine. The veterinary profession should continue to work towards establishing processes for determining what veterinary practices are ethical, optimal, excessive, permissible and impermissible.


Performance of Paracoccus pantotrophus MA3 in heterotrophic nitrification-anaerobic denitrification using formic acid as a carbon source.
Excess amount of nitrogen in wastewater has caused serious concerns, such as water eutrophication. Paracoccus pantotrophus MA3, a novel isolated strain of heterotrophic nitrification-anaerobic denitrification bacteria, was evaluated for nitrogen removal using formic acid as the sole carbon source. The results showed that the maximum ammonium removal efficiency was observed under the optimum conditions of 26.25 carbon to nitrogen ratio, 3.39% (v/v) inoculation amount, 34.64 °C temperature, and at 180 rpm shaking speed, respectively. In addition, quantitative real-time PCR technique analysis assured that the gene expression level of formate dehydrogenase, formate tetrahydrofolate ligase, 5,10-methylenetetrahydrofolate dehydrogenase, serine hydroxymethyltransferase, respiratory nitrate reductase beta subunit, L-glutamine synthetase, glutamate dehydrogenase, and glutamate synthase were up-regulated compared to the control group, and combined with nitrogen mass balance analysis to conclude that most of the ammonium was removed by assimilation. A small amount of nitrate and nearly no nitrite were accumulated during heterotrophic nitrification. MA3 exhibited significant denitrification potential under anaerobic conditions with a maximum nitrate removal rate of 4.39 mg/L/h, and the only gas produced was N2. Additionally, 11.50 ± 0.06 mg/L/h of NH4+-N removal rate from biogas slurry was achieved.


Conventional radiology and right heart catheterization in estimating primary pulmonary hypertension and pulmonary hypertension secondary to left-sided valvular disease.
to estimate the comparative value of conventional radiology and cardiac catheterization in establishing the diagnosis and severity of primary and secondary pulmonary hypertension. We also tried to achieve some correlations between the radiological and invasive parameters. we performed a retrospective study over an 11-years time period, analyzing data from a group of 14 patients diagnosed with primary pulmonary hypertension compared to a matched group of 20 patients suffering from pulmonary hypertension secondary to mitral and aortic valvular disease. All the patients had undergone conventional radiology (chest X-ray) and catheterization of the right heart cavities and pulmonary artery. we detected significantly elevated pulmonary artery pressures and resistances in the primary pulmonary hypertension group compared to secondary hypertension patients. Cardiac output values were much lower in the primary pulmonary hypertension individuals compared with secondary pulmonary hypertension in left-sided valvular disease. The pulmonary artery arch diameter, the diameter of the right descending pulmonary artery and the value of the arterio-bronchial ratio were similar in the two groups. in both groups, we found a statistically significant positive correlation between the values of the pulmonary artery vascular resistance and the diameter of the right descending pulmonary artery, which are very specific parameters in the diagnosis of pulmonary hypertension. In the primary pulmonary hypertension group we identified a significant inverse correlation between the diameter of the right descending pulmonary artery and the values of cardiac output. This finding was not confirmed in the secondary group.


AUA Quality Improvement Summit 2014: Conference Proceedings on Infectious Complications of Transrectal Prostate Needle Biopsy.
The AUA Quality Improvement Summit is a continuing AUA effort to provide education around issues related to quality improvement and patient safety. Due to the rapidly increasing rates of hospitalization following prostate needle biopsy, Infectious Complications of Transrectal Prostate Needle Biopsy was selected as the inaugural topic. The information is largely unpublished data provided by the presenting physicians. Infection rates are predominantly self-reported with protocols specified by the physicians' home institutions. Beyond the identified speakers, the open forum of this summit allowed for input from a majority of the participants. Current hospitalization rates for transrectal prostate needle biopsy infections vary widely from 0.5% to 6%. Antibiotic resistance of coliform organisms appears to be a major risk of these infectious complications. Prophylactic protocols also vary widely among the represented institutions. Antibiotic resistance profiles showed extreme regional variation and, as such, a prophylactic antibiotic protocol should be based on the current local antibiogram in order to reduce infection rates. Opinions vary in relation to the specific antibiotics appropriate for an augmented antibiotic prophylaxis, in the use of rectal swab and prebiopsy enema, and povidone-iodine preparation of the rectal vault. Standardization of the transrectal antibiotic prophylaxis across practices has been proven to reduce the infectious complications rates. Urologists should monitor the prostate biopsy infection rates of the practice and consult the current local antibiogram. Physicians should query patients to assess whether they are at high risk for resistant organisms. If so, prophylactic protocols might be intensified.


Assessing the clinical utility of color Doppler ultrasound for ovarian torsion in the setting of a negative contrast-enhanced CT scan of the abdomen and pelvis.
The purpose of this study is to evaluate the utility of color Doppler ultrasound (CDU) in the assessment of ovarian torsion following a negative contrast-enhanced computed tomography (CT) examination. This is a retrospective study of women who presented to the ED with abdominal pain and received both a contrast-enhanced CT and CDU within a 24-h period. The abdominal/pelvic CT examinations were evaluated for findings specific to torsion, including ovarian size greater than 5 cm, the presence of free fluid, uterine deviation, fallopian tube thickening, ovarian fat stranding, smooth wall thickening, the presence of the "twisted pedicle" sign, and abnormal ovarian enhancement. The results were compared to the presence or absence of ovarian torsion on the concurrent US. The initial query yielded 834 cases among 789 women. Of those 834 cases, 283 cases in 261 women received both imaging modalities within a 24-h period. The CT examinations demonstrated 48 cases with an ovarian size greater than 5 cm. 84 cases showed the presence of free fluid. Three cases of fallopian tube thickening were identified. One case of smooth wall thickening and a "twisted pedicle" sign were noted. Fifteen cases demonstrated stranding of the peri-ovarian fat. Twenty nine cases showed abnormal ovarian enhancement. A total of 111 cases showed at least one positive finding. Fourteen positive cases were identified on the CDU studies. Of the 14 positive cases, 11 had ovarian size greater than 5 cm. Twelve cases demonstrated the presence of free fluid. There was no uterine deviation or smooth wall thickening. One twisted pedicle was noted. Seven cases showed peri-ovarian fat stranding. Ten cases showed abnormal enhancement. Abnormalities on CT were noted in all cases suspicious for ovarian torsion on CDU. No negative CT examinations were associated with a positive CDU. In this small sample size, the negative predictive value of a negative CT examination was 100%. A negative contrast-enhanced CT examination of the abdomen and pelvis is sufficient to rule out ovarian torsion. Therefore, there is no utility in the addition of CDU specifically to evaluate for ovarian torsion following a negative contrast-enhanced CT scan of the abdomen and pelvis.


Overestimation of orthophosphate monoesters in lake sediment by solution 31P-NMR analysis.
Solution 31P nuclear magnetic resonance spectroscopy (31P-NMR) is a useful method for analyzing organic phosphorus (Po). Unfortunately, the extraction conditions, which are highly alkaline and require long extraction times, make this analysis less effective. In this research, according to the lability of orthophosphate monoesters (mono-Po) and orthophosphate diesters (diesters-Po), we verified the hypothesized overestimation of mono-Po in lake sediment using solution 31P-NMR. We set three scenes to redistribute the mono-Po and diesters-Po. Six components, including eight mono-Po species, were detected in the NaOH-EDTA extracts of sediment samples using 31P-NMR. The results showed that mono-Po (212.7 mg kg-1) was the dominant Po in the surface sediment. In the three scenes, mono-Po decreased from 212.7 to 112.0 mg kg-1, and diesters-Po increased from 31.9 to 132.7 mg kg-1. The ratio of mono-Po to diesters-Po increased from 6.7 to 0.8. Therefore, we deduced that the concentration of mono-Po was overestimated, while that of diesters-Po was underestimated, in most research because of the high pH and long extraction process. Diesters-Po might be an important labile P source during the P "exhausted" period.


Stratifying features for diagnosing hypertrophic stenosis on ultrasound: a diagnostic accuracy study.
Our aims were to determine if the diagnostic threshold for diagnosing hypertrophic pyloric stenosis (HPS) on ultrasound scan (USS) should be adjusted based on birth weight (BW), current weight (CW), gestational age (GA), chronological age (CA) or corrected gestational age (CGA). All patients who underwent either an USS and pyloromyotomy (Group 1) or an USS for possible HPS (Group 2) at our tertiary centre between July 2013 and June 2019 were identified. Ideal threshold values are identified by measuring Youden's Index (J = sensitivity + specificity - 1; higher is better). Mean maximum Youden's Index for stratified results was compared to that for combined results. Two hundred and eighty-four patients were included (142 patients in both Group 1 and Group 2). Combined maximum Youden's Index for all patients was 0.92 for pyloric canal thickness (PMT) and 0.87 for pyloric canal length (PCL). Mean maximum Youden's Index was higher when patients were stratified by GA, CGA, BW or CW, and equivalent for CA. For pyloric canal length (PCL), mean maximum Youden's Index was lower for all variables when stratified compared to combined. There was no visual trend observed in the diagnostic thresholds between groups. Stratifying USS PMT diagnostic thresholds values based on age and weight is statistically more accurate than a single threshold in diagnosing HPS. However, the lack of visual correlation indicates a larger dataset is required to validate these results.


Antenatal inflammation and lung injury: prenatal origin of neonatal disease.
Antenatal inflammation in utero may be associated with lung injury and subsequent aberrant lung development resulting in bronchopulmonary dysplasia (BPD). BPD has become a developmental disease with a uniform arrest in lung development. The role of antenatal inflammation in the induction of lung injury was explored in a sheep model suitable for the study of lung development with respect to human development. Chorioamnionitis was induced by a single injection of endotoxin into the amniotic cavity under ultrasound guidance. Endotoxin-induced chorioamnionitis caused a cascade of lung injury, pulmonary inflammation and remodeling in the fetal lung similar to lung injury previously described in adult animal models. The structural changes in the fetal lung after chorioamnionitis showed little to no fibrosis and alveolar/microvascular simplification similar to new BPD. The identified cytokine networks and regulators may explain the absence of fibrosis and lung simplification after strictly intra-uterine inflammation. The mechanisms of antenatal inflammation in the fetal lung were multifactorial and could be antenatally modulated. Fetal pulmonary inflammation was temporarily suppressed by maternal glucocorticoid therapy. However, pulmonary inflammation could be augmented postnatally by resuscitation, oxygen toxicity, mechanical ventilation and pulmonary and systemic infection, which opens a broad window of clinical options.


Cloning of a cDNA encoding adenylosuccinate lyase by functional complementation in Escherichia coli.
Adenylosuccinate lyase was cloned by functional complementation of an Escherichia coli purB mutant using an avian liver cDNA expression library. The derived amino acid sequence is homologous to the bacterial purB-encoded adenylosuccinate lyase which catalyzes the same two steps in purine biosynthesis as the enzyme from animals. Avian adenylosuccinate lyase also shows regions of extensive sequence similarity to the urea cycle enzyme, argininosuccinate lyase. This homology suggests a similar mechanism for catalysis. Homology of adenylosuccinate and argininosuccinate lyases is intriguing because chickens do not utilize the urea cycle in nitrogen excretion. This is the first report of the cloning of a eukaryotic cDNA encoding adenylosuccinate lyase, and it affords a route to isolate the corresponding human gene which has been suggested to be defective in autistic children.


Effect of p-chloromercuribenzene sulfonate on gastric parietal and surface cell function in the dog.
p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition.


Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients.
During pregnancy, patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) can experience active disease, which might be influenced by adjustment of treatment around conception. The aim of this study was to identify possible risk factors of disease flares during pregnancy and to evaluate the effect of treatment in pregnant patients experiencing a flare. Pregnant patients with RA and axSpA were prospectively followed before, during, and after pregnancy. Disease activity and flares of disease activity were analyzed in regard to medication. Among 136 pregnant patients, disease flares during pregnancy occurred in 29% of patients with RA and in 25% of patients with axSpA. In both diseases, active disease and tumor necrosis factor inhibitor (TNFi) discontinuation in early pregnancy were identified as risk factors for disease flares during pregnancy. Of 75 patients with RA, 15 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. After stopping TNFi, disease activity increased, which was reflected by peaking C-reactive protein levels at the first trimester. The relative risk of flare in patients with RA stopping TNFi was 3.33 (95% CI 1.8-6.1). Initiation of TNFi or glucocorticosteroid (GC) treatment in 60% of these patients resulted in disease improvement at the second and third trimesters. In comparison, patients with RA without TNFi in the preconception period, most of whom had used pregnancy-compatible antirheumatic drugs, showed mild and stable disease activity before and during pregnancy. Of 61 patients with axSpA, 24 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. In patients with axSpA stopping TNFi, a disease aggravation at the second trimester could be observed. The relative risk of flare in this group was 3.08 (95% CI 1.2-7.9). In spite of initiated TNFi or GC treatment in 62.5% of these patients, disease activity remained elevated throughout pregnancy. Patients with axSpA without TNFi in the preconception period showed persistent high disease activity from prepregnancy until the postpartum period. On the basis of a risk-benefit analysis, to stabilize disease activity and to prevent a flare during pregnancy in patients with RA and axSpA, tailored medication including TNF inhibitors should be considered beyond conception.


Association of Public Interest in Preventive Measures and Increased COVID-19 Cases After the Expiration of Stay-at-Home Orders: A Cross-Sectional Study.
Following stay-at-home (SAH) orders issued for coronavirus disease (COVID-19), state-level economic concerns increased and many let these orders expire. As a method to measure public preparedness, we sought to explore the association between public interest in preventive measures and the easing of SAH orders - specifically the increases in COVID-19 cases and fatalities after the orders expired. Search volume was collected from Google Trends for "hand sanitizer," "social distancing," "COVID testing," and "contact tracing" for each state. Bivariate correlations were computed to analyze associations between public interest in preventive measures, changes in confirmed COVID-19 cases after SAH expirations, COVID-19 case-fatality rates, and by-state presidential voting percentages. A higher interest in preventive measures was associated with lower rates of confirmed cases after SAH orders had expired (r = -0.33), higher state-wide deaths per capita (r = 0.42), and case-fatality rates (r = 0.60). Moderate to strong negative correlations were found between states' percentage of voters supporting the Republican nominee in 2016 and proportion of queries for average preventive measures (r = -0.77). Our investigation shows that increased public interest in COVID-19 prevention was associated with longer SAH orders and less COVID-19 cases after the SAH orders' expiration; however, it was also associated with higher case-fatality rates.


Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice.
The autoimmune disease of the central nervous system (CNS), experimental allergic encephalomyelitis (EAE), is induced by challenge of genetically susceptible animals with spinal cord homogenates or myelin basic protein (MBP). Chronic and relapsing forms of the disease have some similarities to human demyelinating disorders, namely, multiple sclerosis, and are of particular interest. EAE can be transferred passively with sensitized lymphoid cells into syngeneic animals but transferred EAE has been believed to have limited relevance to human disease because it is usually monophasic and manifested by minimal demyelination. We report here that a single transfer of MBP-sensitized lymph node cells or T cell, in the absence of a peripheral antigen depot, leads to both acute EAE with significant primary demyelination, and chronic relapsing disease with lesions typical of demyelination over a long period. These findings have major implications for the immunological mechanisms involved in experimental and human demyelinating diseases.


Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants.
It has been suggested that homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disease of White ethnic origin but little is known regarding its ethnic distribution. We estimated ethnic-specific homozygous c.985A>G MCADD birth prevalence from a large-scale UK newborn screening study. Homozygous c.985A>G MCADD cases were ascertained in six English newborn screening centres between 1 March 2004 and 28 February 2007 by screening approximately 1.1 million newborns using tandem mass spectrometry analysis of underivatised blood spot samples to quantitate octanoylcarnitine (C8). Follow-up biochemistry and mutation analyses for cases (mean triplicate C8 value >/=0.5 micromol/L) were reviewed to confirm diagnosis. Ethnicity was ascertained from clinician report and denominators from 2001 UK Census estimates of ethnic group of children less than one year. Sixty-four infants were c.985A>G MCADD homozygotes (overall prevalence 5.8 per 100,000 live births; 95% CI 4.4-7.2). Sixty (93%) were White, two (3%) were mixed/other and two were of unknown ethnic origin. No Asian or Black homozygotes were identified. Proportions of White, mixed/other, Asian and Black births in screening regions were estimated, yielding homozygous c.985A>G MCADD birth prevalence of 6.9 per 100,000 (95% CI 5.2-8.8) in White, and 95% CI estimates of 0-2.7 per 100,000 in Asian and 0-5.8 in Black populations. The c.985A>G carrier frequency in the White group was estimated at one in 65 (95% CI 1/74, 1/61) under Hardy-Weinberg conditions. c.985A>G homozygous MCADD is not found in Black and Asian ethnic groups that have been screened at birth in England. This is consistent with the earlier published observations suggesting that MCADD due to the c.985A>G mutation is a disease of White ethnic origin.


Capturing the dynamics of identity formation in various ethnic groups: development and validation of a three-dimensional model.
The aim of this study was to develop a model of identity formation comprising three structural dimensions: commitment, in-depth exploration and reconsideration of commitment. A new tool, the Utrecht-Management of Identity Commitments Scale, was designed to assess these processes. Early and middle adolescents (N=1952) participated in this study. Confirmatory factor analyses revealed that the three-factor model provided a better fit than alternative one- and two-factor models. The model applied not only to the whole adolescent sample, but also to male and female subsamples and to early and middle adolescent age groups. Additionally, we established interethnic equivalence of the model, in that it also fit well for ethnic minority adolescents. In accordance with hypotheses, regression analyses showed that commitment, in-depth exploration and reconsideration of commitment were significantly related to measures of self and personality, psychosocial problems and parent-adolescent relations. Implications and suggestions for future research are discussed.


Correlates of hematuria on glomerular histology and electron microscopy in IgA nephropathy.
Hematuria is the most important clinical manifestation of IgA nephropathy. This study was undertaken with the objective to describe the spectrum of histological changes with reference to the Oxford classification and the ultrastructural changes in the glomerular basement membrane and to correlate them with hematuria. 66 patients who underwent renal biopsy for IgA nephropathy were evaluated histologically by the Oxford system and also subject to electron microscopic examination for glomerular immune deposits, as well as alterations in the glomerular basement membrane. On comparing the histological scores generated by the Oxford classification with degree of hematuria, it was found that the status of 'endocapillary proliferation' and the status of 'tubular atrophy and interstitial fibrosis showed a significant correlation. Correlation of hematuria with location of the deposits, i.e. mesangial only, and mesangial with capillary wall deposits (subendothelial and subepithelial) did not show any association. Other alterations of the GBM were seen in 12 cases. The changes included thinning alone in 4 cases, thinning and lamellar splitting in 5 cases, and lamellar splitting alone in 2 cases. At presentation, endocapillary proliferation is one histological parameter which shows close association with hematuria.


Perception of neurology among undergraduate medical students - what can be done to counter neurophobia during clinical studies?
With a global increase in the burden of neurological diseases, the aversion towards neurology (neurophobia) may challenge the sufficient provision of new specialists in this field. We investigated the possible determinants of neurophobia among medical students and its influence on the intent to pursue neurology residency. From September 2021 to March 2022, an online questionnaire was distributed to medical students in Lithuania. It included questions about knowledge, confidence, interest, and teaching quality of various medical specialties (including neurology), as well as the willingness to choose neurology for residency. Eight hundred fifty-two students responded to the survey (77.2% female) - they rated neurology as significantly more difficult than other medical areas and lacked confidence in assessing patients with neurological problems (p < 0.001). However, neurology was selected as one of the most interesting subjects and was reportedly well-taught. The prevalence of neurophobia among respondents was 58.9%. Most of them (207, 87.7%) indicated that neurology professors positively affected their outlook towards this medical specialty - such experience was associated with lower odds of neurophobia (odds ratio (OR) = 0.383, 95% confidence interval (CI) = 0.223 to 0.658). Being less neurophobic (OR = 1.785, 95% CI = 1.152 to 2.767) and having conducted neurology research (OR = 2.072, 95% CI = 1.145 to 3.747) increased the odds of a student being willing to pursue a career in neurology. Neurophobia was frequent among students in Lithuania and was inversely related to the positive influence by neurology professors. Together with previous research experience in the field, low levels of neurophobia were associated with the inclination to enter neurology residency.


Martius flap harvest site: patient self-perception.
We elucidated patient perception of the external genitalia after Martius flap harvesting. We identified 8 women in whom a Martius interposition flap was used in association with transvaginal urethrolysis. Patients were contacted by an independent nurse and asked to evaluate the cosmetic appearance of the labium majus harvest site. They were also queried on any associated pain, numbness or altered sensation, or perceived interference with vaginal sexual relations. Of the 8 patients 2 (25%) believed that the harvest site appeared to be identical to its preoperative appearance, 2 (25%) believed that there were only minimal changes from the preoperative appearance, 1 (12%) believed that it appeared markedly different from the contralateral side and 3 (38%) stated that they had never performed self-examination. Of the 8 patients 1 (13%) complained of dyspareunia, 3 (38%) had intermittent discomfort in the harvest area 1 year after the operation and 5 (62%) perceived permanently decreased sensation or numbness at the harvest site. The Martius flap is not associated with a significant amount of perceived cosmetic disfigurement. It has relatively little effect on sexual relations. Postoperatively discomfort is minimal but there may be associated numbness or decreased sensation at the harvest site.


Transcatheter Aortic Valve Replacement: Procedure and Outcomes.
Initially, transcatheter aortic valve replacement (TAVR) was only used in patients with severe symptomatic aortic stenosis and prohibitive risk for surgical aortic valve replacement. Subsequently, TAVR was extended to patients with high and intermediate surgical risk. Recently, the results of randomized trials in low-surgical-risk patients showed superiority or noninferiority of TAVR versus surgical aortic valve replacement in this population. Procedural outcomes have been improved. Long-term durability of transcatheter heart valves remains to be confirmed. This article presents the evolution and current status of TAVR, with respect to the different types of devices and procedures as well as its outcomes.


Human cytomegalovirus induces apoptosis in promonocyte THP-1 cells but not in promyeloid HL-60 cells.
The effect of human cytomegalovirus (HCMV) infection on the viability of the cells in the monocyte/myeloid lineage was investigated. Two cell lines at different stages in the differentiation pathway, the less differentiated promyeloid HL-60 and the more differentiated promonocyte THP-1 cells, were used in this study. While the viability of THP-1 cells was significantly impaired by HCMV infection, the viability of HL-60 cells was not affected. The decrease in the viability of THP-1 cells appears to result from the increase in apoptosis following HCMV infection. Interestingly, HL-60 cells were more sensitive than THP-1 cells to the apoptotic effect of other apoptogenic agents such as ultraviolet irradiation and hydrogen peroxide. When HL-60 cells were induced to differentiate by treating cells with 12-O-tetradecanoyl-phorbol 13-acetate (TPA), HCMV infection induced an increase in apoptosis of the differentiated HL-60 cells by TPA. Therefore, HCMV-induced apoptosis in the cells of the myeloid/monocyte lineage appears to depend on the degree of cell differentiation.


Interaction of glyceraldehyde-3-phosphate dehydrogenase and heme: The relevance of its biological function.
GAPDH was speculated to function as a transient trap to reduce the potential toxicity of free heme by a specific and reversible binding with heme. Up to now, there has been lack of studies focused on this effect. In this paper, the efficiency of GAPDH-heme complex on catalyzing protein carbonylation and nitration, the cross-linking of heme to protein formation, and cytotoxicity of GAPDH-heme were studied. It was found that the binding of GAPDH could inhibit H2O2-mediated degradation of heme. Peroxidase activity of GAPDH-heme complex was higher than that of free heme, but significantly lower than that of HSA-heme. Catalytic activity of heme corresponded complex toward tyrosine oxidation/nitration was decreased in the order of HSA-heme, heme and GAPDH-heme. GAPDH also inhibited heme-H2O2-NO2- induced protein carbonylation. No covalent bond was formed between heme and GAPDH after treated with H2O2. GAPDH was more effective than HSA on protecting cells against heme-NO2--H2O2 induced cytotoxicity. These results indicate that binding of GAPDH inhibits the activity of heme in catalyzing tyrosine nitration and protects the coexistent protein against oxidative damage, and the mechanism is different from that of HSA. This study may help clarifying the protective role of GAPDH acting as a chaperone in heme transfer to downstream areas.


Distribution of serotonin in the brain of the mormyrid teleost Gnathonemus petersii.
The distribution of serotonin-immunoreactive neurons and fibers was studied in the highly developed brain of the weakly electric fish Gnathonemus petersii with the aid of specific antibodies against serotonin. Serotoninergic cell bodies occur in three regions: the raphe region of the brainstem, the hypothalamus, and the transition zone between the dorsal thalamus and the pretectum. Serotoninergic raphe neurons are clustered in three groups: nucleus raphes superior, intermedius, and inferior. The latter has not been described in other teleosts and thus might be the source of the serotoninergic innervation of specific mormyrid electrosensory brain regions. Most hypothalamic serotoninergic neurons have cerebrospinal-fluid (CSF)-contacting processes and thus belong to the paraventricular organ (PVO), which in Gnathonemus is located around a number of small infundibular recesses. The distribution of serotonin in the PVO precisely matches the distribution of dopamine, as described previously. Serotoninergic cells in the thalamopretectal transition zone also have been described in other teleosts, but not in other vertebrate groups, and thus seem to represent a teleostean specialization. Serotoninergic fiber density is especially high in the medial forebrain bundle and surrounding preoptic and hypothalamic regions as well as in several telencephalic and preoptic subependymal plexus. Serotoninergic fibers appear to be almost completely absent in the large and differentiated corpus and valvula cerebelli. Comparison with the literature on teleostean serotoninergic innervation patterns reveals several mormyrid specializations, including the absence of serotonin in large parts of the mormyrid telencephalic lobes, a differentiated innervation pattern of distinct electrosensory and mechanosensory subnuclei of the torus semicircularis, a refined serotoninergic lamination pattern in the midbrain tectum, and a prominent innervation of the electrosensory lateral line lobe, the associated caudal cerebellar lobe, and the electromotor medullary relay nucleus. A distinct innervation of several types of (pre)motor neurons, such as the Mauthner cells and facial motor neurons, has not been reported previously for other teleosts. Consequently, the distribution of serotoninergic fibers as well as neurons in the mormyrid brain is substantially adapted to the high degree of differentiation of its electrosensory and telencephalic brain regions, but serotoninergic innervation is not involved in the circuitry of the most impressive part of the mormyrid brain; i.e., its large corpus and valvula cerebelli.


Mild to moderate postnatal hydronephrosis--grading systems and management.
No universal guidelines exist for the management of patients with mild to moderate antenatal hydronephrosis (ANH). Unsurprisingly, practice patterns vary considerably with respect to recommendations for postnatal evaluation and follow-up imaging schedule. Although some clinical tools are available to specifically grade ANH and postnatal hydronephrosis, these are commonly used interchangeably with varying degrees of success. A universal classification system and nomenclature are needed to best identify patients at risk of renal deterioration, UTI and need for surgical intervention. We present our own approach to postnatal risk stratification and management, including recommendations regarding serial ultrasonography schedule, prophylactic antibiotics, voiding cystourethrogram and renal scintigraphy.


High-frequency vocalizations in Andean hummingbirds.
Hummingbirds possess a number of unique features. A recent report in Current Biology[1] showed that the Black Jacobin (Florisuga fusca), a Brazilian hummingbird in the Topazes clade, produces high-frequency vocalizations outside the known hearing range of birds. Here, we report that four hummingbird species in the Andean clade [2,3] also exhibit high-frequency vocalizations: the Ecuadorian Hillstar (Oreotrochilus chimborazo), with the highest fundamental frequency (mean F0 = 13.4 kHz), the Buff-tailed Coronet (Boissonneaua flavescens), Speckled Hummingbird (Adelomyia melanogenys) and Violet-tailed Sylph (Aglaiocercus coelestis). The presence of high-frequency vocalizations in hummingbirds belonging to different lineages poses the question of whether high-frequency vocalizations in this group of birds have been, so far, overlooked. These Andean species are closely related but live in two different habitats. Our characterization of ambient noise in each habitat suggests that the hummingbirds are exposed to different acoustic challenges, and that the frequency content of the vocalizations of the cloud-forest species is adapted accordingly. The function of these signals and the selection pressures driving their evolution remain unknown.


Central venous catheter sepsis: prognosis and treatment.
The purpose of this study was to evaluate the prognosis of patients with central venous catheter (CVC) sepsis, with particular reference to two therapeutic procedures, 1) CVC exchange over a guide wire and 2) removal of the catheter An evaluation was made of the clinical records of 22 cancer patients receiving total parenteral nutrition because of severe malnutrition and of 27 CVC-related septic episodes defined as growth of the same microorganism on the CVC and in peripheral blood. Bacteriological findings included Candidae n = 17, S albus n = 4, E Cloacae n = 4, Enterococcus n = 1 and P aeruginosa n = 1. In 22 cases the CVC was exchanged and in five cases it was removed on the clinical suspicion of CVC-related sepsis. Nineteen of the 22 patients had their blood culture rendered negative with CVC exchange and in three of the other five patients it was resolved bacteriologically after removal of the CVC. There was no clear effect of the CVC sepsis on the final outcome of the patients' illness. In fact, seven patients eventually died because of reasons apparently unrelated to the CVC sepsis-which had bacteriologically and clinically resolved-and seven patients recovered and were discharged in good condition despite the initial failure of CVC manipulation. The conclusion reached was that death should not occur as a result of CVC sepsis, provided this is properly identified and adequately treated. Since CVC change allows earlier recognition of the complication and effective treatment, it may be considered the therapy of choice in the management of suspected CVC sepsis.


High altitude medicine in China in the 21st century: opportunities and challenges.
China has the largest plateau, Qinghai-Tibet Plateau, where inhabited the most high altitude populations. Moreover, millions of people from plain areas come to the plateau for travel and work purposes and the number of the newcomers has been increasing every year. The hypoxic environment of plateau raised a series of related health issues in the new immigrants, so have created a special medical discipline - High Altitude Medicine. Over the past decades, researches on high altitude medicine have never being ceased in China, and lots of research findings have been reported. Application and practice of these achievements have greatly decreased the mobility and mortality of high-altitude diseases, however, there remained lots of questions to be elucidated. In view of this, the authors were granted a special project from the National Health and Family Planning Commission of China, and conducted a multi-center, prospective, on-scene high altitude medicine study for the acute mountain sickness. Some innovative findings were achieved, and the parameters for diagnosis and application conditions were proposed. Furthermore, the different diagnoses and treatment effects were compared, and a more standardized, reasonable scheme was drawn up. Regarding the unbalanced medical resources in the vast high altitude area, an application system for the public and the army has been established. In the 21st century, innovations in China and novel research approaches have provided great opportunities for the development of high altitude medicine. It is believed that the researchers in China are able to catch the opportunities and address the challenges.


Financial impact of delayed graft function in kidney transplantation.
Increased utilization of suboptimal organs in response to organ shortage has resulted in increased incidence of delayed graft function (DGF) after transplantation. Although presumed increased costs associated with DGF are a deterrent to the utilization of these organs, the financial burden of DGF has not been established. We used the Premier Healthcare Database to conduct a retrospective analysis of healthcare resource utilization and costs in kidney transplant patients (n = 12 097) between 1/1/2014 and 12/31/2018. We compared cost and hospital resource utilization for transplants in high-volume (n = 8715) vs low-volume hospitals (n = 3382), DGF (n = 3087) vs non-DGF (n = 9010), and recipients receiving 1 dialysis (n = 1485) vs multiple dialysis (n = 1602). High-volume hospitals costs were lower than low-volume hospitals ($103 946 vs $123 571, P < .0001). DGF was associated with approximately $18 000 (10%) increase in mean costs ($130 492 vs $112 598, P < .0001), 6 additional days of hospitalization (14.7 vs 8.7, P < .0001), and 2 additional ICU days (4.3 vs 2.1, P < .0001). Multiple dialysis sessions were associated with an additional $10 000 compared to those with only 1. In conclusion, DGF is associated with increased costs and length of stay for index kidney transplant hospitalizations and payment schemes taking this into account may reduce clinicians' reluctance to utilize less-than-ideal kidneys.


Correction: Chaby et al. Cross-Platform Evaluation of Commercially Targeted and Untargeted Metabolomics Approaches to Optimize the Investigation of Psychiatric Disease. Metabolites 2021, 11, 609.
In the original publication [...].


In vitro and in situ antimicrobial action and mechanism of glycinin and its basic subunit.
Glycinin, basic subunit and β-conglycinin were isolated from soybean protein isolate and tested for their antimicrobial action against pathogenic and spoilage bacteria as compared to penicillin. The three fractions exhibited antibacterial activities equivalent to or higher than penicillin in the next order; basic subunit>glycinin>β-conglycinin with MIC of 50, 100 and 1000 μg/mL, respectively. The IC(50%) values of the basic subunit, glycinin and β-conglycinin against Listeria\monocytogenes were 15, 16 and 695 μg/mL, against Bacillussubtilis were 17, 20, and 612 μg/mL, and against S. Enteritidis were 18, 21 and 526 μg/mL, respectively. Transmission electron microscopy images of L. monocytogenes and S. Enteritidis exhibited bigger sizes and separation of cell wall from cell membrane when treated with glycinin or basic subunit. Scanning electron microscopy of B. subtilis indicated signs of irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged cells or cellular debris when treated with glycinin or the basic subunits but not with penicillin. All tested substances particularly the basic subunit showed increased concentration-dependent cell permeation assessed by crystal violet uptake. The antimicrobial action of glycinin and basic subunit was swifter than that of penicillin. The cell killing efficiency was in the following descending order; basic subunit>glycinin>penicillin>β-conglycinin and the susceptibility of the bacteria to the antimicrobial agents was in the next order: L. monocytogenes>B. Subtilis>S. Enteritidis. Adding glycinin and the basic subunit to pasteurized milk inoculated with the three bacteria; L. monocytogenes, B. Subtilis and S. Enteritidis (ca. 5 log CFU/mL) could inhibit their propagation after 16-20 days storage at 4 °C by 2.42-2.98, 4.25-4.77 and 2.57-3.01 log and by 3.22-3.78, 5.65-6.27 and 3.35-3.72 log CFU/mL, respectively.


Consistency in ratings of clinical performance of the same students throughout medical school and internship.
Ratings of student clinical performance were analyzed to determine consistency of supervisor and coordinator judgements of the same students as they progressed through medical school and on into the internship. The results suggested that students were consistently and progressively rated higher.


Evaluation of control transcripts in real-time RT-PCR expression analysis during maritime pine embryogenesis.
In order to determine the suitability of reference or housekeeping genes as internal controls in real-time reverse transcriptase PCR (RT-PCR) assays for quantification of target mRNAs, we studied the levels of expression of four candidate reference genes in maritime pine by real-time RT-PCR. The expression levels obtained for glyceraldehyde-3-phosphate-dehydrogenase, 18S ribosomal RNA, eukaryotic translation initiation factor eIF4AII and ubiquitin in nine stages of embryo development revealed that none of the genes tested proved to be suitable as an internal control. Copy number quantification of the four transcripts showed an average relative variation of seven fold. We propose that the combination of a precise method for RNA quantification, internal controls for monitoring RT reaction and PCR efficiency and a robust external standard curve can guarantee a reliable absolute quantification of mRNA transcripts in real time RT-PCR. This approach may avoid the controversy in the use of housekeeping genes and may assume special significance in tissues undergoing developmental changes.


Site specific demethylation in the promoter of human gamma-globin gene does not alleviate methylation mediated suppression.
Human gamma A-globin genes with different patterns of methylation were synthesized in vitro. These methylated constructs were transfected into mouse L cells and their expression analyzed by S1-nuclease protection assays. We show that methylation downstream of +92 does not affect transcription while methylation downstream of -210 abolishes transcription. To test which of the six CpG dinucleotides between -210 and +92 plays a role in DNA methylation mediated suppression of transcription, we generated mutant gamma-globin genes which lack the three CpGs 5' to the cap site, the three CpGs 3' to the cap site, or all six CpGs. After in vitro methylation, we show that removal of methylated residues 5' or 3' to the cap site did not alleviate suppression, whereas removal of both 5' and 3' methylated residues restored partial expression. These results indicate that CpG methylation at different positions can cause suppression of expression and they are inconsistent with the hypothesis that site-specific demethylations in the promoter region can alleviate suppression. We propose that a minimum length of methylation-free DNA in the promoter area is the only requirement for expression of this promoter by ubiquitous transcription factors, and discuss these results with reference to methylation-free islands.


Tribolium castaneum Apolipophorin-III acts as an immune response protein against Bacillus thuringiensis Cry3Ba toxic activity.
In this study, a 2.1-fold Apolipophorin-III mRNA up-regulation was found in Tribolium castaneum larvae challenged with Bacillus thuringiensis Cry3Ba spore-crystal mixture. Knockdown of Apolipophorin-III by RNAi resulted in increased T. castaneum larvae susceptibility following Cry3Ba spore-crystal treatment, demonstrating Apolipophorin-III involvement in insect defense against B. thuringiensis. We showed that Apolipophorin-III participates in T. castaneum immune response to B. thuringiensis activating the prophenoloxidase cascade since: (i) phenoloxidase activity significantly increased after Cry3Ba spore-crystal treatment compared to untreated or Cry1Ac spore-crystal treated larvae and (ii) phenoloxidase activity in Cry3Ba spore-crystal treated Apolipophorin-III silenced larvae was 71±14% lower than that of non-silenced intoxicated larvae.


Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors.
Administration of anandamide (AEA) or 2-arachidonoylglycerol (2AG) induces CB1 coupling and activation of TRKB receptors, regulating the neuronal migration and maturation in the developing cortex. However, at higher concentrations AEA also engages vanilloid receptor TRPV1, usually with opposed consequences on behavior. Using primary cell cultures from the cortex of rat embryos (E18) we determined the effects of AEA on phosphorylated TRKB (pTRK). We observed that AEA (at 100 and 200 nM) induced a significant increase in pTRK levels. Such effect of AEA at 100 nM was blocked by pretreatment with the CB1 antagonist AM251 (200 nM) and, at the higher concentration of 200 nM by the TRPV1 antagonist capsazepine (200 nM), but mildly attenuated by AM251. Interestingly, the effect of AEA or capsaicin (a TRPV1 agonist, also at 200 nM) on pTRK was blocked by TRKB.Fc (a soluble form of TRKB able to bind BDNF) or capsazepine, suggesting a mechanism dependent on BDNF release. Using the marble-burying test (MBT) in mice, we observed that the local administration of ACEA (a CB1 agonist) into the prelimbic region of prefrontal cortex (PL-PFC) was sufficient to reduce the burying behavior, while capsaicin or BDNF exerted the opposite effect, increasing the number of buried marbles. In addition, both ACEA and capsaicin effects were blocked by previous administration of k252a (an antagonist of TRK receptors) into PL-PFC. The effect of systemically injected CB1 agonist WIN55,212-2 was blocked by previous administration of k252a. We also observed a partial colocalization of CB1/TRPV1/TRKB in the PL-PFC, and the localization of TRPV1 in CaMK2+ cells. Taken together, our data indicate that anandamide engages a coordinated activation of TRKB, via CB1 and TRPV1. Thus, acting upon CB1 and TRPV1, AEA could regulate the TRKB-dependent plasticity in both pre- and postsynaptic compartments.


Elastomeric separation to aid the diagnosis and treatment of anterior proximal caries lesions.
Elastomeric separation of anterior teeth for the diagnosis and treatment of small proximal lesions has been described. A case report illustrates the technique.