Use of an at-home multilevel pregnancy test and an automated call-in system to follow-up the outcome of medical abortion.
To assess the feasibility of using an at-home multilevel pregnancy test (MLPT) and interactive voice response (IVR) call-in system for remote follow-up of medical abortion. A prospective pilot study was conducted among women who had a medical abortion at up to 70 days at a clinic in Mexico City, Mexico, between June 1, 2015, and January 30, 2016. Participants took an MLPT at the initial clinic visit and another MLPT at home 2 weeks later. They were requested to report their MLPT results via the IVR system and attend the clinic for follow-up evaluation. Of 200 women considered for inclusion, 163 (81.5%) were included in the analysis. Only 10 (6.6%) of the 152 women who had a medical abortion on or before 63 days from last menstrual period reported MLPT results to the IVR system that required clinical evaluation to assess medical abortion outcome. The remaining 142 (93.4%) women in this group reported MLPT results that ruled out ongoing pregnancy (confirmed at clinical evaluation). Reported MLPT results ruled out ongoing pregnancy among the 11 women who had a medical abortion after 63 days; however, 1 (9%) had an ongoing pregnancy at clinical evaluation. Use of MLPTs and the IVR system provided a streamlined approach to follow-up after medical abortion.


Capillary electrophoresis for the analysis of the effect of sample preparation on early stages of Aβ1-40 aggregation.
Aggregation of the amyloid-β protein (Aβ) contributes to the neurodegeneration characteristic of Alzheimer's disease. Of particular importance are the early stages of aggregation, which involve the formation of soluble oligomers and protofibrils. In these studies, we demonstrate the potential for CE with UV detection using a polyethylene oxide separation matrix to identify the evolution of various oligomeric species of Aβ1-40 . To demonstrate the efficacy of this technique, UV-CE was utilized to compare two methods commonly used to prepare Aβ for aggregation experiments and their effect on the formation of early aggregates. SEC-purified Aβ1-40 initially contained more small species, including monomer, than did freshly dissolved Aβ1-40 pretreated with hexafluoroisopropanol. Strikingly, the lag time to oligomer formation for SEC-isolated Aβ1-40 samples was ∼23 h shorter compared to freshly dissolved Aβ1-40 samples. Furthermore, oligomers formed from the aggregation of SEC-purified Aβ1-40 persisted within solution for a longer period of time. These results indicate that the initial sample preparation has a drastic influence on the early stages of Aβ1-40 aggregation. This is the first report of the use of UV-CE with a separation matrix to study the effect of sample preparation on early aggregation of Aβ1-40 . UV-CE was also used in parallel with dot blot analysis and inhibitory compounds to discern structural characteristics of individual oligomer peaks, demonstrating the capacity of UV-CE as a complimentary technique to further understand the aggregation process.


Revision of the genus Ferkeria Roewer, 1947, with the description of a new species (Opiliones: Laniatores: Cosmetidae).
A new diagnosis for the cosmetid genus Ferkeria Roewer, 1947 is proposed. The type species, F. vestita Roewer, 1947 is redescribed and a new species, Ferkeria flavicoxae sp. nov., is described from Zongo, La Paz, Bolivia. The new species differs from the only other species of the genus by: yellow-white colored coxa IV (orange-brown in F. vestita); armature of scutal areas I-III with rounded tubercles (spiniform in F. vestita) and conspicuous tarsal process (reduced in F. vestita).


Informal settlements, the emerging response to COVID and the imperative of transforming the narrative.
The COVID pandemic has exposed several faultlines of urbanism in India. This paper is a narrative of the remarkable continuities between the past legacies of governance of informal settlements, pandemic response and emerging ideas of alternate urbanisms and their inability to address issues of inequity, exclusion and vulnerability. The pandemic and the resultant situation exposes the limits of the current policies, programming linked to informal settlements, their imagination of informality and outlines the urgent need to escape the trap of bracketing of informal settlements as an 'issue' within itself delinked from the dynamic and ever-changing processes of urbanization through community led policy responses and effective local governance. In the absence of effective state response, informal settlements authored their own script of coping with the challenges thrown by the pandemic; their presence, participation and centrality in scripting future policies is a much-needed transformation of the narrative.


Cerebral oxygenation monitor during head-up and -down tilt using near-infrared spatially resolved spectroscopy.
Reflectance near-infrared spectroscopy (NIRS) has become a suitable and easily manageable method to monitor cerebral oxygenation changes in presyncopal and syncopal symptoms caused by postural changing or standing. A new clinical tissue oxygenation monitor has been recently developed which measures absolute tissue haemoglobin saturation (Tissue Oxygenation Index, TOI) utilizing spatially resolved spectroscopy (SRS). The present study examined the effects of postural changes on cerebral oxygenation as reflected in SRS-NIRS findings. Cerebral oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and the TOI were recorded from both sides of the forehead in five healthy male subjects (age range, 28-40 years) during 90 degrees head-up tilt (HUT) and -6 degrees head-down tilt (HDT). Three series of measurements were carried out on separate days. O2Hb was decreased during HUT. TOI was significantly lower in HUT than in the supine position (SUP). There was no significant change in TOI during HDT. A significant session effect was observed in the left forehead TOI during SUP, but not in the right. SRS-NIRS measurements confirmed sub-clinical alterations of cortical oxygenation during HUT. NIRS data from the left side of the forehead, which may vary with cognitive or emotional activation, were more variable than those from the right side.


Search for hard X-ray emission from the galactic plane.
An X-ray survey experiment, consisting of four balloon-borne X-ray telescopes, was flown over Texas last year to search for hard X-ray emission (E(x) > 20 keV) from the Galaxy.


The use and limits of eye-tracking in high-fidelity clinical scenarios: A pilot study.
To explore the potential of mobile eye-tracking to identify healthcare students' area of visual interest and its relationship to performance ratings. Eye-tracking identifies an individual's visual attention focus, and has been used as a training technique in medicine and in nursing. In this study participants wore a point of view (PoV) camera within a spectacle frame during simulation education experiences. Thirty-nine final year nursing and paramedicine students individually participated in three 8 minute clinical simulations with debriefing using videoed eye-tracking recordings. Coloured dots on the video depicted the participant's pupil fixation on five targeted areas. Data extracted from the video camera were collated to report time spent on each target (their 'gaze'). The mean total gaze of expert designated targets in the environment for three 8 minute scenarios was 40-77%. Of 35 participants' focus on three main areas of interest, their priority was the patient's head (34%), the patient's trunk (24%) and their clinical assistant (5%), with significant differences between nursing and paramedic disciplines (P < 0.05). Objectively rated clinical performance improved significantly by the third scenario (P ≤ 0.001). Participants were positive regarding use of eye tracking during debriefing. Eye tracking has the potential to enhance debriefing and educational outcomes, although there are limitations to gaze capture in high fidelity environments and resource cost is high. Further study is warranted to enable better understanding of how expert clinicians achieve high levels of performance.


Cooperation is the key: the CCN biological system as a gate to high complex protein superfamilies' signaling.
Cellular signaling is generally understood as the support of communication between contiguous cells belonging to the same tissue or cells being far apart of each other, at a molecular scale, when the message emitted by the transmitters is traveling in liquid or solid matter to reach recipient targets. Subcellular signaling is also important to ensure the proper cell constitution and functioning. However cell signaling is mostly used in the first understanding, to describe how the message sent from one point to another one, will reach a target where it will be interpreted. The Cellular Communication Network (CCN) factors (Perbal et al. 2018) constitute a family of biological regulators thought to be responsible for signaling pathways coordination (Perbal 2018). Indeed, these proteins interact with a diverse group of cell receptors, such as integrins, low density lipoprotein receptors, heparan sulfate proteoglycan receptors (HSPG), and the immunoglobulin superfamily expressed exclusively in the nervous system, or with soluble factors such as bone morphogenetic proteins (BMPS) and other growth factors such as vascular endothelial growth factor, fibroblastic growth factor, and transforming growth factor (TGFbeta). Starting from the recapitulation of basic concepts in enzymology and protein-ligands interactions, we consider, in this manuscript, interpretations of the mechanistic interactions that have been put forward to explain the diversity of CCN proteins biological activities. We suggest that the cross-talks between superfamilies of proteins under the control of CCNs might play a central role in the coordination of developmental signaling pathways.


Extreme differences in charge changes during protein evolution.
The maintenance of a proper distribution of charged amino acid residues might be expected to be an important factor in protein evolution. We therefore compared the inferred changes in charge during the evolution of 43 protein families with the changes expected on the basis of random base substitutions. It was found that certain proteins, like the eye lens crystallins and most histones, display an extreme avoidance of changes in charge. Other proteins, like phospholipase A2 and ferredoxin, apparently have sustained more charged replacements than expected, suggesting a positive selection for changes in charge. Depending on function and structure of a protein, charged residues apparently can be important targets for selective forces in protein evolution. It appears that actual biased codon usage tends to decrease the proportion of charged amino acid replacements. The influence of nonrandomness of mutations is more equivocal. Genes that use the mitochondrial instead of the universal code lower the probability that charge changes will occur in the encoded proteins.


Deep learning-based multi-model approach on electron microscopy image of renal biopsy classification.
Electron microscopy is important in the diagnosis of renal disease. For immune-mediated renal disease diagnosis, whether the electron-dense granule is present in the electron microscope image is of vital importance. Deep learning methods perform well at feature extraction and assessment of histologic images. However, few studies on deep learning methods for electron microscopy images of renal biopsy have been published. This study aimed to develop a deep learning-based multi-model to automatically detect whether the electron-dense granule is present in the TEM image of renal biopsy, and then help diagnose immune-mediated renal disease. Three deep learning models are trained to classify whether the electron-dense granule is present using 910 electron microscopy images of renal biopsies. We proposed two novel methods to improve the model accuracy. One model uses the pre-trained ResNet convolutional layers for feature extraction with transfer learning which was firstly improved with skip architecture, then uses Support Vector Machine as the classifier. We developed a multi-model to combine the traditional ResNet model with the improved one to further improve the accuracy. Deep learning-based multi-model has the highest model accuracy, and the average accuracy is about 88%. The improved ReseNet + SVM model performance is much better than the traditional ResNet model. The average accuracy of the improved ResNet + SVM model is 83%, while the traditional ResNet model accuracy is only 58%. This study presents the first models for electron microscopy image classification of Renal Biopsy. Identifying whether the electron-dense granule is present plays an important role in the diagnosis of immune complex nephropathy. This study made it possible for Artificial Intelligence models assist to analyze complex electron microscopy images for disease diagnosis.


Adriamycin-induced antitumor response in lethally irradiated mice.
Lethally irradiated mice pretreated with a wide range of Adriamycin (ADM) doses were tested for their in vivo antitumor response against transplanted lymphoma cells. Tumor growth, as assessed by 125IUdR uptake, was markedly impaired by treatment with ADM by a variety of different administration schedules. This ADM-induced antitumor response was largely dose-dependent, occurred regardless of route of administration, and was detectable as late as 15-30 days following drug treatment. No genetic restriction could be found to regulate the development of this response, since tumor growth inhibition occurred in syngeneic as well as allogeneic tumor-host combinations. ADM-induced antitumor response did not appear to be due to direct antitumor action by the drug, but rather to some interaction with host immune mechanisms. Antimacrophage agents, such as silica or carrageenan, abrogated the response. The possible implication of different cells as effectors of this response is discussed.


Association of Glaucoma with Poor Quality of Sleep in an Ethiopian Glaucoma Population - A Comparative Cross-Sectional Study.
Glaucoma is a group of ocular disorders characterized by progressive optic nerve damage resulting in irreversible visual field defects. Poor quality of sleep in glaucoma patients could be explained by the reduction of the light input to the circadian system as a result of damage to photosensitive retinal ganglion cells in the retina. Information is limited on the association of poor quality of sleep with glaucoma in general and the Ethiopian glaucoma population in particular. The study aimed to explore the association between poor quality of sleep and glaucoma at a Tertiary Eye Care Center in Ethiopia. An institutional-based comparative cross-sectional study was conducted among 200 glaucoma and 201 non-glaucoma participants recruited by systematic random sampling. Each group was administered with a Pittsburgh Sleep Quality Index (PSQI) questionnaire. Stata-14 was employed for data analysis; an independent t-test was used to show the statistical difference in the global mean PSQI score for the two groups. A binary logistic regression model was applied to identify factors associated with poor quality of sleep. Statistical significance was declared at a 95% confidence interval and a p-value of <0.05. The prevalence of poor quality of sleep was 82.5% among the glaucoma population, which statistically differed (p<0.001) from the non-glaucomatous population (55.7%). Poor quality of sleep in glaucoma was associated with older age (adjusted odds ratio (AOR)=4.4, 95% confidence interval (CI): 1.5-5.4), depression (AOR=2.9, 95% CI: 1.1-7.3), visual impairment (AOR=3.9, 95% CI: 1.3-12.3) and severe glaucoma (AOR=2.5, 95% CI: 1.1-5.9). Poor quality of sleep was significantly higher in the glaucoma population compared to their non-glaucoma control. It was associated with older age, depression, visual impairment and advanced glaucoma. Incorporating psychiatric counseling into the existing glaucoma follow-up was recommended.


Functional testosterone receptors in plasma membranes of T cells.
T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors (AR). Here, we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR. Binding sites for testosterone on the surface of both CD4(+) and CD8(+) subsets of T cells are directly revealed with the impeded ligand testosterone-BSA-FITC by confocal laser scanning microscopy (CLSM) and flow cytometry, respectively. Binding of the plasma membrane impermeable testosterone-BSA conjugate induces a rapid rise (<5 s) in [Ca2+]i of Fura-2-loaded T cells. This rise reflects influx of extracellular Ca2+ through non-voltage-gated and Ni2+-blockable Ca2+ channels of the plasma membrane. The testosterone-BSA-induced Ca2+ import is not affected by cyproterone, a blocker of the AR. In addition, AR are not detectable on the surface of intact T cells when using anti-AR antibodies directed against the amino and carboxy terminus of the AR, although T cells contain AR, as revealed by reverse transcription-polymerase chain reactions and Western blotting. AR can be visualized with the anti-AR antibodies in the cytoplasm of permeabilized T cells by using CLSM, though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand. Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone, in contrast to cytoplasmic AR in human cancer LNCaP cells. These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway. By contrast, the cell surface receptors for testosterone are in a functionally active state, enabling T cells a nongenomic response to testosterone.


Investigation of the photosynthetic response of Chlorella vulgaris to light changes in a torus-shape photobioreactor.
An efficient use of light is essential to achieve good performances in microalgae cultivation systems. This can be challenging particularly under solar conditions where light is highly dynamic (e.g., day/night cycles, rapid changes in wind and weather conditions). Microalgae display different mechanisms to optimize light use efficiency. In the short term, when high light is encountered, several processes of photoprotection can be involved to avoid cell damages (e.g., xanthophyll cycle). In the long term, when cells are exposed to a different light intensity, pigment content changes, i.e., photoacclimation. The purpose of this study is to investigate the photosynthetic response of Chlorella vulgaris cultures grown in closed lab-scale, torus-shape photobioreactor under well-controlled light conditions, namely, constant and dynamic light transitions. Experiments were conducted in continuous mode with detailed characterization of the light attenuation conditions for each condition, as represented by the mean rate of photon absorption (MRPA), so as to characterize the time responses of the photosynthetic cells toward light changes. This enables to observe short-term and long-term responses with their own characteristic times. The mechanisms involved were found to be different between increasing and decreasing light transitions. Furthermore the MRPA was found a valuable parameter to relate the effect of light to biological responses (i.e., pigment changes) under constant light and dynamic light conditions.Key points• MRPA proved valuable to relate C. vulgaris responses to light changes.• A linear evolution was found between pigment content and MRPA in continuous light.• A rising PFD step induced fast protection and acclimation mechanisms.


1H/13C chemical shifts and cation binding dataset of the corticosteroid Prednisolone titrated with metal cations.
We here reported the 1H/13C chemical shifts, binding affinity and binding free energy of 1,4-pregnadiene-11β,17α,21-triol-3,20-dione (Prednisolone; Prd) interacting with metal cations. Six different Prd/Ni or Co mixtures were examined at different molar ratios (1:0, 1:0.1, 1:0.2, 1:0.3, 1:0.4 and 1:0.5). In this analysis, the 1H and 13C chemical shifts were measured for the Prd/cation mixtures using a Bruker AV 500 MHz spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany), equipped with a 5 mm z-gradient Prodigy BBO 500 MHz probehead at 298 K, and simulation of the 1H spectra were determined from the Daisy software package (Bruker BioSpin GmbH). Binding affinity and free energy values were deduced from the 13C NMR peak intensities involved in the cation interaction, for more insight on the steroid/cation interactions please see Magnesium and Calcium Reveal Different Chelating Effects in a Steroid Compound: A Model Study of Prednisolone Using NMR Spectroscopy [1].


Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. I.
Interferon-sensitive (745) and interferon-resistant (3C1-8) Friend leukemia cells (FLC) are highly tumorigenic for DBA/2 mice. The phenotype of interferon sensitivity or resistance does not change with in vivo passage. Daily administration of mouse interferon markedly enhanced the survival time of mice injected with either 745 or 3C1-8 cells. Use of quantitative methods for determining the number of FLC (colony formation in agarose and immunofluorescence) permitted us to show that potent, partially purified or highly purified mouse interferon (s.a. 0.5 to 1 X 10(9) u/mg protein) induced a 100- to 1,000-fold decrease in the number of tumor cells in the peritoneal cavity in the days following inoculation of 745 or 3C1-8 cells. Interferon decreased the number of FLC even when treatment was initiated at a time when tumor cells were multiplying exponentially in the peritoneal cavity. There was no evidence that interferon acted as an inducer of FLC differentiation in vivo. The finding that interferon was equally effective in mice inoculated with interferon-resistant cells as in mice inoculated with interferon-sensitive cells suggests that in this experimental system interferon does not act directly on the tumor cells, but that the interferon-induced antitumor activity is mediated by the host.


Combined modality therapy for rectal and colon cancer.
Combined modality therapy (CMT) with radiation therapy and chemotherapy plays an important role in the management of rectal cancer. Postoperatively, pelvic irradiation and 5-fluorouracil-based chemotherapy have been used to improve local control and survival for high-risk patients after local excision, as well as for patients undergoing abdominoperineal or low anterior resection. For patients treated preoperatively, CMT can also be used to facilitate sphincter-sparing surgery for distal rectal tumors. Preoperative CMT in conjunction with surgery and intraoperative radiation therapy has been useful for patients with locally advanced and recurrent rectal cancer as well. While chemotherapy has benefit for patients with stage III colon cancer above the peritoneal reflection, the role of CMT is less well defined. Retrospective reviews suggest improved local control and survival in subgroups of patients treated with postoperative radiation therapy and chemotherapy. Active areas of investigation in CMT for colorectal cancer include the integration of biologic predictors, radiation modulators, and novel systemic agents.


[Effect of the filler and liquid medium on the surface quality in the vibration treatment of medical equipment products].
The surface quality of products made from stainless steel 40--13 are determined mainly by methods and parameters used for their final processing. Investigation of technological characteristics of different fillers used in vibration processing and, as well, the influence of polyvinyl emulsion-water solution has shown that T-trihedral granules (made at the Moscow Plant of Abrasive Articles) can be the choice for the vibration processing of details of stainless steel 40 X 13. The polymeric component in the liquid technological medium, instead of Na2CO3 water-solution, permits a threefold increase in the metal removal, improves the surface roughness by 1.5 times, and considerably improves the surface reflectivity.


Von Hippel-Lindau syndrome with a rare complication of dilated cardiomyopathy: a case report.
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disease affecting multiple organs, with pheochromocytoma in 26% of cases. However, VHL syndrome with congestive heart failure and dilated cardiomyopathy as the primary clinical manifestations has been rarely reported. A 35-year-old male patient was admitted to the hospital with dyspnea. The patient had a history of cerebellar hemangioblastoma that had been resected, and a one-year history of hypertension. Echocardiography and cardiac magnetic resonance imaging demonstrated a dilated left ventricle, decreased systolic function, and nonischemic myocardial changes. Contrast-enhanced abdominal computed tomography showed pheochromocytoma, neoplastic lesions, and multiple cysts in the kidneys and pancreas. Genetic analysis revealed a missense mutation of the VHL gene, c.269 A > T (p.Asn90Ile), which was identified as the cause of the disease. Dilated cardiomyopathy and VHL syndrome type 2 were diagnosed. The patient was administered a diuretic, α-blocker, β-blocker, and an angiotensin receptor neprilysin inhibitor (ARNI), but refused pheochromocytoma resection. At the six-month follow-up, the patient was asymptomatic with improved cardiac function. Cardiac involvement is an atypical manifestation in VHL syndrome. Early diagnosis with genetic screening is essential for avoiding life-threatening complications associated with VHL. The management of this rare manifestation of VHL syndrome requires further investigation.


Bridging multiscale interfaces for developing ionically conductive high-voltage iron sulfate-containing sodium-based battery positive electrodes.
Non-aqueous sodium-ion batteries (SiBs) are a viable electrochemical energy storage system for grid storage. However, the practical development of SiBs is hindered mainly by the sluggish kinetics and interfacial instability of positive-electrode active materials, such as polyanion-type iron-based sulfates, at high voltage. Here, to circumvent these issues, we proposed the multiscale interface engineering of Na2.26Fe1.87(SO4)3, where bulk heterostructure and exposed crystal plane were tuned to improve the Na-ion storage performance. Physicochemical characterizations and theoretical calculations suggested that the heterostructure of Na6Fe(SO4)4 phase facilitated ionic kinetics by densifying Na-ion migration channels and lowering energy barriers. The (11-2) plane of Na2.26Fe1.87(SO4)3 promoted the adsorption of the electrolyte solution ClO4- anions and fluoroethylene carbonate molecules, which formed an inorganic-rich Na-ion conductive interphase at the positive electrode. When tested in combination with a presodiated FeS/carbon-based negative electrode in laboratory- scale single-layer pouch cell configuration, the Na2.26Fe1.87(SO4)3-based positive electrode enables an initial discharge capacity of about 83.9 mAh g-1, an average cell discharge voltage of 2.35 V and a specific capacity retention of around 97% after 40 cycles at 24 mA g-1 and 25 °C.


Molecular Detection of Avipoxvirus in Wild Birds in Central Italy.
Avipoxviruses (APVs) are important pathogens of both domestic and wild birds. The associated disease is characterized by skin proliferative lesions in the cutaneous form or by lesions of the first digestive and respiratory tracts in the diphtheritic form. Previous studies investigated these infections in symptomatic wild birds worldwide, including Italy, but data about the circulation of APVs in healthy avian wildlife are not available. The present study tested spleen samples from 300 wild birds without typical lesions to detect Avipoxvirus DNA. Overall, 43.33% of the samples scored positive. Aquatic birds were more frequently infected (55.42%) than other animals (26.40%), and in Anseriformes, high positivity was found (52.87%). The obtained results suggest that wild birds could be asymptomatic carriers of Avipoxviruses, opening new possible epidemiological scenarios.


Detection of benign hilar bile duct stenoses - A retrospective analysis in 250 patients with suspicion of Klatskin tumour.
The aim of this study was to identify clinical, laboratory and radiological parameters to distinguish benign from malignant stenoses of the proximal bile duct. Between 1997 and 2011, 250 patients were referred to our clinic with hilar bile duct stenoses suspicious for Klatskin tumour. Medical histories, clinical data, pre-interventional laboratory tests, imaging findings, as well as therapeutic approach and patient outcome were compared to final histological results. All data were retrieved from our prospectively maintained database and analysed retrospectively. We found benign bile duct lesions in 34 patients (13.6%). Among the entire study population, uni- and multivariate analyses of 18 clinicopathological parameters revealed that patient age, serum alkaline phosphatase, tumour marker CA19-9 and presence of tumour mass in computed tomography were independent predictors for malignant biliary stenoses (p < 0.05). Receiver operator characteristic curve showed that a CA19-9 serum level of 61.2 U/ml or more has a sensitivity, specificity and diagnostic accuracy for predicting the malignant nature of the hilar biliary stenoses of 74.6%, 80.0% and 83.5%, respectively. Surgical resection could be avoided by preoperative work-up and surgical exploration in 10 out of 34 patients with benign lesions. Rates of major liver resections performed were 66.7% in the benign lesion group and 90.7% in the Klatskin tumour group. Despite improvements of preoperative diagnostics, it remains difficult to differentiate between benign and malignant hilar bile duct stenosis. Even explorative laparotomy was not able to safely exclude Klatskin tumour in all cases and therefore major liver resection was inevitable.


Ontogeny of the T-cell antigen receptor within the thymus.
The expression of T-cell antigen receptors during T-cell ontogeny is an important issue that bears directly on such questions as where T-cell tolerance is acquired, at what stage T cells become susceptible to repertoire selection, and why most thymocytes die within the thymus. The thymus rudiment is colonized during days 11 and 12 of gestation, but it is not until day 19 that significant numbers of functional thymocytes are present. Although much is known about the ontogeny of function- and specificity-associated surface molecules such as Ly2 and MT4 (the murine equivalent of human T4) during this period, the ontogeny of the T-cell antigen receptors remains obscure. We have now addressed this question on three levels: DNA rearrangement, messenger RNA transcription and expression of cell-surface receptor-like proteins. Our results suggest that T-cell receptors are first expressed within the thymus around day 17 of gestation, independently of and probably before the expression of Ly2 and MT4. Furthermore, these data suggest that all major adult thymocyte subpopulations, including the small cortical cells, most of which die within the thymus, express receptors.


Synthesis of new antioxidant conjugates and their in vitro hydrolysis with Stratum corneum enzymes.
The aim of this study was to synthesize new precursors, combinations of well-known antioxidant molecules: resveratrol, lipoic acid and vitamin E to improve their photo-stability and to modulate their lipophylic character. Active antioxidants are available through a controlled release by the action of skin enzymes upon a topic application. Two conjugates are described, the combinations of resveratrol-lipoic acid (6) and resveratrol-vitamin E (10). Both compounds are new molecules. This work describes their synthesis, characterization, stability study and in vitro biohydrolysis. Stratum corneum enzymes efficiently hydrolysed in vitro precursor 6 and liberate both active molecules, resveratrol and lipoic acid over the period of 72 h. Precursor 10 was hydrolysed in vitro by combination of Stratum corneum enzymes and the cholesterol esterase. A simple technique of preparation of the human Stratum corneum hydrolases is also described.


IgG Stimulates the Formation of Neutrophil Extracellular Traps and Modifies Their Structure.
We studied the neutrophils and monocytes obtained from 37 patients with various inflammatory diseases such as psoriasis, acute infectious process in the abdominal cavity (acute appendicitis/abscess of the abdominal cavity, and acute cholecystitis), acute pancreatitis, and post-COVID syndrome after mild COVID infection. The number and the morphological structure of neutrophil extracellular traps (NET) as well as the effect of IgG on NET were examined. NET were visualized and counted by fluorescence microscopy with fluorescent dye SYBR Green. All the studied types of inflammation were accompanied by spontaneous formation of NET. After application of IgG, the number of NET doubled, their size increased, and transformation of net-like traps into the cloud forms was observed. The clouds form structure of the network is not capable of capturing pathogens with subsequent retraction, the products of its enzymatic degradation can be the factors of secondary alteration. The study results demonstrate a previously unknown mechanism of infection resistance.


Comparative study of the stridulatory sulcus, buccula and rostrum of the nymphs of Triatoma guazu Lent & Wygodzinsky, 1979 and Triatoma jurbergi Carcavallo, Galvão & Lent, 1998 by scanning electron microscopy (Hemiptera, Reduviidae).
The ultrastructural morphology of the ventral region of the head (rostrum and buccula) and proesternum (stridulatory sulcus) of nymphs from the 1st to 5th instars of Triatoma guazu Lent & Wygodzinsky, 1979 and Triatoma jurbergi Carcavallo, Galvão & Lent, 1998 was described. Morphological differences between the two species and of the five nymphal stages development of each species were observed. These structures showed systematic differential characteristics of the studied species and may be used to increase their taxonomic range.


Comparative evaluation of the efficacy and safety of two doses of terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis.
The aim of this study was to evaluate the safety and efficacy of oral terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis. A culture for Sporothrix schenckii was required for inclusion into this multicentre, randomized, double-blind, parallel-group study. Patients received either 250 mg b.i.d. or 500 mg b.i.d. oral terbinafine for up to a maximum of 24 weeks and were assessed up to 24 weeks post-treatment. The main efficacy outcome measure was cure, defined as no lesion and absence of adenopathy at the end of follow-up. Adverse events (AEs), laboratory tests, vital signs and ophthalmological examinations were also assessed. Sixty-three patients (14-85 years of age) were treated with 500 mg day(-1) (n = 28) or 1000 mg day(-1) terbinafine (n = 35). The majority of patients were cured after 12-24 weeks of treatment, and the response was dose-dependent throughout the study and at the end of follow-up. The cure rate was significantly higher in patients treated with 1000 mg day(-1) terbinafine compared with those treated with 500 mg day(-1) terbinafine (87% vs. 52%, respectively; P = 0.004). There were no cases of relapse after 24 weeks of follow-up in the 1000 mg day(-1) terbinafine group, compared with six relapses in the terbinafine 500 mg day(-1) group. Terbinafine was well tolerated and the frequency of drug-related AEs was slightly higher in the 1000 mg treatment group. Both doses of terbinafine were well-tolerated and effective for the treatment of sporotrichosis. The 1000 mg day(-1) terbinafine dose was more efficacious than 500 mg day(-1) in the treatment of cutaneous or lymphocutaneous sporotrichosis.


Single-step RT real-time PCR for sensitive detection and discrimination of Potato virus Y isolates.
Potato virus Y (PVY) has a worldwide distribution and infects several economically important crops from the Solanaceae family. The emergence and spread of the PVYNTN strain, which is the causative agent of potato tuber necrotic ringspot disease (PTNRD), has lead to large economic losses and highlighted the need for accurate discrimination of the different PVY strains. Detection and differentiation of PVY isolates is mainly based on a combination of ELISA, RT-PCR and bioassays; however, PVYNTN isolates are particularly difficult to differentiate from standard PVYN without the use of time-consuming bioassays. A strong correlation has been identified previously between the ability to induce PTNRD and the presence of a recombination point in the virus coat protein. An RT real-time PCR assay has been developed to enable detection of isolates with the recombination point, therefore, enabling rapid differentiation between potentially tuber necrotic PVYNTN isolates and standard PVYN isolates. The assay is also able to detect the presence of PVYO isolates. To aid with routine testing, immuno-capture and post-ELISA virus release were introduced; when coupled with RT real-time PCR the sensitivity of the assays were up to seven orders of magnitude higher than ELISA. The assay was shown to be a suitable method for rapid large-scale diagnostic testing of PVY in different types of plant material including tubers, and specific screening for potentially tuber necrotic recombinant isolates.


The effects of mental and physical stress on the incidence of skin disorders.
The effect of civil unrest and terrorism in Northern Ireland from 1969 on skin diseases which are generally accepted to be aggravated by stress and strain has been studied (1) by reporting cases making claims against the government for skin diseases developed as the result of violence and (2), studying changes in the pattern of skin diseases at skin clinics in Northern Ireland over the last 10 years. There has been little change in the pattern of skin diseases which could be attributed to mental or physical stress.


Efficacy and safety of tisagenlecleucel in adult Japanese patients with relapsed or refractory follicular lymphoma: results from the phase 2 ELARA trial.
Tisagenlecleucel yielded a high durable response rate in patients with relapsed/refractory (r/r) follicular lymphoma (FL) in the global phase 2 ELARA trial. Here, we report the efficacy, safety, and cellular kinetics of tisagenlecleucel in a subgroup of Japanese patients with r/r FL from ELARA. ELARA (NCT03568461) is a global single-arm trial of tisagenlecleucel in patients with r/r FL who received ≥ 2 prior lines of therapy. The primary endpoint was the complete response rate (CRR), and the secondary endpoints were the overall response rate, duration of response, progression-free survival, overall survival, safety, and cellular kinetics. As of March 29, 2021, nine Japanese patients were enrolled and received tisagenlecleucel with a median follow-up of 13.6 months (range, 10.5‒19.3). Per independent review committee, CRR was 100% (95% CI 63.1‒100). Within 8 weeks of infusion, cytokine release syndrome (CRS) of any grade was reported in 6 patients (66.7%); however, no grade ≥ 3 CRS or any grade serious neurological events or treatment-related deaths were observed. Tisagenlecleucel showed high efficacy and manageable safety in adult Japanese patients with r/r FL. Moreover, the clinical outcomes were similar to the global population, which supports the potential of tisagenlecleucel in Japanese patients with r/r FL.


Efficacy of bismuth-based quadruple therapy for eradication of Helicobacter pylori infection based on previous antibiotic exposure: A large-scale prospective, single-center clinical trial in China.
This study aims to evaluate the efficacy and safety of three bismuth-based quadruple regimens for eradication of Helicobacter pylori (H pylori) infection in a large number of H pylori-positive patients with or without previous eradication therapy. Consecutive adult patients with H pylori infection, regardless of previous eradication therapy, were eligible for the present study. Three bismuth-based quadruple regimens were selected according to the past history of antibiotics use: (A) esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth tartrate; (B) esomeprazole, amoxicillin, furazolidone, and colloidal bismuth tartrate; and (C) esomeprazole, doxycycline, furazolidone, and colloidal bismuth tartrate. All patients received a 14-day course of treatment, and 13 C/14 C urea breath test was utilized at four weeks after the completion of treatment to determine the H pylori eradication. Then, the eradication rates were calculated in terms of intention-to-treat (ITT) and per-protocol (PP) analyses. Adverse events (AEs) were recorded during the treatment. Overall, 1,226 patients were recruited, and 331, 57, and 838 patients were allocated to receive regimens A, B, and C, respectively. The H pylori eradication rates were 84.0%, 82.5%, and 82.9% (ITT) and 94.6%, 92.2%, and 93.7% (PP), respectively, in regimens A, B, and C. However, there was no significant difference among these three regimens. The incidence of AEs was 4.6% for all patients during the study, that is, 3.3%, 10.5%, and 4.7% for regimens A, B, and C, respectively. All AEs were mild and recovered at the follow-up visit. All three bismuth-based quadruple regimens based on the previous antibiotic use can achieve satisfactory eradication rates for H pylori infection and are safe.


Pattern reversal visual evoked potentials (white-black- and colour-black-PVEPs) in the study of eye dominance.
We investigated the influence of eye dominance scaled by 6 tests on the parameters (N80, P100 latency and N80-P100 amplitude) of the white-black-, green-black-, red-black- and blue-black-pattern visual evoked potentials (PVEPs) of 40 healthy subjects (20 males and 20 females) with normal visual acuity. The P100 latency of the white-black PVEPs was, for both sexes, shorter (P less than or equal to 0.001) in the PVEPs of the dominant eyes. This P100 latency shortening could also be verified for both right dominant and left dominant eyes with no significant difference between them. A consistent relationship, however, between the different degrees of eye dominance and the P100 latency shortening could not be established. In contrast to the P100 latency findings the N80 latencies of the white-black-PVEPs and the N80-P100 amplitudes did not show any significant differences with respect to eye dominance. Furthermore, the colour-black PVEPs did not present any differences of latency and amplitude depending on eye dominance. Thus our results give further electrophysiological evidence for eye dominance as a lateralized CNS phenomenon that is not influenced by colour.


Incorporation and release of fluorescein isothiocyanate-linked dextrans from a bead-formed macroporous hydrophilic matrix with potential for sustained release.
Freeze-thaw polymerization has been used to generate a bead-formed (100-3000 microns) macroporous hydrophilic matrix with potential for the sustained release of macromolecules. While the incorporation of FITC-dextrans marginally increased the equilibrium water content, their in vitro release profiles were characterized by an initial burst followed by a low but sustained release lasting > 21 d. The total cumulative release of FD-150 and the percentage of the incorporated FD-150 load subsequently released were reduced compared with FD-20S but for both dextrans these parameters could be enhanced by increasing the bead size and increasing the incubation temperature to 37 degrees C.


An Injectable Cytokine Trap for Local Treatment of Autoimmune Disease.
Systemic cytokine therapy is limited by toxicity due to activation of unwanted immune cells in off-target tissues. Injectable nanomaterials that interact with the immune system have potential to offer improved pharmacokinetics and cell specificity compared to systemic cytokine therapy by instead capturing and potentiating endogenous cytokine. Here we demonstrate the use of high aspect ratio polycaprolactone nanowires conjugated to cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. Nanowires are well tolerated in vivo over several weeks, incite minimal foreign body response and resist clearance. Nanowires conjugated with JES6-1, an anti-interleukin-2 (IL-2) antibody, were designed to capture endogenous IL-2 and selectively activate tissue resident regulatory T cells (Tregs). Together these nanowire-antibody matrices were capable of sequestering endogenous IL-2 in the skin and were successful in rebalancing local immune compartments to a more suppressive, Treg-mediated phenotype in both wild type and transgenic murine autoimmune disease models.


Patient-Perceived Patient-Centeredness During Pregnancy.
Although patient-centeredness is a pinnacle in high-quality healthcare, there is a lack of research measuring patient-centeredness from the perspective of the patient in the context of perinatal care. Therefore, the objectives of this study were to (1) measure patient-perceived patient-centeredness from pregnant people receiving prenatal care in Nova Scotia, and (2) explore potential correlates of patient-perceived patient-centeredness. Participants completed an e-survey through REDCap software. Questions comprised of the Patient-Perceived Patient-Centeredness (Revised) (PPPC-R) questionnaire and demographic questions. The PPPC-R total score was calculated. Descriptive statistics were calculated to describe the sample, and inferential statistics were conducted. Linear regression analysis was used to determine how the independent variables predicted the PPPC-R total score. A total of 98 patients participated in the survey to completion. The mean PPPC-R total score was 62.2 (SD 10.5), equivalent to a score of 3.45/4. No significant correlates of the PPPC-R total score were identified; however, trends were observed related to age, parity, Body mass index, race/ethnicity, and education. Participants in our study rated their clinicians' patient-centeredness very highly. There was no significant difference in PPPC-R score among pregnant people based on the independent variables we collected.


Effects of acute stress on the contents of catecholamines and neuropeptides in chromaffin tissues of the newborn rabbit.
The neuropeptides enkephalin (ENK), galanin (GAL) and neuropeptide Y (NPY) are abundantly expressed in the paraaortic body (PAB) and adrenal glands of the newborn rabbit. To examine whether these neuropeptides are affected by acute stress, we exposed neonatal rabbits to asphyxia, insulin-induced hypoglycemia, and reserpine. Asphyxia, caused by rebreathing for 60 min in an airtight box, reduced the content of catecholamines (CAs) in the adrenal glands and increased ENK-like immunoreactivity (-LI) in the PAB. Insulin-induced hypoglycemia reduced the content of CAs as well as ENK-LI in the adrenal glands. Reserpine caused a marked depletion of the CAs both in the PAB and in the adrenal glands. In contrast, reserpine did not cause any change in the contents of the neuropeptides in either organ. These data indicate that tissue levels of the neuropeptides GAL-LI and NPY-LI, coexisting with CA in the PAB and the adrenal glands, are not biochemically affected by asphyxia, hypoglycemia or reserpine, whereas tissue levels of ENK-LI are reduced by hypoglycemia and, to some extent, are increased by asphyxia. Furthermore, even the CAs in the PAB were unaffected by asphyxia and hypoglycemia. Also, while reserpine reduces CA content, peptide levels are unaffected.


Graves' disease with thyrotoxicosis following subacute thyroiditis.
Two patients are described who manifested the sequential occurrence of Graves' disease and subacute thyroiditis. The literature on this very unusual event is reviewed and speculation is offered on a possible mechanism linking thyroiditis to activation of Graves' disease in susceptible persons.


Expression and immunological characteristics of the surface-localized pyruvate kinase in Mycoplasma gallisepticum.
The widespread avian pathogen Mycoplasma gallisepticum is a causative agent of respiratory disease. The wall-less prokaryotes lack some tricarboxylic acid cycle enzymes, therefore, the glycolysis metabolic pathway is of great importance to these organisms. Pyruvate kinase (PK) is one of the key enzymes of the glycolytic pathway, and its immunological characteristics in Mycoplasma are not well known. In this study, the M. gallisepticum pyruvate kinase fusion protein (PykF) was expressed in a pET system. The full-length of the gene was subcloned into the expression vector pET28a(+) to construct the pET28a-rMGPykF plasmid, which was then transformed into Escherichia coli strain BL21 (DE3) cells. The expression of the 62 kDa recombinant protein of rMGPykF in E. coli strain BL21 (DE3) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Coomassie blue staining. Purified rMGPykF exhibited PK catalytic activity, which could reflect the conversion of NADH to NAD(+). Mouse anti-PykF antibodies were generated by immunization of mice with rMGPykF. Immunoblot and immunoelectron microscopy assays identified PykF as an immunogenic protein expressed on the surface of M. gallisepticum cells. Bactericidal assay showed that anti-rMGPykF antiserum killed 70.55% of M. gallisepticum cells, suggesting the protective potential of PykF. Adherence inhibition assay on immortalized chicken fibroblasts (DF-1) cells revealed more than 39.31% inhibition of adhesion in the presence of anti-rMGPykF antiserum, suggesting that PykF of M. gallisepticum participates in bacterial adhesion to DF-1 cells.


Sensitivity analysis of biomechanical effect in vertebral body of two different augmenters.
Transvertebral Bone Graft and Augmentation (TBGA) has achieved good clinical effects in the treatment of osteoporotic vertebral compression fractures (OVCFs). This study aimed to investigate the postoperatively biomechanical effects of TBGA and compare the biomechanical sensitivity of two different augmenters: a cylindrical enhancement device (CED) and bone cement. Finite element models of the spine segment T11-L3 were created, including one model based on normal segment and the other three with L1 augmentation for pathological conditions. Three treatments were simulated including CED implant treatment A, CED implant treatment B, and bone cement treatment. The stress distribution and maximum displacement of the four models under different treatments were analyzed. A method of linear fitting of dummy variables was used to analyze the sensitivity of biomechanical parameters to the degree of osteoporosis (DO) and load. The reduction of stress with increasing DO in augmented and adjacent vertebral bodies under bone cement augmentation was less than that under CED augmentation. The stress of augmented vertebral body and the adjacent vertebral body was most sensitive to extension and rotation loading conditions. As DO increasing, the bone cement augmentation significantly increased the stress level on the upper and lower endplates. When the degree of osteoporosis increased, CED outperforms bone cement in terms of the stress reduction in augmented vertebral and adjacent vertebral, which could be beneficial for avoiding re-fracture. Using TBGA to treat OVCFs, especially with Plan B method, the condition of the pathological spine is closer to the original status in terms of the sensitivity to stress and the spinal range of motion. The TBGA treatment is sensitive to lateral bending and torsion, therefore patients should be advised to avoid high-risk motions like lateral bending and rotation.


Two pontine micturition centers in the cat are not interconnected directly: implications for the central organization of micturition.
The urinary bladder muscle and its external urethral sphincter are innervated, respectively, by the parasympathetic preganglionic motoneurons in the sacral intermediolateral cell column and somatic motoneurons in Onuf's nucleus. Neurons coordinating the activity of these muscles during micturition and urinary continence are not located in the sacral cord but in two pontine regions, the medial (M)-region (or pontine micturition center) and the lateral (L)-region (or pontine storage center). The M-region excites the bladder muscle through projections to its motoneurons and inhibits the urethral sphincter through excitatory projections to sacral cord gamma-amino butyric acid (GABA)-immunoreactive interneurons, which, in turn, inhibit urethral sphincter motoneurons. The L-region, through direct projections, excites urethral sphincter motoneurons. The present study investigated whether there are interconnections between the M- and L-regions. Anterograde tracing injections in the M-region resulted in labeled fibers to the intermediolateral cell column containing bladder motoneurons but not to Onuf's nucleus. No specific projections were found to the L-regions or to the contralateral M-region. L-region injections resulted in distinct projections to the Onuf's nucleus but not to the sacral intermediolateral cell column. No specific projections were observed either to the M-region or to the contralateral L-region. In conclusion, the M- and L-regions have direct long fiber projections, respectively, to the motoneurons of the bladder muscle and the external urethral sphincter, but they do not influence one another through direct pathways. The results strongly suggest that the M- and L-regions represent separate functional systems that act independently.


Erratum to microRNA-155 inhibition attenuates myocardial infarction-induced connexin 43 degradation in cardiomyocytes by reducing pro-inflammatory macrophage activation.
[This corrects the article DOI: 10.21037/cdt-21-743.].


Surface topography of immunoglobulin molecules. I. Accessibility of aromatic chromophores of rabbit IgG.
Non-ionic detergent, Tween-20, was used in solvent perturbation studies of accessibility of aromatic amino acid residues in rabbit IgG molecules. It has been found that surface aromatic residues are localized in cervices inaccessible to perturbant molecules larger than ca. 10 A in diameter.


Sequential changes in lower extremity function after total knee arthroplasty.
The effectiveness of total knee arthroplasty (TKA) for recovering ambulation and balance functions has not been investigated in detail. The present study aimed to measure functional changes in the lower limb before and after TKA by measuring ambulation function with the 3 m Timed Up and Go (TUG) test and balance function using one-leg standing time (ST). The study included 137 patients (116 women and 21 men) with osteoarthritis of the knee who underwent primary TKA. The mean age of the patients was 74.4 years. The mean postoperative hospital stay for rehabilitation was 23.9 days. The TUG test and ST were performed preoperatively, 2 weeks postoperatively, at discharge, and 3, 6, and 12 months postoperatively. These results from these six measurements were also compared using one-way repeated measures analysis of variance. The TUG test and ST were significantly improved at 3 months after surgery. However, both the TUG test and ST did not improve further from 3 months to 6 months postoperatively or from 6 months to 1 year postoperatively. TKA is useful for restoring lower limb function, as both ambulation and balance functions were significantly improved 3 months after surgery. However, no further improvement in ambulation or balance function was recognized beyond 3 months.


Evaluation of endocrine disruption and gestational disorders in women residing in areas with intensive pesticide application: An exploratory study.
The proximity to areas of intensive pesticide application is a risk factor that favors xenobiotic exposure. Pesticides may interfere with hormonal function and cause alterations in the reproductive system, pregnancy complications, and adverse fetal development. We evaluated potential endocrine disruption and the evolution of the third trimester of pregnancy in women residing in a rural area of Argentina with intense pesticide applications, and the characteristics of their newborns. Blood samples were collected from healthy women in the third trimester of pregnancy during the pesticide spraying (SP) (n = 26) and nonspraying (NSP) (n = 27) periods. Plasma cholinesterase activity and cortisol and DHEA-S levels were lower in SP than in NSP. The percentage of preterm premature rupture of membranes was higher in SP than in NSP. Macrosomia at birth was17% in both periods. This study reinforces the importance of preventing potential cases of cumulative toxicity during the perinatal period through monitoring and epidemiological studies.


Ethnic and racial differences in mental health service utilization for suicidal ideation and behavior in a nationally representative sample of adolescents.
This study examined racial/ethnic differences in mental health treatment utilization for suicidal ideation and behavior in a nationally representative sample of adolescents. Data were drawn from the National Survey on Drug Use and Health. Participants included 4176 depressed adolescents with suicidal ideation and behavior in the previous year. Weighted logistic regressions were estimated to examine whether adolescent racial/ethnic minorities had lower rates of past-year treatment for suicidal ideation and behavior in inpatient or outpatient settings, while adjusting for age, depressive symptom severity, family income, and health insurance status. Among adolescents with any suicidal ideation and behavior, and suicide attempts specifically, non-Hispanic blacks and Native Americans were less likely than whites to receive outpatient treatment, and multiracial adolescents were less likely to be admitted to inpatient facilities. Apart from Hispanics, racial/ethnic minorities were generally less likely to receive mental health care for suicidal ideation, particularly within psychiatric outpatient settings. A pattern emerged with racial/ethnic differences in treatment receipt being greatest for adolescents with the least severe suicidal ideation and behavior. The cross-sectional data limits our ability to form causal inferences. Strikingly low rates of treatment utilization for suicidal ideation and behavior were observed across all racial/ethnic groups. Certain racial/ethnic minorities may be less likely to seek treatment for suicidal ideation and behavior when symptoms are less severe, with this gap in treatment use narrowing as symptom severity increases. Native Americans were among the racial/ethnic groups with lowest treatment utilization, but also among the highest for rates of suicide attempts, highlighting the pressing need for strategies to increase mental health service use in this particularly vulnerable population.


Application of numerical methods for diffusion-based modeling of skin permeation.
The application of numerical methods for mechanistic, diffusion-based modeling of skin permeation is reviewed. Methods considered here are finite difference, method of lines, finite element, finite volume, random walk, cellular automata, and smoothed particle hydrodynamics. First the methods are briefly explained with rudimentary mathematical underpinnings. Current state of the art numerical models are described, and then a chronological overview of published models is provided. Key findings and insights of reviewed models are highlighted. Model results support a primarily transcellular pathway with anisotropic lipid transport. Future endeavors would benefit from a fundamental analysis of drug/vehicle/skin interactions.


[Prostheses of the head of the radius. What outcome can be expected?].
We report our results after primary implantation of 30 radial head prostheses in a retrospective study from 1978 to 1996. If there was intraoperatively a remaining instability of the elbow after resection of the radial head, we implanted a prosthesis. The average age of our patients was 40.7 years. The results were evaluated concerning the recommendations of Radin and Riseborough. In 22 patients (73%) we found good to satisfactory results, in 8 patients (27%), there was a free range of motion. Heterotopic ossifications with a remarkable decrease in the range of motion were discovered in 3 patients (10%). The implant had to be removed in three (10%) patients (2 incorrect implantations, one broken prosthesis). To conclude, the primary implantation of a radial head prosthesis after a strict indication improves the clinical benefit for the patient. A correct surgical technique avoids unnecessary complications.


Streamlined in vitro screening system of synthetic signal peptides in Chinese hamster ovary cells for therapeutic protein production.
Increasing the screening efficiency and maintaining the N-terminal cleavage pattern are key factors in the development of an in vitro synthetic signal peptide screening system for high therapeutic protein production in Chinese hamster ovary (CHO) cells. This study improved the in vitro screening system of synthetic signal peptides in CHO cells for therapeutic protein production by modifying the expression vector. Incorporating a leaky stop codon with IgG transmembrane and cytoplasmic domains into the expression vector improved the proportion of high producers in establishing stable CHO cell pools. The selected signal peptides from stable CHO cell pools that were generated using degenerate codon-based oligonucleotides with a conserved polar carboxy-terminal domain in the native signal peptide showed similar N-terminal cleavage patterns to the native one. In addition, replacing native signal peptide with selected synthetic signal peptides did not influence the sialylated N-linked glycan formation and biological activity of therapeutic Fc-fusion glycoprotein in CHO cells. Thus, an in vitro synthetic signal peptide screening system can be used for therapeutic Fc-fusion glycoprotein production in CHO cells with an enhanced specific protein productivity while maintaining the N-terminal cleavage pattern similar to the native one.


[Effect of angiotensin II on potassium channels of ischemic ventricular myocytes of the guinea pig].
The experiments were carried out on guinea pig isolated ventricular myocytes by using whole-cell patch clamp. The effects of angiotensin II (Ang II) on potassium ion channels of acute ischemic myocytes were observed. Whole-cell patch clamp recordings showed that physiological potassium current, including delayed rectifier potassium current and inward rectifier potassium current were inhibited under the condition of simulated ischemia, and then further inhibited by treatment with Ang II. ATP-sensitive potassium currents were increased under simulated ischemia and were further enhanced by Ang II treatment.


A highly sensitive NIR fluorescence probe for hypoxia imaging in cells and ulcerative colitis.
Ulcerative colitis, a kind of inflammatory bowel disease (IBD), is caused by dysregulated immune response of intestinal bacteria. This chronic disorder can lead to a deficiency of O2 (hypoxia) in the colon microenvironment. Nitroreductase (NTR) is a highly expressed endogenous enzyme under hypoxia, so the detection of NTR can provide diagnostic information about ulcerative colitis. Herein, an ultrasensitive NTR-triggered fluorescence probe (WS-1-NO2) is developed for hypoxia imaging in ulcerative colitis. The probe shows a significant fluorescence enhancement (45-fold) after reacting with NTR, with an extremely low detection limit of 0.096 ng/mL. Furthermore, we apply it for fluorescence imaging of hypoxia in living cells, tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse models. We believe that the probe may be investigated as an effective potential tool for gaining insight into the hypoxia-relevant diseases, such as cancer and ulcerative colitis.


Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review.
Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose. To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS. We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain). The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability. TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes.


Hematological differentiation of bladder rupture and complete/partial urethral obstruction in castrated Hanwoo (Korean indigenous cattle) with urolithiasis.
This case report describes the hematological and radiological examination of urinary bladder rupture and complete urethral obstruction. associated with urolithiasis in Hanwoo. Hyponatremia, hypochloremia, azotemia, and hyperglycemia were observed in both urethral obstruction and urinary bladder rupture. However, cattle with urethral obstruction showed hyperkalemia and mild hyperglycemia, whereas cattle with bladder rupture showed marked hyperglycemia and normal potassium levels. In ultrasonography, the urethral obstruction showed a dilated bladder with a thick bladder wall. In contrast to previous literature, in this study, severe electrolyte changes such as severe hyponatremia, hypochloremia, and hyperkalemia occurred in a case of complete urethral obstruction.


Spectroscopic and metal binding properties of a de novo metalloprotein binding a tetrazinc cluster.
De novo design provides an attractive approach, which allows one to test and refine the principles guiding metalloproteins in defining the geometry and reactivity of their metal ion cofactors. Although impressive progress has been made in designing proteins that bind transition metal ions including iron-sulfur clusters, the design of tetranuclear clusters with oxygen-rich environments remains in its infancy. In previous work, we described the design of homotetrameric four-helix bundles that bind tetra-Zn2+ clusters. The crystal structures of the helical proteins were in good agreement with the overall design, and the metal-binding and conformational properties of the helical bundles in solution were consistent with the crystal structures. However, the corresponding apo-proteins were not fully folded in solution. In this work, we design three peptides, based on the crystal structure of the original bundles. One of the peptides forms tetramers in aqueous solution in the absence of metal ions as assessed by CD and NMR. It also binds Zn2+ in the intended stoichiometry. These studies strongly suggest that the desired structure has been achieved in the apo state, providing evidence that the peptide is able to actively impart the designed geometry to the metal cluster.


Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development.
Changes in mitochondrial function were studied in perfused liver from rats aged 24-365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage.


Treatment with midostaurin and other FLT3 targeting inhibitors is associated with an increased risk of cardiovascular adverse events in patients who underwent allogeneic hematopoietic stem cell transplantation with FLT3-mutated AML.
The addition of midostaurin to standard chemotherapy has improved survival in patients with FLT3-mutated AML. However, the impact of midostaurin and other FLT3 inhibitors (FLT3i) on cardiovascular adverse events (CAEs) has not been studied in patients who underwent allogeneic hematopoietic stem cell transplantation in a real-world setting. We reviewed 132 patients with AML who were treated with intensive induction therapy and consecutive allogeneic stem cell transplantation at our institution (42 FLT3-mutated AML and 90 with FLT3 wildtype). We identified treatment with midostaurin and/or FLT3i as an independent risk factor for CAEs not resulting in higher non-relapse mortality (NRM) or impaired overall survival (OS). Hence, close monitoring for CAEs is warranted for these patients.


[Observation on the immediate effects of acupuncture at Yanglingquan(GB 34) on passive movement in cerebral infarction patients].
To observe central immediate effect of acupuncture at Yanglingquan (GB 34) on passive movement of cerebral infarction paitents with hemiplegia by functional magnetic resonance imaging (fMRI) and provide reference for clinical treatment. With 1. 5 T MRI scanner, six cases of right cerebral infarction paitents with left hemiplegia in recovery stage were scanned during passive fingers movement before and after acupuncture at Yanglingquan (GB 34), which was controlled with sham-acupoint acupuncture to observe immediate activated part of the corresponding brain. The activated areas of the passive movement in all the patients were mainly motor sensory cortex on the right side. Compared with sham-acupoint, in the left anterior insula, in ferior frontal gyrus, central gyrus, fusiform gyrus, cerebellum, acupuncture at Yanglingquan (GB 34) has better central effect. These areas were involved with several brain networks. The acupuncture at Yan glingquan (GB 34) could promote recover of helmiplegia by regulating motor-related network.


Developmental and comparative aspects of nonsynaptic release by the egg-laying controlling caudodorsal cells of basommatophoran snails.
In an immunoelectron microscope study the postembryonic development of the cerebral caudodorsal cells (CDC) in the freshwater snail Lymnaea stagnalis was studied as well as the development of similar neurons in other basommatophoran families. The CDC of adult L. stagnalis control egg-laying and associated behaviors by releasing various peptides, including the ovulation hormone CDCH. The CDC release peptides from neurohemal axon terminals and from nonsynaptic release sites of axon collaterals. During postembryonic development the collateral system develops synchronously with the neurohemal area. The first collaterals appear in the cerebral commissure of juvenile snails (10 mm shell height; S = 10). Up to S = 30 they gradually increase in size and length and eventually run through the entire inner compartment. Secretory granules in both collaterals and neurohemal axon terminals increase in size as well. Immunoelectron microscopy combined with the TARI-method for the demonstration of exocytosis indicates that CDCH-release from collaterals and neurohemal terminals occurs already in S = 10; exocytosis of immunoreactive granule contents takes place from nonsynaptic release sites, unspecialized areas of the axolemma of the collaterals. Release activity in the collaterals gradually increases up to S greater than or equal to 20. Neurohemal release activity shows a similar picture except for a steep increase in adult snails. A distinct glial sheath, separating the neurohemal area from the collateral system, appears around S = 15. Representatives of three families of Basommatophora, viz. the lymnaeid L. ovata, the planorbid Planorbis planorbis, and the bulinid Bulinus truncatus possess a well-developed collateral system showing many signs of exocytosis. A glial sheath separates the collaterals from the neurohemal area. Secretory granules of the CDC in L. ovata stain weakly positive with the anti-CDCH antiserum. Since the other Basommatophora did not show immunoreactivity, the chemical structure of egg laying peptides in Basommatophora seems to be genus specific. Apparently the secretory activity of both the neurohemal area and the collateral system is not only important in the sexually mature animal, being involved in the control of egg laying and egg-laying behavior, but also in the juvenile snail. The finding of a collateral system in representatives of three basommatophoran families strongly indicates the importance of the system for the control of reproduction in basommatophoran snails in general.


Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach.
The optimal margin width and its influence on outcomes after hepatic resection for colorectal liver metastases is still controversial: a meta-analysis was conducted to analyze the impact of subcentimeter margin width on patient and disease-free survival after resection. A systematic search was performed, covering the last decade, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Relative risks (RRs) for patient and disease-free survival (DFS) were calculated after resection in relationship to a margin width >1 cm (R0 > 1 cm) and between 1 mm and 1 cm (R0 < 1 cm) using the DerSimonian and Laird random-effects model. Meta-regression was applied for covariate adjustment. Eleven observational studies were identified involving 2823 patients. Overall, 59.1% of patients were R0 < 1 cm and 40.9% were R0 > 1 cm. Meta-analysis showed that compared with patients with margins R0 > 1 cm, a R0 < 1 cm margin lead to decreased 1-, 3-, and 5-year DFS with a RR of 1.17 (95% confidence interval [CI] 1.07-1.27), 1.38 (95% CI 1.16-1.65), and 1.55 (95% CI 1.25-1.91), respectively, but patient survival was obviously affected (P > .05 in all cases). Patients with margins of R0 < 1 cm differ from those with R0 > 1 cm for greater proportions of multiple metastases (RR 1.43; 95% CI 0.25-1.61) and synchronous bowel disease (RR 1.42; 95% CI 0.8-1.92). Meta-regression showed that these two covariates had a significant impact on DFS but not on patient survival. A resection margin width >1 cm is desirable even if patient survival is at best only slightly affected by subcentimeter margin as a consequence of a decreased DFS. The presence of multiple metastases and synchronous bowel neoplasm represent potential study selection biases that significantly decrease DFS; well-conducted, matched analyses consequently are essential to clarify the issue.


'High-affinity' binding sites for glycine in synaptosomal-mitochondrial fractions of rat CNS-regions.
'High-affinity' binding mechanisms for glycine exist in synaptosome-enriched preparations of various regions of rat CNS. Such mechanisms may represent interactions of glycine with its synaptic receptors.


Intrauterine therapy of goitrous hypothyroidism in a boy with a new compound heterozygous mutation (Y453D and C800R) in the thyroid peroxidase gene. A long-term follow-up.
We report the results of intrauterine L-thyroxine therapy, and the long-term follow-up in a fetus who presented at 32 weeks' gestation with goitrous hypothyroidism, hyperextension of the neck, and polyhydramnios. Spontaneous delivery was possible and hypothyroidism improved. Molecular analysis revealed a new compound heterozygous mutation (Y453D/C800R) in the TPO gene.


ApoE deficiency exacerbates the development and sustainment of a semi-chronic K/BxN serum transfer-induced arthritis model.
The risk for developing cardiovascular disease is greater in patients with rheumatoid arthritis (RA) than in the general population. While patients with RA also have dyslipidemia, the impact of dyslipidemia on the severity of inflammatory arthritis and associated cardiovascular disease is unclear. Currently, there are conflicting results regarding arthritis incidence in apolipoprotein E (ApoE) deficient mice, which spontaneously exhibit both hyperlipidemia and atherosclerosis. Here, we utilize a distinct approach to investigate the contribution of a hyperlipidemic environment on the development of arthritis and atherosclerosis in mice lacking ApoE. K/BxN serum transfer-induced arthritis (STIA) was assessed in C57BL/6 (control) and ApoE(-/-) mice using clinical indices and immunohistochemical staining. Ankle synoviums were processed for flow cytometry. Aortic atherosclerosis was quantitated using Sudan IV staining. Serum cholesterol and cytokine levels were determined via enzymatic and luminex bead-based assays, respectively. ApoE(-/-) mice developed a sustained and enhanced semi-chronic inflammatory arthritis as compared to control mice. ApoE(-/-) mice had increased numbers of foamy macrophages, enhanced joint inflammation and amplified collagen deposition versus controls. The presence of arthritis did not exacerbate serum cholesterol levels or significantly augment the level of atherosclerosis in ApoE(-/-) mice. However, arthritic ApoE(-/-) mice exhibited a marked elevation of IL-6 as compared to non-arthritic ApoE(-/-) mice and arthritic C57BL/6 mice. Loss of ApoE potentiates a semi-chronic inflammatory arthritis. This heightened inflammatory response was associated with an increase in circulating IL-6 and in the number of foamy macrophages within the joint. Moreover, the foamy macrophages within the arthritic joint are reminiscent of those within unstable atherosclerotic lesions and suggest a pathologic role for foamy macrophages in propagating arthritis.


A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation.
Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a "real-world" population with agitation. We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy--the necessity for additional medication intervention for agitation (AMI)--as our primary outcome measure. Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples. Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective--at least in requiring AMI--than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.


The failure of conventional drug therapy in the management of infantile colic.
During five years, 97 young infants with colic were studied. One of us (J. C. O'D.) compared homatropine methylbromide plus phenobarbital in a 20% alcohol solution, and all of the individual components of that solution, to see which was most effective in the symptomatic relief of colic. Regardless of the child's age on entry into the study, conditions in no treatment group improved more rapidly than in those treated with a placebo.


Effects of triptolide on the sphingosine kinase - Sphingosine-1-phosphate signaling pathway in colitis-associated colon cancer.
Triptolide (TP) exhibits effective activity against colon cancer in multiple preclinical models, but the mechanisms underlying the observed effects are not fully understood. Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in the regulation of colon cancer progression. The aim of this study was to investigate the effect of TP on the sphingosine kinase (SPHK)-S1P signaling pathway in colitis-associated colon cancer. An azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model and the THP-1 cell line were used to evaluate the therapeutic effects and mechanisms of TP in colitis-associated colon cancer (CACC). Various molecular cell biology experiments, including Western blotting, real-time PCR and immunofluorescence, were used to obtain relevant experimental data. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was also established to detect the levels of S1P in tissue and plasma. In the AOM/DSS mouse model, TP treatment induced a dose-dependent decrease in tumor incidence and inhibited macrophage recruitment and M2 polarization in the tumors. TP also efficiently decreased the S1P levels and SPHK1/S1PR1/S1PR2 expression and significantly inhibited activation of the S1P-mediated phosphorylation of ERK protein in macrophages. The results indicated that TP might influence the recruitment and polarization of tumor-associated macrophages by suppressing the SPHK-S1P signaling pathway.


Long-term effects of drought on wild and cultivated plants in the Negev desert : II. Diurnal patterns of net photosynthesis and daily carbon gain.
The seasonal change in diurnal patterns of net photosynthesis and daily carbon gain is studied in relation to the plant water status of the irrigated and non-irrigated naturally growing desert species Hammada scoparia, Zygophyllum dumosum, Artemisia herba-alba and Reaumuria negevensis. Comparison is made to cultivated Prunus armeniaca. Under non-irrigated natural conditions Hammada scoparia, a C4 plant, showed one-peaked flat diurnal courses of CO2 uptake which changed into a pattern of a high morning peak of CO2 uptake or slightly two-speaked curves in the late dry season. In contrast, the C3 species Zygophyllum dumosum, Artemisia herba-alba and Prunus armeniaca changed from one-peaked to distinct two-peaked patterns. At the end of the dry season, non-irrigated plants showed respiration only. Reaumuria negevensis had one-peaked curves with a low level of CO2 uptake.There is no general relation between day-time CO2 gain and pre-dawn water potential for the investigated species. In order to characterize the effect of soil drought, the CO2 gain during day-time of non-irrigated plants is expressed as a percentage of the CO2 gain of the irrigated counterparts. After an initial period of minimal drought effect, the relative day-time CO2 gain decreases almost linearly with cumulative water stress as determined by the daily addition of pre-dawn water potentials for the non-irrigated plants since the last rainfall. The slope of decrease differs from species to species. The relation of daily CO2 gain to maximal net photosynthesis is discussed. Initially, at a good plant water status, the daily CO2 gain does not decrease in proportion to the maximal photosynthetic rates as a result of stomatal control at high photosynthetic activity. At increasing water stress the daily CO2 gain decreases more than proportionally to the decrease of the maximal rates.


Sex differences in Alzheimer's disease: plasma MMP-9 and markers of disease severity.
Studies have reported higher plasma matrix metalloproteinase-9 (MMP-9) levels in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Despite evidence that MMP-9 activity and its influence on AD pathophysiology may be modulated by sex hormones, sex differences in the association between MMP-9 and AD biomarkers and cognition have not been explored. Our sample included 238 amyloid-β (Aβ)-positive participants with MCI or AD dementia from the Alzheimer's Disease Neuroimaging Initiative (37.4% women, 74.6 ± 7.3 years). We used linear regression models to examine whether sex modified free and total plasma MMP-9 associations with CSF t-tau, p-tau181, and Aβ42. We used linear mixed effects models to examine whether sex modified total and free plasma MMP-9 associations with cognition, using longitudinal Mini-Mental Status Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) data. Total and free MMP-9 levels did not differ by sex, but AD dementia patients had higher total MMP-9 levels than participants with MCI (β = 0.06 [-0.11 to -0.01], p = 0.031). Sex modified the association of CSF t-tau with total (β = 128.68 [55.37 to 201.99], p < 0.001) and free MMP-9 (β = 98.61 [33.61 to 163.62], p = 0.003), whereby higher total and free MMP-9 correlated with higher CSF t-tau in women and lower CSF t-tau in men. Higher free MMP-9 correlated with lower CSF p-tau181 among men (β = -14.98 [-27.37 to -2.58], p = 0.018), but not women. In participants with MCI, higher free MMP-9 levels were associated with higher CSF Aβ42 among men (β = 26.88 [4.03 to 49.73], p = 0.022) but not women. In the overall sample, higher free and total MMP-9 at baseline predicted worsening MMSE scores in women (β = -2.10 [-3.97 to -0.27], p = 0.027 and β = -2.24 [-4.32 to -0.18], p = 0.035) but not men. Higher free MMP-9 correlated with worse ADAS-cog scores (β = 12.34 [3.02 to 21.65], p = 0.011) in women (β = 12.34 [3.02 to 21.65], p = 0.011) but not men with AD dementia cross-sectionally but correlated with worsening ADAS-cog scores longitudinally only in men (β = 8.98 [0.27 to 17.68], p = 0.042). MMP-9 may have more detrimental effects on AD-related pathological and cognitive changes in women. If replicated, our findings could help uncover potential mechanisms contributing to women's elevated susceptibility to AD.


Solvent effect on MCD of Fe(III) heme complexes: magnetic circular dichroism spectra of five-coordinated high-spin iron(III) protoporphyrin-IX-dimethylester in the visible region and their environmental effect. A characterization of the visible electronic transitions in Fe(III) high-spin porphyrins.
Magnetic circular dichroism (MCD) spectra were observed to characterize the nature of the visible bands for high-spin Fe(III) protoheme derivatives with p-nitrothiophenolate, p-nitrophenolate, and methoxy anion as the fifth ligands in several solvents. The visible MCD bands for p-nitrophenolate heme were very sensitive to the solvent polarity, but that those for p-nitrothiophenolate heme and methoxy heme were not dependent on solvent polarity. Thus, both the two visible MCD band positions and the magnitudes were dependent on ET value (a solvent polarity parameter) in the former complex, but not in the latter two complexes. The results are consistent with previously proposed electronic structures of high-spin Fe(III) heme complexes.


Recovery of photosynthesis after exposure of intertidal algae to osmotic and temperature stresses: comparative studies of species with differing distributional limits.
This study examines possible relationships between stress tolerance by marine algae and distributions of these species. The ability to recover photosynthetic activity following dehydration or temperature treatments was the assay used to evaluate stress tolerance, and Porphyra perforata, Rhodoglossum affine, Gelidium coulteri, and Smithora naiadum differed in thresholds of tolerance, even though plants were collected from low tidal sites.Limits of dehydration tolerance were well correlated with limits of tidal distribution for these species. Additionally, other high tidal species tolerated severe dehydration while subtidal and low tidal species were sensitive to dehydration. High tidal individuals of P. perforata were also more tolerant of dehydration than were low tidal thalli of P. perforata.Limits of high or low temperature tolerance were not well correlated with tidal elevation for any groups of algae studied. However, cold-tolerant species had more northerly extensions, and warm-tolerant species had more southerly distributions. Thus, differential tolerance to temperature extremes may be an important influence for latitudinal ranges of species.By comparing the experimentally determined thresholds of stress with distributions of species, we test the role of stress in influencing photosynthesis and ultimately distributions of marine algae.


Rb function is required for E1A-induced S-phase checkpoint activation.
It is widely accepted that adenoviral E1A exerts its influence on recipient cells through binding to the retinoblastoma (Rb) family proteins, followed by a global release of E2F factors from pocket-protein control. Our study challenges this simple paradigm by demonstrating previously unappreciated complexity. We show that E1A-expressing primary and transformed cells are characterized by the persistence of Rb-E2F1 complexes. We provide evidence that E1A causes Rb stabilization by interfering with its proteasomal degradation. Functional experiments supported by biochemical data reveal not only a dramatic increase in Rb and E2F1 protein levels in E1A-expressing cells but also demonstrate their activation throughout the cell cycle. We further show that E1A activates an Rb- and E2F1-dependent S-phase checkpoint that attenuates the growth of cells that became hyperploid through errors in mitosis and supports the fidelity DNA replication even in the absence of E2F complexes with other Rb family proteins, thereby functionally substituting for the loss of p53. Our results support the essential role of Rb and E2F1 in the regulation of genomic stability and DNA damage checkpoints.


A novel approach for an ECG electrode integrated into a transcutaneous sensor.
The integration of an ECG-electrode into a common transcutaneous sensor allows simple handling and leads to a reduction of the physiological stress of pre-term infants. Furthermore it may allow future replacement of an invasive method to measure the ECG under labour by a non-invasive one.


Human monocytes represent a competitive source of interferon-alpha in peripheral blood.
Interferon-alpha (IFN-alpha) has a critical role in antiviral immunity and plasmacytoid dendritic cells (pDCs) have been demonstrated as the principal IFN-alpha source after Toll-like receptor (TLR) 7 and 9 stimulation. Little is known about the contribution of pDC-independent IFN-alpha sources to total IFN-alpha production capacity of human peripheral blood. Using an array of pathogen associated molecular patterns (PAMPs), Poly(I:C)/Dotap represented the second strongest IFN-alpha stimulus in total PBMC. Poly(I:C)/Dotap induced three times more IFN-alpha, when compared to TLR7-stimulation (R848) and four times less, when compared to TLR9-stimulation. Dotap (mediator of cellular uptake) dramatically increased Poly(I:C)-induced IFN-alpha production. Sorting experiments and ELISpot assays revealed that monocytes and not myeloid DCs are the main IFN-alpha source after Poly(I:C)/Dotap stimulation. ELISpot analyses demonstrated the highest IFN-alpha spot numbers after Poly(I:C)/Dotap stimulation. Although pDCs produced highest IFN-alpha levels per cell, monocytes represent a competing IFN-alpha source in total PBMC due to their high frequency.


TDP-43: gumming up neurons through protein-protein and protein-RNA interactions.
Since the discovery that 43 kDa TAR DNA binding protein (TDP-43) is involved in neurodegeneration, studies of this protein have focused on the global effects of TDP-43 expression modulation on cell metabolism and survival. The major difficulty with these global searches, which can yield hundreds to thousands of variations in gene expression level and/or mRNA isoforms, is our limited ability to separate specific TDP-43 effects from secondary dysregulations occurring at the gene expression and various mRNA processing steps. In this review, we focus on two biochemical properties of TDP-43: its ability to bind RNA and its protein-protein interactions. In particular, we overview how these two properties may affect potentially very important processes for the pathology, from the autoregulation of TDP-43 to aggregation in the cytoplasmic/nuclear compartments.


Cytomegalovirus retinitis following corticosteroid overdose for Vogt-Koyanagi-Harada disease.
A 33-year-old patient was diagnosed with acute Vogt-Koyanagi-Harada (VKH) disease and was prescribed prednisolone (1 mg/kg/day) and azathioprine (2.5 mg/kg/day). She mistakenly took an excessively high dose (4 mg/kg/day) of prednisolone for 14 days. The erroneous dose of corticosteroids was progressively corrected. Several weeks after initial presentation, the patient developed a polymerase chain reaction-proven bilateral cytomegalovirus retinitis, with extensive occlusive arteritis in the right eye. Systemic immunosuppressive therapy was temporarily discontinued and viral retinitis was successfully managed with systemic and intravitreal ganciclovir. Corticosteroids were reintroduced to control recurrent VKH disease. Final visual acuity was 20/1000 in the right eye and 20/50 in the left eye.


Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice.
Exposure to di-(2-ethylhexyl) phthalate (DEHP) induces spermatogenic disturbance (SD) through oxidative stress, and affects the immune system by acting as an adjuvant. Recently, we reported that in mice, a low dose of DEHP, which did not affect spermatogenesis, was able to alter the testicular immune microenvironment. Experimental autoimmune orchitis (EAO) can be induced by repeated immunization with testicular antigens, and its pathology is characterized by production of autoantibodies and SD. In the present study, we investigated the effect of a low-dose DEHP on the susceptibility of mice to EAO. The exposure to DEHP-containing feed (0.01%) caused a modest functional damage to the blood-testis barrier (BTB) with an increase in testicular number of interferon gamma (IFN-γ)-positive cells and resulted in the production of autoantibodies targeting haploid cells, but did not affect spermatogenesis. While only single immunization with testicular antigens caused very mild EAO, the concurrent DEHP exposure induced severe EAO with significant increases in number of interferon gamma-positive cells and macrophages, as well as lymphocytic infiltration and serum autoantibody titer accompanied by severe SD. To summarize, the exposure of mice to the low-dose DEHP does not induce significant SD, but it may cause an increase in IFN-γ positive cells and modest functional damage to the BTB in the testis. These changes lead to an autoimmune response against haploid cell autoantigens, resulting in increased susceptibility to EAO.


Technicity as a quality indicator of excellence in gynaecology.
The objective of this study was to calculate the technicity index (TI) for hysterectomies at a tertiary care university hospital in Oman. This is a retrospective chart review of patients who had hysterectomies at Sultan Qaboos University Hospital (SQUH), a tertiary care university hospital. Profiles were reviewed for all patients who had hysterectomies at SQUH in the period 2003-2009. The cumulative frequencies for all types of hysterectomies were tallied and the year-specific TI was calculated. Overall, we enumerated a total of 258 hysterectomies, of which 6 (2.3%) were laparoscopic assisted hysterectomies, 42 (16.3%) vaginal hysterectomies, and 208 (80.6%) total abdominal hysterectomies. The average TI was 19% (48/258), and it ranged from 11% to 24%. The trend of change fluctuated over the years starting with 16% (2003) and increasing gradually during 2004-2006, but then declining again during 2007-2008 (trend P value 0.02). This low and fluctuating trend was mainly attributed to the inconsistency in the availability of trained surgeons and laparoscopic equipment. TI at our institution can be improved by increasing the number of minimally invasive hysterectomies through providing more trained surgeons and laparoscopic equipment.