Lobular neoplasia on core-needle biopsy--clinical significance.
Approximately 25% of all cases of atypical ductal hyperplasia (ADH) diagnosed on core biopsy of the breast are associated with ductal carcinoma in situ (DCIS) or invasive malignancy at the same site. As a result, surgical excision has become the standard of care for patients with ADH. In contrast, because data on the relation between breast malignancy and lobular neoplasia (LN) detected on core biopsy are limited, clinical management of patients with LN remains controversial. The goal of the current study was to determine the incidence of breast carcinoma at sites of core biopsy exhibiting LN compared with sites of core biopsy exhibiting ADH. The results of 2053 core biopsies were reviewed to identify cases of LN and cases of ADH. Follow-up findings on excisional biopsy were categorized as malignancy (DCIS or invasive malignancy) or no malignancy and were compared between the LN group and the ADH group. Mammograms and medical records were reviewed for patients with atypical findings on core biopsy. One hundred six (5.2%) of 2053 biopsy samples exhibited atypia on core biopsy. Among these 106 samples, ADH was found in 49 (46%), LN was found in 45 (42%), and both ADH and LN were found in 12 (12%). Malignant disease was detected on follow-up excisional biopsy in 22% of patients with ADH (9 of 41), 14% of patients with LN (3 of 21), and 33% of patients with both ADH and LN (4 of 12) on core biopsy. In the LN group, two cases of malignant disease were associated with lobular carcinoma in situ, and the third case was associated with atypical lobular hyperplasia. Mammographic and clinical features were unable to distinguish patients with malignant findings on excisional biopsy from patients without malignant findings. Malignant disease was found in a substantial percentage of excisional biopsy samples (14%) following the detection of LN on core biopsy. Thus, like patients with ADH, patients with LN on core biopsy could be considered candidates for surgical excision, which would allow full assessment of breast carcinoma risk and thereby facilitate the planning of prevention strategies.


Understanding the sources of mercury release from coal: A combined experimental and molecular simulation study.
Understanding the occurrence modes of mercury in coal is important as its release poses long-term adverse effects on the environment and human health during coal production and utilization. However, the matter still remains a subject of controversy due to differing results from direct and indirect analyses, which suggest various possible modes of occurrence for mercury in coal. Additionally, the experimental measurement of Hg concentration presents challenges, further contributing to the complexity of the issue. A comprehensive investigation of experiments and molecular simulations is conducted herein. Electron probe microanalysis and elemental mapping analysis show that elemental Hg is concentrated in framboidal pyrites while absent in organic matter. To understand the occurrence modes of mercury in inorganic and organic materials at the atomic level, molecular simulations are performed for Hg2+ adsorption and retention in MMT, pyrite, and kerogen slit nanopores. It is found that the inorganic MMT and pyrite surfaces have a greater adsorption capacity than the organic kerogen surface (pyrite > MMT > kerogen). The outer-sphere adsorption is mainly observed with at least one monolayer of water molecules exiting between the ion and mineral surfaces. MMT has the highest retention for Hg2+ transport as the self-diffusion coefficient is the smallest among the three slit pores (MMT < pyrite < kerogen). The high adsorption and retention originate from the strong Hg2+-mineral interaction. These results suggest that mercury in coal is most likely associated with inorganic minerals instead of organic matter.


Flexible endoscope visualization to assist in the removal of a string of 10 schwannomas at the cauda equina: technical case report.
Bead-like schwannomas at the cauda equina are rare but benign intraspinal tumors. They can involve multiple nerve roots and spread within the spinal canal, and open resection would cause significant trauma. The authors have successfully applied a novel minimally invasive technique for the total removal of such schwannomas. A 68-year-old woman presented with a 1-month history of left waist and leg pain. MRI demonstrated multiple intraspinal lesions located from L1 to S1. The diagnosis was bead-like schwannomas at the cauda equina. Two incisions were made at the T12 and L5 levels. A flexible endoscope was introduced into the spinal canal following hemisemilaminectomy under a microscope to identify the relationship between the tumors and the carrying nerves. After dissecting both cranial and caudal ends of the carrying nerve, the string of bead-like tumors was gently pulled out from the caudal end as a whole. The endoscope was reintroduced into the spinal canal to ensure complete tumor removal. The patient recovered quickly, and no tumor residual was found at postoperative MRI. Flexible endoscope-assisted visualization plus microscopic hemisemilaminectomy via 2 incisions is a feasible minimally invasive approach for selected patients with bead-like schwannomas at the cauda equina.


Angioedema: Clinical Presentations and Pharmacological Management.
Angioedema (AE) is a unique clinical presentation of an unchecked release of bradykinin. The origin of this clinical presentation can be either genetic or acquired. The outcome within the patient is subcutaneous swelling of the lower layers of the epidermis. Symptoms are most often localized to the upper airway or the gastrointestinal tract. A typical course resolves in 5 to 7 days, but in some patients, the clinical manifestations exist up to 6 weeks. Hereditary AE is rare and genetically linked, and typically, the patient has episodes for many years before diagnosis. Episodes of acquired AE may be drug induced, triggered by a specific allergen, or idiopathic. Angioedema can elicit the need for critical care interventions, for advanced airway management, or unnecessary abdominal surgery. The treatment for these patients is evolving as new pharmacological agents are developed. This article addresses subtypes of AE, triggers, pharmacology, and information for interdisciplinary team planning of individualized case management.


Appropriate Management of the Nonvigorous Meconium-Stained Newborn Meconium.
Before 2015, major changes in Neonatal Resuscitation Program (NRP) recommendations not supporting previously endorsed antepartum, intrapartum and postpartum interventions to prevent meconium aspiration syndrome were based on adequately powered multicenter randomized controlled trials. The 2015 and 2020 American Heart Association guidelines and 7th and 8th edition of NRP suggest not performing routine intubation and tracheal suctioning of nonvigorous meconium-stained newborns. However, this was given as a weak recommendation with low-certainty evidence. The purpose of this review is to summarize the evidence and explore the question of appropriate delivery room management for nonvigorous meconium-stained newborns.


Contamination and decontamination of Doppler probes.
Nosocomial infection occurs in 2-9% of patients undergoing vascular surgery and can lead to death, amputation or require complex revision surgery. Neck ties, pagers, stethoscopes and Doppler probes have been shown to carry pathogens. We measured bacterial colonisation of Doppler probes on a vascular unit and audited the effect of staff education at reducing this contamination. Bacteriological culture swabs were taken from hand-held Doppler probes on the vascular surgical ward and clinic. There was no protocol for cleaning the Doppler probes, so manufacturers were contacted for their recommendations. The results of cultures were presented to nursing and medical staff, who were then asked to clean the probes with alcohol wipes after each use. After an interval of 1 week, bacteriological cultures from the same Doppler probes was repeated. Fifty bacteriological cultures were performed from 10 Doppler probes over a 4-week period. Thirteen (26%) cultures were positive for diphtheroids, coliforms, coagulase-negative staphylococci and skin flora. After staff education, 42 further swabs were taken from the same probes; two positive cultures were obtained with scanty growth of skin flora (chi2 P < 0.05). Staff education and simple cleaning significantly reduces the contamination of hand-held Doppler probes and may help prevent nosocomial infection.


Radiation therapy in the treatment of Gorham disease.
An adolescent male with Noonan syndrome presented with a nonhealing fracture of the proximal right humerus. Over a 7-month period there was progressive loss of bone in this region, resulting in a flail arm at 9 months. Radiographic review was consistent with Gorham disease. In addition, there was significant bleeding in the soft tissues and pain. Radiation was delivered. Seven years passed, until the patient re-presented with right hemithorax near collapse secondary to chylothorax. A chest tube was placed with temporary relief, but significant effusion remained. Radiation was again administered, and by the end of therapy the chest tube was removed. The effusion has not recollected at last follow-up, which is now 6 months. The use of radiation in the treatment of Gorham disease has been demonstrated to have excellent palliative ability.


An improved variational approach to off-diagonal exciton-phonon coupling.
A state-of-the-art variational wave function incorporating Jastrow-type exciton-phonon correlations, the global-local Ansatz, is utilized to elucidate exciton-phonon correlations in a generalized form of the Holstein Hamiltonian with the simultaneous presence of diagonal and off-diagonal exciton-phonon coupling. Much lowered ground-state energies are found for the global-local Ansatz when compared with the previously studied Toyozawa Ansatz. A three-dimensional phase diagram spanned by the transfer integral and two forms of exciton-phonon coupling is given to illustrate polaronic self-trapping near the zone center.


Characteristics of glycosaminoglycans in chicken eggshells and the influence of disaccharide composition on eggshell properties.
Glycosaminoglycans (GAG) are linear, highly negatively charged polysaccharides that may perform an important role in biomineralization. GAG were isolated from chicken eggshell membranes and calcified shells. Disaccharide compositional analysis was performed using liquid chromatography-mass spectrometry. All 4 groups of GAG - hyaluronan (HA), keratan sulfate (KS), chondroitin sulfate (CS), and heparan sulfate (HS) - were detected in shell membranes and in calcified shells. HA was the most plentiful GAG in shell membranes, and CS was the most abundant in calcified shells. The CS present, in both membranes and calcified shells, consisted primarily of 6SCS-C, 4SCS-A, and 0SCS-0 disaccharides. Neither 4S6SCS-E nor 2SCS was detectable in shell components. Small amounts of 2S4SCS-B were detected in membranes and TriSCS, and 2S4SCS-B and 2S6SCS-D were detected in calcified shells. HS in calcified shells contained all disaccharides except for 2S6S. In shell membranes, HS contained primarily NS and 0S as well as small amounts of TriS, NS2S, NS6SHS, and 6S, but neither 2S6S nor 2S was detectable. The disaccharide composition of membrane CS, as well as membrane and calcified shell HS, were very similar in all eggshells. In contrast, the composition of calcified shell CS disaccharides was highly variable. In membranes, both HA and KS content showed a correlation with egg shape index. The 4SCS-A content correlated with eggshell strength, and 0SCS-0 correlated with eggshell strength and calcified shell thickness. HS content and its disaccharide composition showed no apparent correlation to properties of calcified shells. In calcified shells, only HS 6S correlated with egg shape index. This study suggests that GAG content and disaccharide composition of shell membranes might impact the quality of chicken eggshells.


Guava Detection and Pose Estimation Using a Low-Cost RGB-D Sensor in the Field.
Fruit detection in real outdoor conditions is necessary for automatic guava harvesting, and the branch-dependent pose of fruits is also crucial to guide a robot to approach and detach the target fruit without colliding with its mother branch. To conduct automatic, collision-free picking, this study investigates a fruit detection and pose estimation method by using a low-cost red⁻green⁻blue⁻depth (RGB-D) sensor. A state-of-the-art fully convolutional network is first deployed to segment the RGB image to output a fruit and branch binary map. Based on the fruit binary map and RGB-D depth image, Euclidean clustering is then applied to group the point cloud into a set of individual fruits. Next, a multiple three-dimensional (3D) line-segments detection method is developed to reconstruct the segmented branches. Finally, the 3D pose of the fruit is estimated using its center position and nearest branch information. A dataset was acquired in an outdoor orchard to evaluate the performance of the proposed method. Quantitative experiments showed that the precision and recall of guava fruit detection were 0.983 and 0.948, respectively; the 3D pose error was 23.43° ± 14.18°; and the execution time per fruit was 0.565 s. The results demonstrate that the developed method can be applied to a guava-harvesting robot.


Confirmation of hybridity using GISH and determination of 18S rDNA copy number using FISH in interspecific F(1) hybrids of Tecoma (Bignoniaceae).
Interspecific hybridization in Tecoma Juss. was conducted to develop novel forms for the nursery industry. We report fertile hybrids from the cross T. garrocha Hieron. (pistillate parent) × T. stans (L.) Juss. ex Kunth. Leaf morphology of the F(1) hybrids of T. garrocha × T. stans was intermediate between the parents. GISH also confirmed hybridity. The F(1) hybrids were successfully backcrossed to both parents and self-pollinated to produce BC and F(2) progeny. Tecoma garrocha , T. stans, and T. guarume A. DC. 'Tangelo' were self-fertile. The F(1) hybrids also were crossed with T. capensis (Thunb.) Lindl. and T. guarume 'Tangelo', resulting in three-species hybrids. FISH conducted on F(1) hybrids identified four copies of the 18S internal transcribed spacer region. Further analysis using FISH has the potential to provide information on the evolution of Bignoniaceae and the potential role of polyploidy.


A rapid, high-throughput, viral infectivity assay using automated brightfield microscopy with machine learning.
Infectivity assays are essential for the development of viral vaccines, antiviral therapies, and the manufacture of biologicals. Traditionally, these assays take 2-7 days and require several manual processing steps after infection. We describe an automated viral infectivity assay (AVIATM), using convolutional neural networks (CNNs) and high-throughput brightfield microscopy on 96-well plates that can quantify infection phenotypes within hours, before they are manually visible, and without sample preparation. CNN models were trained on HIV, influenza A virus, coronavirus 229E, vaccinia viruses, poliovirus, and adenoviruses, which together span the four major categories of virus (DNA, RNA, enveloped, and non-enveloped). A sigmoidal function, fit between virus dilution curves and CNN predictions, results in sensitivity ranges comparable to or better than conventional plaque or TCID50 assays, and a precision of ∼10%, which is considerably better than conventional infectivity assays. Because this technology is based on sensitizing CNNs to specific phenotypes of infection, it has potential as a rapid, broad-spectrum tool for virus characterization, and potentially identification.


Isolation and characterization of phage-displayed single chain antibodies recognizing nonreducing terminal mannose residues. 2. Expression, purification, and characterization of recombinant single chain antibodies.
Since phage-display technology is probably the best available strategy to produce antibodies directed against various carbohydrate moieties, we employed phage-display technology to generate human single chain antibodies (scFvs) using neoglycolipids as carbohydrate antigens. An accompanying paper in this issue describes how phage-displayed antibodies (phage Abs) that recognized nonreducing terminal mannose residues were isolated and characterized. In this study, four independent scFv genes, isolated by a mannotriose (Man3)-bearing lipid as an antigen as previously described, were used to construct expression vectors to produce soluble scFv proteins in quantity. Both bacterial and mammalian expression systems were used to produce glutathione S-transferase-scFv fusion proteins and scFv-human IgG1 Fc conjugates, respectively. The expressed scFv fusion proteins were purified to apparent homogeneity with yields of approximately 1 and 48 mg, from 1 L of bacterial culture and myeloma cell media, respectively. Surface plasmon resonance and ELISA analyses confirmed that purified scFv proteins showed Man3 specificity. The humanized antibody in scFv-Fc form, derived from clone 5A3, was a disulfide-liked dimer with a molecular mass of 108 kDa. According to a bivalent model, the kinetics parameters of its binding to Man3 were determined to be ka = 4.03 x 104 M-1 s-1, kd = 5.77 x 10-4 s-1, KA = 6.98 x 107 M-1, and KD = 1.43 x 10-8 M. This study thus established the foundation for isolation of carbohydrate-specific scFv genes and eventual production of humanized scFv-Fc type antibodies.


Glucuronidation of drugs in humanized UDP-glucuronosyltransferase 1 mice: Similarity with glucuronidation in human liver microsomes.
Uridine 5'-diphosphate-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that catalyze glucuronidation of various endogenous and exogenous substrates. Among 19 functional human UGTs, UGT1A family enzymes largely contribute to the metabolism of clinically used drugs. While the UGT1A locus is conserved in mammals such as humans, mice, and rats, species differences in drug glucuronidation have been reported. Recently, humanized UGT1 mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice) have been developed. To evaluate the usefulness of hUGT1 mice to predict human glucuronidation of drugs, UGT activities, and inhibitory effects on UGTs were examined in liver microsomes of hUGT1 mice as well as in those of wild-type mice and humans. Furosemide acyl-glucuronidation was sigmoidal and best fitted to the Hill equation in hUGT1 mice and human liver microsomes, while it was fitted to the substrate inhibition equation in mouse liver microsomes. Kinetic parameters of furosemide glucuronidation were very similar between hUGT1 mice and human liver microsomes. The kinetics of S-naproxen acyl-glucuronidation and inhibitory effects of compounds on furosemide glucuronidation in hUGT1 liver microsomes were also slightly, but similar to those in human liver microsomes, rather than in wild-type mice. While wild-type mice lack imipramine and trifluoperazine N-glucuronidation potential, hUGT1 mice showed comparable N-glucuronidation activity to that of humans. Our data indicate that hUGT1 mice are promising tools to predict not only in vivo human drug glucuronidation but also potential drug-drug interactions.


Studies towards the synthesis of bielschowskysin. Construction of the highly functionalized bicyclo[3.2.0]heptane segment.
A stereocontrolled approach for the construction of a highly functionalized bicyclo[3.2.0]heptane derivative embodying the bridged lactone present in the diterpene bielschowskysin is reported. The key step involves a stereoselective Cu(I)-catalyzed [2 + 2] photocycloaddition of a 1,6-diene embedded in a sugar derivative.


The use of blood culture bottles in endophthalmitis.
To study the use of blood culture bottles for culturing vitreous specimens in acute-onset postoperative infectious endophthalmitis cases. Forty-eight eyes of 48 patients with mean age of 66.4 +/- 14.7 years with postoperative endophthalmitis that occurred within 6 weeks after ocular surgery, presenting from June 2001 to January 2005, were retrospectively studied. Vitreous fluid specimens of these patients were cultured in blood culture bottles. The measured outcome is the yield of positive culture. Vitreous specimens yielded positive in 34 of 48 (70.8%) eyes with blood culture bottles. The most common organism isolated was Staphylococcus epidermidis in 17.6% (6/34) of cases. The direct inoculation of vitreous specimens into the blood culture bottles is easy to perform, with a high yield positive rate (70.8%). It may be an alternative to conventional culture media for culturing vitreous specimen in infectious endophthalmitis especially in clinics or hospitals that are unable to have adequate microbiology laboratory facilities.


Argiope hoiseni, a new species of the spider genus Argiope (Araneae, Araneidae) from Peninsular Malaysia based on morphology and molecular analyses.
A new species of Argiope Audouin 1826, A. hoiseni new species is described from Perak and Selangor, Peninsular Malaysia based on morphology and DNA information of the mitochondrial (16S rRNA, COI and COII) and nuclear-encoded (H3A, 18S rRNA) molecular markers. Epigynal structure suggested Argiope hoiseni to be similar to A. jinghongensis Yin, Peng Wang 1994, A. luzona (Walckenaer 1841), A. pulchella Thorell 1881 and A. taprobanica Thorell 1887. Molecular sequence data including the new species inferred that it is monophyletic with an intraspecific variation of 0.87-3.59 % based on the 16S+COI+COII+H3A dataset. Phylogenetic analyses also revealed insights into the evolutionary lineages of Argiope species in Southeast Asia as well as corroborated recent taxonomic changes and species synonymies associated with Argiope. Two new distribution records were also reported for A. chloreis Thorell,1877 and A. doleschalli Thorell, 1873 in Peninsular Malaysia.


Synaptic activity protects against AD and FTD-like pathology via autophagic-lysosomal degradation.
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein. In this study, we investigated the effect of synaptic stimulation on Tau pathology and synapses in in vivo and in vitro models of AD and frontotemporal dementia (FTD). We found that chronic DBS or chemically induced synaptic stimulation reduced accumulation of pathological forms of Tau and protected synapses, while chronic inhibition of synaptic activity worsened Tau pathology and caused detrimental effects on pre- and post-synaptic markers, suggesting that synapses are affected. Interestingly, degradation via the proteasomal system was not involved in the reduction of pathological Tau during stimulation. In contrast, chronic synaptic activation promoted clearance of Tau oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic activity resulted in opposite outcomes, with build-up of Tau oligomers in enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the negative effects of Tau in AD and FTD by acting on autophagy, providing a rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.


Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.
Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine. A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission. Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3β-Hydroxysteroid dehydrogenase (3βHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified. Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants presenting with salt-wasting are immediately started on steroid therapy to avoid life-threatening complications, before the correct diagnosis is reached. Physicians involved in the management of infants with salt-wasting of suspected hormonal origin should remember that, whenever practicable, a blood sample for the essential hormonal investigations should be collected before starting steroid therapy, to guide the subsequent diagnostic procedures and in particular to address the analysis of candidate genes.


Mortality and causes of death among patients with opioid use disorder receiving opioid agonist treatment: a national register study.
Mortality rates and causes of death among individuals in opioid agonist treatment (OAT) vary according to several factors such as geographical region, age, gender, subpopulations, drug culture and OAT status. Patients in OAT are ageing due to effective OAT as well as demographic changes, which has implications for morbidity and mortality. Norway has one of the oldest OAT populations in Europe. Because of the varying mortality rates and causes of death in different subgroups and countries, research gaps still exist. The aims of this study were to describe the causes of death among OAT patients in Norway, to estimate all-cause and cause-specific crude mortality rates (CMRs) during OAT and to explore characteristics associated with drug-induced cause of death compared with other causes of death during OAT. This was a national, observational register study. Data from the Norwegian Cause of Death Registry and the Norwegian Patient Registry were combined with data from medical records. We included all patients in the Norwegian OAT programme who died not more than 5 days after the last intake of OAT medication, between 1 January 2014 and 31 December 2015. In the 2-year observation period, 200 (1.4%) of the OAT patients died. A forensic or medical autopsy was performed in 63% of the cases. The mean age at the time of death was 48.9 years (standard deviation 8.4), and 74% were men. Somatic disease was the most common cause of death (45%), followed by drug-induced death (42%), and violent death (12%). In general, CMRs increased with age, and they were higher in men and in patients taking methadone compared with buprenorphine. Increasing somatic comorbidity, measured by the Charlson comorbidity index, reduced the odds of dying of a drug-induced cause of death compared with other causes of death. Both somatic and drug-induced causes of death were common during OAT. Improved treatment and follow-up of chronic diseases, especially in patients aged > 40 years, and continuous measures to reduce drug-induced deaths appear to be essential to reduce future morbidity and mortality burdens in this population.


Comparative study of separation between ex vivo prostatic malignant and benign tissue using electrical impedance spectroscopy and electrical impedance tomography.
Currently no efficient and reliable technique exists to routinely assess surgical margins during a radical prostatectomy. Electrical impedance spectroscopy (EIS) has been reported as a potential technique to provide surgeons with real-time intraoperative margin assessment. In addition to providing a quantified measure of margin status, a co-registered electrical impedance tomography (EIT) image presented on a surgeon's workstation could add value to the margin assessment process. To investigate this, we conducted a comparative study between EIS and EIT to evaluate the potential these technologies might have for margin assessment. EIS and EIT data was acquired from ex vivo human prostates using a multi-electrode endoscopic impedance acquisition probe. EIS and EIT show good predictive performance with a 0.76 and 0.80 area-under-curve (AUC), respectively, when considering discrete frequencies only. A machine learning (ML) algorithm is implemented to combine features, which improves the AUCs of EIS and EIT to 0.84 and 0.85, respectively. Single-step EIT takes significantly less time to reconstruct than multi-step EIT, yet provides similarly accurate classification results, making the single-step approach a potential candidate for real-time margin assessment. While the ML-based approach clearly exhibits benefits as compared to the single feature assessment, the decision to use EIS versus EIT is unclear since each approach performs better for different subsets of tissue classifications. The results presented in this paper corroborate our previous studies and present the strongest evidence yet that an intraoperative-capable impedance probe can be used to distinguish benign from malignant prostate tissues. An in vivo study with a large cohort will be necessary to definitively determine the preferred approach and to show the clinical effectiveness of using this technology for margin assessment.


Persistent cytogenetic abnormalities in patients undergoing intensive chemotherapy for acute myeloid leukemia.
We evaluated the impact of bone marrow sample characteristics on the detection of persistent cytogenetic abnormalities (PCA) following induction chemotherapy for acute myeloid leukemia (AML). PCA's were identified in 20.4% of patients and were more common with complete remission without count recovery (CRi) vs. those with count recovery (CR, 45.8 vs. 13.5%, p = .001), with >2% blasts vs. ≤2% blasts (42 vs. 12%, p = .001) and with hypocellular trephine biopsies relative to those with normo/hypercellular biopsies (42.1 vs. 17.3%, p = .03), although in a multivariate analysis only CRi and blast count >2% were independently associated with a PCA. PCA's were not observed in patients with favorable risk karyotype. Amongst patients with intermediate and unfavorable risk karyotypes PCA were not associated with differences in overall or, amongst non-transplanted patients, relapse free survival. Thus, although PCAs are common post-induction it is unclear whether they provide any independent prognostic information beyond the diagnostic karyotype.


An obstructive bicuspid aortic valve in the setting of tetralogy of Fallot with pulmonary atresia: a rare combination.
As far as we are aware, a bicuspid aortic valve has not previously been reported in the setting of tetralogy of Fallot and pulmonary atresia. We describe this association in a newborn who presented with a murmur and cyanosis. Echocardiography showed tetralogy of Fallot with pulmonary atresia, and also a moderately stenotic bicuspid aortic valve. The patient underwent open-heart surgery guided by transesophageal echocardiography. Postoperatively, there was only mild obstruction across both outflow tracts. We have also reviewed the pertinent data from our Jesse E. Edwards Registry of Cardiovascular Disease to establish the incidence of bicuspid aortic valve in the setting of obstruction of the right ventricular outflow tract, finding the association in no patients with pulmonary atresia and tetralogy of Fallot, in 0.7% of those with tetralogy of Fallot and pulmonary stenosis, but in 6.6% of those with pulmonary atresia and intact ventricular septum.


Vaginoplasty in Male-to-Female Transsexual Surgery: A Training Concept Incorporating Dissection Room Experience to Optimize Functional and Cosmetic Results.
Learning a new technique, even for an established surgeon, requires a learning curve; however, in transsexual surgery especially, there is a lack of professional and public tolerance for suboptimal aesthetic and functional results due to a learning curve. In this context, we have tried to build a learning concept for vaginoplasty that includes four steps: (i) formal identification of the surgical steps in order to provide both measure of surgical process and measures of outcomes; (ii) training on cadavers with expert assistance; (iii) performing the live surgery with assistance from expert; and (iv) performing the surgery alone. Herein, we emphasize the second step of our learning concept. Between September 2013 and December 2013, 15 cadavers were operated on by an established surgeon learning vaginoplasty under assistance from two expert practitioners. Mean global time and mean time necessary to perform each step of the operation were recorded by the experts. Intraoperative complications were systematically registered. The final depth and diameter of the neaovaginal cavity were precisely measured. For each cadaver, the aesthetic results were assessed by one of the experts. Mean total operating time was 179 ± 34 minutes and decreased from 262 minutes for the first training attempt to 141 minutes for the last one. Intraoperative expert correction included modification of the scrotal triangular flap design and change of position of the urethra: This happened during the first training. No lesion of the urethra or of the anus occurred. The two experts judged the outcomes as excellent in seven cases, very good in four cases, good in two cases, and fair in two cases. Despite the numerous reports on vaginoplasty in the literature, there is a real lack of published information on the learning curve of this operation. We make the hypothesis that introducing a learning concept with assistance from expert practitioners at the beginning of the surgeon's experience can optimize both the duration of his learning curve and reduce the risk of major complications.


7-Hydroxystaurosporine-induced apoptosis in 9L glioma cells provides an effective antigen source for dendritic cells and yields a potent vaccine strategy in an intracranial glioma model.
On the basis of recent studies indicating that tumoral apoptotic bodies may provide a potent source of antigen for delivery to antigen-presenting cells, as well as observations that signal transduction modulation may constitute a promising approach for inducing glioma cell apoptosis, we explored the efficacy of vaccination with glioma apoptotic body-pulsed dendritic cells (DCs) for inhibiting tumor growth in the syngeneic 9L glioma/Fischer rat model. For induction of apoptosis, 7-hydroxystaurosporine (UCN-01) (200-300 ng/ml), a selective protein kinase C inhibitor, was co-incubated with 9L cells in vitro for 72 or 96 hours. After this pretreatment period, glioma cells and DCs were mixed, and the interaction between DCs and apoptotic 9L tumor cells was assessed using two-color flow cytometry. In a series of experiments, the efficacy of vaccination strategies using DCs co-cultured with apoptotic 9L cells was then examined in animals harboring intracranial tumors. Pretreatment of 9L cells with UCN-01 resulted in approximately 50% of cells' being observed to undergo apoptosis as compared with less than 3% of controls. After subsequent co-culture, two-color flow cytometry demonstrated a time-dependent physical association of DCs with the apoptotic glioma cells. Survival in animals harboring intracranial tumors was significantly longer for the animals treated with a glioma apoptotic body-pulsed DC vaccine than in the animals that received apoptotic glioma cells and DCs alone or vehicle (i.e., the controls), especially those that underwent a sequential vaccination strategy (P < 0.0001). Long-term survival (>90 d) was demonstrated in 6 (75%) of 8 animals that underwent this vaccination approach versus 0 (0%) of 16 controls. In contrast, no survival benefit was observed in animals that received DCs that were co-cultured with vehicle-treated (non-apoptotic) 9L cells. Three of four long-term survivors that were rechallenged intracranially with tumor cells also survived over the long term. These studies suggest that induction of apoptosis in glioma cells by use of UCN-01 may promote the uptake of tumor antigens by DCs. This finding is important because apoptotic body-stimulated DCs may hold promise in promoting a host response against an established intracranial glioma, particularly if the parameters for apoptotic induction, duration of co-culture, and vaccination can be optimized.


Physiology of the widespread pulsating soft coral Xenia umbellata is affected by food sources, but not by water flow.
Coral energy and nutrient acquisition strategies are complex and sensitive to environmental conditions such as water flow. While high water flow can enhance feeding in hard corals, knowledge about the effects of water flow on the feeding of soft corals, particularly those pulsating, is still limited. In this study, we thus investigated the effects of feeding and water flow on the physiology of the pulsating soft coral Xenia umbellata. We crossed three feeding treatments: (i) no feeding, (ii) particulate organic matter (POM) in the form of phytoplankton and (iii) dissolved organic carbon (DOC) in the form of glucose, with four water volume exchange rates (200, 350, 500 and 650 L h-1) over 15 days. Various ecophysiological parameters were assessed including pulsation rate, growth rate, isotopic and elemental ratios of carbon (C) and nitrogen (N) as well as photo-physiological parameters of the Symbiodiniaceae (cell density, chlorophyll-a and mitotic index). Water flow had no significant effect but feeding had a substantial impact on the physiology of the X. umbellata holobiont. In the absence of food, corals exhibited significantly lower pulsation rates, lower Symbiodiniaceae cell density and lower mitotic indices compared to the fed treatments, yet significantly higher chlorophyll-a per cell and total N content. Differences were also observed between the two feeding treatments, with significantly higher pulsation rates and lower chlorophyll-a per cell in the DOC treatment, but higher C and N content in the POM treatment. Our findings suggest that the X. umbellata holobiont can be viable under different trophic strategies, though favouring mixotrophy. Additionally, the physiology of the X. umbellata may be regulated through its own pulsating behaviour without any positive or negative effects from different water flow. Therefore, this study contributes to our understanding of soft coral ecology, particularly regarding the competitive success and widespread distribution of X. umbellata.


Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients.
Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01-2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07-3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03-5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45-10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.


Inhibitors of hepatic mixed function oxidase. 3. Inhibition of hepatic microsomal aniline hydroxylase and aminopyrine demethylase by 2,6- and 2,4-dihydroxyphenyl alkyl ketones and related compounds.
A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor. In the 2,4 series, activity against aniline hydroxylase was poor or absent in most cases. tthe most potent inhibitor was 5-ethyl-2,4-dihydroxyacetophenone (31). In contrast, high activity against aminopyrine demethylase was frequently displayed in this series, 3,5-dibromo-2,4-dihydroxypropiophenone (36) showing greatest inhibitory potency. The effects of some compounds on hexobarbital sleeping times and zoxazolamine paralysis times in mice were also examined.


In-vivo oxidized albumin- a pro-inflammatory agent in hypoalbuminemia.
Hypoalbuminemia of Hemodialysis (HD) patients is an independent cardiovascular risk factor, however, there is no mechanistic explanation between hypoalbuminemia and vascular injury. In the event of oxidative stress and inflammation to which HD patients are exposed, albumin is oxidized and undetected by common laboratory methods, rendering an apparent hypoalbuminemia. We wanted to show that these circulating modified oxidized albumin molecules cause direct vascular damage, mediating inflammation. Once these in-vivo albumin modifications were reduced in- vitro, the apparent hypoalbuminemia concomitantly with its inflammatory effects, were eliminated. Albumin modification profiles from 14 healthy controls (HC) and 14 HD patients were obtained by mass spectrometry (MS) analyses before and after reduction in- vitro, using redox agent 1,4 dithiothreitol (DTT). Their inflammatory effects were explored by exposing human umbilical endothelial cells (HUVEC) to all these forms of albumin. Albumin separated from hypoalbuminemic HD patients increased endothelial mRNA expression of cytokines and adhesion molecules, and augmented secretion of IL-6. This endothelial inflammatory state was almost fully reverted by exposing HUVEC to the in-vitro reduced HD albumin. MS profile of albumin modifications peaks was similar between HD and HC, but the intensities of the various peaks were significantly different. Abolishing the reversible oxidative modifications by DTT prevented endothelial injury and increased albumin levels. The irreversible modifications such as glycation and sulfonation show low intensities in HD albumin profiles and are nearly unobserved in HC. We showed, for the first time, a mechanistic link between hypoalbuminemia and the pro-inflammatory properties of in-vivo oxidized albumin, initiating vascular injury.


Neonatal pain management practice in the neonatal intensive care unit of public hospitals: a survey of healthcare providers in eastern Ethiopia.
Newborns experience multiple painful and stressful procedures during their hospitalization in neonatal intensive care units (NICUs). Repeated or untreated pain can have negative consequences for the health and development of newborns. Despite the growing knowledge of pain assessment and intervention, several studies have shown that the practice of neonatal pain management among healthcare providers is poor. Therefore, data regarding neonatal pain management practice and affecting factors are essential for taking appropriate actions. This study assessed neonatal pain management practice and associated factors among healthcare providers working in the NICUs of public hospitals in eastern Ethiopia from 1 January to 28 February 2022. An institution-based cross-sectional study design was used among 372 randomly selected healthcare providers working in the NICUs of public hospitals in eastern Ethiopia. Data were collected using a pre-tested structured self-administered questionnaire and an observation checklist. The collected data were reviewed, coded and entered into Epi-data version 3.1 and exported to SPSS version 25 for analysis. Bivariate and multivariable logistic regression were used to identify the associations between outcome and predictor variables at a 95% confidence level and P-values <0.05 were considered statistically significant. The study found that 185 (53.9%; 95% confidence interval [CI] 48.4 to 59.2) of the 343 respondents had good neonatal pain management practice with a mean of 11.38 (standard deviation 3.64). Receipt of in-service training in neonatal pain management (adjusted odds ratio [AOR] 2.12 [95% CI 1.15 to 3.91]), availability of protocols and guidelines in the NICUs (AOR 2.94 [95% CI 1.74 to 4.91]) and accessibility of analgesics in the NICUs (AOR 4.302 [95% CI 2.46 to 7.53]) were significantly associated with good neonatal pain management practice. The overall practice of healthcare providers in neonatal pain management in public hospitals in eastern Ethiopia is relatively high compared with previous studies conducted in Ethiopia. Improving the availability of analgesics as well as neonatal pain management protocols and guidelines in NICUs will aid in the promotion of good neonatal pain management practices. In addition, providing ongoing in-service training on neonatal pain management will allow healthcare providers to better care for newborns in pain.


Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine-1-phosphate signaling in epigenetic regulation of inflammation and gene expression.
Phospholipids, sphingolipids, and cholesterol are integral components of eukaryotic cell organelles, including the nucleus. Recent evidence shows characteristic features of nuclear lipid composition and signaling, which are distinct from that of the cytoplasm and plasma membrane. While the nuclear phosphoinositol lipid signaling in cell cycle regulation and differentiation has been well described, there is a paucity on the role of nuclear sphingolipids and sphingolipid signaling in different physiological and pathophysiological human conditions. In this prospective, we describe the role of sphingolipids and specifically focus on the sphingoid bases, such as sphingosine, ceramide, and sphingosine-1-phosphate (S1P) generation and catabolism in nuclear signaling and function. Particularly, S1P generated in the nucleus by phosphorylation of SPHK2 modulates HDAC activity either by direct binding or through activation of nuclear reactive oxygen species and regulates cell cycle and pro-inflammatory gene expression. Potential implication of association of SPHK2 with the co-repressor complexes and generation of S1P in the nucleus on chromatin remodeling under normal and pathological conditions is discussed. A better understanding of sphingolipid signaling in the nucleus will facilitate the design and development of new and novel therapeutic approaches to modulate expression of pro-inflammatory and cell cycle dependent genes in human pathologies such as cancer, bacterial lung infection, neurodegeneration, and cystic fibrosis.


[Plaque features in saphenous vein graft evaluated by virtual histology intravascular ultrasound].
Objective: To investigate the features of plaques of saphenous venous graft (SVG) with virtual histology intravascular ultrasound (VH-IVUS) in patients underwent coronary artery bypass graft surgery. Methods: From March 2016 to March 2018, a total of 45 patients ((64.4±7.9) years old, 88.9% male (40 cases)) with ischemic symptoms after coronary artery bypass graft surgery and with coronary artery angiography evidenced SVG stenosis greater than or equal to 50%, who received percutaneous coronary intervention in Tianjin chest hospital were continuously included in this study, and the clinical data were retrospectively analyzed. VH-IVUS was performed before PCI to analyze plaque composition. The patients were divided into no smoking group (21 cases) and smoking group (24 cases), no diabetes group (30 cases) and diabetes group (15 cases), normal very low density lipoprotein cholesterin (VLDL-C) group (24 cases) and elevated VLDL-C group (21 cases), stable angina pectoris group (5 cases) and acute coronary syndrome group (40 cases), plaque burden (PB) < 70% group (11 cases) and PB ≥ 70% group (34 cases), without thin-cap fibroatheroma group (35 cases) and thin-cap fibroatheroma group (10 cases), and plaque features were compared between different groups. Results: The graft age was (8.9±3.7) years.The stenosis degree of SVG lesions was 90 (90, 98) %. The minimum lumen diameter was 1.6 (1.5, 1.8) mm. The vessel cross-sectional area was (12.1±4.0) mm(2). The plaque area was 8.6 (5.7,12.0) mm(2). The minimum lumen area was 2.5 (2.1,3.3) mm(2). The plaque burden was (75.3±8.3)%. The fibrotic tissue (FI) ratio was (65.1±10.1)%, fibrofatty plaque (FF) ratio was 13.8 (5.4,25.3) %, necrotic core tissue (NC) ratio was 12.0 (5.4,24.0)%, and dense calcium tissue (DC) ratio was1.0 (0.2,3.8)% in SVG lesions. There were no significant differences in SVG plaque area, FI area,FF area,NC area,and DC area between no smoking group and smoking group, no diabetes group and diabetes group, and normal VLDL-C group and elevated VLDL-C group. SVG plaque volume was significantly higher in acute coronary syndrome group than in stable angina pectoris group (262.2 (148.5,401.2) mm(3) vs. 93.1 (50.6,155.9) mm(3),P=0.006), and plaque area (10.1 (6.6,13.3) mm(2) vs. 5.0 (3.6,6.9) mm(2), P<0.001), FI area(4.8 (3.2,6.8) mm(2) vs. 2.8 (1.9,3.0) mm(2), P<0.001),and FF area (1.15 (0.60, 2.07) mm(2) vs. 0.30 (0.10,0.90) mm(2), P=0.009) were significantly larger in PB ≥ 70% group than in PB < 70% group.The NC area (1.75(0.40,2.78) mm(2) vs. 0.60 (0.20,1.30) mm(2), P=0.030) and DC area (0.35 (0.10,0.50) mm(2) vs. 0.00 (0.00,0.10) mm(2), P=0.006) were significantly larger in thin-cap fibroatheroma group than that in without thin-cap fibroatheroma group. Spearman correlation analysis showed that the plaque area of SVG lesion was positively correlated with FF area (r=0.64, P<0.001) and NC area (r=0.43, P=0.003). PB was positively correlated with FF area (r=0.50, P<0.001) and NC area (r=0.33, P=0.028). Graft age was positively correlated with FF area (r=0.30, P=0.047). Conclusions: The main components of SVG plaque are fibrotic tissue, conversely, calcified tissue is rare in patients with SVG stenosis after coronary artery bypass graft surgery. Fibrofatty tissue is increased in the plaque in patients with PB ≥ 70%. The necrotic component is also increased in patients with thin-cap fibroatheroma. The fibrofatty component increases and the plaque tends to be unstable in proportion with increaing age of the graft in this patient cohort.


Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.
A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.


The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease.
With the increasing use of mycophenolic acid (MPA) as an immunosuppressant in solid organ transplantation and in treating autoimmune diseases such as systemic lupus erythematosus, the need for strategies to optimize therapy with this agent has become increasingly apparent. This need is largely based on MPA's significant between-subject and between-occasion (within-subject) pharmacokinetic variability. While there is a strong relationship between MPA exposure and effect, the relationship between drug dose, plasma concentration and exposure (area under the concentration-time curve [AUC]) is very complex and remains to be completely defined. Population pharmacokinetic models using various approaches have been proposed over the past 10 years to further evaluate the pharmacokinetic and pharmacodynamic behaviour of MPA. These models have evolved from simple one-compartment linear iterations to complex multi-compartment versions that try to include various factors, which may influence MPA's pharmacokinetic variability, such as enterohepatic recycling and pharmacogenetic polymorphisms. There have been major advances in the understanding of the roles transport mechanisms, metabolizing and other enzymes, drug-drug interactions and pharmacogenetic polymorphisms play in MPA's pharmacokinetic variability. Given these advances, the usefulness of empirical-based models and the limitations of nonlinear mixed-effects modelling in developing mechanism-based models need to be considered and discussed. If the goal is to individualize MPA dosing, it needs to be determined whether factors which may contribute significantly to variability can be utilized in the population pharmacokinetic models. Some pharmacokinetic models developed to date show promise in being able to describe the impact of physiological processes such as enterohepatic recycling. Most studies have historically been based on retrospective data or poorly designed studies which do not take these factors into consideration. Modelling typically has been undertaken using non-controlled therapeutic drug monitoring data, which do not have the information content to support the development of complex mechanistic models. Only a few recent modelling approaches have moved away from empiricism and have included mechanisms considered important, such as enterohepatic recycling. It is recognized that well thought-out sampling schedules allow for better evaluation of the pharmacokinetic data. It is not possible to undertake complex absorption modelling with very few samples being obtained during the absorption phase (which has often been the case). It is important to utilize robust AUC monitoring which is now being propagated in the latest consensus guideline on MPA therapeutic drug monitoring. This review aims to explore the biological factors that contribute to the clinical pharmacokinetics of MPA and how these have been introduced in the development of population pharmacokinetic models. An overview of the processes involved in the enterohepatic recycling of MPA will be provided. This will summarize the components that complicate absorption and recycling to influence MPA exposure such as biotransformation, transport, bile physiology and gut flora. Already published population pharmacokinetic models will be examined, and the evolution of these models away from empirical approaches to more mechanism-based models will be discussed.


Mass smallpox immunization program in a deployed military setting.
A prospective, observational study of immunizing over 6,000 active-duty troops against smallpox in a 4-week time period was conducted. It focused on the complications of the vaccine and lost workdays. Comparison is made to the complication rates of earlier smallpox immunization programs. In direct response to elevated bioterrorism concerns, the United States military and civilian first-responders have begun a mass smallpox immunization program. This article reviews the experience with implementing such a program in a forward-deployed location while maintaining military readiness. The objectives were to assess the impact of a mass smallpox immunization program on operations in a forward-deployed military setting and to comment on lessons learned in the screening and immunization process. From January 16, 2003 through February 11, 2003 6,002 members of the United States military were immunized in a forward-deployed location. Information was obtained using data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan to calculate the following Main Outcome Measures data: (1)Percentage of individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC criteria, (3) Number of serious complications, (4) Number of life-threatening complications, and (5) Number of manpower days lost as a complication of the vaccine. A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. The "take" rate for the vaccine was 98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The immunization program produced an additional 156 medical visits (2.6% of patients required one visit). A total of 0.55% of immunized individuals lost one or more work days. In conclusion, a mass smallpox vaccination program can be effectively administered in a forward-deployed military setting despite high tempo military operations with minimal operational impact.


Design of Small Nanoparticles Decorated with Amphiphilic Ligands: Self-Preservation Effect and Translocation into a Plasma Membrane.
Design of nanoparticles (NPs) for biomedical applications requires a thorough understanding of cascades of nano-bio interactions at different interfaces. Here, we take into account the cascading effect of NP functionalization on interactions with target cell membranes by determining coatings of biomolecules in biological media. Cell culture experiments show that NPs with more hydrophobic surfaces are heavily ingested by cells in both the A549 and HEK293 cell lines. However, before reaching the target cell, both the identity and amount of recruited biomolecules can be influenced by the pristine NPs' hydrophobicity. Dissipative particle dynamics (DPD) simulations show that hydrophobic NPs acquire coatings of more biomolecules, which may conceal the properties of the as-engineered NPs and impact the targeting specificity. Based on these results, we propose an amphiphilic ligand coating on NPs. DPD simulations reveal the design principle, following which the amphiphilic ligands first curl in solvent to reduce the surface hydrophobicity, thus suppressing the assemblage of biomolecules. Upon attaching to the membrane, the curled ligands extend and rearrange to gain contacts with lipid tails, thus dragging NPs into the membrane for translocation. Three NP-membrane interaction states are identified that are found to depend on the NP size and membrane surface tension. These results can provide useful guidelines to fabricate ligand-coated NPs for practical use in targeted drug delivery, and motivate further studies of nano-bio-interactions with more consideration of cascading effects.


A Safe Method of Tracheal Polyflex Stent Placement: A Review of 20 Patients.
Surgery is an appropriate therapeutic approach for tracheal stenosis due to various benign and malignant conditions. When surgery is postponed for certain reasons, other options are chosen for airway patency. One alternative is using airway stents. We aimed to introduce a safe method of tracheal polyflex stent placement in patients with tracheal stenoses. During a 7-year period (2002 - 2008), polyflex stents were used 29 times among 20 patients for various indications. After encountering many difficulties in earlier cases, we gradually developed our new method and used it in most of our patients. In this method, without using large rigid bronchoscopes, the introducer tube could be used as a bronchoscope with the aid of a zero-degree lens and ventilating apparatus. In this method, the rate of possible trauma to the airway can be minimized by avoiding the use of thick rigid bronchoscopies and the stent can be placed faster and more accurately. Polyflex stents were used in 11 men (55%) and 9 women with a mean age of 38.5 years. Stents were removed and changed in 12 cases and replaced with another type of stent in 3 patients. Indications were recurrence of tracheal stenosis (7), multisegmental tracheal stenosis (3), anesthesia limitations (3), tracheal tumors (2), dehiscence of tracheal anastomosis (1), severe inflammation of the tracheal mucosa (1), esophagobronchial fistula (1), and external pressure on the left main bronchus (1). In one patient, a stent was used to open a kinked Dumon stent as a temporary life-saving procedure. We found 6 cases of stent migration, 3 cases of granulation tissue formation, 1 case of infection, and 1 case of surgical site dehiscence. Stents would be regarded as a temporary means of reaching the ideal condition for resection and reconstruction in most patients with tracheal stenoses. Although an optimal stent has not been introduced yet, we used polyflex stents in most of our patients with tracheal stenosis due to its availability and ease of use. We suggest that this method is safe and less time consuming than its traditional method of placement.


Portable Ultrasonography Onboard Deployment in the PLA(N) Peace Ark Hospital Ship in Mission Harmony 2018.
From June 28 to November 22, 2018, the Chinese People's Liberation Army Navy - PLA(N) - Peace Ark hospital ship had conducted Mission Harmony 2018, providing humanitarian medical assistance and carrying out international cooperation, in 4 Pacific island countries and 6 Central and South American countries. Compared with its application only in onshore outreach medical teams in the previous Mission Harmony, portable ultrasonography was used both onboard and onshore in Mission Harmony 2018. The purpose of this study was to assess the performance of onboard portable ultrasonography in PLA(N) Peace Ark hospital ship during Mission Harmony-2018, share our onboard working experience, and provide a reference for humanitarian assistance missions in the future. A retrospective review was performed on a cohort of patients checked by onboard portable ultrasonography. Patients' gender, age, the distribution of examined organs, and multiple applications of the portable ultrasonography were analyzed. Some limitations of portable ultrasonography on the mission and possible improvements in the future were also discussed. A total of 5277 cases (mean age: 43.74 years; range: 2 months-105 years) of ultrasound examinations were performed during the mission; among them, 3126 (59.2%) cases were performed by portable ultrasonography, including 3024 onboard cases and 102 onshore cases. The portable ultrasonography had been applied in many scenarios, for example, onboard emergency triage process, onboard bedside medical support, and onshore outreach medical service, which had become one of the indispensable auxiliary examination methods for its compatibility, portability, and flexibility. The onboard deployment of portable ultrasonography played a versatile and irreplaceable role in the humanitarian medical assistance and medical cooperation carried out by the PLA(N) Peace Ark hospital ship, and will contribute to such kind of missions in the future.


The long-term results of aortic valve replacement.
Reliable aortic valve replacement was one of the most significant advances in the treatment of cardiac disease in this century. It allowed, for the first time, a reliable and reproducible method to palliate the symptoms of aortic stenosis and regurgitation and significantly improved longterm survival over that after medical treatment. Sporadic attempts at aortic valve replacement had been conducted in the late 1950s, but the pioneering work of Harken et al, followed by the final development of a reliable device by Starr, Edwards, and coworkers, opened the era of successful aortic valve replacement. We review the prognosis of patients following aortic valve replacement with aortic stenosis and regurgitation with and without associated procedures and evaluate the various types of bioprosthetic and prosthetic valves in current use, presenting advantages and disadvantages of each type of replacement device.


Lateral preference and skill in dyslexics: implications of the right shift theory.
The lateral preferences and L-R skill of 109 male and 20 female dyslexics were as expected if the distribution of lateral asymmetry is shifted less far to the right in dyslexics than in controls. Several aspects of the data were consistent with Annett's hypothesis that some dyslexics lack the left hemisphere speech-organising factor postulated by the right shift theory of handedness and that this would be sufficient to account for the proportion of affected relatives. Some dyslexics were strongly dextral and these differed from the less dextral cases in several ways which resembled the distinction between backward and retarded readers.


Antral washout with nasal polypectomy: should both be combined?
Two hundred and sixteen patients with nasal polyps were studied. All patients had antral washouts performed at the same time as nasal polypectomy. Two hundred and sixty aspirates were sent for culture and microscopy; bacteria were cultured from 58 of these specimens in 38 patients. One hundred and one patients had pre-operative sinus radiographs of which 94 were reported as abnormal with a 52% false-positive result. It is concluded that antral washouts should be routine in all patients having nasal polypectomy. Sinus radiographs are an unnecessary pre-operative investigation in patients with uncomplicated nasal polyps.


Conditional mutagenesis in vivo reveals cell type- and infection stage-specific requirements for LANA in chronic MHV68 infection.
Gammaherpesvirus (GHV) pathogenesis is a complex process that involves productive viral replication, dissemination to tissues that harbor lifelong latent infection, and reactivation from latency back into a productive replication cycle. Traditional loss-of-function mutagenesis approaches in mice using murine gammaherpesvirus 68 (MHV68), a model that allows for examination of GHV pathogenesis in vivo, have been invaluable for defining requirements for specific viral gene products in GHV infection. But these approaches are insufficient to fully reveal how viral gene products contribute when the encoded protein facilitates multiple processes in the infectious cycle and when these functions vary over time and from one host tissue to another. To address this complexity, we developed an MHV68 genetic platform that enables cell-type-specific and inducible viral gene deletion in vivo. We employed this system to re-evaluate functions of the MHV68 latency-associated nuclear antigen (mLANA), a protein with roles in both viral replication and latency. Cre-mediated deletion in mice of loxP-flanked ORF73 demonstrated the necessity of mLANA in B cells for MHV68 latency establishment. Impaired latency during the transition from draining lymph nodes to blood following mLANA deletion also was observed, supporting the hypothesis that B cells are a major conduit for viral dissemination. Ablation of mLANA in infected germinal center (GC) B cells severely impaired viral latency, indicating the importance of viral passage through the GC for latency establishment. Finally, induced ablation of mLANA during latency resulted in complete loss of affected viral genomes, indicating that mLANA is critically important for maintenance of viral genomes during stable latency. Collectively, these experiments provide new insights into LANA homolog functions in GHV colonization of the host and highlight the potential of a new MHV68 genetic platform to foster a more complete understanding of viral gene functions at discrete stages of GHV pathogenesis.


Nonoperative treatment of intracapsular fractures of the proximal femur.
Of 2776 intracapsular fractures of the proximal femur, 18% of the patients were treated nonoperatively. Included in the group of patients who were treated conservatively were children, patients with cardiac problems or mental problems, stroke, renal failure, multiple disseminated malignancies, and patients who chose nonoperative treatment. The medical treatment protocol can be divided into two stages: Initially, (1) nursing of a bedridden patient with emphasis on the prevention of complications; and (2) once partial bone union has occurred, the attempted rehabilitation to independent ambulation. Paramedical services provide a major contribution during inpatient therapy and during the preparation for returning the patient to the community. A multidisciplinary medical team evaluates and assesses the patient's needs and rehabilitation potential and in cooperation with the patient and the family, an operative plan then is established.


Hybrid Functional Polymer-Enabled Multiplexed Chemosensor Patch for Wearable Adrenocortex Stress Profiling.
Measuring bioactive stress hormones, including cortisol and dehydroepiandrosterone (DHEA), allows for evaluating the hypothalamic-pituitary-adrenal (HPA) axis functioning, offering valuable insights into an individual's stress response through adrenocortex stress profiles (ASPs). Conventional methods for detecting steroid hormones involve sample collections and competitive immunoassays, which suffer from drawbacks such as time-consuming labeling and binding procedures, reliance on unstable biological receptors, and the need for sophisticated instruments. Here, we report a label-free and external redox reagent-free amperometric assay directly detecting sweat cortisol and DHEA levels on the skin. The approach utilizes multitarget sensors based on redox-active molecularly imprinted polymers (redox MIPs) capable of selectively binding cortisol and DHEA, inducing changes in electrochemical redox features. The redox MIP consists of imprinted cavities for specific capture of cortisol or DHEA in a poly(pyrrole-co-(dimethylamino)pyrrole) copolymer containing hydrophobic moieties to enhance affinity toward steroid hormones. The polymer matrix also incorporates covalently linked interpenetrating redox-active polyvinylferrocene, offering a stable electrochemical redox feature that enables sensitive current change in response to the target capture in the vicinity. The multiplexed sensor detects cortisol and DHEA within 5 min, with detection limits of 115 and 390 pM, respectively. Through the integration of redox MIP sensors into a wireless wearable sensing system, we successfully achieved ambulatory detection of these two steroid hormones in sweat directly on the skin. The new sensing method facilitates rapid, robust determination of the cortisol-DHEA ratio, providing a promising avenue for point-of-care assessment of an individual's physiological state.


Unscheduled bleeding and contraceptive choice: increasing satisfaction and continuation rates.
Approximately half (51%) of the 6.6 million pregnancies in the US each year are unintended and half of those pregnancies (54%) occur among women not using contraception. Many women discontinue their contraceptives due to method dissatisfaction. Bothersome unscheduled bleeding is one of the main reasons cited by women for stopping a birth control method. Improving counseling and management of these side effects will aide in increasing satisfaction with contraceptive methods. The following review will discuss the bleeding profiles associated with the contraceptive options available in the US. A valuable resource from the Centers for Disease Control and Prevention, the US Selected Practice Recommendations for Contraceptive Use, will be introduced. Definitions of the types of unscheduled bleeding are included, as well as strategies for treatment for each contraceptive method. The evidence whether or not anticipatory counseling increases continuation rates will also be reviewed.


Embedding a membrane protein into an enveloped artificial viral replica.
Natural enveloped viruses, in which nucleocapsids are covered with lipid bilayers, contain membrane proteins on the outer surface that are involved in diverse functions, such as adhesion and infection of host cells. Previously, we constructed an enveloped artificial viral capsid through the complexation of cationic lipid bilayers onto an anionic artificial viral capsid self-assembled from β-annulus peptides. Here we demonstrate the embedding of the membrane protein Connexin-43 (Cx43), on the enveloped artificial viral capsid using a cell-free expression system. The expression of Cx43 in the presence of the enveloped artificial viral capsid was confirmed by western blot analysis. The embedding of Cx43 on the envelope was evaluated by detection via the anti-Cx43 antibody, using fluorescence correlation spectroscopy (FCS) and transmission electron microscopy (TEM). Interestingly, many spherical structures connected to each other were observed in TEM images of the Cx43-embedded enveloped viral replica. In addition, it was shown that fluorescent dyes could be selectively transported from Cx43-embedded enveloped viral replicas into Cx43-expressing HepG2 cells. This study provides a proof of concept for the creation of multimolecular crowding complexes, that is, an enveloped artificial viral replica embedded with membrane proteins.


Compact glow discharge for the elemental analysis of aqueous samples.
Glow discharge sources have shown impressive analytical performance, cost effectiveness, and versatility but have traditionally been ill-suited for the analysis of liquids or solutions. However, in recent years, glow discharges operated at atmospheric pressure have shown progress in this direction. In particular, glow discharges have been operated with the solution to be analyzed acting as one of the electrodes (most typically, and most successfully, the cathode). These sources exhibit many of the traditional advantages of glow discharges (such as low power requirements) and possess the additional benefit of not requiring vacuum equipment. In the present study, a modified design is introduced and its analytical performance is evaluated. The modification from the most similar source is primarily a reduction in discharge volume (nearly 5-fold, to 2 mm(3)) and a corresponding increase in power density. With the new design, detection limits for a range of metals are greatly improved, with most now in the single and sub-part per billion range.


Sustained Benefit Over Four-Year Follow-Up of Michigan's Project Healthy Schools.
We determined the sustainability of effects of a school-based intervention to improve health behaviors and cardiovascular risk factors among middle school children. We administered a questionnaire and health screenings to 5 schools in Ann Arbor and 2 schools in Ypsilanti, Michigan. We assessed demographics, physiological factors, diet, physical activity, and sedentary behaviors from 1126 students who received a health curriculum (Project Healthy Schools) in the fall of sixth grade in 2005, 2006, and 2007. We administered the questionnaire and screening again in the spring and each subsequent spring through ninth grade to all available, consenting students. In the 4 years following the school-based intervention, total cholesterol, low-density lipoprotein cholesterol, and triglycerides improved, and for most years systolic and diastolic blood pressure improved. Serum glucose and body mass index did not change. Physical activity increased and sedentary behaviors diminished. Project Healthy Schools is associated with sustainable improvements in both cardiovascular parameters and healthy behaviors.


Weight loss patterns and success rates in high school wrestlers.
The purposes were to: 1) examine the weight loss patterns in a group of high school varsity wrestlers whose teams participated in a body composition measurement@nutrition education program, and 2) test the hypothesis that wrestling at a weight below recommended Minimum Wrestling Weight (MWW) results in decreased wrestling success. We measured skinfold thickness in 465 wrestlers at 16 schools and, using the Lohman method, determined their percent body fat. An educational program presented at each school explained the results, provided nutritional information regarding proper diet and methods of weight loss, and suggested a voluntary MWW corresponding to 5% body fat. After excluding the heavyweight wrestlers, there were 159 varsity wrestlers. At the end of the season, we noted their weight class and whether they placed in post-season state championship qualifying tournaments. We found that 53 wrestlers (33%) wrestled below MWW. When analyzed by school, wrestlers' non-adherence to MWW ranged from 0% to 56% of all wrestlers. In the lightest four weight classes, 62% wrestled below MWW; in the middle four classes, 29%; and in the heaviest four classes, 6%. Of the 53 wrestlers below MWW, 57% placed and of the 106 above MWW, 33% placed (P < 0.01). These results show that a substantial number of wrestlers who participate in a voluntary body fat measurement and diet education program wrestle below recommended MWW. This is particularly true at lower weight classes. Further, wrestling below MWW was associated with greater wrestling success. The current concept of MWW should not be based on wrestling performance effects.


Breast milk oligosaccharides: effects of 2'-fucosyllactose and 6'-sialyllactose on the adhesion of Escherichia coli and Salmonella fyris to Caco-2 cells.
Background: It is well known that human milk oligosaccharides play an important role as prebiotics, anti-inflammatory, and anti-infective agents. In the last few years, several studies have been performed using specific oligosaccharides, such as 2'-fucosyllactose and 6'-sialylactose, to evaluate their biological functions. Objectives: The aim of the present study is to evaluate the anti-adhesive effect of the above oligosaccharides on Escherichia coli and Salmonella fyris. Methods: Adhesion experiments were performed in the presence of 2'-fucosyllactose and 6'-sialyllactose as potential inhibitors of Escherichia coli and Salmonella fyris adhesion to Caco-2 cells. The oligosaccharides were used at different concentrations and the adhesion experiments were performed in triplicate and repeated at least three times. Results: A significant reduction of Escherichia coli adhesion was observed in the presence of 2'-fucosyllactose and 6'-sialyllactose at the human milk concentration. On the contrary, no positive effects were observed in both oligosaccharides on Salmonella firis. Conclusions: Our results suggest that the supplementation in infant formulas of 2'-fucosyllactose and 6'-sialyllactose, actually commercially available and absent in cow milk, could play positive effects in artificially fed infants.


Prevalence of Helicobacter pylori infection in children with recurrent abdominal pain.
The present study was performed to study the prevalence of Helicobacter pylori (H. pylori) infection in children with recurrent abdominal pain (RAP). Children above 3 years of age of both sexes attending the OPD of a teaching hospital, with complaints of at least three discrete episodes of abdominal pain of sufficient severity to interrupt normal daily activities, occurring over a period of one month or more and with out identifiable cause of pain were enrolled in the study. The subjects were divided into 3 age groups of 3-5 years, 5-8 years and 8-12 years. Thirty normal controls from each age group were also enrolled. Detailed history was taken and thorough physical examination was done. Estimation of haemoglobin and specific IgG antibodies to H. pylori by Immunocomb II was done. Upper gastrointestinal endoscopy was performed with a fibreoptic pediatric sized endoscope in RAP cases after obtaining informed parental consent. Multiple biopsy samples were taken and subjected to Rapid Urease Test (RUT), Gram's Staining, Culture and histology. Data obtained were analyzed, using Fisher's Z Test, Students t-test or Chi Square as applicable. Sixty-eight cases and 90 controls were enrolled, the number in various age groups being comparable (p >0.05). Seropositivity rate was significantly more in cases (60.3%) compared to controls (10%) (p <0.001) even among various age groups (<0.01). Prevalence increased with advancing age from 3.3% to 16.7% in controls, but not among cases. Seropositivity rates among males and females were comparable both among cases and controls. Incidence of malnutrition, stunting and anemia were similar irrespective of serological status. Total duration of illness, frequency, duration of each episode, and location of pain were also comparable. Among 10 seropositive children who underwent upper gastrointestinal endoscopy 80% showed one or more abnormalities, while the single seronegative child had no abnormal finding. Half the seropositive cases had gastritis, hyperemia or erosion on gross examination. Histopathological evidence of gastritis was present in 40%, but culture was negative in all. There is a significant association of H. pylori infection and RAP. But studies involving larger number of children undergoing endoscopy is required for definite evidence of a 'cause and effect'.


Mental health promotion through resilience and resiliency education.
The article provides a brief review of the metatheory of resilience and resiliency, a description of a resiliency training program, and also a summary of results of a resiliency training program. Resilience in this paper is a self-righting force within everyone that drives him/her to pursue self actualization, altruism, wisdom, and harmony with a spiritual source of strength. The resiliency process is the experience of being disrupted by change, opportunities, adversity, stressors or challenges and, after some disorder, accessing personal gifts and strengths to grow stronger through the disruption. The resiliency training program is presented as a five-day progressive program that provides experiences for participants to enhance personal resilience and to pursue resilient relationships. Research previously conducted in a large government organization showed immediate and posttest improvements in resilience, locus of control, purpose in life, self-esteem, interpersonal relationships, and job satisfaction.


Orientational Transition in a Liquid Crystal Triggered by the Thermodynamic Growth of Interfacial Wetting Sheets.
In liquid crystal (LC) physical chemistry, molecules near the surface play a great role in controlling bulk orientation. Thus far, mainly to achieve desired molecular orientation states in LC displays, the "static" surface property of LCs, so-called surface anchoring, has been intensively studied. As a rule of thumb, once the initial orientation of LCs is "locked" by specific surface treatments, such as rubbing or treatment with a specific alignment layer, it hardly changes with temperature. Here, we present a system exhibiting an orientational transition upon temperature variation, which conflicts with the consensus. Right on the transition, the bulk LC molecules experience the orientational rotation, with 90° between the planar (P) orientation at high temperatures and the vertical (V) orientation at low temperatures in the first-order transitional manner. We have tracked thermodynamic surface anchoring behavior by means of polarizing optical microscopy (POM), dielectric spectroscopy (DS), high-resolution differential scanning calorimetry (HR-DSC), and grazing incidence X-ray diffraction (GI-XRD) and reached a plausible physical explanation: that the transition is triggered by a growth of surface wetting sheets, which impose the V orientation locally against the P orientation in the bulk. This landscape would provide a general link explaining how the equilibrium bulk orientation is affected by surface-localized orientation in many LC systems. In our characterization, POM and DS are advantageous by offering information on the spatial distribution of the orientation of LC molecules. HR-DSC gives information about the precise thermodynamic information on transitions, which cannot be addressed by conventional DSC instruments due to limited resolution. GI-XRD provides information on surface-specific molecular orientation and short-range orderings. The goal of this paper is to present a protocol for preparing a sample that exhibits the transition and to demonstrate how the thermodynamic structural variation, both in the bulk and on surfaces, can be analyzed through the abovementioned methods.


A Flexible Escape Skin Bioinspired by the Defensive Behavior of Shedding Scales.
Artificial skins with functions such as sensing, variable stiffness, actuation, self-healing, display, adhesion, and camouflage have been developed and widely used, but artificial skins with escape function are still a research gap. In nature, every species of animal can use its innate skills and functions to escape capture. Inspired by the behavior of fish-scale geckoes escaping predation by shedding scales when grasped or touched, we propose a flexible escape skin by attaching artificial scales to a flexible film. Experiments demonstrate that the escape skin has significant effects in reducing escape force, escaping from harmful force environments, and resisting mechanical damage. Furthermore, we enabled active control of escape force and skin hardness by changing temperature, increasing the adaptability of the escape skin to the surrounding. Our study helps lay the foundation for engineering systems that depend on escape skin to improve robustness.


"Jnking" atherosclerosis.
Numerous studies in animal models established a key role of the C-jun N-terminal kinase (JNK) family (JNK1, JNK2 and JNK3) in numerous pathological conditions, including cancer, cardiac hypertrophy and failure, neurodegenerative disorders, diabetes, arthritis and asthma. A possible function of JNK in atherosclerosis remained uncertain since conclusions have mainly been based on in vitro studies investigating endothelial cell activation, T-effector cell differentiation and proliferation of vascular smooth muscle cells, all of which represent crucial cellular processes involved in atherosclerosis. However, recent experiments demonstrated that macrophage-restricted deletion of JNK2 was sufficient to efficiently reduce atherosclerosis in mice. Furthermore, it has been shown that JNK2 specifically promotes scavenger receptor A-mediated foam cell formation, an essential step during early atherogenesis, which occurs when vascular macrophages internalize modified lipoproteins. Thus, specific inhibition of JNK2 activity may emerge as a novel and promising therapeutic approach to attenuate atheroma formation in the future. In this review, we discuss JNK-dependent cellular and molecular mechanisms underlying atherosclerosis.


Structure of cholinium glycinate biocompatible ionic liquid at graphite electrode interface.
We use constant potential molecular dynamics simulations to investigate the interfacial structure of the cholinium glycinate biocompatible ionic liquid (bio-IL) sandwiched between graphite electrodes with varying potential differences. Through number density profiles, we observe that the cation and anion densities oscillate up to ∼1.5 nm from the nearest electrode. The range of these oscillations does not change significantly with increasing electrode potential. However, the amplitudes of the cation (anion) density oscillations show a notable increase with increasing potential at the negative (positive) electrode. At higher potential differences, the bulkier N(CH3)3CH2 group of cholinium cations ([Ch]+) overcomes the steric barrier and comes closer to the negative electrode as compared to oxygen atom (O[Ch]+ ). We observe an increase in the interaction between O[Ch]+ and the positive electrode with a decrease in the distance between them on increasing the potential difference. We also observe hydrogen bonding between the hydroxyl group of [Ch]+ cations and oxygens of glycinate anions through the simulated tangential radial distribution function. Orientational order parameter analysis shows that the cation (anion) prefers to align parallel to the negative (positive) electrode at higher applied potential differences. Charge density profiles show a positive charge density peak near the positive electrode at all the potential differences because of the presence of partially positive charged hydrogen atoms of cations and anions. The differential capacitance (Cd) of the bio-IL shows two constant regimes, one for each electrode. The magnitude of these Cd values clearly suggests potential application of such bio-ILs as promising battery electrolytes.


Intraductal papillary mucinous neoplasm of the biliary tract in the caudate lobe of the liver: a case report and literature review.
An intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) in the caudate lobe of the liver is a rare tumor originating from the bile duct. Approximately 40% of the intraductal papillary neoplasms of the biliary tract (IPNB) secrete mucus and can grow in the intrahepatic or extrahepatic bile ducts. A 65-year-old woman presented with recurrent episodes of right upper pain. She developed her first episode 8 years ago, which resolved spontaneously. The frequency of symptoms has increased in the last 2 years. She underwent laparoscopic hepatectomy and choledochal exploration and was pathologically diagnosed with a rare BT-IPMN of the caudate lobe after admission. Here, we review studies on IPNB cases and systematically describe the pathological type, diagnosis, and treatment of IPNB to provide a valuable reference for hepatobiliary surgeons in the diagnosis and treatment of this disease.


Influence of renal involvement on peripheral blood mononuclear cell expression behaviour of tumour necrosis factor-alpha and interleukin-6 in type 2 diabetic patients.
Type 2 diabetes is associated with a high cardiovascular risk, which is even increased if renal damage is superimposed. Peripheral blood mononuclear cells (PBMCs) and pro-inflammatory cytokines are key factors linking type 2 diabetes and atherosclerosis. We investigated the influence of renal damage on serum, urinary and PBMCs expression behavior of TNF-alpha and IL-6 in these patients. PBMCs were isolated by density gradient centrifugation (Ficoll-Paque method) from fasting blood samples of 22 non-diabetic control subjects and 78 diabetic patients with normal renal function and different stages of diabetic nephropathy (18 with normoalbuminuria, 29 with microalbuminuria and 31 with macroalbuminuria). Expression levels of TNF-alpha and IL-6 were analyzed by real-time quantitative RT-PCR. Serum and urinary TNF-alpha and IL-6 concentrations were measured by a solid-phase, chemiluminescent immunometric assay. The mean percent increases in the serum and urinary levels of TNF-alpha and IL-6 in diabetic patients with respect to control subjects were 176% (P < 0.0001), 250% (P < 0.0001), 114% (P < 0.0001) and 39.6% (P = 0.01), respectively. The mRNA expression level of TNF-alpha was higher by 68.8% (P < 0.001) and IL-6 mRNA levels were higher by 64.1% (P < 0.001) with respect to non-diabetic controls. TNF-alpha mRNA expression in patients with macroalbuminuria was higher by 84.8% with respect to subjects with normalbuminuria (P < 0.001) and by 29% with respect to individuals with microalbuminuria (P < 0.05). Likewise, microalbuminuric patients showed a 44.5% increase in TNF-alpha mRNA expression compared to subjects with normoalbuminuria (P < 0.05). Concerning IL-6, the mRNA expression levels of this cytokine was higher by 63.1% with respect to normoalbuminuric subjects (P < 0.01), and by 23.1% with respect to patients with microalbuminuria (P < 0.05). However, with respect to controls, diabetic patients with normoalbuminuria had similar serum TNF-alpha and urinary excretion of IL-6, without any differences in the mRNA expression levels of these cytokines in PBMCs. Partial correlation and multiple regression analysis using TNF-alpha and IL-6 mRNA levels as the dependent variables showed that urinary albumin excretion (UAE) was direct and independently associated with the expression profile of these pro-inflammatory cytokines in PBMCs. These data show for the first time the relationship between inflammatory activation of PBMCs (reflected by enhanced mRNA expression of TNF-alpha and IL-6) and renal involvement (reflected by increased UAE) in type 2 diabetic patients. These results provide potential insights for the increased inflammation, accelerated atherosclerosis and cardiovascular risk associated with nephropathy in type 2 diabetes.


Fulminant Pyoderma Gangrenosum After Outpatient Knee Arthroscopy.
Pyoderma gangrenosum is an immunologic, ulcerative cutaneous condition often associated with systemic disease and frequently precipitated by trauma. It is noninfectious, but the inflammatory assault can resemble a malignant infection such as necrotizing fasciitis. Despite its clinical resemblance to infection, surgical débridement worsens the condition and may remove morphologic clues to the true disease, thus creating a vicious cycle of surgical débridements and disease progression. Furthermore, diagnostic histopathologic and laboratory features are nonspecific, requiring exclusion of other processes. Therefore, appropriate nonsurgical treatment and immunosuppression are commonly delayed, often at a significant cost to the patient. We present a case of pyoderma gangrenosum occurring after outpatient knee arthroscopy that masqueraded as a postsurgical infection. We discuss the diagnostic approach and how a complex reconstruction involving cartilage restoration and soft-tissue coverage was achieved.


Replication across space and time must be weak in the social and environmental sciences.
Replicability takes on special meaning when researching phenomena that are embedded in space and time, including phenomena distributed on the surface and near surface of the Earth. Two principles, spatial dependence and spatial heterogeneity, are generally characteristic of such phenomena. Various practices have evolved in dealing with spatial heterogeneity, including the use of place-based models. We review the rapidly emerging applications of artificial intelligence to phenomena distributed in space and time and speculate on how the principle of spatial heterogeneity might be addressed. We introduce a concept of weak replicability and discuss possible approaches to its measurement.


[Fludrocortisone in the treatment of orthostatic hypotension: ophthalmodynamography during standing(author's transl)].
The effect of fludrocortisone (Astonin -H) in the management of orthostatic hypotension was tested in a double-blind trial of 30 patients who were receiving 0.3 mg fludrocortisone for seven days, a control group of 30 subjects receiving placebos. Systolic and diastolic brachial and ophthalmic arterial pressures, pulse amplitude and pulse rate were measured at rest, immediately after standing up and 10 minutes later. Comparing the treatment and placebo groups, the former had a higher systolic ophthalmic blood pressure on standing, a smaller fall of pulse volume and less of a rise in heart rate on standing up, and a raised systolic brachial artery pressure even in recumbency. At the same time there was an improvement in symptoms.


[Discussion on the principle and treatment pathway of Jin's three-needle technique for mind regulation and treatment from the "adjusting qi to regulate mind, adjusting blood to regulate mind"].
The Jin's three-needle technique is famous for mind regulation and treatment. From the perspective of qi and blood, the special principle and treatment pathway of Jin's three-needle technique for mind regulation and treatment were summarized and analyzed. Moreover, themethods of invigorating brain and regulating mind, calming heart and tranquilizing mind, strengthening spleen and stomach, dredging the meridian and channel were applied to guide the qi into the brain to regulate the mind. The mind is regulated by adjusting heart and blood, nourishing the yang with yin, adjusting the source of blood and qi and dredging the channel of qi and blood. With "adjusting qi to regulate mind, adjusting blood to regulate mind", a comprehensive treatment is achieved to increase the efficacy of mind regulation and treatment.