Accurate Arthroscopic Cam Resection Normalizes Contact Stresses in Patients With Femoroacetabular Impingement.
Femoroacetabular impingement (FAI) is increasingly recognized as a cause of hip pain in young adults. The condition leads to chondrolabral separation and chondral delamination and eventually predisposes to osteoarthritis of the hip. FAI that inflicts cartilage damage has been observed in hips with abnormal morphological characteristics and is related to a long-term evolution toward osteoarthritis. Arthroscopic surgery, which allows for correction of morphological characteristics and restores impingement-free motions, is the current standard of treatment. Arthroscopic cam resection can restore the normal mechanical environment of the hip joint in cam-type FAI. Descriptive laboratory study. Patient-specific discrete element models from 10 patients with cam-type FAI (all male; age, 18-40 years) were defined based on preoperative computed tomography scans and postoperative magnetic resonance imaging (MRI) scans. Complete cam resection postoperatively on MRI was confirmed with alpha angles <55°. The preoperative and postoperative peak contact stress findings during impingement testing were compared against a matched control group. Peak contact stress was significantly elevated in patients with cam-type FAI during impingement testing, with increasing amounts of internal hip rotation (26.6 ± 11.64 MPa in cam patients preoperatively, 12.1 ± 4.62 MPa in those same patients postoperatively, and 11.4 ± 1.72 MPa in the virtual control group during impingement testing at 20° of internal hip rotation; P < .01). This effect was normalized after arthroscopic cam resection and loading patterns matched those of the control group. Accurate arthroscopic cam resection restored the normal peak joint contact stresses in the hip joint. This highlights the importance of early and complete cam resections in the face of a positive diagnosis of cam-type FAI. Treatment of cam-type FAI effectively normalizes hip joint contact mechanics.


Feeding Roux-en-Y jejunostomy in the management of severely neurologically impaired children.
Feeding problems are legion in severely neurologically impaired children. Many patients do well with a gastrostomy with or without fundoplication. Unfortunately, fundoplication is not without complication, emphasizing the need for other options in the management of these difficult patients. Since 1990 six patients (age range, 2 months to 6 years) have been treated by the creation of a permanent Roux-en-Y end-jejunostomy and a gastrostomy. The Roux limb is closed tightly around a mushroom catheter. The gastrostomy is left for gastric decompression, and the jejunostomy tube is used for all nutrition and most medications. One patient died in the postoperative period. All the others have done well, without significant complication and with a high level of parent satisfaction (average follow-up, 12 months). Previously four other patients were treated with a Roux-en-Y jejunostomy in which, rather than closing the Roux limb around the catheter, it was brought out as a catheterizable stoma. Frequent leakage and prolapse make this approach less desirable.


Echocardiography and cardiac transplantation: a literature review and practical approach.
This article reviews the utility of noninvasive echocardiography in the detection of early cardiac transplant rejection before and after the use of cyclosporine. It addresses the use of Doppler and two-dimensional echocardiography in the routine cardiac evaluation of the heart-transplant patient, including the use of two-dimensional echocardiography in guiding the endomyocardial biopsy procedure.


Eye drop delivery of nano-polymeric micelle formulated genes with cornea-specific promoters.
This study evaluates the eye drop delivery of genes with cornea-specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms. Three PM-formulated plasmids (pCMV-Lac Z, pK12-Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta-Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine-aspartic acid) peptide. The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment. Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport.


Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
To assess post-treatment effects in endometriosis patients of a 12-month course of GnRH agonist alone or with one of three "add-back" regimens. This is a post-treatment follow-up analysis of a randomized, double-masked, placebo-controlled 52-week trial. All patients had received monthly leuprolide acetate and were randomized to one of four groups: A-daily placebo; B-daily norethindrone acetate 5 mg; C-daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg; and D-daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial, 123 completed at least 280 days of therapy and entered the follow-up period. Physical findings and symptoms were quantified, and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post-therapy. Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups (P <.05). Findings were not affected by endometriosis scores noted on screening laparoscopy. Mean bone mineral density values remained at or above baseline in all add-back groups. The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow-up visit (P <.001). GnRH agonist and norethindrone acetate alone or combined with low-dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy.


Undue burdens created by the Texas Abortion Law for vulnerable pregnant women.
The new Texas abortion law requires the physician to determine whether a fetal heartbeat is present and prohibits abortion after a heartbeat has been documented. An exception is allowed when a "medical emergency necessitated the abortion." These and other provisions of the statute are to be enforced through "civil actions" brought by private citizens. This article identifies 3 populations of vulnerable women who will experience undue burdens created by the Texas abortion law. We begin with an account of the concept of undue burden in the jurisprudence of abortion, as expressed in the 1992 US Supreme Court case, Planned Parenthood v. Casey of Southeastern Pennsylvania. We then provide an evidence-based account of the predictable, undue burdens for 3 populations of vulnerable women: pregnant women with decreased freedom of movement; pregnant minors; and pregnant women with major mental disorders and cognitive disabilities. The Texas law creates an undue burden on these 3 populations of vulnerable women by reducing or even eliminating access to abortion services outside of Texas. The Texas law also creates an undue burden by preventably increasing the risks of morbidity, including loss of fertility, and mortality for these 3 populations of vulnerable women. For these women, it is indisputable that the Texas law will create undue burdens and is therefore not compatible with the jurisprudence of abortion as set forth in Planned Parenthood v. Casey because a "significant number of women will likely be prevented from obtaining an abortion." Federal courts should therefore strike down this law.


Striped weakfish (Cynoscion guatucupa): a biomonitor of organochlorine pesticides in estuarine and near-coastal zones.
The general goal of this study was to investigate the role of Cynoscion guatucupa as a biomonitor of organochlorine pesticides (OCP) contamination in Bahía Blanca estuary. Thus, we evaluated whether or not OCP fish distribution pattern reflects the OCP land sources, and if size-related bioaccumulation and biomagnification of these contaminants does occur by comparing different tissues of juvenile and adults of C. guatucupa (Cuvier, 1830). Size-related bioaccumulation in C. guatucupa was observed and it was more important for the more lipophilic and biomagnifying OCP, being determined over time by diet influence. Endosulfan sulfate, chlordanes, HCH isomers and DDT compounds predominated in tissues and ingested food of C. guatucupa, being alpha-chlordane, heptachlor and p,p'-DDE highly bioaccumulated and biomagnificated. Our findings also showed that male adults of C. guatucupa are biomonitors of OCP pollution so we propose this species for further investigations in other coastal zones of South America.


A human liver alcohol dehydrogenase enzyme-linked immunosorbent assay method specific for class I, II, and III isozymes.
A sensitive and convenient method for the quantitative measurement of human alcohol dehydrogenase (ADH) isozymes based on enzyme-linked immunosorbent assay has been devised. The procedure was optimized with respect to antigen coating density, antiserum dilution, and incubation times with rabbit antisera raised against beta 1 beta 1-ADH to achieve a limit of sensitivity of 1 ng/ml for this isozyme when purified. Using the optimal conditions established, quantitative measurement of alpha beta 1, alpha gamma 1, beta 1 gamma 1, pi, and chi-ADH were obtained with antisera raised in rabbits toward these individual isozymes. The incorporation into the procedure of thimerosal (ethyl(4-mercaptobenzoato-S)mercury) or other sulfhydryl specific reagents improved the soluble phase antiserum avidity for all ADH isozymes, thereby increasing the sensitivity. Thimerosal is an absolute requirement for chi-ADH antigen-antibody binding. The polyclonal rabbit antisera elicited by the individual isozymes of the three classes of ADH exhibit a high degree of isozyme class specificity. Cross-reactivity of the antibodies with the beta 1 beta 1, alpha gamma 1, alpha gamma 2, alpha beta 1, beta 1 gamma 1, beta 1 gamma 2, pi and chi isozymes were evaluated. Antisera against the class I isozymes beta 1 beta 1 and beta 1 gamma 1 cross-react with all class I isozymes and with pi-ADH. Antibodies against pi and chi-ADH are selective and specific only for their respective antigens. Neither one cross-reacts with any class I isozyme. Conformational effects resulting from subunit interactions likely account for differences in cross-immunoreactivity between the closely homologous class I isozymes.


Review: A species comparison of the kinetic homogeneous and heterogeneous organization of sodium-dependent glucose transport systems along the intestine.
The targeted use of carbohydrates by feed and food industries to create balanced and cost-effective diets has generated a tremendous amount of research in carbohydrate digestion and absorption in different species. Specifically, this research has led us to a larger observation that identified different organizations of intestinal sodium-dependent glucose absorption across species, which has not been previously collated and reviewed. Thus, this review will compare the kinetic segregation of sodium-dependent glucose transport across the intestine of different species, which we have termed either homogeneous or heterogeneous systems. For instance, the pig follows a heterogeneous system of sodium-dependent glucose transport with a high-affinity, super-low-capacity (Ha/sLc) in the jejunum, and a high-affinity, super-high-capacity (Ha/sHc) in the ileum. This is achieved by multiple sodium-dependent glucose transporters contributing to each segment. In contrast, tilapia have a homogenous system characterized by high-affinity, high-capacity (Ha/Hc) throughout the intestine. Additionally, we are the first to report glucose transporter patterns across species presented from vertebrates to invertebrates. Finally, other kinetic transport systems are briefly covered to illustrate possible contributions/modulations to sodium-dependent glucose transporter organization. Overall, we present a new perspective on the organization of glucose absorption along the intestinal tract.


Congenital fusion of the little and ring finger metacarpal bones.
A child with bilateral congenital synostoses of the little and ring finger metacarpal bones is described. The resulting abduction deformities of the little fingers were corrected by metacarpal osteotomies.


Seasonal variation of androgen interconversion in testicular tissue of Rana temporaria in vitro.
Testicular steroid metabolism of winter and spring frogs, Rana temporaria, were studied by in vitro incubation with radioactively labelled dehydroepiandrosterone and androst-4-ene-3,17-dione. Marked seasonal differences were observed which are in line with the findings of others.


Drug-selected complete restoration of superoxide generation in Epstein-Barr virus-transformed B cells from p47phox-deficient chronic granulomatous disease patients by using a bicistronic retrovirus vector encoding a human multi-drug resistance gene (MDR1) and the p47phox gene.
Chronic granulomatous disease (CGD) is a group of disorders characterized by the failure of phagocytes to produce superoxide. One-third of the cases of CGD in the USA and Europe results from defects in the gene encoding p47phox, a cytoplasmic component of NADPH oxidase for superoxide generation. In this study, we constructed the bicistronic retrovirus vector Ha-MDR-IRES-p47, which carries cDNAs for a human multi-drug-resistance gene (MDR1) and p47phox. The amphotropic retroviral producer cells were generated, and the supernatant of the producer cells was used to transduce Epstein-Barr virus-transformed B (EBV-B) cells, established from B cells of p47phox-deficient CGD patients, as an in vitro model of gene therapy for p47phox-deficient CGD. The transduced cells expressed both P-glycoprotein and p47phox protein, and the expression levels were increased after appropriate vincristine selection. The levels of superoxide production in the vincristine-selected cells were increased to a level similar to normal EBV-B cells. This result suggests that it is possible to achieve 100% correction of the CGD defect in p47phox-deficient EBV-B cells by using the bicistronic vector. This strategy could be employed not only in vitro, but also in vivo, in the gene therapy of a number of inherited diseases.


Eco-friendly cellulose-based hydrogel functionalized by NIR-responsive multimodal antibacterial polymeric ionic liquid as platform for promoting wound healing.
With the trend of sustainable development and the complex medical environment, there is a strong demand for multimodal antibacterial cellulose wound dressing (MACD) with photothermal therapy (PTT). Herein, a novel MACD fabrication strategy with PTT was proposed and implemented through graft polymerization of an imidazolium ionic liquid monomer containing iron complex anion structure. The fabricated hydrogels exhibited excellent antibacterial properties because of the efficient photothermal conversion ability (68.67 %) of ionic liquids and the intrinsic structural characteristic of quaternary ammonium salts. The antibacterial ratio of cellulosic hydrogel dressings to S. aureus and E. coli could reach 99.57 % and 99.16 %, respectively. Additionally, the fabricated hydrogels demonstrated extremely low hemolysis rates (<5 %) and excellent cell viability (~>85 %). Furthermore, in vivo antibacterial experimental results proved that the fabricated antibacterial dressings could significantly accelerate wound healing. Therefore, the proposed strategy would provide a new method of designing and preparing high-performance cellulose wound dressings.


Correction to: Benefit:Risk Profile of Budesonide in Obstructive Airways Disease.
Page 5, Fig. 2 Key milestones in the development of budesonide.


Immunohistochemical investigation of topographic localization of phenobarbital and methamphetamine in the rat retina.
The topographic localization of methamphetamine and phenobarbital in the rat retina was studied. It is interesting that the secondary and primary ganglionic cells were stained predominantly only in the case of methamphetamine while in phenobarbital these were not stained. The staining patterns of the inner plexiform layer (strong reaction in phenobarbital and weak reaction in methamphetamine), outer nuclear layer (weak reaction in phenobarbital and strong reaction in methamphetamine) and choroid (very strong reaction in phenobarbital and no reaction in methamphetamine) also showed some differences.


COVID-19 with acute cholecystitis: a case report.
The 2019 novel coronavirus (COVID-19) presents a major threat to public health and has rapidly spread worldwide since the outbreak in Wuhan, Hubei Province, China in 2019. To date, there have been few reports of the varying degrees of illness caused by the COVID-19. A case of 68-year-old female with COVID-19 pneumonia who had constant pain in the right upper quadrant of her abdomen during her hospitalization that was finally diagnosed as acute cholecystitis. Ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) was performed, and the real-time fluorescence polymerase chain reaction (RT-PCR) COVID-19 nucleic acid assay of the bile was found to be negative. PTGD, antibacterial and anti-virus combined with interferon inhalation treatment were successful. The time course of chest CT findings is typical for COVID-19 pneumonia. PTGD is useful for acute cholecystitis in COVID-19 patients. Acute cholecystitis is likely to be caused by COVID-19 .


Optical Coherence Tomography-Guided Decisions in Retinoblastoma Management.
Assess the role of handheld optical coherence tomography (OCT) in guiding management decisions during diagnosis, treatment, and follow-up of eyes affected by retinoblastoma. Retrospective, noncomparative, single-institution case series. All children newly diagnosed with retinoblastoma from January 2011 to December 2015 who had an OCT session during their active treatment at The Hospital for Sick Children (SickKids) in Toronto, Canada. The OCT sessions for fellow eyes of unilateral retinoblastoma without any suspicious lesion and those performed more than 6 months after the last treatment were excluded. Data collected included age at presentation, sex, family history, RB1 mutation status, 8th edition TNMH cancer staging and International Intraocular Retinoblastoma Classification (IIRC), and number of OCT sessions per eye. Details of each session were scored for indication-related details (informative or not) and assessed for guidance (directive or not), diagnosis (staging changed, new tumors found or excluded), treatment (modified, stopped, or modality shifted), or follow-up modified. Frequency of OCT-guided management decisions, stratified by indication and type of guidance (confirmatory vs. influential). Sixty-three eyes of 44 children had 339 OCT sessions over the course of clinical management (median number of OCT scans per eye, 5; range, 1-15). The age at presentation and presence of a heritable RB1 mutation significantly correlated with an increased number of OCT sessions. Indications included evaluation of post-treatment scar (55%) or fovea (16%), and posterior pole scanning for new tumors (11%). Of all sessions, 92% (312/339) were informative; 19 of 27 noninformative sessions had large, elevated lesions; of these, 14 of 19 were T2a or T2b (IIRC group C or D) eyes. In 94% (293/312) of the informative sessions, OCT directed treatment decisions (58%), diagnosis (16%), and follow-up (26%). Optical coherence tomography influenced and changed management from pre-OCT clinical plans in 15% of all OCT sessions and 17% of directive sessions. Optical coherence tomography improves the accuracy of clinical evaluation in retinoblastoma management.


Cannabidiol inhibits Nav channels through two distinct binding sites.
Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Nav1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Nav1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Nav1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated "wedged" position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.


Directed differentiation of human embryonic stem cells to dendritic cells.
Embryonic stem cells represent a pluripotent population of cells capable of self-renewal, large-scale expansion, and differentiation in various cell lineages including cells of hematopoietic lineage. In this chapter, we describe a three-step cell culture method for directed differentiation of human embryonic stem cells (hESCs) to dendritic cells (DCs) that includes (1) hESC differentiation into hematopoietic progenitors by coculture with OP9 stromal cells, (2) expansion of myeloid DC precursors in suspension bulk cultures with granulocyte monocyte-colony stimulating factor (GM-CSF), and (3) differentiation of myeloid precursors to DCs in the serum-free medium with GM-CSF and interleukin-4 (IL-4). The method employs cell culture conditions selecting an almost pure population of myeloid DC precursors and does not require isolation of hematopoietic progenitors. With this method, hESCs can be differentiated to functional DCs within 30 days at an efficiency of at least four DCs per single undifferentiated hESC. Directed differentiation of DCs from hESCs could be useful for studying cellular and molecular mechanisms of DC development and potentially for the generation of antigen-presenting cells for cellular immunotherapy.


[Imaging of primary muscular diseases : What do neurologists expect from radiologists?]
Imaging, in particular magnetic resonance imaging (MRI), has in recent years increasingly become a crucial tool for the diagnostics of inherited and acquired muscular diseases. The aim of imaging in neuromuscular disorders goes beyond the detection and quantification of degenerative muscular changes, such as fatty degeneration and includes recognition of very early signs of muscular pathologies presenting as muscular edema. Therefore, imaging is a valuable diagnostic method to support the clinical diagnosis and to narrow down the differential diagnoses, leading to specific additional diagnostic tests in order to establish the correct diagnosis. Although advances in MRI hardware and technology have led to a faster, more accurate and advanced image acquisition allowing whole body examination in a feasible fashion, the standardization of image acquisition and interpretation remains a challenge. The aim of this review article is to address the important and clinically relevant issues concerning the role of imaging of neuromuscular diseases in order to facilitate a good interdisciplinary management for the diagnostics and monitoring of neuromuscular diseases.


Heated tobacco products: another tobacco industry global strategy to slow progress in tobacco control.
There has been a global decline in tobacco consumption that, if continued, will negatively impact the tobacco industry's profits. This decline led the industry to invent and market new products, including heated tobacco products (HTP). HTP are an extension of the industry's strategies to undermine government's tobacco regulatory efforts as they are being promoted as part of the solution for the tobacco epidemic. Under the moniker of 'harm reduction', the tobacco companies are attempting to rehabilitate their reputation so they can more effectively influence governments to roll back existing tobacco control policies or create exemptions for their HTP. Rolling back tobacco control policies will make it easier for the companies to renormalise tobacco use to increase social acceptability for all their products. When regulations are absent or when loopholes exist in classifying HTP as a tobacco product (thus subject to all tobacco control regulations), the industry's marketing of HTP is making these products more visible to the public and more accessible. Governments need to ensure that HTP are regulated as tobacco products or drugs and reject partnerships with the tobacco companies to promote 'harm reduction'. The tobacco companies remain the vector of the tobacco-caused epidemic and cannot be part of the global tobacco control solution.


Comatose within 6 weeks, but still alive after 3 years, Creutzfeldt-Jakob disease with unusual progression.
Creutzfeldt-Jakob disease (CJD) should still be considered in a patient presenting with rapidly progressive dementia and negative CSF 14-3-3 protein and RT-QulC. Treatable causes of encephalopathy must be ruled out. Neurodegenerative diseases must also be considered.


Genetic diversity and relationships among Nopalea sp. and Opuntia spp. accessions revealed by RAPD, ISSR and ITS molecular markers.
Dactylopius opuntiae (Cockerell) (carmine cochineal) is an insect pest highly noxious that has spread through cactus pear crops in the Brazilian semiarid region. Knowledge of diversity and genetic relationships of the cactus pear accessions is fundamental to create new varieties resistance to carmine cochineal. Therefore, this investigation was undertaken to assess the genetic diversity and genetic relationships that existed among cactus pear accessions of Nopalea sp. and Opuntia spp. with contrasting resistance to D. opuntiae. We conducted a molecular analysis in seven cactus pear accessions from the "reference collection" of the Agronomic Institute of Pernambuco, Brazil using RAPD, ISSR and ITS molecular markers. A total of 242 bands were detected from 26 polymorphic primers. The high percentage of polymorphism by RAPD (89.8%), ISSR (81.2%) and ITS (75%) markers suggests that the cactus pear accessions have high genetic diversity. The combined analysis of markers systems enabled the accessions discrimination of about the genus and ploidy, but were incongruous in relation to resistance level to D. opuntiae. Genetic diversity, discrimination of about the genus and ploidy was confirmed by merging information from ISSR, RAPD and ITS markers systems. The IPA-200016, IPA-200149, IPA-100004, IPA-200205 accessions are genetically divergent, therefore could be potentially incorporated into any further breeding programs directed to create new varieties of cactus pear resistant to D. opuntiae.


Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector Treg Cells.
Effector regulatory T (eTreg) cells are essential for immune tolerance and depend upon T cell receptor (TCR) signals for generation. The immunometabolic signaling mechanisms that promote the differentiation and maintenance of eTreg cells remain unclear. Here, we show that isoprenoid-dependent posttranslational lipid modifications dictate eTreg cell accumulation and function by intersecting with TCR-induced intracellular signaling. We find that isoprenoids are essential for activated Treg cell suppressive activity, and Treg cell-specific deletion of the respective farnesylation- and geranylgeranylation-promoting enzymes Fntb or Pggt1b leads to the development of fatal autoimmunity, associated with reduced eTreg cell accumulation. Mechanistically, Fntb promotes eTreg cell maintenance by regulating mTORC1 activity and ICOS expression. In contrast, Pggt1b acts as a rheostat of TCR-dependent transcriptional programming and Rac-mediated signaling for establishment of eTreg cell differentiation and immune tolerance. Therefore, our results identify bidirectional metabolic signaling, specifically between immunoreceptor signaling and metabolism-mediated posttranslational lipid modifications, for the differentiation and maintenance of eTreg cells.


Smooth muscle choristoma of the internal auditory meatus.
Choristomas of the internal auditory meatus are very uncommon tumors. Because of their rarity and the lack of a consistent clinical and radiological pattern, they are usually misdiagnosed as vestibular schwannomas. Surgical exploration usually shows involvement of the vestibular, cochlear or facial nerve by the tumor, representing a diagnostic and therapeutic challenge to the surgeon. In this report, a case of a smooth muscle choristoma of the internal auditory meatus is presented. The lesion involved the vestibular and cochlear nerves and was extremely adherent to the facial nerve. Microscopic examination of the tumor revealed nerve fibers, smooth muscle and a small amount of adipose tissue. No striated muscle was found. The contemporary terminology, diagnosis and management of this infrequent lesion are analyzed.


Effects of fibric acid derivatives and metformin on postprandial lipemia.
It was suggested that postprandial lipoproteins (PPLp) may play an important role in atherogenesis. We studied PPLp metabolism and its response to drugs in seven hypertriglyceridemic subjects, 23 men with isolated low HDL-C levels, and nine non-diabetic glucose intolerant subjects. Results were compared with those found in a group of 19 healthy normolipidemic individuals. We used the vitamin A-fat loading test which specifically labels PPLp with retinyl palmitate (RP). In the hypertriglyceridemics the areas under RP curves of the chylomicrons were 6.3-fold and those of non-chylomicrons 2.9-fold higher than in normals (P < 0.01). Gemfibrozil 1200 mg/day caused a dramatic decrease in chylomicrons 73% and nonchylomicrons 31%. In subjects with isolated low HDL-C, RP chylomicron curves were significantly higher than in normals (17.733+/-6.821 vs 13939+/-6217 microg/l per h, P < 0.005). Bezafibrate 400 mg/day reduced RP chylomicrons and nonchylomicron levels by 35% (P < 0.0001) in 15 responders with an increase in fasting HDL-C 35+/-3 to 40+/-22 mg/dl (P < 0.0001). No response was found in eight subjects. In the nine glucose intolerant subjects, metformin reduced postprandial insulin area under the curve from 389 to 245 mU/ml (P <0.01) chylomicron and nonchylomicron RP areas were 3.6- and 3-fold higher than in normals and were reduced by 56 and 32%, respectively. In conclusion gemfibrozil, bezafibrate and metformin were shown to be beneficial in the clearance of PPLp in hypertriglyceridemic patients, subjects with isolated low HDL-C levels and nondiabetic glucose intolerant subjects, respectively.


Framework for Risk Communication and Community Engagement to Improve Vaccine Uptake for COVID-19 and other Vaccine-Preventable Diseases in Low- and Middle-Income Countries (LMIC).
A framework for guiding risk communication and community engagement (RCCE) during COVID-19 vaccination roll-out is worthwhile in order to guide interventions aimed at improving vaccine uptake. This requires setting up standardised early-warning indicators to predict or detect low uptake; coordination of response activities by all partners, real-time information exchange, innovativeness in designing strategies to deal with arising and anticipated challenges; flexibility to adapt quickly to changing demands and evolving circumstances; and documentation of progress and lessons learnt.


Cystic lymphangioma arising in the tip of the tongue in an adult.
Cystic lymphangioma is a benign malformation of the lymphatic channels. Most cystic lymphangiomas are present at birth and are usually diagnosed in infancy or early childhood. The head and neck region appears to be the favored site for cystic lymphangiomas. We present the first reported case of a cystic lymphangioma arising from the tip of the tongue in a 75-year-old male.


Liquid-liquid extraction of lysozyme using a dye-modified ionic liquid.
An affinity-dye, Cibacron Blue 3GA (CB), derivatized organic salt [BMIM]3[CB] was synthesized for lysozyme extraction. This compound was formed by mixing an ionic liquid (IL) [BMIM][Cl] and the silver salt of CB. Liquid-liquid extractions of lysozyme from the aqueous and [BMIM]3[CB] in [BMIM][PF6] solutions were examined in this study. The transfer of lysozyme from the aqueous phase to the IL phase decreased while the pH of the aqueous phase increased. An extraction higher than 90% was observed at pH 4. Under a high ionic strength, the lysozyme would transform back from the IL phase into the aqueous phase. Lysozyme molecules were almost quantitatively recovered from the IL phase to the aqueous solutions of 1M KCl under pH 9-11. It appeared that the extraction was specific for lysozyme in contrast to cytochrome c, ovalbumin, and bovine serum albumin. The extraction efficiency of the IL phase remained essentially the same after eight cycles of extraction.


Outcomes of adult orthotopic heart transplantation with extended allograft ischemic time.
Heart procurement for orthotopic heart transplant (OHT) is limited by the conventional 4 hours of ischemic time (IT). Based on a recent report from our center showing that extended IT from a young donor group is safe, we widened our geographical reach, resulting in almost 40% of our transplants having an IT > 4 hours. We retrospectively reviewed records of adult patients who underwent OHT from January 2006 to December 2011. The primary outcome was survival, and secondary outcomes included resource utilization, end-organ dysfunction, and acute cellular rejection. Overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a combination of parametric and nonparametric statistics. A total of 323 patients underwent OHT. There was a significant difference in overall survival between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were no significant differences between the groups for secondary outcomes except a higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P = .01). Further analysis revealed that mortality remains similar if IT is below 4 hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the difference between our standard and extended IT. Limited donor availability for OHT dictates alternative strategies to enlarge the donor pool. Although there is an overall increasing risk with extended IT beyond 4 hours, it may be possible to safely increase the threshold to at least 5 hours without compromising the outcomes.


Duck hepatitis B virus DNA in liver, spleen, and pancreas: analysis by in situ and Southern blot hybridization.
Tissues from a 10-week-old Pekin duck, experimentally infected at 1 day of age with duck hepatitis B virus (DHBV), were examined for the presence of replicative levels of DHBV DNA by in situ and Southern blot hybridization. Hepatocytes, pancreatic lymphoid follicle, exocrine, and endocrine cells, and splenic mononuclear cells all contained DHBV DNA localized predominantly to the cytoplasm of infected cells. Duck hepatitis B surface antigen distribution in the same tissues correlated well with the presence of DHBV DNA in many of these cells. In hepatocytes and pancreatic islet cells, 60% of DHBV DNA was present as single-stranded DNA, indicating the likelihood of ongoing virus replication in these cell types and providing further evidence that hepadnavirus DNA replication occurs largely within the cell cytoplasm. In contrast, DHBV in mononuclear cells within splenic germinal centers was wholly double-stranded, suggesting that limited, if any, DHBV DNA replication was occurring in this cell type. These data provide further information about the pathogenesis and cell-specific sites of DHBV infection.


A comprehensive methodology to study double emulsion stability.
The stability of emulsions requires the fast formation of viscoelastic interfaces between water and oil phases. In double emulsions, two surfactant types (hydrophilic and lipophilic) are present and two interfacial films are involved. Understanding cooperative adsorption of these surfactants and its implication on properties of water/oil/water interfacial films will enable replacing the empirical methodologies used in designing double emulsion systems with a knowledge-based approach. The distribution of surfactants between the water/oil interfaces was investigated using single droplet diffusion experiments and simulation of equilibrium surfactant density profiles. The stability of the interfaces against coalescence was characterized by dye transport in a leach cell and coalescence time of single droplets in a model experiment. The conformation of the surfactants at an interface was then examined via surface rheology, sum frequency generation spectroscopy, and dissipative particle dynamics simulation. Two selected hydrophilic surfactants combined with a lipophilic surfactant induce very different properties at water/oil interfaces and different dye release behaviour from their corresponding double emulsions. Competitive adsorption of sodium dodecyl sulfate and lipophilic surfactant results in the improvement of encapsulation efficiency, elasticity of the interface, and resistance against coalescence due to the intercalation of surfactant alkyl chains into the oil chains.


Epithelial cells and fibroblasts: structural repair and remodelling in the airways.
Extensive lesions and changes in the architecture of the airway walls are commonly described in patients with respiratory infections, asthma, chronic bronchitis and interstitial lung diseases. Current knowledge identifies in airway epithelial cells and in fibroblasts the two cell types mainly involved in tissue repair after injury. During inflammatory respiratory disorders, extensive injury of airway epithelium may occur, with shedding of a large sheet of damaged cells in the bronchial and alveolar lumen but also with activation of the surviving epithelial cells and of the underlying fibroblasts. Indeed, besides acting as a physical and functional barrier to external agents, the epithelial surface of the bronchi has the capability to modulate the repair processes through the secretion of extracellular matrix proteins and the interaction with interstitial fibroblasts. Besides releasing pro-inflammatory cytokines and chemokines, the surviving epithelial cells and the underlying fibroblasts secrete factors contributing to airway repair, including the formation of the provisional extracellular matrix. This is indeed the substrate to which the epithelial cells at the edge of the lesion can attach to migrate in order to reconstitute the surface layer. In these processes airway epithelial cells receive the support of bronchial wall fibroblasts which actively release cytokines stimulating epithelial cell functions.


Corpus callosum: microsurgical anatomy and MRI.
The anatomy of the corpus callosum has received renewed interest during recent years due to the increasing number of callosotomies performed to treat intraventricular lesions, as well as some forms of generalized epilepsy. We have previously reported on the microsurgical anatomy of the corpus callosum and identified specific anatomical reference landmarks that can be used during surgery. In the present study we have continued the anatomical aspect of this earlier work in a larger number of cases, with in vitro observations (brain out of skull) being compared with the corresponding in vivo features seen in sagittal MRI slices. Fifty-three in vitro microsurgical callosotomies was performed and the data collected compared with a series of 57 in vivo normal MR callosal images. Callosal dimensions were measured on both the anatomical and MRI material, thus overcoming the problems associated with in vitro callosal deformation. Of the anatomical landmarks studied the distance from the genu of the corpus callosum to the bifurcation of the columns of the fornix was found to be useful for the intraoperative evaluation of the extent of rostral callosotomy, as it is not significantly changed in in vitro. The main microsurgical features of rostral callosotomy are presented.


(2-Hy-droxy-phen-yl)(4,2':4',4''-terpyridin-6'-yl)methanone.
The title compound, C22H15N3O2, can be described as a ketone with a phenol substituent and a terpyridine ligand coordinated to the carbonyl group. The three six-membered rings of the terpyridine ligand are not coplanar. The dihedral angles between the mean planes of the central ring and the external pyridine ligands are 22.77 (9) and 26.77 (7)°. The central ring of the terpyridine ligand is also not coplanar with the o-hy-droxy phenyl ring, the dihedral angle being 39.72 (5)°. An intra-molecular O-H⋯O hydrogen bond occurs. The crystal structure of the title compound is consolidated by C-H⋯O and C-H⋯N hydrogen bonding inter-actions.


Lignocellulosic biomass conversion via greener pretreatment methods towards biorefinery applications.
Lignocellulose biomass during pretreatment releases various compounds, among them the most important is reducing sugars, which can be utilized for the production of biofuels and some other products. Thereby, innovative greener pretreatment techniques for lignocellulosic materials have been considered to open a new door in the aspects of digestibility of the rigid carbohydrate-lignin matrix to reduce the particle size and remove hemicellulose/lignin contents to successfully yield valid bioproducts. This article reviews about the composition of lignocelluloses and emphasizes various green pretreatments viz novel green solvent-based IL and DES steam explosion, supercritical carbon dioxide explosion (Sc-CO2) and co-solvent enhanced lignocellulosic fractionation (CELF) along with suitable mechanistic pathway of LCB pretreatment process. Finally, this article concludes that the existing pretreatments should be redesigned to conquer the demands by large scale production and suggests combined pretreatment methods to carry out various biomass pre-processing.


Aortic aneurysm rupture into a retroaortic left renal vein.
We report the case of a patient who was transferred to our facility after a CT scan obtained at a local hospital revealed a leaking abdominal aortic aneurysm. Review of the scan showed an aorto-left renal vein fistula. Knowing this fistula was present made the operative repair of the aneurysm and control of the fistula much more straightforward than might otherwise have been the case. Although relatively rare, major anomalies of the renal veins and perirenal vena cava should be borne in mind when operating on the abdominal aorta. This case illustrates the merit of contrast-enhanced CT scanning prior to aortic surgery.


Changes of transcranially evoked motor responses in man by midazolam, a short acting benzodiazepine.
The present study investigated the effects of midazolam, a short acting benzodiazepine, on muscle responses elicited by magnetic brain stimulation. During continuous midazolam infusion (0.3 mg/kg/h for up to 30 min) amplitudes and durations of transcranially elicited compound muscle action potentials decreased progressively while latencies remained unchanged. The results can be accounted for by midazolam enhancement of the inhibitory action of GABAergic cortical interneurons, which decreases the excitability of pyramidal cells and reduces the number of neurons available for generation of descending pyramidal tract activity.


The dorsal and medial raphe projections to the substantia nigra in the rat: electrophysiological, biochemical and behavioural observations.
Electrophysiological experiments have been performed in urethane anaesthetized rats to investigate the projections from the dorsal (DRN) and medial raphe nuclei (MRN) to the substantia nigra. The biochemical and behavioural effects following discrete electrolytic lesions in the dorsal and medial raphe have also been investigated. Stimulation of the DRN produced predominantly inhibition of spontaneous activity of single neurones in the substantia nigra though some neurones were also excited. Bilateral stimulation of the substantia nigra produced antidromic spikes in DRN and MRN neurones. Lesions of the DRN and MRN produced a significant reduction in substantia nigra 5-HT concentration. Additionally, DRN lesions reduced striatal 5-HT, while MRN lesions reduced hippocampal 5-HT. Both lesions increased substantia nigra HVA concentration but did not affect DA concentration. Neither DRN nor MRN lesions affected striatal HVA, although DA levels were significantly elevated after 14 days. Animals with DRN lesions explored more than controls or MRN-lesioned animals. However, this behaviour was transient and was not observed after 14 days. On the other hand, MRN-lesioned animals were significantly hyperactive. These observations suggest that the substantia nigra receives a direct monosynaptic inhibitory input from the DRN and MRN and that these pathways use 5-HT as a neurotransmitter serving to tonically inhibit dopaminergic neurones. While 5-HT and dopamine appear to be involved in the control of motor behaviour, the precise relationship between these serotoninergic and dopaminergic systems in this respect is unclear.


Mechanisms Underlying the Hydrogen Sulfide Actions: Target Molecules and Downstream Signaling Pathways.
Significance: As a new important gas signaling molecule like nitric oxide (NO) and carbon dioxide (CO), hydrogen sulfide (H2S), which can be produced by endogenous H2S-producing enzymes through l-cysteine metabolism in mammalian cells, has attracted wide attention for long. H2S has been proved to play an important regulatory role in numerous physiological and pathophysiological processes. However, the deep mechanisms of those different functions of H2S still remain uncertain. A better understanding of the mechanisms can help us develop novel therapeutic strategies. Recent Advances: H2S can play a regulating role through various mechanisms, such as regulating epigenetic modification, protein expression levels, protein activity, protein localization, redox microenvironment, and interaction with other gas signaling molecules such as NO and CO. In addition to discussing the molecular mechanisms of H2S from the above perspectives, this article will review the regulation of H2S on common signaling pathways in the cells, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer, and activator of transcription (STAT) signaling pathway. Critical Issues: Although there are many studies on the mechanism of H2S, little is known about its direct target molecules. This article will also review the existing reports about them. Furthermore, the interaction between direct target molecules of H2S and the downstream signaling pathways involved also needs to be clarified. Future Directions: An in-depth discussion of the mechanism of H2S and the direct target molecules will help us achieving a deeper understanding of the physiological and pathophysiological processes regulated by H2S, and lay a foundation for developing new clinical therapeutic drugs in the future. Innovation: This review focuses on the regulation of H2S on signaling pathways and the direct target molecules of H2S. We also provide details on the underlying mechanisms of H2S functions from the following aspects: epigenetic modification, regulation of protein expression levels, protein activity, protein localization, redox microenvironment, and interaction with other gas signaling molecules such as NO and CO. Further study of the mechanisms underlying H2S will help us better understand the physiological and pathophysiological processes it regulates, and help develop new clinical therapeutic drugs in the future.


Neonatal liver failure.
Liver failure in the neonatal period is challenging to diagnose and manage, and still carries a high mortality. With ongoing developments in the field of metabolic disorders and antiviral therapy, and the ability to offer liver transplantation to small babies, an overall survival of 40% has been achieved. Early recognition of liver failure, good supportive care and prompt referral to a paediatric liver transplant centre are essential elements in improving the outcome for these babies. Decisions about contra-indications to and timing of transplantation are complex as many of the disease processes are still evolving in the neonatal period, and extrahepatic disease, which cannot be corrected by a transplant, may appear later.


Genetic and transcriptomic analyses support a switch to lytic phase in Epstein Barr virus infection as an important driver in developing Systemic Lupus Erythematosus.
To investigate the molecular mechanisms through which Epstein-Barr virus (EBV) may contribute to Systemic Lupus Erythematosus (SLE) pathogenesis, we interrogated SLE genetic risk loci for signatures of EBV infection. We first compared the gene expression profile of SLE risk genes across 459 different cell/tissue types. EBV-infected B cells (LCLs) had the strongest representation of highly expressed SLE risk genes. By determining an SLE risk allele effect on gene expression (expression quantitative trait loci, eQTL) in LCLs and 16 other immune cell types, we identified 79 SLE risk locus:gene pairs putatively interacting with EBV infection. A total of 10 SLE risk genes from this list (CD40, LYST, JAZF1, IRF5, BLK, IKZF2, IL12RB2, FAM167A, PTPRC and SLC15A) were targeted by the EBV transcription factor, EBNA2, differentially expressed between LCLs and B cells, and the majority were also associated with EBV DNA copy number, and expression level of EBV encoded genes. Our final gene network model based on these genes is suggestive of a nexus involving SLE risk loci and EBV latency III and B cell proliferation signalling pathways. Collectively, our findings provide further evidence to support the interaction between SLE risk loci and EBV infection that is in part mediated by EBNA2. This interplay may increase the tendency towards EBV lytic switching dependent on the presence of SLE risk alleles. These results support further investigation into targeting EBV as a therapeutic strategy for SLE.


Treatment for the addictions in a psychiatric setting.
The Alcoholism, Chemical Dependency and Compulsive Gambling Services at South Oaks Hospital (a 334-bed private psychiatric facility in Amityville, New York) are discussed. Psychodrama and other group methods are integral parts of the program the interdisciplinary treatment team, headed by a psychiatrist, includes addiction counsellors. Outpatient continuing care and self-help groups are stressed.


Studying MHC class I peptide loading and exchange in vitro.
In the endoplasmic reticulum (ER), MHC class I molecules associate with several specialized proteins, forming a large macromolecular complex referred to as the "peptide-loading complex" (PLC). In the PLC, antigenic peptides undergo a stringent selection process for binding onto MHC class I molecules. This ensures that the immune system elicits robust CD8+ T-cell responses to viruses and solid tumors. The ability to reconstitute in vitro MHC class I molecules in association with key proteins of the PLC provides a mean for studying at the molecular level how antigenic peptides are selected for presentation to CD8+ T-cells. Here, we describe practical procedures for generating a cell-free system involving MHC class I molecules and tapasin, a critical protein of the PLC, that can be used as a versatile tool for biochemical and mechanistic studies of peptide loading and exchange.


Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders.
Manganese superoxide dismutase (MnSOD) activity is highly elevated in the biopsies of human asbestos-associated malignant mesothelioma. We therefore examined if polymorphism in the mitochondrial targeting sequence of the MnSOD gene modified individual susceptibility to this malignancy or related asbestos-associated pulmonary disorders. The study population consisted of 124 male Finnish asbestos insulators who were all classified as having been exposed to high levels of asbestos; 63 of the workers had no pulmonary disorders and 61 either had malignant mesothelioma or the non-malignant pulmonary disorders asbestosis and/or pleural plaques. No significant associations were found between the MnSOD genotypes and these ill-health. This study therefore suggest no major modifying role for the MnSOD polymorphism in development of asbestos-associated pulmonary disorders.


Mebendazole and insulin secretion from isolated rat islets.
In a preliminary communication we reported that mebendazole, a vermicide, decreased plasma glucose and free fatty acid concentrations and increased plasma C peptide concentrations in both type II diabetic patients. Therefore, we suggested that mebendazole was an insulin secretagogue. However, these were uncontrolled studies, and improved metabolic control in these patients due to spontaneous remission rather than drug-induced insulin secretion was a possibility. To investigate the direct effect of mebendazole on insulin secretion we used intact islets isolated from normal rat pancreata. Mebendazole in concentrations as low as 10 to 20 mumol/L caused a twofold to threefold increase in acute-phase insulin release from isolated perifused rat islets. This heightened insulin release occurred in the presence of glucose-stimulated insulin secretion.


Trace gas emissions from German agriculture as obtained from the application of simpler or default methodologies.
For the assessment of emission inventories matching pairs of activities (emission explaining variables) and emission factors are used. Simpler and detailed methodologies are proposed within the emission inventory handbooks. The data sets needed to serve the detailed methodologies have not been at public disposal so far. Therefore, this paper investigates the applicability of simpler methodologies to the statistical data sets of activities officially available in Germany. The statistical data base for the assessment of emissions from fertilised soils is adequate if one assumes that fertilisers sold in one financial year are applied in the same year. For grassland, statistical data describing the actual management do not exist. Lack of nitrogen inputs with crop residues and due to nitrogen fixation make it impossible to deduce the respective emissions. The assessment of indirect emissions due to reactions of leached nitrogen is also impossible. For extensively managed grasslands, data concerning fertiliser application or grazing are missing when calculating emissions. The determination of emissions from organic soils presupposes the knowledge of both the area concerned and the degree of mineralisation which has been attained at the time of the inventory. The results of the biennial animal census meet the requirements of the simpler methodologies. However, the assumptions made to evaluate the mean emission factors are not correct in many cases, as far as animal performance, housing, storage and application of animal excreta are concerned. The simpler methodologies are biassed, as the emission factors are (Northwest) European means. Changes in the raising of statistical data make the construction of meaningful time-series difficult.


Transthoracic echocardiography visualization of bicaval dual lumen catheters for veno-venous extracorporeal membrane oxygenation.
Bicaval dual lumen catheters improve the efficiency of veno-venous extracorporeal membrane oxygenation by minimizing recirculation with an innovative design, which requires precise placement of three catheter ports in the superior vena cava, right atrium, and inferior vena cava, respectively. However, the exact position of these catheter ports is usually not known during placement because they cannot be visualized with conventional radiography. We performed a retrospective review of our experience over the past year using transthoracic echocardiography to evaluate the position of the catheter ports. From a subcostal, sagittal imaging approach, we were able to identify all three catheter ports in 11 of 11 studies. At least one of the catheter ports was incorrectly positioned in 5 of 11 studies. Further prospective evaluation is necessary to determine if catheter repositioning based on transthoracic echocardiography findings can further improve the clinical efficiency of veno-venous extracorporeal membrane oxygenation.


Psychometric properties of the physical environment problems and barriers scale in older adults' homes using an ergonomic approach.
As older adults prefer to live in their homes, it is of paramount importance to examine the adaptation of the environment to the older adults' capabilities. The aim of this study was to develop and evaluate psychometric properties of a scale to measure physical environment problems and barriers in older adults' homes using an ergonomic approach in Iran. This mixed-method investigation was conducted in two stages in Yazd, Iran. The primary 71-item version of the questionnaire was developed according to qualitative findings and a thorough review of the literature. Then the psychometric characteristics, including face, content, construct validity, were assessed. Content validity was also assessed using CVI and CVR. Finally, its reliability and construct validity were confirmed by composite reliability (CR), Fornell-Larker matrix, and confirmatory factor analysis (CFA) using Smart PLS software version 3. The face validity of the developed scale was acceptable, and the mean scores of CVI and CVR were 0.78 and 0.84, respectively. The preliminary draft of the scale was categorized into seven dimensions. Factor validity and reliability were confirmed by acceptable factor loadings, and desirable realms of composite reliability (>0.7) average variance extracted (>0.5). The cross-loading method and the Fornell-Larker matrix were used to evaluate the divergent validity of the scale, and the results confirmed its acceptable fit. The findings indicated that reliability reached acceptable values, and different aspects of validity were almost confirmed. Accordingly, the questionnaire was to measure physical environment problems and barriers in older adults' homes; however, it requires further validation for future use in other contexts.


Percutaneous Coronary Intervention for Left Main Coronary Artery Disease: Present Status and Future Perspectives.
For several decades, coronary artery bypass grafting has been regarded as the standard choice of revascularization for significant left main coronary artery (LMCA) disease. However, in conjunction with remarkable advancement of device technology and adjunctive pharmacology, percutaneous coronary intervention (PCI) offers a more expeditious approach with rapid recovery and is a safe and effective alternative in appropriately selected patients with LMCA disease. Several landmark randomized clinical trials showed that PCI with drug-eluting stents for LMCA disease is a safe option with similar long-term survival rates to coronary artery bypass grafting surgery, especially in those with low and intermediate anatomic risk. Although it is expected that the updated evidence from recent randomized clinical trials will determine the next guidelines for the foreseeable future, there are still unresolved and unmet issues of LMCA revascularization and PCI strategy. This paper provides a comprehensive review on the evolution and an update on the management of LMCA disease.


Regional mapping of the gene for human lysosomal acid phosphatase (ACP2) using a hybrid clone panel containing segments of human chromosome 11.
A clone panel containing various segments of human chromosome 11 has been selected and use for regional assignment of the gene for human lysosomal acid phosphatase (ACP2) to the short arm of chromosome 11, in the region 11p11 leads to 11p12. Further evidence has also been presented to update the regional assignment of the gene for lactate dehydrogenase A (LDHA) to 11p12 leads to 11p13, and to support a previous assignment of the genes for the two components of the human cell-surface antigens of the SA11 (previously designated AL) group, SA11-1 and SA11-3 (previously designated AL-a1 and AL-a3), to 11pter leads to 11p13. This regional clone panel will be useful for rapid regional mapping of other genes assigned to chromosome 11.


Cardiologist's knowledge and attitudes about obstructive sleep apnea: a survey study.
Obstructive sleep apnea (OSA) is associated with cardiovascular diseases, yet available data suggests cardiologists underreport OSA. This study assessed whether cardiologists' knowledge and attitudes about OSA contribute to this finding. A previously validated questionnaire, the "Obstructive Sleep Apnea Knowledge and Attitudes Questionnaire" (OSAKA), was modified by the addition of 20 knowledge items and one attitude question to include a total of 38 knowledge items and six attitude questions. The questionnaire was mailed to a random sampling of 420 cardiologists in the USA. Ninety-two cardiologists (22%) returned completed questionnaires. Mean age was 48 +/- 10 years, 74% were male, and 52% were general cardiologists. Mean score on the original OSAKA portion of the questionnaire (76%) was similar to previously reported scores of primary care physicians (PCPs), while the total knowledge score was 77%. Scores did not differ by gender (p = 0.7) or subspecialty (p = 0.3), and there were no correlations between knowledge and age or years in practice. While 80% stated that identifying patients at risk for OSA was very or extremely important, only 68% felt confident identifying these patients, and only 18% felt confident managing OSA patients. There was no difference in mean total attitude score when analyzed by age, gender, years of practice, and subspecialty. Total knowledge scores correlated with attitude scores (r = 0.29, p = 0.004). Cardiologists' knowledge about OSA is comparable to that of PCPs. Cardiologists may lack confidence identifying and managing patients with OSA, factors that may contribute to their low rate of reporting OSA.


Unusual Presentation of Guillain-Barré Syndrome After Mandibular Fracture Treatment: A Review of the Literature and a New Case.
Guillain-Barré syndrome (GBS) is a multifactorial and lethal inflammatory demyelinating neuronal disorder with concurrent polyradiculopathy and polyneuropathy presentations. This rare syndrome affects the peripheral nerve myelin sheath and is characterized by ascending muscle weakness and paralysis. There have been rare reports of GBS after head or brachial plexus trauma, general anesthesia, neurosurgery, orthopedic surgery, cesarean section, laparoscopy, and general surgery, and the occurrence of GBS after oral and maxillofacial surgery is not common. A review of the related literature and a new case of GBS after maxillofacial surgery are presented.


Topological charge-sharing background reduction for the Silicon Drift Detectors used by the VIP experiment at LNGS.
Large area Silicon Drift Detectors are employed in high sensitivity tests of the Pauli Exclusion Principle by the VIP-2 Collaboration. The experiment is operated in the extremely low cosmic background environment of the Gran Sasso underground National Laboratory of INFN. In this work an off-line analysis method is proposed which provides an additional background reduction, as well as a better calibration procedure. The study concerns in particular the charge sharing between nearby cells, and is applied to the data set collected during the 2018 VIP-2 campaign. The cross-talk effect inside the detectors array is described and an effective topological method to reject the background induced by charge sharing is outlined.


Intestinal microbiota analyses of five economic fishery resources in the South China Sea.
The investigation of intestinal microbiota can provide evidence for revealing the growth and development regulation, feeding habits, environmental adaptability and pollutant indication of marine organisms. To data, the intestinal microbiota of marine organisms in the South China Sea is relatively lacking. To supplement these information, we sequenced intestinal microbiota from five fishery resources (including Auxis rochei, A. thazard, Symplectoteuthis oualaniensis, Thunnus albacores, and Coryphaena equiselis) in the South China Sea using high-throughput Illumina sequencing technology. After filtering, a total of 18,706,729 reads were finally produced and then clustered into OTUs. The mean number of OTUs detected in A. rochei, A. thazard, C. equiselis, S. oualaniensis, and T. albacores was 127, 137, 52, 136, and 142, respectively. Although the Actinobacteria, Bacteroidetes, Cyanobacteria, Deferribacteres, Firmicutes, Proteobacteria, Spirochaetes, Tenericutes, [Thermi], and unclassified_Bacteria were the most abundant in the five species, Photobacterium is the most abundant microbiota. Meanwhile, intestinal microbiota showed species- and sampling sites- specificity, thus only 84 microbiota species were common to all species. Additionally, the potential functions of OTUs in the five species is mainly involved in the synthesis and metabolism of carbohydrate, amino acid, fatty acid and vitamin. This study can provide basic data for clarifying the diversity and species- specificity of intestinal microbiota of five species in the South China Sea, and help to improve the intestinal microbiota database of marine organisms.


Neurocysticercosis in persons with epilepsy in Medellín, Colombia. The Neuroepidemiological Research Group of Antioquia.
A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellín, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. Prevalence of neurocysticercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellín. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.


Induced electric and magnetic fields due to wave propagation in a tubular bone.
Electric and magnetic fields in tubular bones induced due to the propagation of travelling axisymmetric torsional waves, are determined in the paper by accounting for the piezoelectricity, inhomogeneity and anisotropy of osseous tissues. Using the derived expressions and experimentally determined values of the involved physical constants, numerical values of the displacement and stress fields, and also the induced fields are computed for points at different locations of the bone specimen.


Self-reported medication adherence and pharmacy refill adherence among persons with ischemic stroke: a cross-sectional study.
To describe and compare self-reported medication adherence assessed with the 5-item version of Medication Adherence Report Scale (MARS-5) and pharmacy refill adherence based on data from the Swedish Prescribed Drug Register (SPDR) among persons with ischemic stroke, and to investigate independent predictors associated with respective assessments. A study questionnaire was sent to persons with ischemic stroke registered in the Swedish Stroke Register between Dec 2011 and March 2012, and who lived at home 3 months after discharge. The primary outcome was dichotomized to adherent/non-adherent based on MARS-5 and SPDR and analyzed with multivariable logistic regression. Adherence according to MARS-5 was defined as score 23 or higher (out of 25). Adherence according to SPDR was defined as at least one filled statin prescription recorded in SPDR in each 6-month interval during 2 years of follow-up. Of 420 participants, 367 (87%) and 329 (78%) were adherent according to MARS-5 and SPDR, respectively, and 294 (70%) participants were adherent according to both assessments. A significant association was shown between medication adherence according to the two assessments (p = 0.020). Independent predictors associated with medication adherence according to MARS-5 were female sex, while factors associated with SPDR were male sex and being younger. The majority of participants were classified as adherent, 87% according to MARS-5 and 78% based on data from SPDR. However, only 70% were adherent according to both MARS-5 and SPDR, and different predictors were associated with the different measurements, suggesting that these assessments are measuring different aspects of adherence.


Time to make some noise about a quiet revolution.
'Tomorrow belongs to those who can hear it coming' David Bowie. Language is a living entity that moves and changes. Use of gender-neutral language in medical literature is increasingly common. It is time for obstetricians and gynaecologists in Australia and New Zealand to interrogate their own bias and desire to maintain the status quo, and to consider reasons for change.


Modulation in cytochrome P-420 and P-450 content in Saccharomyces cerevisiae according to physiological conditions and genetic background.
The diploid strain D5 of Saccharomyces cerevisiae, relative to other strains of yeast, has a large amount of cytochrome P-450 present during the logarithmic phase of growth and a low amount of cytochrome P-420. As the stationary phase of growth is approached, an increasing intensity of absorbance is observed at 420 nm. If the cells are suspended in buffer during mid-logarithmic growth, the absorbance at 450 nm disappears and absorbance at 420 nm is increased after the cells have been held in buffer for 24 h. At late logarithmic growth, the absorbance at 450 nm is still retained after the cells have been held in buffer for 24 h. Within 44 h of the time of harvest, the absorbance at 450 nm disappears completely and the absorbance at 420 nm is intense. Cytoplasmic petite variants of strain D5 have less of both cytochromes P-450 and P-420 than does the grande D5 strain; the absorbances at 450 and 420 nm are retained up to 96 h when the cells are held in buffer. Haploid spores of strain D5 exhibit absorbances at 450 and 420 nm during the logarithmic phase of growth, and these absorbances are retained after the cells are held in buffer for 24 h. An hypothesis is proposed which states that cytochrome P-450 is the membrane-bound form and cytochrome P-420 is free in the cytosol; the cytochromes interconvert and are active in either state until the associated enzymes disassociate.


Concomitant oxidation of fatty acids other than DHA and EPA plays a role in the characteristic off-odor of fish oil.
The aim of the present research was to explore the development of off-odors in fish oil from the perspective of fatty acid oxidation. It was found that the off-odors elicited by the two major ω-3 PUFAs in fish oil, i.e. DHA and EPA, were different from those by fish oil. Results showed that simultaneous oxidation of fatty acids other than DHA and EPA can be involved. The off-odors of fish oil was successfully simulated by combining oxidized samples of DHA, EPA and sunflower oil. Therefore, oxidation of oleic and linoleic acids also contributed to the off-odors in fish oil. A novel analytical approach that consisted in the combination of gas chromatography-ion mobility spectrometry (GC-IMS) and orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify differences in the volatile components between the recombinant oil and the fish oil.


Recombinogenic targeting: a new approach to genomic analysis--a review.
Currently, recombinational cloning procedures based upon methods developed for yeast, Saccharomyces cerevisiae, are being exploited for targeted cloning and in-vivo modification of genomic clones. In this review, we will discuss the development of large-insert vectors, homologous recombination-based techniques for cloning and modification, and their application towards functional analysis of genes using transgenic mouse model systems.


Long term metabolic arrest and recovery of HEK293 spheroids involves NF-kappaB signaling and sustained JNK activation.
Understanding how cells withstand a depletion of intracellular water is relevant to the study of longevity, aging, and quiescence because one consequence of air-drying is metabolic arrest. After removal of medium, HEK293 spheroids with intracellular water content of approximately 65% survived partial vacuum, with antistatic control, for weeks in the dark at 25 degrees C. In contrast, only a limited exposure of monolayers to air was lethal; the mitochondrion being a target of this stress. The pathways activated during the long-term arrest and recovery of spheroids depended on both NF-kappaB signaling and sustained JNK activation. A cyclical cascade, presumably originating from an intercellular stress signal, led to endogenous cytokine production (TNF-alpha, IL-1b, and IL-8) and propagation of the cellular stress signal through the co-activation of NF-kappaB and JNK. Increased levels of downstream pathway signaling members, specifically Gadd45beta, c-jun, and ATF3 were observed, as was activation of c-jun (phosphorylation). Activation of these pathways permit cells to survive long-term storage and recovery because chemical inhibition of both NF-kappaB nuclear translocation and JNK phosphorylation led to cell death. The capacity of an immortalized cell to enter, and then exit, a state of long-term quiescence, without genetic or chemical intervention, has implications for the study of cell transformation. In addition, the ability to monitor the relevant signaling pathways at endogenous levels, from effector to transcriptional regulator, emphasizes the utility of multicellular aggregate models in delineating stress response pathways.


Quantification of nine psychotropic drugs in postmortem dried blood spot samples by liquid chromatography-tandem mass spectrometry for simple toxicological analysis.
Dried blood spot (DBS) sampling has evolved to become the method of choice for collecting samples for newborn screening and therapeutic drug monitoring worldwide. The major advantage of this approach is that it requires only a small amount of blood. In addition, the collection of DBSs on filter paper is simple, sample storage costs are small, and the process deactivates microorganisms and viruses. However, despite these advantages, DBS sampling is seldom used in forensic toxicological analyses. Here, we developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry for quantifying nine psychotropic drugs (citalopram, duloxetine, mirtazapine, olanzapine, paroxetine, quetiapine, sertraline, zolpidem and zopiclone) in cadaveric DBS samples. Most of them are frequently used by self-harm but are not already targeted by an existing drug screening kit. Our method use only one 3-mm disk excised from each DBS and does not require the troublesome purification process. The linearities of the calibration curves were good in the concentration range of 0.05-1.0 μg/mL. Our method allows for repeatable and accurate quantification with intra- and inter-assay coefficients of variation of below 11.9% and below 12.5%, respectively, for each of the target drugs. In addition, the target drug concentrations in the DBSs remained stable for at least one month when stored at - 80 °C. Compared with our institute's routine method for cadaveric blood sampling, the QuEChERS method, quantifiable concentrations showed a good positive correlation for each of the target drugs. In addition, the concentrations of almost all the target drugs obtained with DBS sampling method were comparable with those obtained with the QuEChERS sampling method. Thus, the present findings extend the possible uses of DBS sampling to the quantification of multiple psychotropic drugs in the field of forensic toxicological testing.


DICOM Image ANalysis and Archive (DIANA): an Open-Source System for Clinical AI Applications.
In the era of data-driven medicine, rapid access and accurate interpretation of medical images are becoming increasingly important. The DICOM Image ANalysis and Archive (DIANA) system is an open-source, lightweight, and scalable Python interface that enables users to interact with hospital Picture Archiving and Communications Systems (PACS) to access such data. In this work, DIANA functionality was detailed and evaluated in the context of retrospective PACS data retrieval and two prospective clinical artificial intelligence (AI) pipelines: bone age (BA) estimation and intra-cranial hemorrhage (ICH) detection. DIANA orchestrates activity beginning with post-acquisition study discovery and ending with online notifications of findings. For AI applications, system latency (exam completion to system report time) was quantified and compared to that of clinicians (exam completion to initial report creation time). Mean DIANA latency was 9.04 ± 3.83 and 20.17 ± 10.16 min compared to clinician latency of 51.52 ± 58.9 and 65.62 ± 110.39 min for BA and ICH, respectively, with DIANA latencies being significantly lower (p < 0.001). DIANA's capabilities were also explored and found effective in retrieving and anonymizing protected health information for "big-data" medical imaging research and analysis. Mean per-image retrieval times were 1.12 ± 0.50 and 0.08 ± 0.01 s across x-ray and computed tomography studies, respectively. The data herein demonstrate that DIANA can flexibly integrate into existing hospital infrastructure and improve the process by which researchers/clinicians access imaging repository data. This results in a simplified workflow for large data retrieval and clinical integration of AI models.


Inferring molecular function: contributions from functional linkages.
In the current era of high-throughput sequencing and structure determination, functional annotation has become a bottleneck in biomedical science. Here, we show that automated inference of molecular function using functional linkages among genes increases the accuracy of functional assignments by > or =8% and enriches functional descriptions in > or =34% of top assignments. Furthermore, biochemical literature supports >80% of automated inferences for previously unannotated proteins. These results emphasize the benefit of incorporating functional linkages in protein annotation.


Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature.
The resurgence of the malaria eradication agenda and the increasing number of severe manifestation reports has contributed to a renewed interested in the Plasmodium vivax infection. It is the most geographically widespread parasite causing human malaria, with around 2.85 billion people living under risk of infection. The Brazilian Amazon region reports more than 50% of the malaria cases in Latin America and since 1990 there is a marked predominance of this species, responsible for 85% of cases in 2009. However, only a few complicated cases of P. vivax have been reported from this region. A systematic review of the Brazilian indexed and non-indexed literature on complicated cases of vivax malaria was performed including published articles, masters' dissertations, doctoral theses and national congresses' abstracts. The following information was retrieved: patient characteristics (demographic, presence of co-morbidities and, whenever possible, associated genetic disorders); description of each major clinical manifestation. As a result, 27 articles, 28 abstracts from scientific events' annals and 13 theses/dissertations were found, only after 1987. Most of the reported information was described in small case series and case reports of patients from all the Amazonian states, and also in travellers from Brazilian non-endemic areas. The more relevant clinical complications were anaemia, thrombocytopaenia, jaundice and acute respiratory distress syndrome, present in all age groups, in addition to other more rare clinical pictures. Complications in pregnant women were also reported. Acute and chronic co-morbidities were frequent, however death was occasional. Clinical atypical cases of malaria are more frequent than published in the indexed literature, probably due to a publication bias. In the Brazilian Amazon (considered to be a low to moderate intensity area of transmission), clinical data are in accordance with the recent findings of severity described in diverse P. vivax endemic areas (especially anaemia in Southeast Asia), however in this region both children and adults are affected. Finally, gaps of knowledge and areas for future research are opportunely pointed out.


Bridging molecules are secreted from the skeletal muscle and potentially regulate muscle differentiation.
Muscle myogenesis is an essential step for muscle development and recovery. During muscle fusion, multiple molecules are thought to be necessary for the formation of normal myotubes. Milk fat globule-EGF factor 8 (MFG-E8) and Gas6 are phosphatidylserine-recognizing bridging molecules that are secreted mainly from immune cells. In this study, we confirmed that these molecules are expressed and secreted from C2C12 cells. Mouse muscle and satellite cells also expressed these molecules. MFG-E8 was highly expressed and secreted in both undifferentiated and differentiated C2C12 cells. We observed that MFG-E8 and Gas6 were bound to the surface of differentiated C2C12 cells more compared with undifferentiated cells. Additionally, the treatment of recombinant MFG-E8 upregulated expression of myogenic genes and suppressed apoptosis during myogenesis in C2C12 cells. In this paper, we discuss the presence of novel functional molecules expressed and secreted in the skeletal muscle. The results of this study suggest that bridging molecules are one of the determinants of myogenesis or other muscle responses.


Defective Fc-dependent processing of immune complexes in patients with systemic lupus erythematosus.
To explore the Fc receptor-dependent handling of immune complexes (ICs) by the fixed mononuclear phagocytic systems (MPS) in patients with systemic lupus erythematosus (SLE). The processing in vivo of soluble model (123)I-hepatitis B/ anti-hepatitis B ICs was studied in 12 healthy subjects and 10 patients with active SLE. ICs that fixed complement poorly were prepared specifically in order to explore Fc receptor-dependent clearance mechanisms. Clearance kinetics and organ uptake were assessed by computer-aided gamma scintigraphy and serial blood sampling. In both patients and controls, the main site of IC clearance was the liver; only 2-6% of injected ICs were taken up in the spleen. The kinetics of initial IC clearance were similar in both groups, but defective hepatic retention of ICs was demonstrated in patients with SLE. At 1 hour, hepatic activity in patients had fallen to 56% of maximum, compared with 74% in controls (P = 0.0002). Precipitation studies performed on serum samples using staphylococcal protein A-Sepharose indicated that antibody-complexed tracer was released from the liver 20-50 minutes after injection. These results indicate that Fc-mediated clearance of ICs is defective in patients with SLE and suggest that ligation of ICs by Fc receptors is critical for their efficient binding and retention by the fixed MPS in the liver.


Vitamin E up-regulates arachidonic acid release and phospholipase A2 in megakaryocytes.
The release of arachidonic acid is the rate limiting step in eicosanoid synthesis. In mammalian cells, the release of arachidonic acid is catalyzed by several enzymes. The 85 kDa cytosolic phospholipase A2 (cPLA2) is the key enzyme for the release reaction because of its specific acyl selectivity in phospholipid substrates. We have previously reported that vitamin E enrichment potentiates the arachidonic acid release as well as the spontaneous prostacyclin release in human endothelial cells. In contrast, similar enrichment of diets caused a dose-dependent suppression of platelet thromboxane synthesis. Therefore, the present study was undertaken to determine the effect of vitamin E on arachidonate release and phospholipaseA2 activity in a platelet precursor cell, the MEG-01 megakaryocyte cell line. When these cells were incubated with different concentrations of vitamin E, cellular incorporation was linear with the dosages of this vitamin. Determination of arachidonate release after labeling cells with [3H]-arachidonate showed that vitamin E enrichment caused a dose-dependent increase in ionophore A23187-induced [3H]-arachidonic acid release. Analysis of PLA2 activity showed that activity was detected in the cytosol and this activity was completely abolished by the addition of anti-cPLA2, antibody. Determination of cPLA2 activity demonstrated that vitamin E enrichment caused an increase in enzyme activity. Analysis of cPLA2 protein by Western blot revealed that vitamin E caused an increase in enzyme protein. These data showed that the potentiation of arachidonic acid release and cPLA2, activity by vitamin E was mediated by the enhanced expression of cPLA2 protein.


Vasculitis associated with connective tissue disorders.
Vasculitis associated with connective tissue disorders is an important cause of secondary vasculitis about which little is written. When vasculitis occurs in the setting of a preexisting connective tissue disorder, it often correlates with disease severity and portends a poorer prognosis. It may involve virtually any organ system and present in a myriad of ways. Prompt recognition and treatment of vasculitis can dramatically improve the outcome for the patient. This review focuses on recent insights into the clinical presentation and pathogenic mechanisms that may be involved.


Decreased plasma serotonin in melancholic patients: a study with clomipramine.
Eighteen unmedicated patients suffering from major depressive disorder with melancholia (DSM-III) were examined for abnormalities in peripheral serotonin (5-HT) and related metabolites. Serotonin in platelet-free plasma and in platelets from melancholics was significantly reduced to 30% and 60% of their respective control values. Plasma 5-hydroxyindoleacetic acid was also found to be reduced, but not significantly. Other plasma compounds related to 5-HT (indoleacetic acid, total tryptophan, and free tryptophan) were found to be unchanged in these patients. Of all variables, only platelet 5-HT was affected while patients were on clomipramine (CIM) treatment. After 2 weeks on CIM (100-150 mg/day, orally), platelet 5-HT was reduced to 8% of pretreatment values, but plasma 5-HT did not change and continued to be reduced upon clinical recovery. The existence of a distinct pool of plasma 5-HT that is clearly independent of the platelet pool is indicated by the differences observed in plasma and platelet 5-HT during CIM treatment, as well as by previous data from this laboratory. The very marked decrease in plasma 5-HT levels may be in accord with the central nervous system changes reported in depression and suggests the possibility of using plasma 5-HT as a peripheral indicator of abnormal serotonin function in melancholia.


Using the New "Life's Essential 8" Metrics to Evaluate Trends in Cardiovascular Health Among US Adults From 2005 to 2018: Analysis of Serial Cross-sectional Studies.
The recently published "Life's Essential 8" (LE8) by the American Heart Association has overcome some limitations in evaluating cardiovascular health (CVH) in the previous "Life's Simple 7." We aimed to examine the secular trends in CVH, as assessed by the LE8, in US adults from 2005 to 2018. Using cross-sectional data from the National Health and Nutrition Examination Survey between 2005-2006 and 2017-2018, we calculated the age-standardized mean scores of overall CVH and each of the LE8 components, where a higher score (range 0-100 points) means a better health status. A total of 21,667 adults aged 20-79 years were included in this analysis. The overall CVH did not significantly change between 2005-2006 and 2017-2018 (65.5, 95% CI 63.9-67.1 to 65.0, 95% CI 62.8-67.1; P=.82). The individual metrics did not significantly change for diet (41.0, 95% CI 38.0-43.9 to 41.5, 95% CI 36.5-46.6; P=.94), physical activity (57.5, 95% CI 53.0-61.9 to 53.0, 95% CI 48.7-57.3; P=.26), and blood pressure (68.4, 95% CI 65.2-71.5 to 68.6, 95% CI 65.3-71.9, P=.35), improved for nicotine exposure (64.7, 95% CI 61.1-68.4 to 71.9, 95% CI 67.7-76.2; P<.001), sleep health (83.7, 95% CI 81.6-85.7 to 84.1, 95% CI 81.2-87.1; P=.006), and blood lipids (61.6, 95% CI 59.1-64.0 to 67.0, 95% CI 63.5-70.4; P<.001), and worsened for BMI (63.4, 95% CI 59.7-67.1 to 56.2, 95% CI 52.5-59.9; P<.001) and blood glucose (83.9, 95% CI 82.4-85.4 to 77.4, 95% CI 74.5-80.3; P<.001). According to the LE8, the overall CVH did not change among US adults from 2005 to 2018, as well as 3 components (diet, physical activity, and blood pressure). Other metrics such as nicotine exposure, blood lipids, and sleep health improved, while BMI and blood glucose deteriorated over time.


Sub-chronic treatment effects of an extract of Hypericum perforatum (St. John's Wort, Li 160) on neuroendocrine responses to the 5-T2A agonist, DOI in the rat.
Clinical studies have demonstrated the antidepressant efficacy of LI 160 extracts, which is comparable to antidepressants such as imipramine. The study was undertaken to assess the sub-chronic effects of LI 160 extract on plasma corticosterone and prolactin (PRL) responses to the post-synaptic 5-HT 2A receptor agonist, 2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in the male rat. Results show that sub-chronic treatment with the LI 160 extract reduced corticosterone and PRL responses to DOI. LI 160 may modify brain 5-HT function in the rat, possibly by reducing the sensitivity of central 5-HT 2A receptors. This may be a result of decreased receptor expression, signal transduction or intracellular messengers. These findings could be relevant to the therapeutic efficacy of St. John's Wort.


Developing Carrier Complexes for "Caged NO": RuCl(3)(NO)(H(2)O)(2) Complexes of Dipyridylamine, (dpaH), N,N,N'N'-Tetrakis (2-Pyridyl) Adipamide, (tpada), and (2-Pyridylmethyl) Iminodiacetate, (pida).
Delivery agents which can carry the {Ru(NO)}(6) chromophore ("caged NO") are desired for vasodilation and for photodynamic therapy of tumors. Toward these goals, complexes derived from [RuCl(3)(NO)(H(2)O)(2)]= (1) have been prepared using dipyridylamine (dpaH) as mono and bis adducts, [Ru(NO)Cl(3)(dpaH)] = (2) and [Ru(NO)Cl(dpaH)(2)]Cl(2) = (3). The dpaH ligands coordinate cis to the Ru(NO) axis.The mono derivative is a model for a potential DNA groove-spanning binuclear complex {[RuNO)Cl(3)](2)(tpada)} = (4) which has two DNA-coordinating Ru(II) centers, photo-labile {Ru(NO)}(6) sites, and a groove-spanning tether moiety.The binuclear assembly is prepared from the tethered dipyridylamine ligand N,N,N',N'-tetrakis(2-pyridylmethyl)adipamide (tpada) which has recently been shown to provide a binuclear carrier complex suited to transporting Ru(II) and Pd(II) agents. A related complex, [Ru(NO)Cl(pida)] = (5) with the {Ru(NO)}(6) moiety bound to (2-pyridylmethyl) iminodiacetate (pida(2-)) is also characterized as a potential "caged NO" carrier. Structural information concerning the placement of the pyridyl donor groups relative to the {Ru(NO)}(6) unit has been obtained from (1)H and (13)C NMR and infrared methods, noting that a pyridyl donor trans to NO+ causes "trans strengthening" of this ligand for [Ru(NO)Cl(pida)], whereas placement of pyridyl groups cis to NO+ causes a weakening of the N-O bond and a lower NO stretching frequency in the dpa-based complexes.


Feasibility and validity were demonstrated of an online case-control study using the prototype of recent-onset systemic lupus erythematosus.
To test the feasibility and validity of the online case-control study design through the empirical deployment of a prototype study of recent-onset systemic lupus erythematosus (SLE). We conducted an Internet-based case-control study of SLE during 2003-2005. The source population comprised Google users searching on medical key terms, solicited using sponsored links. Cases fulfilled a self-administered algorithm for SLE diagnosed within 5 years. A subset underwent confirmation by medical record review. Controls were matched to cases using a propensity score. Four hundred and two cases and 693 control applicants finished the questionnaires, yielding 389 matched case-control pairs. Eighty-two percentage of the records documented a clinical diagnosis of SLE, and 61% documented >or=4 American College of Rheumatology criteria for SLE. Control applicants resembled Internet users, with the exceptions of comprising more women (86% vs. 52%) and fewer minority individuals (e.g., 5% vs. 9% for African-Americans). There was a broad representation of clinical manifestations. SLE was associated with miscarriage (odds ratio [OR]=3.0, 95% confidence interval [CI]=2.0-4.7), allergy to sulfonamides (OR=2.2, CI=1.5-3.2), hives (OR=1.9, CI=1.4-2.5), and shingles (OR=2.3, CI=1.4-3.7). It is possible to perform case-control studies over the Internet using an internally valid design, obtain reliable information from participants, and confirm established associations.


A US-based survey on ventriculostomy practices.
The incidence of ICP monitoring has increased over the years and the indications for placement have expanded. Although ventriculostomy and ICP monitor placement are among the most commonly performed neurosurgical procedures, the current practice patterns have rarely been studied. A 10-question survey was sent to 2006 neurosurgeons and 1060 neurosurgery residents in the US. Demographic information and data regarding estimated success rates of ventriculostomies, the steps taken in failure and use of technological aids used was sought. 479 neurosurgeons and 108 residents responded to our survey (response rates 23.9% and 10.2%, respectively). No catheter misplacements were reported by 19.8% respondents in the previous year whereas 2.2% reported misplacing more than 30%. With regards to ventriculostomy for patients with slit ventricles, image guidance was used by 51.7%; freehand technique was preferred by 41.6% and the Ghajar guide was used by 6.7% of respondents. We found that 56.9% of respondents abandoned free-hand placement after 3 failed passes. After abandoning free-hand cannulation, respondents used an ICP bolt or similar intra-parenchymal pressure monitoring device in trauma patients. Other approaches included leaving the catheter in place and readjusting it after repeating a CT scan. This survey sheds light on the current practice of ventriculostomy placement. Both residents and neurosurgeons admit to multiple attempts and frequent catheter misplacement. In order to consider a change in practice, respondents cited an increase in available data about guidance systems and ability to accommodate abnormal ventricular anatomy as primary requirements. A prospective study could help establish true evidence based practice for this common neurosurgical procedure.