Anti-phospholipase A2 receptor antibodies and the pathogenesis of membranous nephropathy.
Since the early 2000s, considerable advances have been achieved in the understanding of molecular pathomechanisms of human membranous nephropathy (MN), inspired by studies of Heymann nephritis, a faithful experimental model. These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively. A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry. The time has come to revisit the spectrum of MN based on the newly identified antigen-antibody systems which should be considered as molecular signatures of the disease, challenging the uniform histological definition. Although some uncertainties remain as to the pathogenic effects of anti-PLA2R antibodies because of the lack of an appropriate experimental model, the value of these antibodies as biomarkers for diagnosis and disease activity is increasingly being recognized. It is not exaggerated to state that they have induced a paradigm shift in the monitoring of patients with MN, thus opening a new era of personalized medicine.


Management and treatment options for epilepsy.
Epilepsy is a major chronic condition of the nervous system affecting almost 380,000 people in England and occasionally results in death of the patient. Although epilepsy and its treatment are complex, there is evidence to support a significant gap in epilepsy care, ranging from a lack of adequate record keeping of seizure occurrence to poor referral systems. This article provides a broad introduction to the condition, discusses the incidence, disease process, diagnosis, classification and the various ways, both conventional and otherwise, in which it can be managed. By understanding the above, it will assist healthcare practitioners to improve their knowledge about management of a client with epilepsy entrusted to their care.


Lowering the concentration limits of detection by on-line solid-phase extraction-capillary electrophoresis-electrospray mass spectrometry.
The use of solid-phase extraction coupled on-line to capillary electrophoresis using electrospray mass spectrometry detection (SPE-CE-ESI-MS) is described for the analysis of peptides in dilute solutions. A SPE microcartridge or analyte concentrator containing C(18) derivatized silica particles as the extraction sorbent was easily constructed near the inlet of the separation capillary using commercially available materials. The reversed-phase sorbent selectively retained the target peptides, enabling large volumes of the sample to be introduced (>100muL). The captured analytes were eluted in a small volume of an appropriate solution (20-50nL). This resulted in sample clean-up and concentration enhancement, with minimum sample handling. As the SPE-CE conditions were compatible with on-line ESI-MS detection, the potential for identifying and characterizing the preconcentrated analytes by SPE-CE-ESI-MS using a sheath-flow CE-ESI-MS interface is also shown. Using separation electrolytes containing N-[carbamoylmethyl]-2-aminoethanesulfonic acid (ACES) at pH 7.4, an elution plug of 80:20 (v/v) (25mM of formic acid in MeCN):H(2)O and a sheath liquid of 20mM of acetic acid in 50:50 (v/v) methanol:H(2)O the concentration limits of detection for the analyzed peptides in the positive ion mode were lowered to nanogram per milliliter levels. The systematic optimization of the operational parameters involved in the development of the SPE-CE method is described in detail, in order to promote robust and quantitative SPE-CE-ESI-MS analysis and facilitate the widespread use of the technique.


Optimal Timing of Serial 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography after Prednisolone Treatment Introduction for Cardiac Sarcoidosis.
Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.


Melatonin Inhibits in Vitro Smooth Muscle Cell Inflammation and Proliferation and Atherosclerosis in Apolipoprotein E-Deficient Mice.
Chronic inflammation and proliferation play important roles in atherosclerosis progression. This study aimed to identify the mechanisms responsible for the anti-inflammatory and antiproliferative effects of melatonin on tumor necrosis factor-α (TNF-α)- and platelet-derived growth factor-BB (PDGF-BB)-treated rat aortic smooth muscle cells (RASMCs). Melatonin reduced TNF-α-induced RASMC inflammation by decreasing vascular cell adhesion molecule-1 (VCAM-1) expression and nuclear factor-kappa B (NF-κB) P65 activity by inhibiting P38 mitogen-activated protein kinase phosphorylation ( P < 0.05). Additionally, melatonin inhibited PDGF-BB-induced RASMC proliferation by reducing mammalian target of rapamycin (mTOR) phosphorylation ( P < 0.05) but not migration in vitro. Melatonin also reduced TNF-α- and PDGF-BB-induced reactive oxygen species (ROS) production ( P < 0.05). Furthermore, melatonin treatment (prevention and treatment groups) significantly repressed high cholesterol diet-stimulated atherosclerotic lesions in vivo (19.59 ± 4.11%, 20.28 ± 5.63%, 32.26 ± 12.06%, respectively, P < 0.05). Taken together, the present study demonstrated that melatonin attenuated TNF-α-induced RASMC inflammation and PDGF-BB-induced RASMC proliferation in cells and reduced atherosclerotic lesions in mice. These results showed that melatonin has anti-inflammatory and antiproliferative properties and may be a novel therapeutic target in atherosclerosis.


Purified human plasma proteins of unknown function.
The development of new analytic and preparative techniques in the field of protein chemistry has essentially extended our knowledge about the variety of human plasma proteins in the last 15 years. In many cases plasma proteins have been particularly determined by immunologic techniques, partially highly purified and physicochemically well characterized, before knowing the biological function. To these proteins belong among others the alpha 1-antitrypsin, Cl-inactivator, alpha 2-macroglobulin, Gc-globulin and the cold-insoluble globulin. Today we know more than 100 proteins being isolated from human plasma and among these are nearly 20, of which the biological function is not yet known. To this group are belonging proteins, which are known since many years, like the alpha 1-acid glycoprotein and the C-reactive proteins as well as proteins, which have only been described in the last years and which partially have an interesting chemical structure, e.g. the histidinerich 3,8S-alpha 2-glycoprotein and the leucine-rich 3,1S-alpha 2-glycoprotein, of which every fifth amino acid is formed by leucine. It is to be hoped that the special chemical structure of some of these human plasma proteins as well as the quantitative immunologic determination in different patient sera will give hints to their biological function.


Hypokalemic Paralysis Complicated by Concurrent Hyperthyroidism and Chronic Alcoholism: A Case Report.
Thyrotoxic periodic paralysis (TPP) is characterized by the presence of muscle paralysis, hypokalemia, and hyperthyroidism. We report the case of a young man with paralysis of the lower extremities, severe hypokalemia, and concurrent hyperthyroidism. TPP was suspected; therefore, treatment consisting of judicious potassium (K+) repletion and β-blocker administration was initiated. However, urinary K+ excretion rate, as well as refractoriness to treatment, was inconsistent with TPP. Chronic alcoholism was considered as an alternative cause of hypokalemia, and serum K+ was restored through vigorous K repletion and the addition of K+ -sparing diuretics. The presence of thyrotoxicosis and hypokalemia does not always indicate a diagnosis of TPP. Exclusion of TPP can be accomplished by immediate evaluation of urinary K+ excretion, acid-base status, and the amount of potassium chloride required to correct hypokalemia at presentation.


Late-stage human African trypanosomiasis in a Sudanese refugee.
A 19-year-old Sudanese woman, who had lived for about a decade in Ugandan refugee camps, was referred for investigation of a 12-month history of a generalised rash. Two months later, her condition had deteriorated to include cachexia and drowsiness. Despite initial negative findings on investigation, human African trypanosomiasis (HAT) was suspected, and parasites were found in a double-centrifuged sample of cerebrospinal fluid. Eflornithine, the appropriate drug for treatment of late-stage disease, was obtained through the World Health Organization. This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country.


Detecting disease-associated genomic outcomes using constrained mixture of Bayesian hierarchical models for paired data.
Detecting disease-associated genomic outcomes is one of the key steps in precision medicine research. Cutting-edge high-throughput technologies enable researchers to unbiasedly test if genomic outcomes are associated with disease of interest. However, these technologies also include the challenges associated with the analysis of genome-wide data. Two big challenges are (1) how to reduce the effects of technical noise; and (2) how to handle the curse of dimensionality (i.e., number of variables are way larger than the number of samples). To tackle these challenges, we propose a constrained mixture of Bayesian hierarchical models (MBHM) for detecting disease-associated genomic outcomes for data obtained from paired/matched designs. Paired/matched designs can effectively reduce effects of confounding factors. MBHM does not involve multiple testing, hence does not have the problem of the curse of dimensionality. It also could borrow information across genes so that it can be used for whole genome data with small sample sizes.


Swyer Syndrome: A Case Report.
Swyer syndrome is a rare form of primary amenorrhea resulting from gonadal dysgenesis. It is characterized by the presence of a female phenotype with a 46, XY karyotype. In our case, CT scans revealed the absence of the uterus and bilateral ovaries of the 16-year-old female patient. Calcific nodules were found in both inguinal areas, which were suspected to be calcified atrophic testes. A chromosomal study confirmed the diagnosis of Swyer syndrome. Herein, we report a rare case of Swyer syndrome.


Definitive surgical treatment of cholelithiasis in selective patients with liver cirrhosis.
A review of 132 cirrhotic patients with cholelithiasis was carried out. Of the 87 patients who underwent definitive surgical procedures for gallstones, patients of Child's A grade had less operative blood loss, blood transfusion and shorter hospital stay than those of B and C grades. No mortality in cirrhotic patients with Child's A and B grade was found in both emergency and elective surgery. Emergency operation in patients with Child's C grade resulted in more operative blood loss and requirement than elective surgery. Patients in this grade had also a higher morbidity rate and four deaths ensued. Of the 83 survivals after definitive procedures, 78 patients (93.9%) were still alive in the following 62.8 months without any biliary tract symptoms. Of patients who survived after cholecystolithotomy, 6 patients (33.3%) had recurrent stones in the same follow-up period. Therefore, we recommend that definitive biliary surgery be selectively carried out in cirrhotic patients in Child's A and B grade. However, a conservative approach is more suitable in Child's C patients in emergency conditions and definitive procedures should be considered when their liver function improves.


Modeling late-life adaptation in affective well-being under a severe chronic health condition: the case of age-related macular degeneration.
Age-related macular degeneration (AMD) was used as a case model to longitudinally study adaptation in affective well-being under a prevalent chronic health condition. Measures of positive and negative affect, obtained at 5 subsequent measurement occasions with 3-month intervals in between, were analyzed in 90 older adults diagnosed with AMD. The authors proposed a pattern of adaptation that shows initial decline in affective well-being after disease outbreak, followed by a turnaround into a restorative phase of increase, implying nonlinear intraindividual trajectories, with changes substantially related to disease duration. Analysis was conducted by means of a nonlinear mixed models approach. Results confirmed the hypothesized adaptation pattern for positive affect but not for negative affect, which was found more stable across measurement occasions.


Bat behavioral immune responses in social contexts: current knowledge and future directions.
Animals often mount complex immune responses to infections. Aside from cellular and molecular defense mechanisms, animals can alter their behavior in response to infection by avoiding, resisting, or tolerating negative effects of pathogens. These behaviors are often connected to cellular and molecular immune responses. For instance, sickness behaviors are a set of behavioral changes triggered by the host inflammatory response (e.g., cytokines) and could aid in resisting or tolerating infection, as well as affect transmission dynamics if sick animals socially withdraw or are being avoided by others. To fully understand the group and population level transmission dynamics and consequences of pathogen infections in bats, it is not only important to consider cellular and molecular defense mechanisms, but also behavioral mechanisms, and how both interact. Although there has been increasing interest in bat immune responses due to their ability to successfully cope with viral infections, few studies have explored behavioral anti-pathogen defense mechanisms. My main objective is to explore the interaction of cellular and molecular defense mechanisms, and behavioral alterations that results from infection in bats, and to outline current knowledge and future research avenues in this field.


Synovial Fluid Cell Proteomic Analysis Identifies Upregulation of Alpha-Taxilin Proteins in Rheumatoid Arthritis: A Potential Prognostic Marker.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting the joints and surrounding tissue. Identification of novel proteins associated with the progression of a disease is a prerequisite for understanding the pathogenesis of RA. The present study was undertaken to identify the potential biomarkers from a less explored biological sample such as synovial fluid (SF) cells which is specific for RA and to analyze their functional aspects using proteomic approach. Two-dimensional gel electrophoresis (2-DE) was performed using synovial fluid cells of RA and osteoarthritis (OA) patients, and 7 differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS/MS). Αlpha-Taxilin (α-Taxilin) has been found as one of the novel, significantly up regulated protein in RA. It has been validated in the synovium, synovial fluid (SF), SF cells, and plasma samples by Western blot, enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS), immunohistochemistry (IHC), and real-time PCR. The identification of autoantibody against α-Taxilin and in silico studies has further helped us to understand its involvement in disease mechanism. The present study will therefore provide knowledge towards the etiology of RA that pave the way for suitable prognostic marker identification along with other clinical parameters.


Adaptor Protein-3-Dependent Vacuolar Trafficking Involves a Subpopulation of COPII and HOPS Tethering Proteins.
Plant vacuoles are versatile organelles critical for plant growth and responses to environment. Vacuolar proteins are transported from the endoplasmic reticulum via multiple routes in plants. Two classic routes bear great similarity to other phyla with major regulators known, such as COPII and Rab5 GTPases. By contrast, vacuolar trafficking mediated by adaptor protein-3 (AP-3) or that independent of the Golgi has few recognized cargos and none of the regulators. In search of novel regulators for vacuolar trafficking routes and by using a fluorescence-based forward genetic screen, we demonstrated that the multispan transmembrane protein, Arabidopsis (Arabidopsis thaliana) PROTEIN S-ACYL TRANSFERASE10 (PAT10), is an AP-3-mediated vacuolar cargo. We show that the tonoplast targeting of PAT10 is mediated by the AP-3 complex but independent of the Rab5-mediated post-Golgi trafficking route. We also report that AP-3-mediated vacuolar trafficking involves a subpopulation of COPII and requires the vacuolar tethering complex HOPS. In addition, we have identified two novel mutant alleles of AP-3δ, whose point mutations interfered with the formation of the AP-3 complex as well as its membrane targeting. The results presented here shed new light on the vacuolar trafficking route mediated by AP-3 in plant cells.


Formate Might Be a Novel Potential Serum Metabolic Biomarker for Type 2 Diabetic Peripheral Neuropathy.
As one of the most frequent complications of type 2 diabetes mellitus (T2DM), diabetic peripheral neuropathy (DPN) shows a profound impact on 50% of patients with symptoms of neuropathic pain, numbness and other paresthesia. No valid serum biomarkers for the prediction of DPN have been identified in the clinic so far. This study is to investigate the potential serum biomarkers for DPN firstly based on 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomics technique. Thirty-six patients enrolled in this study were divided into two groups: 18 T2DM patients without DPN (T2DM group) and 18 T2DM patients with DPN (DPN group). Serum metabolites were measured via 1H-NMR spectroscopy. Bioinformatic approaches including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), independent sample t-test, Fisher's test, Pearson and Spearman correlation analysis, Stepwise multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the potential altered serum biomarkers. A total of 20 metabolites were obtained and further analyzed. Formate was identified as the only potential biomarker that decreased in the DPN group with statistical significance after multiple comparisons (p<0.05). Formate also displayed a negative relationship with some elevated clinical markers in DPN. ROC curve analysis showed a good discriminative ability for formate in DPN with an area under the curve (AUC) value of 0.981. Formate could be considered a potential serum metabolic biomarker for DPN. The reduced level of formate in DPN may be associated with mitochondrial dysfunction and gut microbiota alteration. Monitoring the level of serum formate would be an important strategy for the early diagnosis of DPN and a supplement of formate may be a promising treatment for DPN in the future.


[The structure, functions and classification of mental states and their study in work activities].
The actuality of the studies and the diagnosis of the psychic conditions, arising from the work activity is well-grounded. The necessity of further extension and perfection of the methodical means and approaches for their investigation is underlined. The experience of the systematic approach is well-grounded, proceeding from the existing in the modern psychologic science ideas for the component structure, functions and classification of the psychic conditions, arising periodically in the work activity.


[Real-time 3D reconstruction CT-jejunography guided direct percutaneous endoscopic jejunostomy for levodopa-carbidopa intestinal gel treatment in a patient with prior gastrojejunostomy].
A 68-year-old woman with Parkinson's disease, who had previously undergone Roux-en-Y gastrojejunostomy for early gastric cancer, complained of wearing-off and troublesome dyskinesia that had progressed over 7-years. After the introduction of levodopa-carbidopa intestinal gel therapy (LCIG) by nasojejunal tube, she had a good clinical response. Percutaneous endoscopic gastrostomy with a jejunal extension tube was difficult in this case, due to lack of gastrostomy site and fibrous postoperative adhesion. We introduced LCIG by direct percutaneous endoscopic jejunostomy (D-PEJ) which offers a less invasive procedure to operative tube placement. The factors affecting the success of D-PEJ could interfere with transillumination, abdominal thickness and the location of other organs. We determined the optimum site of catheter insertion with the assistance of real-time 3D reconstruction CT-jejunography. She was discharged home on postoperative day 14 without any procedure-related complications. Real-time 3D reconstructive CT-jejunography guided D-PEJ is a useful method for a patient who benefit from LCIG with prior gastrojejunostomy.


Cardiac problems in the fetus: a review for pediatric providers.
The aim of this study was to provide pediatric providers with a review of the diagnosis and management of fetal cardiac disease in the current era. Prenatal detection of congenital heart disease (CHD) has improved but is still imperfect. In experienced hands, fetal echocardiography can detect severe CHD as early as the first trimester and a majority of more subtle conditions in the second and third trimesters. Beyond detection, a prenatal diagnosis allows for lesion-specific counseling for families as well as for development of a multidisciplinary perinatal management plan, which may involve in-utero treatment. Given the diversity of cardiac diagnoses and the rarity of some, collaborative multicenter fetal cardiac research has gained momentum in recent years. Accurate diagnosis of fetal cardiac disease allows for appropriate counseling, pregnancy and delivery planning, and optimization of immediate neonatal care. There is potential for improving fetal CHD detection rates. Fetal interventions are available for certain conditions, and fetal and pediatric cardiac centers have developed management plans specific to the expected postnatal physiology.


Excitation of a Single Compound by Light and Ultrasound Enhanced the Long-Term Cure of Mice Bearing Prostate Tumors.
Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using PhotofrinTM as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of PhotofrinTM). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.


Synthesis of metal oxide nanoparticles via a robust "solvent-deficient" method.
We report an efficient, general methodology for producing high-surface area metal oxide nanomaterials for a vast range of metal oxides, including at least one metal oxide nanomaterial from nearly every transition metal and semi-metal group in the periodic table (groups 3-4 and 6-15) as well as several from the lanthanide group (see ). The method requires only 2-3 simple steps; a hydrated metal salt (usually a nitrate or chloride salt) is ground with bicarbonate (usually NH4HCO3) for 10-30 minutes to form a precursor that is then either untreated or rinsed before being calcined at relatively low temperatures (220-550 °C) for 1-3 hours. The method is thus similar to surfactant-free aqueous methods such as co-precipitation but is unique in that no solvents are added. The resulting "solvent-deficient" environment has interesting and unique consequences, including increased crystallinity of the products over other aqueous methods and a mesoporous nature in the inevitable agglomerates. The products are chemically pure and phase pure with crystallites generally 3-30 nm in average size that aggregate into high surface area, mesoporous agglomerates 50-300 nm in size that would be useful for catalyst and gas sensing applications. The versatility of products and efficiency of the method lend its unique potential for improving the industrial viability of a broad family of useful metal oxide nanomaterials. In this paper, we outline the methodology of the solvent-deficient method using our understanding of its mechanism, and we describe the range and quality of nanomaterials it has produced thus far.


Conditioned media of deer antler stem cells accelerate regeneration of alveolar bone defects in rats.
The destruction of periodontal alveolar bone (AB) caused by periodontitis is regarded as one of the major reasons for tooth loss. The inhibition of bone resorption and regeneration of lost AB are the desirable outcomes in clinical practice but remain in challenge. The use of mesenchymal stem cells (MSCs) is one current approach for achieving true restoration of AB defects (ABD). Antler stem cells (AnSC) are capable of renewing a huge mammalian bony appendage, the deer antler, suggesting an unparalleled potential for bone regeneration. Herein, we investigated the effectiveness of deer AnSCs conditioned medium (CM, AnSC-CM) for repair of surgically-created ABD using a rat model and sought to define the underlying mechanisms. The results showed that AnSC-CM effectively induced regeneration of AB tissue; the outcome was significantly better than human bone marrow mesenchymal stem cell conditioned medium (hBMSC-CM). AnSC-CM treatment upregulated osteogenic factors and downregulated osteoclastic differentiation factors; stimulated proliferation, migration and differentiation of resident MSCs toward osteogenic lineage cells; modulated macrophage polarization toward the M2 phenotype and suppressed osteoclastogenesis. That AnSC-CM resulted in better outcomes than hBMSC-CM in treating ABD was attributed to the cell compatibility as both AnSCs and AB tissue are neural crest-derived. In conclusion, the effects of AnSC-CM on AB tissue regeneration were achieved through both promotion of osteogenesis and inhibition of osteoclastogenesis. We believe that AnSC-CM is a candidate for effective treatment of ABD in dental clinical practice but will require investment in further development.


L-Arginine, ADMA, SDMA, creatinine, MDRD formula: detour to renal function testing.
We report the case of a 50-year-old woman in whom a laboratory work-up for a suspected L-arginine deficiency and the concomitant determination of elevated symmetrical dimethylarginine (SDMA) led to a diagnosis of chronic kidney disease. This diagnosis had been missed due to the '';normal'' serum creatinine. This case illustrates that patients and physicians, while perusing non-evidence-based treatment strategies, such as L-arginine supplementation, fail to recognize the importance of evidence-based medicine, such as renal function testing. It also supports the notion that routine estimation of glomerular filtration rate should be mandatory in every patient for whom a serum creatinine test is ordered.


[Metabolic effects of acute experimental hypoxia and hypercapnia].
Hypoxia and the hypercapnia were produced in anesthetized dogs by artificial respiration with appropriate gas mixtures, and a study was conducted of the effects of these conditions on various metabolic parameters, viz. catecholamines, renin activity, lactate, pyruvate, cortisol, non-esterified free fatty acids (FFA), and ammonia, in the plasma of the arterial blood. Hypercapnia caused a distinct increase in catecholamine concentrations, renin activity and ammonia, and a decrease in lactate and pyruvate; cortisol and FFA levels were only slightly altered. Hypoxia increased lactate, pyruvate and--though only to a slight extent--FFA, cortisol and NH3. The changes induced by hypercapnia were chiefly attributable to activation of the sympathico-adrenal system; those induced by hypoxia were not.


Analysis of perioperative morbidity according to whether the uterine cavity is opened or remains closed during abdominal myomectomy--results of 423 abdominal myomectomy cases.
For women who desire pregnancy or who wish to retain their uterus, myomectomy is the standard approach for the treatment of fibroids. Abdominal myomectomy seems to be the best choice when there are large subserosal or intramural fibroids (> 5-7 cm), or submucosal fibroids > 3 cm or when multiple fibroids (> 3) are to be removed. When submucosal myomas are present or multiple fibroids are to be removed, opening the uterine cavity during the surgical procedure is more likely to happen. There is lack of published evidence about whether there is any difference in perioperative morbidity and management of those cases where the uterine cavity is opened during the surgical procedure compared with those where the uterine cavity remains closed. We undertook a retrospective review of 423 abdominal myomectomies via either an opened or closed uterine cavity. As a primary outcome we assessed the overall perioperative morbidity rate and as a secondary outcome we compared the necessity of pre and postoperative transfusions, intraoperative bleeding, febrile morbidity, unintended surgical interventions, life-threatening events, need for relaparotomies and duration of hospital stay between the opened and non opened uterine cavity groups. The overall perioperative morbidity rate was significantly higher in those cases where the uterine cavity was opened during surgery; however the difference was caused only by the increased risk of intraoperative bleeding. All the other variables, such as febrile morbidity, number of relaparotomies, unintended surgical procedures and life-threatening events did not differ between the two groups. Although there is an increased risk of intraoperative bleeding it seems that entering the uterine cavity during abdominal myomectomy can be considered as safe a procedure as in those cases where the uterine cavity remains closed.


Human immunodeficiency virus: strategies for protection and therapy.
Never before has so much been learned about the molecular biology of a virus in such a short time since its discovery and yet effective strategies for fighting the human immunodeficiency virus that causes AIDS remain elusive. This review and the accompanying colour centrespread outline some of the options available at the present time. The centrespread illustrates areas within the complex virus infection cycle with potential for therapeutic intervention and lists other possible modes of treatment, while the review below concentrates on the identification and presentation of candidate vaccines and discusses the problems of evaluation that face investigators.


A Revised Neural Framework for Face Processing.
Face perception relies on computations carried out in face-selective cortical areas. These areas have been intensively investigated for two decades, and this work has been guided by an influential neural model suggested by Haxby and colleagues in 2000. Here, we review new findings about face-selective areas that suggest the need for modifications and additions to the Haxby model. We suggest a revised framework based on (a) evidence for multiple routes from early visual areas into the face-processing system, (b) information about the temporal characteristics of these areas, (c) indications that the fusiform face area contributes to the perception of changeable aspects of faces, (d) the greatly elevated responses to dynamic compared with static faces in dorsal face-selective brain areas, and (e) the identification of three new anterior face-selective areas. Together, these findings lead us to suggest that face perception depends on two separate pathways: a ventral stream that represents form information and a dorsal stream driven by motion and form information.


Nano-biosupercapacitors enable autarkic sensor operation in blood.
Today's smallest energy storage devices for in-vivo applications are larger than 3 mm3 and lack the ability to continuously drive the complex functions of smart dust electronic and microrobotic systems. Here, we create a tubular biosupercapacitor occupying a mere volume of 1/1000 mm3 (=1 nanoliter), yet delivering up to 1.6 V in blood. The tubular geometry of this nano-biosupercapacitor provides efficient self-protection against external forces from pulsating blood or muscle contraction. Redox enzymes and living cells, naturally present in blood boost the performance of the device by 40% and help to solve the self-discharging problem persistently encountered by miniaturized supercapacitors. At full capacity, the nano-biosupercapacitors drive a complex integrated sensor system to measure the pH-value in blood. This demonstration opens up opportunities for next generation intravascular implants and microrobotic systems operating in hard-to-reach small spaces deep inside the human body.


The impact of buprenorphine transdermal delivery system on activities of daily living among patients with chronic low back pain: an application of the international classification of functioning, disability and health.
The buprenorphine transdermal delivery system (BTDS) is indicated for reduction of pain in moderate to severe chronic low back pain (CLBP), which can affect patients' ability to perform routine activities of daily living (ADLs). This post hoc analysis of clinical trial data examines the impact of BTDS treatment on CLBP patients' ability to perform ADLs that relate to functioning with low back pain. Data are drawn from a multicenter, enriched enrollment, randomized, placebo-controlled, double-blind 12-week trial of BTDS for pain control among opioid-naive patients with moderate to severe CLBP. The 23 selected ADLs are those that (1) appear in the Low Back Pain Core Set of the International Classification of Functioning, Disability and Health and (2) link to the content of 3 patient-reported outcome instruments administered during the trial. Logistic regression models estimated the odds ratios (ORs) of BTDS patients' ability to perform each ADL at 12 weeks, controlling for baseline ability, relative to placebo. The ORs for 10 ADLs related to sleeping, lifting, bending, and working reached multiplicity-adjusted statistical significance and indicated a greater ability to perform ADLs among BTDS users than among the placebo group. These 10 ORs ranged from 1.9 (no physical health-related restrictions on the kind of work performed) to 2.4 (being able to sleep undisturbed by pain). These results suggest that for patients with moderate to severe CLBP, 12 weeks use of BTDS improves the ability to carry out certain ADLs related to sleeping, lifting, bending, and working.


Observational, pragmatic, and clinical trials in bipolar disorder.
Course of illness, treatment effectiveness, and outcomes in bipolar disorder are studied in various ways, including randomized controlled clinical and pragmatic trials and observational studies. Clinical trials have important limitations that often make the application of findings difficult in real-world settings. Pragmatic trials study a treatment intervention in a more practical setting, but recent pragmatic trials of bipolar disorder treatment have yielded disappointing results. Observational studies can complement randomized trials because they provide valuable insight into the course, treatment response, and outcomes of patients who would generally be excluded from clinical trials.


Clubfoot management in the Middle East: a survey-based review.
Clubfoot is the most frequent congenital deformity involving the foot. Little is known about the management of this disease in the Middle East as sparse data is available in the literature. Through the last 5 decades, congenital clubfoot management in the Middle East went from manipulation through Kite's technique in the late seventies, to early primary surgical intervention in the late eighties and early nineties of the previous century, and then back to manipulation with Ponseti's technique and the French functional technique in the late nineties, with the latter falling out of favor with time. This is comparable to the evolution of management witnessed in the United States and in Europe, with 10 to 15 years of delay. The delay is getting shorter with time due to the easier access to published scientific data and the increasing number of fellows from Middle East travelling to referral centers in Europe and the USA. A survey was performed among pediatric orthopedic surgeons in the Middle East to assess their approach to clubfoot management. This is the first survey of its kind in the region. It showed a wide adoption (97.1%) of the Ponseti's technique with serial manipulation and casting, Achilles tenotomy followed by abduction bracing. Divergent practices were found concerning the upper age limit for Ponseti treatment and the setting of the Achilles tenotomy. Nevertheless, these subjects are still a matter of debate in the literature and international conferences. All in all, pediatric orthopedic surgeons in the Middle East are offering their patients the gold standard of care. However, lot of work is to be done in raising awareness for this disease in the community, and among our colleagues as prenatal screening for clubfoot in the Middle East is practically nonexistent.


[Methods to improve patient's adherence: is there hope?].
An estimated 50% of all asthma patients do not take the medication as prescribed, i.e. are non-compliant. Numerous interventions have been done to improve patients' compliance have been evaluated in clinical studies, ranging from simple adjustments in the medication regimen to complex multidisciplinary interventions that address health system barriers and communication between patients and health care professionals. Beliefs or disbeliefs of health care professionals affect patients' compliance. Efforts to improve the adherence of physicians to asthma guidelines have been tested in numerous studies. Although several types of interventions are effective in improving compliance to medication for asthma, only a few indicated whether this success would actually result in clinical improvement. This review surveys the different options for enhancing compliance rates in patients with asthma.


Failure of enhanced recovery after surgery in laparoscopic colorectal surgery: a systematic review.
Enhanced recovery after surgery programs has been applied extensively in laparoscopic colorectal surgery. However, several studies have found that some patients fail from ERAS programs. It is important to identify these patients so that remedial action can be taken in a timely manner. The aim of this study was to perform a systematic review of ERAS failure and related risk factors following laparoscopic colorectal surgery. A literature search of the PubMed, EMBASE, OVID, and Cochrane databases was performed. The search strategy involved terms related to ERAS, failure, and colorectal surgery. The main outcomes were definitions of ERAS failure and related risk factors. Seven studies including 1463 patients were analyzed. The definition of ERAS failure was mostly associated with a prolonged postoperative length-of-stay (poLOS). Twenty-four kinds of identified risk factors were divided into three parts, the operative part, the pathophysiological part, and the ERAS elements, of which operative factors including more intraoperative blood loss and longer operative duration were the most frequently identified. ERAS failure was mostly related to a prolonged poLOS, and operative factors were the most frequently identified risk factors for ERAS failure following laparoscopic colorectal surgery. These findings will help physicians to take remedial action in a timely manner. Nonetheless, high-quality randomized controlled trials following a standardized framework for evaluating ERAS programs are needed in the future.


Effective Learning Support Towards Sustainable Student Learning and Well-Being Influenced by Global Pandemic of COVID-19: A Comparison Between Mainland China and Taiwanese Students.
The novel coronavirus disease that emerged at the end of 2019 began threatening the health and lives of millions of people after a few weeks. However, social and educational problems derived from COVID-19 have changed the development of individuals and the whole country. This study examined the learning method of Taiwanese versus mainland China college students, and evaluated the relationship between learning support mechanism and subjective well-being from a social cognition theory perspective. In this study, a total of 646 Taiwanese questionnaires and 537 mainland China questionnaires were collected to compare the two sample groups in development of students' subjective well-being. The results showed that social capital and learning support had significant positive correlations with self-efficacy, student employability and well-being and self-efficacy and student employability had significant positive correlations with well-being in Taiwanese sample. In mainland China sample, except paths among social capital, learning support, student employability and well-being, all paths were significant and positive related. Finally, based on the conclusions this study proposed some suggestions specific to theoretical mode for future study.


Multistability driven by inhibitory kinetics in a discrete-time size-structured chemostat model.
In this paper, we consider a discrete size-structured nonlinear chemostat model with inhibitory kinetics and multiple competing species. We show that, same as in models with monotone increasing nutrient uptake response functionals studied in the literature, one essential growth-limiting nutrient can support at most one species. More interestingly, we show that, differing from monotone increasing kinetics, inhibitory kinetics can induce several types of multistability and the competitive outcome is initial condition dependent. The species with the smallest lower break-even value is not always the winning species, and the winning species can exhibit sustained periodic oscillations and even chaotic irregular oscillations.


High-speed absolute three-dimensional shape measurement using three binary dithered patterns.
This paper describes a method to reconstruct high-speed absolute three-dimensional (3D) geometry using only three encoded 1-bit binary dithered patterns. Because of the use of 1-bit binary patterns, high-speed 3D shape measurement could also be achieved. By matching the right camera image pixel to the left camera pixel in the object space rather than image space, robust correspondence can be established. Experiments demonstrate the robustness of the proposed algorithm and the potential to achieve high-speed 3D shape measurements.


[Theoretical bases of a cardio-synchronised jet injection system into the vena cava].
Aim of this paper is to present a procedure aimed at raising the flow rate in the vena cava. To this purpose some fluid is injected at high speed in the vessel, accelerating the flow and dragging the stagnating flow upstream the catheter. In order to raise the efficiency of the system and to avoid damage to heart valves, the injection is synchronised with the diastole. A prototype of an injection system has been designed and built, in order to reach these goals. The injection times are controlled by the electrocardiogram track of the patient, in such a way that the maximum flow rate occurs when the tricuspid valve is open. A "dragging effect" index, that is the ratio between overall flow rate induced by any injection (injected flux plus dragged flux) and injected flux flow rate has been evaluated, both theoretically and experimentally. An experimental model of the lower vena cava has been built and used to measure the velocity profile in the vessel. The dragging effect at the confluence between the two iliac and the vena cava has been verified. By making the catheter sections smaller and/or raising the feeding pressure it is possible to have the injection of small volumes at high speed, capable of moving the blood in the vena cava with a minor contribution of external fluid, thus reducing risks of volume overload and overdiluition of blood.


Primary care of adults with mental retardation.
There is a national trend to deinstitutionalize mentally retarded adults, placing them in community residential settings. As a result, community-based primary care physicians will assume responsibility for their medical care. Primary care physicians may have uncertainties regarding the medical care of this population. The purpose of this case series is to describe the medical care of a group of adults with mental retardation during their first year of community residence following deinstitutionalization, and to provide practical advice to family physicians who care for these adults. Medical diagnoses and medications at the time of deinstitutionalization of a series of 21 adults were abstracted from institutional records and transfer forms. Follow-up data were obtained from office medical records. In the first year following deinstitutionalization, each patient averaged 6.6 office visits to a family physician. Newly identified major health impairments were: chronic persistent hepatitis due to hepatitis B, acid peptic disease, gastroesophageal reflux disease, dysphagia, primary degenerative dementia, absence seizures, bronchiectasis, and idiopathic iridocyclitis. Significant changes in pharmacotherapy included consolidation of multidrug anticonvulsant regimens and discontinuance of psychotropics and laxatives. Health maintenance practices included hepatitis B immunizations, cholesterol determinations, smoking cessation counseling, and calcium supplementation. Newly deinstitutionalized patients require careful diagnostic and therapeutic reassessment. Family physicians assuming their care need to look for conditions common in this population, including dysphagia, seizure disorders, chronic hepatitis B, and sensory impairments. Previously neglected health maintenance practices need to be instituted. Pharmacotherapies, particularly anticonvulsants, psychotropics, and laxatives, may be amenable to dosage reduction or discontinuance.


Law & psychiatry: Death row delusions: when is a prisoner competent to be executed?
This column examines a recent U.S. Supreme Court decision in Panetti v. Quarterman, which embraced a broader view of what makes death row prisoners incompetent to be executed. Although the defendant understood that he was to be executed and the state's purported reason for seeking his death--two criteria suggested by the Court's 1986 decision in Ford v. Wainwright--he suffered from a fixed delusion about the actual reason for his death. The Court indicated that competent prisoners must have a "rational understanding" of the reason that a death penalty is being imposed but declined to define a clear standard.


Anger, guilt, and repeated cooperation in social dilemmas.
A consistent finding in behavioral economics is that in social dilemma situations in which individuals must decide between individual and group welfare, cooperation declines over time eventually resulting in noncooperation. Extant theorizing addressing phenomena such as adaptive belief-learning focus solely on cognitive explanations. Based on the appraisal-tendency framework, we propose and show that the development of cooperation has a strong emotional component. Others' actual cooperative behavior compared to their expected cooperative behavior does not only result in adapting beliefs (cognition) but also gives rise to feelings of anger and guilt. These, in turn, drive individuals' subsequent cooperative behavior. Whereas experienced anger exacerbates the decline of cooperation, experienced guilt has a cushioning effect, potentially countering the progression toward noncooperation. Results also show differences in the emotional experience and resulting emotionally driven cooperation behavior between cooperative types. Particularly free riders tend to act on anger but not on guilt, shedding additional light on the emotionally driven role of free riders in the development of noncooperation. Finally, we find evidence for emotional carryover. Emotionally driven cooperation behavior is not limited to individuals causing the emotions, but is also transferred to individuals who are not directly responsible. Overall, the study provides further evidence for the appraisal and action tendency of anger and guilt and highlights the importance of emotions in repeated cooperative interactions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Effects of Hydrolysable Tannins as Zinc Oxide Substitutes on Antioxidant Status, Immune Function, Intestinal Morphology, and Digestive Enzyme Activities in Weaned Piglets.
Zinc oxide (ZnO) has negative environmental effects and bioavailability in weaned piglets. Thus, finding safe and effective ZnO substitutes to improve intestinal health and to prevent diarrhea of weaned piglets is urgently required. Therefore, this experiment was conducted to evaluate the effects of hydrolysable tannins (HT), ZnO and HT versus ZnO on growth performance, antioxidant status, serum immunity, intestinal morphology, and digestive enzyme activities in weaned pigs. A total of 144 piglets (28 d-old, initial body weight 7.81 ± 0.99 kg) were assigned to 4 treatments with 6 replicates of 6 piglets each. The experiment lasted 28 d (d 1 to 14 as for phase 1 and d 15 to 28 as for phase 2). The dietary treatments include a corn-soybean meal basal diet (CON); ZnO diet (CON + 2000 mg/kg ZnO in phase 1 and 137.5 mg/kg ZnO in phase 2); HT diet (CON + 1000 mg/kg HT in the overall period (d 1 to 28); HT + ZnO diet (CON + 2000 mg/kg ZnO + 1000 mg/kg HT in phase 1, and 137.5 mg/kg ZnO + 1000 mg/kg HT in phase 2). In phase 1, the incidence of diarrhea was lower (p < 0.05) in the HT + ZnO group than CON. Serum catalase (CAT) and glutathione peroxidase (GSH-Px) were increased (p < 0.01) and malondialdehyde (MDA) was decreased (p < 0.01) in the HT + ZnO group than CON. Compared with CON, immunoglobulin M (IgM), immunoglobulin A (IgA) were increased (p < 0.05) in the HT + ZnO group. In phase 2, both HT and HT + ZnO had a trend to improve (p < 0.10) daily gain. The concentration of total antioxidant capacity (T-AOC) and IgM in serum was higher (p < 0.01) in HT compared with CON. Supplementation of HT improved (p < 0.01) GSH-Px activities in ileum mucosa than the ZnO group. Compared with CON, trypsin, lipase activities, and villus height of jejunum were improved (p < 0.05) in HT and HT + ZnO. The ratio of villus height to crypt depth in the jejunum was improved (p < 0.05) in the HT + ZnO group and which also was increased (p < 0.05) in ileum in the HT group compared with CON. Propionic acid, butyric acid, and acetic acid concentrations in the colon were increased (p < 0.05) in the HT group than CON. Overall, HT + ZnO treatments could be used to replace ZnO for reducing diarrhea and improving antioxidant capacity, immunity, and digestive enzyme activities in weaned piglets.


Teratogenic effect of an inhibitor of cholesterol synthesis (AY 9944) in rats: correlation with maternal cholesterolemia.
The teratogenic action of AY 9944, an inhibitor of cholesterol synthesis, was previously shown. Its prevention by simultaneous administration of cholesterol led to the hypothesis that this action is correlated with the decrease in cholesterol. The present investigation demonstrates that there is an inverse correlation between holoprosencephalic type of malformations and maternal cholesterolemia and that, in Wistar rats, 0.30 g/liter of cholesterolemia is a threshold under which these malformations can be observed.


Effect of a Reduced-Calorie Diet on Plasma Levels of Inflammatory and Metabolic Factors in Overweight/Obese Patients with Cardiovascular Risk Factors.
Calorie restriction without malnutrition is likely to improve cardiovascular risk factors. The aim of this study was to investigate calorie restriction on markers of cardiometabolic risk in overweight/obese adults with cardiovascular risk factors. In a parallel controlled trial, patients with overweight or obesity and one or more cardiovascular risk factor were randomized to a modest reduced-calorie diet (75% of the total calculated energy requirements) or control (no calorie restriction) groups and followed up for two months. Body weight, dietary intake, fasting plasma levels of C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), lipids, and glycemic factors were measured at baseline, and after two months. The differences were analyzed with analysis of covariance (ANCOVA). Sixty-six participants (33 in each group) completed the study. Body weight changed in the reduced-calorie diet group (- 3.05 ± 2.65 kg), and blood pressure was improved (systolic -6.96 ± 12.04 and diastolic - 3.90 ± 8.97 mmHg). The reduced-calorie diet improved plasma ICAM-1 (change from baseline - 0.45 ± 1.99 ng/mL, P = 0.033, ANCOVA), MCP-1 (change from baseline - 0.50 pg/mL, P = 0.011, ANCOVA), low-density lipoprotein cholesterol (change from baseline - 9.35 ± 19.61 mg/dL, P < 0.001, ANCOVA), and triglyceride (change from baseline -33.66 ± 49.08, P = 0.001, ANCOVA), but BDNF, NPY, and other cardiometabolic factors were not different. In overweight/obese subjects with cardiovascular risk factors which have been under medical treatment with risk-reducing medications, a modest weight loss induced by a reduced-calorie diet improved lipid profile, blood pressure, and reduced ICAM-1 and MCP-1 levels but had no effect on plasma BDNF or glycemic factors.


The effect of polydextrose and probiotic lactobacilli in a Clostridium difficile-infected human colonic model.
Clostridium difficile is a natural resident of the intestinal microbiota; however, it becomes harmful when the normal intestinal microbiota is disrupted, and overgrowth and toxin production occurs. The toxins can cause bloating and diarrhoea, which may cause severe disease and have the potential to cause outbreaks in hospitals and other healthcare settings. Normally, antibiotic agents are used for treatment, although for some of the patients, these treatments provide only a temporary relief with a recurrence of C. difficile-associated diarrhoea. The effects of polydextrose (PDX), Lactobacillus acidophilus NCFM, and L. paracasei Lpc-37 on the growth of C. difficile were investigated in an in vitro model of infected human large intestine. The semi-continuous colonic model is composed of four connected vessels inoculated with human faecal microbes and spiked with pathogenic C. difficile (DSM 1296). PDX in two concentrations (2 and 4%), NCFM, and Lpc-37 were fed to the system during the 2-day simulation, and the growth of C. difficile and several other microbial groups were monitored using quantitative polymerase chain reaction (qPCR) and 16S rDNA sequencing. The microbial community structure of the simulation samples was closely grouped according to treatment, and the largest shifts in the microbial composition were seen with PDX. The microbial diversity decreased significantly with 4% PDX, and the OTU containing C. difficile was significantly (p<0.01) decreased when compared to control and lactobacilli treatments. The mean numbers of C. difficile also decreased as detected by qPCR, although the reduction did not reach statistical significance. The treatments influenced the colonic microbiota, and a trend for reduced numbers of C. difficile as well as alterations of several microbial groups could be detected. This suggests that PDX may be able to modulate the composition and/or function of the colonic microbiota in such manner that it affects the pathogenic C. difficile.


Pharmacologic atrial defibrillation by drug delivery into the temporarily occluded coronary sinus. A canine study.
Venous blood draining from the left atrium (LA) flows into the coronary sinus (CS) through the Marshall vein which has no valvular apparatus, thus allowing LA retroperfusion if reflow in the right atrium is hindered. We investigated pharmacologic atrial defibrillation via the CS in dogs with chronic atrial fibrillation (AF). Chronic AF was induced by rapid atrial pacing for 4-16 weeks in 6 mongrel dogs. A 7F occlusion balloon catheter was introduced into the proximal CS. Boluses of low doses of the class Ic antiarrhythmic drug, pilsicainide (2, 4, 6, and 8 mg as needed) or class III antiarrhythmic drug, nifekalant (0.5, 1, 2, and 4 mg) were infused directly within 3-4 seconds at 10 minute intervals into the temporarily balloon occluded CS near its orifice. In 4 of the 5 dogs (balloon catheter could not be placed in the CS in 1 dog), the cumulative dose of 11.5 ± 7.4 mg of pilsicainide was effective in restoring sinus rhythm; the venous concentration of pilsicainide was 1.23 ± 0.79 µg/mL. A cumulative dose of 7.5 mg nifekalant restored sinus rhythm in only 1 of the 6 dogs. Our results in dogs with sustained AF indicate that delivery of a class Ic or III antiarrhythmic drug near the CS ostium via the temporarily occluded CS is feasible and effective for pharmacologic atrial defibrillation; however, the effect may be related to the elevation of the serum concentration of the drug to the therapeutic range rather than to the delivery method itself.


Synthesis of (2 H)-Indazoles through Rh(III)-Catalyzed Annulation Reaction of Azobenzenes with Sulfoxonium Ylides.
The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.


A new method for quantitative determination of two uronic acids by CZE with direct UV detection.
A new method using capillary zone electrophoresis was developed for the rapid quantification of two common uronic acids, galacturonic acid and glucuronic acid, based on utilization of an alkaline background electrolyte with reversed electroosmotic flow (EOF) within 16 min. The method relies on in-capillary reaction and direct UV detection at the wavelength 270 nm. The optimum electrolyte solution was prepared of 130 mm sodium hydroxide, 36 mm disodium hydrogen phosphate dihydrate and 0.5 mm cetyltrimethylammonium bromide. EOF was reversed to detect uronic acids and to improve the separation of neutral sugars. The established method was validated and the results showed good linearity, high precision and satisfactory sensitivity. The newly developed method was successfully applied to analyze galacturonic acid and glucuronic acid content in Forsythia suspensa polysaccharides. The method is fast since only sample hydrolysis and dilution are required in the sample preparation.


Regional and general effects of hepatic lobes with impaired blood flow after hepatic resection.
In hepatic surgery, blood flow to some parts of the liver may become impaired. At present, no consensus has been reached on ways to treat such affected parts of the liver with impaired blood supply. After the ligation of branches of rat's hepatic artery and/or portal vein, the ligated and non-ligated lobes were studied at fixed intervals up to 84 days. Parameters include hepatic tissue blood flow assessed by a laser Doppler flowmeter, liver regeneration ability using bromodeoxyuridine, apoptosis using anti-single-stranded DNA Ig-G antibody, and vulnerability to an endotoxic injection. Hepatic artery ligation group showed no obvious changes in either the ligated or non-ligated lobes, and these lobes had no effects on the whole body. Of the portal vein ligation group, although the ligated lobes underwent marked atrophy, the compensatory hypertrophy of the non-ligated lobes took place sufficiently and no life-threatening conditions were observed. With regard to the hepatic artery/portal vein ligation (HA/PVL) group, hepatic blood flow in the ligated lobes rapidly decreased, and all hepatocytes underwent necrosis 1 day after surgery. In the non-ligated lobes, however, significant increases in the bromodeoxyuridine labeling index were detected at 1, 2, and 3 days after surgery, and compensatory hypertrophy was recognized. Indocyanine green 15-minute retention rate rapidly increased 1 day after surgery, and there were significant differences compared to the sham group up to 7 days after surgery. The postsurgical mortality rate in the HA/PVL group was significantly high at 13%, and mortality rate following endotoxin injection was as high as 75%. Affected parts of the liver with blockage of both the hepatic artery and portal vein should be resected.


Temperature dependent development of Lygus hesperus (Hemiptera: Miridae) nymphs.
Lygus hesperus Knight (Hemiptera: Miridae) is a key pest of fruit and vegetable crops, forages, and cotton (Gossypium spp.) in the western United States. Accurate models describing relationships between temperature and L. hesperus development are critical to the study of seasonal L. hesperus population dynamics. Development of L. hesperus nymphs was assessed at nine constant temperatures from 10 to 37.8 degrees C. The relationships between temperature and development for each L. hesperus instar, and for the entire nymphal stage, were best described by six-parameter biophysical models indicating both low- and high-temperature inhibition of development. Development rates asymptotically approached zero with decreasing temperature in the lower thermal range, and decreased with increasing temperatures above 32.2 degrees C. Nymphs did not survive from egg hatch to adulthood at either 10 or 37.8 degrees C, and nymph mortality was > 90% at both 12.8 and 35.0 degrees C. The fifth instar exhibited the longest stadium, whereas the shortest stadia were associated with the second and third instars. Development rates of males and females did not differ, and the ratio of males to females was not different from 1:1 at any temperature. Our temperature-dependent development rate models for L. hesperus nymphs will facilitate control of insect physiological age in controlled laboratory experiments, and should be useful in planning and interpreting field studies on L. hesperus population dynamics.


Activation of human NKCC by moderate exercise: increased frequency of NK cells with enhanced capability of effector--target lytic interactions.
In the present study we examined the mechanism of human natural killer cellular cytotoxicity (NKCC) augmentation by 5 min of moderate exercise and its interrelationship to in vitro interferon (IFN) activation. Cytotoxicity was measured by employing both a single-cell cytotoxic assay and a standard 3-hr chromium-51 (51Cr) release assay. The former was used to assess changes at the single NK cell--target cell level and the latter to assess changes in overall lytic capacity of a given population of NK cells. Several findings were obtained: (1) moderate exercise augmented NKCC in vivo by recruiting a 'new' population of active cytotoxic NK cells. (2) This 'new' population of active cells probably was derived from cells which can bind targets but are non-cytotoxic. (3) In a standard 51Cr-release assay, additional augmentation of these exercise-activated cells occurred in vitro following exposure to interferon. (4) This additional increase in cytotoxicity produced no alteration in the frequency of killer cells as viewed at the single cell level. (5) Thus interferon's capacity to increase further the overall lytic ability of exercise-activated NK cells was not due to its activation of an additional subset of pre-NK cells, but due to its increasing the capacity of effector--target lytic interactions (recycling) of the same set of NK and pre-NK cells.


[Cutaneous gene therapy: the graft takes].
Prospects of ex vivo cutaneous gene therapy rely on stable corrective gene transfer in epidermal stem cells followed by engraftment of corrected cells in patients. In the case of cancer prone genodermatoses, such as xeroderma pigmentosum, cells that received the corrective gene must be selected. However, this step is potentially harmful and can increase risks of immune rejection of grafts. These obstacles have recently been overcome thanks to the labeling of genetically modified stem cells using a small epidermal protein naturally absent in stem cells. This approach was shown to be respectful of the fate of epidermal stem cells that retained full growth and differentiation capacities, as well as their potential to regenerate normal human skin when grafted in a mouse model in the long term. These progresses now open realistic avenues towards ex vivo cutaneous gene therapy of cancer prone genodermatoses such as xeroderma pigmentosum. However, major technical improvements are still necessary to preserve skin appendages which would contribute to aesthetic features and comfort of patients.


Developing a Culturally Informed Survey Instrument to Assess Biomedical Research Participation Among Latinos on the U.S.-Mexico Border.
Racial/ethnic minorities, rural populations, and those with low socioeconomic status income are underrepresented in research in the United States (U.S.). Assessing preferences for recruitment, participation, and the role of beliefs about biomedical research in specific and unique underserved communities represents a potentially critical step in reducing barriers to biomedical research participation. We developed a culturally informed survey to measure factors related to participation, knowledge, expectations, and barriers to biomedical research participation among Latinos living in a U.S. border community. We employed a multidisciplinary team approach to a sequential, three-phase qualitative study that included interviews ( n = 35), focus groups ( n =24), and "think-aloud" cognitive interviews ( n = 5). Our study demonstrates the value of applying multiple qualitative approaches to inform a culturally relevant quantitative survey incorporating words and constructs relevant to the population of interest. The study contributes to qualitative method research paradigms by developing a research protocol that integrates the expertise and perspectives of researchers and community members from multiple disciplines and institutions.


Improvement in social anxiety following a return-to-work intervention for patients with depression.
To retrospectively examine depression and social anxiety improvement in patients on sick leave due to depression who participated in a return-to-work intervention (RTW-I) program. Patients visited a psychiatric outpatient clinic simulating workplaces to learn recurrence prevention skills through RTW-Is, including group cognitive behavioral therapy, from April 1, 2013, to September 30, 2017. The Beck Depression Inventory-Second Edition (BDI-II), Social Adaptation Self-Evaluation Scale (SASS), and Liebowitz Social Anxiety Scale (LSAS) scores of 112 patients were analyzed before and after the intervention program. Missing postprogram data were substituted using the last observation carried forward scores. Next, 45 patients who responded to the work continuity survey 1 year after RTW-I were categorized into Group A (patients who continued working: 37) and Group B (those who did not continue: 8). The mean BDI-II scores significantly decreased from preintervention 19.4 to postintervention 7.9 (t = 13.303, P < .001). The mean SASS scores significantly increased from preintervention 31.9 to postintervention 36.0 (t = -5.953, P < .001). The mean LSAS scores significantly decreased from preintervention 54.7 to postintervention 37.0 (t = 8.682, P < .001), and all scores demonstrated an improvement. Patients who continued working showed improved depressive and social anxiety symptoms. The BDI-II and SASS scores showed no significant differences between the groups, but the postintervention LSAS scores were significantly different (P = .041). LSAS score changes: Group A = -26.2; Group B = -9.8; estimated difference: -17.920, 95% CI: -32.181 to -3.659, P = .015. The RTW-I program improved depressive and social anxiety symptoms. Patients with improved scores continued working for 1 year after the intervention.Trial registration: This trial was retrospectively registered with the UMIN Clinical Trial Registry (UMIN-CTR) (ID: UMIN000037662) on August 10, 2019.


Functional outcomes and quality of life at 1-year follow-up after an open tibia fracture in Malawi: a multicentre, prospective cohort study.
Injuries are a major cause of disability globally and injury incidence is rapidly increasing, largely due to road traffic injuries in low-income and middle-income countries. Current estimates of the scale and consequences of disability from injury are largely based on modelling studies, with a scarcity of empirical evidence from severe injuries in low-income countries. We aimed to better understand the outcomes for individuals with open tibia fractures in Malawi. In this multicentre, prospective cohort study, adults (aged ≥18 years) with open tibia fractures were systematically recruited at six hospitals in Malawi (two tertiary hospitals and four district hospitals). Follow-up lasted at least 1 year, during which in-person follow-up reviews were done at 6 weeks, 3 months, 6 months, and 1 year post-injury. The primary outcome was function at 1 year post-injury, measured by the Short Musculoskeletal Functional Assessment (SMFA) score. Secondary outcomes included quality-adjusted life-years (QALYs; as determined via the European Quality of Life 5-Dimensions 3-Levels [EQ-5D-3L] survey) and fracture-related infection at 1 year post-injury. Multilevel regression models investigated associations between SMFA score, EQ-5D-3L, baseline factors, and orthopaedic management. Between Feb 12, 2021, and March 14, 2022, 287 participants were enrolled (median age 34 years [IQR 25-44]; 84% male). The most common mode of injury was road traffic injuries (194 [68%] of 287). Overall, 268 (93%) participants had debridement; of the 63 participants who were debrided in district hospitals, 47 (75%) had the procedure under local or no anaesthesia. Following substantial declines by 6 weeks after injury, function and quality of life had not recovered by 1 year post-injury for participants with Gustilo grade I-II fractures (posterior mean SMFA at 1 year: 10·5, 95% highest density interval [HDI]: 9·5-11·6; QALYs: 0·73, 95% HDI: 0·66-0·80) nor Gustilo grade III fractures (posterior mean SMFA at 1 year: 14·9, 95% HDI: 13·4-16·6; QALYs: 0·67, 95% HDI: 0·59-0·75). For all fracture grades, intramedullary nailing substantially improved function and quality of life at 1 year post-injury. Delayed definitive fixation after 5 days had 5-times greater odds of infection compared with early management within 2 days (adjusted odds ratio: 5·1, 95% CI 1·8-16·1; p=0·02). Adults with open tibia fractures in Malawi have poor function and quality of life in the 1 year following injury. Centralised orthopaedic surgical management, including early definitive fixation and intramedullary nailing for more severe injuries, might improve outcomes. Wellcome Trust. For the Chichewa translation of the abstract see Supplementary Materials section.


Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma.
BackgroundThis study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history. Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors. Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043). Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically.Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.


Umbilical pilonidal sinus.
Pilonidal sinuses are commonly encountered, but their occurrence in the umbilical area is rare. The author presents one such case of an umbilical pilonidal sinus in an obese male patient that presented with recurrent episodes of umbilical discharge. The condition was treated with sinus excision and umbilical reconstruction. There was no recurrence of the disease until one year of follow up.


Lactic dehydrogenase in the monitoring and prognosis of testicular cancer.
In a prospective study of 80 patients with germinal testicular cancer, serial determinations of lactic dehydrogenase (LDH), alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were followed for a mean of 18.1 months. Serum LDH was found to be elevated more frequently with increasing tumor bulk. LDH was elevated in 78.0% of the patients with Stage III disease but only 26.3% of the Stage II patients and 20.0% of the pre-orchiectomy Stage I patients. In this study, serum HCG and AFP levels were always elevated in the presence of elevated serum LDH levels except in one patient when LDH was the only elevated marker, in which case it correlated with clinical disease. Correlation of these three serum markers is shown by elevation of LDH in 78.0% of the Stage III patients, AFP in 78.6%, and HCG in 76.2%. In addition, of the 43 patients who had normal LDH levels on initial presentation, their mean survival time (MST) at the end of the study was 15.5 months while the 26 patients who had elevated LDH levels on initial presentation had an MST of 9.2 months. Serum LDH, therefore, may be useful in evaluating patient prognosis as well as an adjunct in monitoring the treatment of patients with bulky testicular cancer. The combination of LDH and HCG has been utilized to monitor the treatment of seminoma.


Nuclear factor-kappaB p65 facilitates longitudinal bone growth by inducing growth plate chondrocyte proliferation and differentiation and by preventing apoptosis.
NF-kappaB is a group of transcription factors involved in cell proliferation, differentiation, and apoptosis. Mice deficient in the NF-kappaB subunits p50 and p52 have retarded growth, suggesting that NF-kappaB is involved in bone growth. Yet, it is not clear whether the reduced bone growth of these mice depends on the lack of NF-kappaB activity in growth plate chondrocytes. Using cultured rat metatarsal bones and isolated growth plate chondrocytes, we studied the effects of two NF-kappaB inhibitors (pyrrolidine dithiocarbamate (PDTC) or BAY11-7082 (BAY)), p65 short interference RNA (siRNA), and of the overexpression of p65 on chondrocyte proliferation, differentiation, and apoptosis. To further define the underlying mechanisms, we studied the functional interaction between NF-kappaB p65 and BMP-2 in chondrocytes. PDTC and BAY suppressed metatarsal linear growth. Such growth inhibition resulted from decreased chondrocyte proliferation and differentiation and from increased chondrocyte apoptosis. In cultured chondrocytes, the inhibition of NF-kappaB p65 activation (by PDTC and BAY) and expression (by p65 siRNA) led to the same findings observed in cultured metatarsal bones. In contrast, overexpression of p65 in cultured chondrocytes induced chondrocyte proliferation and differentiation and prevented apoptosis. Although PDTC, BAY, and p65 siRNA reduced the expression of BMP-2 in cultured growth plate chondrocytes, the overexpression of p65 increased it. The addition of Noggin, a BMP-2 antagonist, neutralized the stimulatory effects of p65 on chondrocyte proliferation and differentiation, as well as its anti-apoptotic effect. In conclusion, our findings indicate that NF-kappaB p65 expressed in growth plate chondrocytes facilitates growth plate chondrogenesis and longitudinal bone growth by inducing BMP-2 expression and activity.


Factors associated with intention for revaccination among patients with adverse events following immunization.
Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.


Toad Alkaloid for Pesticide Discovery: Dehydrobufotenine Derivatives as Novel Agents against Plant Virus and Fungi.
Plant viruses and fungi are a serious threat to food security and natural ecosystems. The efficient and environment-friendly control methods are urgently needed to help safeguard such resources. Here, we achieved the efficient synthesis of toad alkaloid dehydrobufotenine in eight steps with an overall yield of 8% from 5-methoxyindole. A series of dehydrobufotenine derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. It was found for the first time that these compounds have good anti-plant virus activities and anti-plant pathogen activities. The antiviral activities of 21 compounds were similar to or better than those of ribavirin. Compounds 12 and 17 displayed better antiviral activities than ningnanmycin which is perhaps the most effective anti-plant virus agent. The antiviral mechanism research study of 12 revealed that it could make 20S CP disk fusion and aggregation. Further molecular docking results showed that there are hydrogen bonds between compounds 12, 17, and tobacco mosaic virus CP. The docking results are consistent with the antiviral activity. These compounds also displayed broad-spectrum fungicidal activities against 14 kinds of fungi, especially for Sclerotinia sclerotiorum. In this work, the synthesis, structure optimization, structure-activity relationship studies, and mode of action research of dehydrobufotenine alkaloids were carried out. It provides a reference for the development of the anti-plant virus agent and anti-plant pathogen agent from toad alkaloids.


Estimating physical activity trends among blacks in the United States through examination of four national surveys.
Physical activity is essential for overall good health and aids in the prevention and reduction of many diseases. In 2008, the U.S. Department of Health and Human Services (DHHS) issued the Physical Activity Guidelines for Americans to foster appropriate levels of physical activity at various ages of development. Despite these guidelines and the known benefit to being physically active; physical activity levels are significantly lower in Blacks, contributing to higher prevalence of poor health outcomes. Therefore, the purpose of this paper was to look at four national datasets [Youth Risk Behavior Survey (YRBS), Behavioral Risk Factor Surveillance System (BRFSS), The National Health and Nutrition Examination Survey (NHANES), and National Health Interview Survey (NHIS)] to identify any patterns and trends that could be used to improve physical activity behavior within this population. These national datasets were used to estimate the proportion of Black adults and youth meeting national physical activity recommendations overall-stratified by age, gender and other demographic characteristics, to help identify patterns. The proportion of Black youth reporting regular physical activity ranged from 33% to 52%; and of Black adults, 27% to 52%. Physical activity was highest among men, younger age groups, highest education and income groups, and those who were employed or married. Trends were consistent across surveys. Among Black youth, physical activity decline with increasing grade level, and improvements over the past 10 years have been minimal. The percentage of Black adults achieving physical activity guidelines has improved slightly over the last ten years, but physical activity participation is still low and continues to decline with age. Trends identified from examining these national datasets can be used to inform development of physical activity interventions aimed at promoting and maintaining regular physical activity behavior among high risk subgroups across the life span.


HIV-1 Vpu Promotes Phagocytosis of Infected CD4+ T Cells by Macrophages through Downregulation of CD47.
Human immunodeficiency virus (HIV) remodels the cell surface of infected cells to facilitate viral dissemination and promote immune evasion. The membrane-associated viral protein U (Vpu) accessory protein encoded by HIV-1 plays a key role in this process by altering cell surface levels of multiple host proteins. Using an unbiased quantitative plasma membrane profiling approach, we previously identified CD47 as a putative host target downregulated by Vpu. CD47 is a ubiquitously expressed cell surface protein that interacts with the myeloid cell inhibitory receptor signal regulatory protein-alpha (SIRPα) to deliver a "don't-eat-me" signal, thus protecting cells from phagocytosis. In this study, we investigate whether CD47 modulation by HIV-1 Vpu might promote the susceptibility of macrophages to viral infection via phagocytosis of infected CD4+ T cells. Indeed, we find that Vpu downregulates CD47 expression on infected CD4+ T cells, leading to enhanced capture and phagocytosis by macrophages. We further provide evidence that this Vpu-dependent process allows a C-C chemokine receptor type 5 (CCR5)-tropic transmitted/founder (T/F) virus, which otherwise poorly infects macrophages in its cell-free form, to efficiently infect macrophages. Importantly, we show that HIV-1-infected cells expressing a Vpu-resistant CD47 mutant are less prone to infecting macrophages through phagocytosis. Mechanistically, Vpu forms a physical complex with CD47 through its transmembrane domain and targets the latter for lysosomal degradation. These results reveal a novel role of Vpu in modulating macrophage infection, which has important implications for HIV-1 transmission in early stages of infection and the establishment of viral reservoir. IMPORTANCE Macrophages play critical roles in human immunodeficiency virus (HIV) transmission, viral spread early in infection, and as a reservoir of virus. Selective capture and engulfment of HIV-1-infected T cells was shown to drive efficient macrophage infection, suggesting that this mechanism represents an important mode of infection notably for weakly macrophage-tropic T/F viruses. In this study, we provide insight into the signals that regulate this process. We show that the HIV-1 accessory protein viral protein U (Vpu) downregulates cell surface levels of CD47, a host protein that interacts with the inhibitory receptor signal regulatory protein-alpha (SIRPα), to deliver a "don't-eat-me" signal to macrophages. This allows for enhanced capture and phagocytosis of infected T cells by macrophages, ultimately leading to their productive infection even with transmitted/founder (T/F) virus. These findings provide new insights into the mechanisms governing the intercellular transmission of HIV-1 to macrophages with implications for the establishment of the macrophage reservoir and early HIV-1 dissemination in vivo.


A painful pulsatile abdominal mass in a young man with elevated blood pressures: an unusual presentation of phaeochromocytoma.
We report an unusual presentation of phaeochromocytoma in a young man with a painful, pulsatile abdominal mass and elevated blood pressures. This led to a delay in diagnosis and resulted in the administration of triggers of catecholamine release, possibly causing a catecholamine surge. This caused the development of catecholamine-induced cardiomyopathy and multiple organ failure, requiring inotropic and ventilatory support, intra-aortic balloon pump and dialysis. Fortunately, his condition reversed with supportive treatment and alpha-adrenergic blockade. This illustrates the importance of having a high index of suspicion of phaeochromocytoma, especially in young patients with elevated blood pressures.


Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor.
Orlistat, an antiobesity drug, is cytostatic and cytotoxic to tumor cells. The antitumor activity of orlistat can be attributed to its ability to inhibit the thioesterase domain of fatty acid synthase (FAS). The objective of the present study was to test the effect of orlistat on endothelial cell proliferation and angiogenesis. Orlistat inhibits endothelial cell FAS, blocks the synthesis of fatty acids, and prevents endothelial cell proliferation. More significantly, orlistat inhibits human neovascularization in an ex vivo assay, which suggests that it may be useful as an antiangiogenic drug. The mechanism of these effects can be traced to the fact that orlistat prevents the display of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR/Flk1) on the endothelial cell surface. Thus, orlistat is an antiangiogenic agent with a novel mechanism of action.


Are tattooed adults really more aggressive and rebellious than those without tattoos?
One stereotype of people with tattoos is that they are more aggressive and rebellious than people without tattoos. However, studies examining differences in these traits between tattooed and non-tattooed individuals are dated and have returned equivocal results. To re-examine this issue, we asked 378 adults from London, UK, to complete self-report measures of aggression and rebelliousness, and to report the number of tattoos they possessed. Of this sample, 25.7% possessed at least one tattoo, with no sex difference in the distribution of tattoo status. We found that tattooed adults had significantly higher reactive rebelliousness, anger, and verbal aggression than non-tattooed adults. However, effect sizes were small and there were also no significant between-group differences in terms of proactive rebelliousness, physical aggression, and hostility. These results suggest that, while stereotypes may contain a kernel of truth, they likely present an outmoded picture of tattooed adults.


Barriers and facilitators to retaining a cohort of street-based cisgender female sex workers recruited in Baltimore, Maryland, USA: results from the SAPPHIRE study.
Despite experiencing HIV/STIs, violence, and other morbidities at higher rates than the general public, street-based female sex workers are often absent from public health research and surveillance due to the difficulty and high costs associated with engagement and retention. The current study builds on existing literature by examining barriers and facilitators of retaining a street-based cohort of cisgender female sex workers recruited in a mobile setting in Baltimore, Maryland who participated in the SAPPHIRE study. Participants completed interviews and sexual health testing at baseline, 3-, 6-, 9-, and 12-months. Retention strategies are described and discussed in light of their benefits and challenges. Strategies included collecting several forms of participant contact information, maintaining an extensive field presence by data collectors, conducting social media outreach and public record searches, and providing cash and non-cash incentives. We also calculated raw and adjusted retention proportions at each follow-up period. Lastly, baseline sample characteristics were compared by number of completed visits across demographic, structural vulnerabilities, work environment, and substance use variables using F-tests and Pearson's chi-square tests. Although there were drawbacks to each retention strategy, each method was useful in tandem in achieving a successful follow-up rate. While direct forms of contact such as phone calls, social media outreach, and email were useful for retaining more stable participants, less stable participants required extensive field-based efforts such as home and site visits that increase the likelihood of random encounters. Overall, adjusted retention exceeded 70% for the duration of the 12-month study. Participants who were younger, recently experienced homelessness, and injected drugs daily were less likely to have completed all or most follow-up visits. Retention of street-based female sex workers required the simultaneous use of diverse retention strategies that were tailored to participant characteristics. With familiarity of the dynamic nature of the study population characteristics, resources can be appropriately allocated to strategies most likely to result in successful retention.


Construction of an enantiopure bivalent nicotine vaccine using synthetic peptides.
Clinical outcomes of anti-nicotine vaccines may be improved through enhancements in serum antibody affinity and concentration. Two strategies were explored to improve vaccine efficacy in outbred mice: the use of enantiopure haptens and formulation of a bivalent vaccine. Vaccines incorporating natural (-) nicotine haptens improved relative antibody affinities >10-fold over (+) haptens, stimulated a two-fold boost in nicotine serum binding capacity, and following injection with 3 cigarette equivalents of nicotine, prevented a larger proportion of nicotine (>85%) from reaching the brain. The activity of a bivalent vaccine containing (-) 3'AmNic and (-) 1'SNic haptens was then compared to dose-matched monovalent groups. It was confirmed that antisera generated by these structurally distinct haptens have minimal cross-reactivity and stimulate different B cell populations. Equivalent antibody affinities were detected between the three groups, but the bivalent group showed two-fold higher titers and an additive increase in nicotine serum binding capacity as compared to the monovalent groups. Mice immunized with the bivalent formulation also performed better in a nicotine challenge experiment, and prevented >85% of a nicotine dose equivalent to 12 cigarettes from reaching the brain. Overall, enantiopure conjugate vaccines appear to improve serum antibody affinity, while multivalent formulations increase total antibody concentration. These findings may help improve the performance of future clinical candidate vaccines.


Reevaluation of reflex responses of the human masseter muscle to electrical lip stimulation.
We examined the reflex response of the human masseter muscle to electrical stimulation of the lip using both single motor unit and surface electromyogram based methods. Using the classical analysis methods, reflex response to mild electrical stimuli generated two distinct short-lasting inhibitions. This pattern may reflect the development of combinations of short- and long-latency inhibitory postsynaptic potentials as a result of the mildly painful electrical lip stimulation. However, this pattern appearing in the classical analysis methods may have developed as a consequence of earlier responses and may not be genuine. This study examined the genuineness of these responses using both the classical analysis methods and the discharge rate method to uncover the realistic postsynaptic potentials in human trigeminal motor nucleus. Using the discharge rate method, we found that the electrical lip stimulation only generated a long-lasting single or compound inhibitory response that is followed by late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.NEW & NOTEWORTHY We examined the human masseter reflex response to electrical stimulation of lower lip to uncover realistic postsynaptic potentials in the trigeminal motor nucleus. We found that the stimulation generates a long-lasting single or compound inhibitory response that is followed by a late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.