Lactocepin as a protective microbial structure in the context of IBD.
Probiotics have been shown to exert beneficial effects in the context of different diseases including inflammatory bowel diseases (IBD). However, clinical use of probiotics is hampered by lack of understanding of the protective mechanisms and by safety concerns regarding the application of high numbers of live bacteria in patients. The identification of protective microbial structure-function relationships might enable to overcome these restraints and might lead to innovative therapies using the isolated active microbial structures. In our study, we aimed to characterize the protective mechanisms of VSL#3, a clinically relevant probiotic mixture in IBD. We found Lactobacillus casei/paracasei-produced lactocepin to selectively degrade pro-inflammatory chemokines, resulting in reduced immune cell infiltration and reduced inflammation in experimental IBD models. As immune cell recruitment is a major proinflammatory mechanism our findings suggest that lactocepin might be of broad therapeutic relevance in an array of inflammatory diseases like IBD, allergic skin inflammation and psoriasis.


Molecular structure of 1,1,2,2-tetra-tert-butyldisilane: unusual structural motifs in sterically crowded disilanes.
The molecular structure of 1,1,2,2-tetra-tert-butyldisilane has been determined by gas-phase electron diffraction supported by ab initio calculations, in the solution phase by Raman spectroscopy, and in the solid phase by Raman spectroscopy and X-ray crystallography. The gas-phase structure (C2 symmetry) was found to be almost anticlinal, a most unusual and unexpected result. In the favoured conformation, contact between tert-butyl groups at each end of the molecule is avoided by a large deviation of the angles around the silicon atoms from the parent tetrahedral angle of 109.5 degrees. In fact, the Si-Si-C angles returned from the gas electron diffraction refinement are 117.0(5) and 110.7(6) degrees, indicating the large degree of flexibility about the silicon centres. The ab initio methods and gas electron diffraction results indicate that there is only one conformer of But2HSiSiHBut2 in the gaseous mixture. Variable temperature Raman studies indicate the possibility of a further higher energy conformer existing in the liquid phase. However, this seems quite improbable from other observations made for the Raman spectra at all temperatures. The X-ray structure is close to that observed in the gas phase, with phiHSiSiH = 94.2(18) degrees. There is a large amount of disorder about one of the silicon postions and one of the tert-butyl groups within the crystal structure, which makes detailed direct comparison with the gaseous structure difficult.


A review of electrocardiography in the high altitude environment.
An ascent to altitude places considerable demands on the cardiovascular system. Changes in the rate, rhythm, and morphology of the electrocardiogram reflect the fall in the partial pressure of inspired oxygen (PiO2) and the adaptive responses that the human body makes. The effect of hypoxia on the autonomic nervous system results in changes to the heart rate during rest and exercise. Although this is raised during rest and submaximal exercise, maximal heart rate at altitude is reduced as a result of changes in parasympathetic activity. Hypoxic pulmonary vasoconstriction leads to a rise in pulmonary artery pressure and morphological changes on the electrocardiogram. Right axis deviation, right bundle branch block, and changes to P and T wave amplitudes are commonly found on ascent and resolve only after a return to low altitude. Although atrial and ventricular ectopic activity is also common, tachyarrhythmias are rare in healthy individuals. However, in those with significant cardiac disease, the hypoxic environment can be hazardous, exposing individuals to ischemia and the risk of sudden cardiac death.


Two-dimensional lanthanide heteropolyvanadates of manganese(IV) and nickel(IV) containing two types of heteropoly anions with 1:13 and 1:12 stoichiometry.
Reactions of 1:13 heteropoly anions [MV13O38](7-) (M = Mn, Ni) and lanthanide cations Ln3+ (Ln = La, Ce, or Pr) produce five isomorphic compounds, which are crystallized in the triclinic crystal system, space group P1, and formulated as [Ln6(H2O)25(MV12O38)(HMV13O38)].nH2O ((1) Ln = La, M = Mn, and n approximately 31; (2) Ln = Ce, M = Mn, and n approximately 29; (3) Ln = Pr, M = Mn, and n approximately 31; (4) Ln = La, M = Ni, and n approximately 28; (5) Ln = Pr, M = Ni, and n approximately 33). These compounds are two-dimensional polymeric structures constructed by hydrated lanthanide cations and two types of heteropoly anions, [MV13O38](7-) and [MV12O38](12-). In contrast to the previous reported 1:13 heteropoly anions, all with disordered structures, [MV13O38](7-) clusters in 1-5 are non-disordered with a distinct mode. The second kind of anionic cluster [MV12O38](12-) with O(h) symmetry, which consists of 13 entire edge-sharing MO(6) (M = V, Mn or Ni) octahedra, has not been reported hitherto. The emergence of the new cluster may be correlated to the six capping lanthanide cations surrounding it with a stabilization effect. In this paper, the syntheses and structures of the five polymeric lanthanide heteropolyvanadates of manganese(IV) and nickel(IV) have been presented.


Near-Infrared Annihilation of Conductive Filaments in Quasiplane MoSe2 /Bi2 Se3 Nanosheets for Mimicking Heterosynaptic Plasticity.
It is desirable to imitate synaptic functionality to break through the memory wall in traditional von Neumann architecture. Modulating heterosynaptic plasticity between pre- and postneurons by another modulatory interneuron ensures the computing system to display more complicated functions. Optoelectronic devices facilitate the inspiration for high-performance artificial heterosynaptic systems. Nevertheless, the utilization of near-infrared (NIR) irradiation to act as a modulatory terminal for heterosynaptic plasticity emulation has not yet been realized. Here, an NIR resistive random access memory (RRAM) is reported, based on quasiplane MoSe2 /Bi2 Se3 heterostructure in which the anomalous NIR threshold switching and NIR reset operation are realized. Furthermore, it is shown that such an NIR irradiation can be employed as a modulatory terminal to emulate heterosynaptic plasticity. The reconfigurable 2D image recognition is also demonstrated by an RRAM crossbar array. NIR annihilation effect in quasiplane MoSe2 /Bi2 Se3 nanosheets may open a path toward optical-modulated in-memory computing and artificial retinal prostheses.


Patient safety is not elective: a debate at the NPSF Patient Safety Congress.
The opening keynote session of the 16th Annual National Patient Safety Foundation Patient Safety Congress, held 14-16 May 2014, featured a debate addressing the merits and challenges of accountability with respect to key issues in patient safety. The specific resolution debated was: Certain safety practices should be inviolable, and transgressions should result in penalties, potentially including fines, suspensions, and firing. The themes discussed in the debate are issues that healthcare professionals and leaders commonly struggle with in their day-to-day work. How do we draw a line between systems problems and personal failings? When should clinicians and staff be penalised for failing to follow a known safety protocol? The majority of those who listened to the live debate agreed that it is time to begin holding health professionals accountable when they wilfully or repeatedly violate policies or protocols put in place by their institutions to protect the safety of patients. This article summarises the debate as well as the questions and discussion generated by each side. A video of the original debate can be found at http://bit.ly/Npsf_debate.


Gastrointestinal surgery in the AIDS patient.
The acquired immunodeficiency syndrome is associated with opportunistic infections and unusual malignancies that may affect the gastrointestinal tract. The number of patients affected by this condition is large and will continue to increase. The manifestations of the disease may mimic acute surgical conditions. In addition, standard surgical problems may occur in the AIDS patient. Diagnosis may be confounded by pre-existing symptoms and atypical presentations. An awareness and understanding of the disease processes distinctive to AIDS patients is essential for surgeons so that they may provide appropriate care to their patients and, at the same time, protect themselves and their fellow health care team members.


Characterization of a 180-kDa intestinal epithelial cell membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial cell interactions.
Previous studies have shown that normal human intestinal epithelial cells stimulate CD8(+) suppressor T cell proliferation in an allogeneic mixed epithelial/T cell co-culture system, which is neither restricted by class I or class II major histocompatibility complex antigens nor by any soluble factors from epithelial cells. Two epithelial specific monoclonal antibodies (mAb), mAb B9 and mAb L12, are potent inhibitors of this mixed epithelial/T cell reaction but not of conventional mixed lymphocyte reactions. While phenotypically distinct by tissue staining, both mAbs recognize a 180-kDa epithelial membrane glycoprotein (gp180). Further characterization of gp180 revealed the following. 1) The protein migrated between 150 and 180 kDa in SDS-polyacrylamide gel electrophoresis and could be resolved by Western blot using mAb B9 or mAb L12. 2) The molecule has two forms, an apically sorted glycosylphosphatidylinositol-anchored form and a basolateral transmembrane form. 3) gp180 is heavily N-glycosylated, since N-glycanase treatment results in a >50% reduction in size. 4) Purified gp180 can bind to peripheral blood T cells and activate p56(lck). 5) gp180 can activate p56(lck) in 3G8 (a murine T cell hybridoma transfected with human CD8alpha cDNA) but not in 3G4 (CD4 transfectant), suggesting that gp180 binds to CD8. Thus, gp180 appears to be a novel regulator of mucosal immune responses.


Ovarian cancer: epigenetics, drug resistance, and progression.
Ovarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation.


High gain/bandwidth off-chip antenna loaded with metamaterial unit-cell impedance matching circuit for sub-terahertz near-field electronic systems.
An innovative off-chip antenna (OCA) is presented that exhibits high gain and efficiency performance at the terahertz (THz) band and has a wide operational bandwidth. The proposed OCA is implemented on stacked silicon layers and consists of an open circuit meandering line. It is shown that by loading the antenna with an array of subwavelength circular dielectric slots and terminating it with a metamaterial unit cell, its impedance bandwidth is enhanced by a factor of two and its gain on average by about 4 dB. Unlike conventional antennas, where the energy is dissipated in a resistive load, the technique proposed here significantly reduces losses. The antenna is excited from underneath the antenna by coupling RF energy from an open-circuited feedline through a slot in the ground-plane of the middle substrate layer. The feedline is shielded with another substrate layer which has a ground-plane on its opposite surface to mitigate the influence of the structure on which the antenna is mounted. The antenna has the dimensions 12.3 × 4.5 × 0.905 mm3 and operates across the 0.137-0.158 THz band corresponding to a fractional bandwidth of 14.23%. Over this frequency range the average measured gain and efficiency are 8.6 dBi and 77%, respectively. These characteristics makes the proposed antenna suitable for integration in sub-terahertz near-field electronic systems such as radio frequency identification (RFID) devices with high spatial resolution.


Circular-array optical-fiber probe for backscattering photon correlation spectroscopy measurements.
A miniaturized probe comprising a circular array of optical fibers coupled to a graded-index microlens has been designed for analyzing colloidal solutions by photon correlation spectroscopy (PCS). The system's suitability for PCS measurements was validated by experimental testing performed in bulk solutions and small drops of monodisperse and bimodal test colloidal solutions.


21st century literacy for a diverse world.
Literacy demands in the 21st century require that proficient readers do more than 'read along the lines' or decode words and know their meaning. Proficient readers must be able to 'read between the lines', making relevant inferences to interpret, analyze, and synthesize information in texts; and 'read across the lines', applying these critical reading processes to multiple texts for purposes of problem-raising and problem-solving. This article will review literature on the cognitive and linguistic skills necessary for reading along the lines in a variety of scripts; the nature of the language and cognitive skills essential for the text comprehension necessary for reading between and across the lines, and the ways that culture and language influence text comprehension.


Glutamate catabolism of Rickettsia rickettsi and factors affecting retention of metabolic activity.
Glutamate catabolism and the factors contributing to metabolic stability of purified suspensions of Rickettsia rickettsi were investigated. By use of (14)C-glutamate, it was shown that CO(2) was produced from all carbons of glutamate and that (14)CO(2) production was reduced by the addition of most of the unlabeled intermediates of the citric acid cycle and pyruvate. Oxalacetate, added in various concentrations, did not stimulate glutamate utilization. When the cells were suspended in bovine plasma albumin (BPA), CO(2) production from glutamate proceeded at a nearly uniform rate for 8 hr at 32 C and for 24 hr at 15 C. When BPA was used, the cells retained their metabolic activity at 0 or 30 C regardless of cell concentration, and were not influenced by the addition of varoius metabolites. Without BPA, metabolic stability was directly related to concentration. Of the stabilizers tested on low concentrations of rickettsiae, reduced glutathione was the most effective, provided that the gas phase contained predominantly N(2). Under these conditions of low partial pressure of O(2), glutamate further stabilized metabolic activity and was actively metabolized. The cells were also stabilized by oxidized glutathione in a gas phase of air, but under these conditions glutamate was utilized at a more moderate rate and it impaired metabolic stability.


Occurrence of ateliosis in Japanese Black calves and their secretory function of growth hormone.
Unthrifty calves occurred sporadically in Japanese Black (beef cattle) in an area in northeastern Japan. The states of unthrifty development, pedigree, clinico-biochemistry and the secretory function of bovine growth hormone (bGH) in pituitary were investigated. The total cholesterol concentration and CK, AST and LDH activities in the serum showed higher values than those of control calves. Basal bGH concentrations in the serum and bGH secretory reactivity in the insulin tolerance test (ITT) were showed to be significantly lower than those of the control calves. Furthermore, sperm donated from a specific bull had been used for these unthrifty calves. This study suggested that the present occurrence of unthrifty calves represented ateliosis possibly caused by congenital hypopituitarism which decreased of bGH secretory function.


Biomarkers to Diagnose Early Arthritis in Patients With Psoriasis.
Psoriatic arthritis is a potentially destructive, inflammatory joint disease that affects 20% to 30% of patients with psoriasis. Psoriasis precedes the onset of joint inflammation by approximately 10 years, providing a unique opportunity to intervene and prevent or delay onset of musculoskeletal manifestations. The emergence of sensitive imaging modalities and cellular biomarkers may facilitate early identification of patients with psoriasis who have subclinical joint disease and might help stratify patients with an early onset of arthritis. The translational studies described herein are focused on the development of cellular biomarkers identified with flow cytometry and cell culture techniques in patients with psoriasis and psoriatic arthritis. The combination of power Doppler ultrasound imaging and cellular biomarkers (ie, CD16 and dendritic cell specific transmembrane protein) to diagnose early psoriatic arthritis and to stratify patients with established psoriatic arthritis provides a new opportunity to optimize treatment outcomes in this potentially disabling disease.


Advances in Neural Recording and Stimulation Integrated Circuits.
In the past few decades, driven by the increasing demands in the biomedical field aiming to cure neurological diseases and improve the quality of daily lives of the patients, researchers began to take advantage of the semiconductor technology to develop miniaturized and power-efficient chips for implantable applications. The emergence of the integrated circuits for neural prosthesis improves the treatment process of epilepsy, hearing loss, retinal damage, and other neurological diseases, which brings benefits to many patients. However, considering the safety and accuracy in the neural prosthesis process, there are many research directions. In the process of chip design, designers need to carefully analyze various parameters, and investigate different design techniques. This article presents the advances in neural recording and stimulation integrated circuits, including (1) a brief introduction of the basics of neural prosthesis circuits and the repair process in the bionic neural link, (2) a systematic introduction of the basic architecture and the latest technology of neural recording and stimulation integrated circuits, (3) a summary of the key issues of neural recording and stimulation integrated circuits, and (4) a discussion about the considerations of neural recording and stimulation circuit architecture selection and a discussion of future trends. The overview would help the designers to understand the latest performances in many aspects and to meet the design requirements better.


Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution.
Androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, and the development of castrate-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-related mortality. While CRPC typically develops through a gain in androgen receptor (AR) signaling, a subset of CRPC will lose reliance on the AR. This process involves genetic, epigenetic, and hormonal changes that promote cellular plasticity, leading to AR-indifferent disease, with neuroendocrine prostate cancer (NEPC) being the quintessential example. NEPC is enriched following treatment with second-generation anti-androgens and exhibits resistance to endocrine therapy. Loss of RB1, TP53, and PTEN expression and MYCN and AURKA amplification appear to be key drivers for NEPC differentiation. Epigenetic modifications also play an important role in the transition to a neuroendocrine phenotype. DNA methylation of specific gene promoters can regulate lineage commitment and differentiation. Histone methylation can suppress AR expression and promote neuroendocrine-specific gene expression. Emerging data suggest that EZH2 is a key regulator of this epigenetic rewiring. Several mechanisms drive AR-dependent castration resistance, notably AR splice variant expression, expression of the adrenal-permissive 3βHSD1 allele, and glucocorticoid receptor expression. Aberrant epigenetic regulation also promotes radioresistance by altering the expression of DNA repair- and cell cycle-related genes. Novel therapies are currently being developed to target these diverse genetic, epigenetic, and hormonal mechanisms promoting lineage plasticity-driven NEPC.


Urinary incontinence in older adults.
Urinary incontinence is a common problem among older women and men, has a significant negative impact on quality of life, and may be costly to treat. Older women experience higher rates of urinary incontinence than older men. The causes and types of urinary incontinence also differ among older women and men. Often, older adults are reluctant to seek treatment, and healthcare providers should inquire about symptoms. Detection of urinary incontinence and determination of severity and related symptoms is important for evaluation and treatment. Urinary incontinence can be evaluated and initially treated by primary-care providers. Evaluation for urinary incontinence involves a focused history, physical examination, a urinalysis, and measurement of postvoid residual volume, if indicated. Office-based treatments include behavioral approaches and medications. Older adults may also consider surgical options and devices to improve urinary incontinence. Older adults with cognitive impairment and incontinence require diagnostic and treatment modifications, but may respond well to treatment.


Listeriolysin O secreted by Listeria monocytogenes induces NF-kappaB signalling by activating the IkappaB kinase complex.
Listeriolysin O (LLO) is a pore-forming cytolysin secreted by the pathogen Listeria monocytogenes and is required for its intracellular survival. We recently demonstrated that in endothelial cells, LLO activates the NF-kappaB signalling pathway. In this work, we studied the LLO-induced molecular cascade of NF-kappaB activation with a cellular model extensively used to analyse the signalling pathway of NF-kappaB activation, i.e. the human embryonic kidney HEK-293 cell line and its derivatives (transfectants or mutants). When the stably transfected derivative HEK-293 cells expressing IL-1RI were exposed to LLO, a strong NF-kappaB activation was detected, contrasting with other cell lines (HEK-293 wild type, HEK-293.T and COS) expressing a very low level of IL-1RI. Although a delayed kinetics of LLO-dependent NF-kappaB activation suggests an autocrine or paracrine IL-1-dependent pathway, we found that LLO-dependent NF-kappaB activation did not require the IL-1 protein synthesis nor the interaction with the IL-1RI specific receptor. Herein, we demonstrated that LLO-dependent NF-kappaB activation requires the activation of the IkappaB kinase beta (IKKbeta) subunit of IKK complex to phosphorylate and degrade cytoplasmic IkappaBalpha, a natural inhibitor of NF-kappaB. The activation induced by LLO does not require the adapters MyD88 and IL-1R-associated kinase (IRAK). We suggested that LLO induces a distinct signalling pathway from that of IL-1 and its receptor.


Au(I)-catalyzed hydrative rearrangement of 1,1-diethynylcarbinol acetates to functionalized cyclopentenones and allenones.
Atom-economical syntheses of isomeric 5-acetoxy-2-alkyl-2-cyclopentenones (2) and acetoxymethyl alpha-alkylallenones (3) have been described via Au-catalyzed hydrative rearrangement of 1,1-diethynylcarbinol acetates (1). In anhydrous condition, Au(I)-catalyzed [3,3]-rearrangement of 1 afforded the 3-alkynylallenyl acetate 4 in low yield. Treatment of 1 with Au(I) catalyst in wet CH(2)Cl(2) produced either 2 or 3 as a major product depending on the temperature, reaction time, and catalyst loading. D has been proposed as an intermediate, which might be formed via Au(I)-induced internal oxacyclization of the intermediate 4 followed by chemoselective nucleophilic attack by the water molecule. Formation of 2 or 3 might be explained via sequential 1,3-dioxole ring opening and gold-promoted 5-endo-dig carbocyclization or simple protonation of the intermediate D, respectively.


Complete Genome Sequences of Seven Avibacterium paragallinarum Isolates from Poultry Farms in Pennsylvania, USA.
Avibacterium paragallinarum, the causative agent of infectious coryza, causes significant economic losses to the poultry industry due to increased culling rates in growing chickens and decreased egg production in layers. We present the complete genome sequences of seven strains of Avibacterium paragallinarum isolated from poultry farms in Pennsylvania during 2019.


Comparison of SAT-1 foot-and-mouth disease virus isolates obtained from East Africa between 1971 and 2000 with viruses from the rest of sub-Saharan Africa.
Foot-and-mouth disease serotype SAT-1 seems to be endemic in many sub-Saharan African countries. Phylogenetic analysis using the 1D gene of 51 SAT-1 isolates from East, West and southern Africa indicated the presence of at least 6 lineages and 11 genotypes with linkages between various geographical regions of the subcontinent. Differences were observed between countries in East Africa, the main focus of this study, with individual countries suffering outbreaks from isolates belonging to various genotypes, which is evidence of reintroduction of strains and long-term circulation of outbreak viruses. The amount of variation observed has significant implications for disease control on the subcontinent.


Synthesis of thromboplastin (tissue factor) by endothelial cells.
Molecular genetics, biochemistry, and cell biology of thromboplastin are briefly reviewed with special emphasis on its biosynthesis by endothelial cells.


Velocity profiles and phasic flow patterns in the non-stenotic human left anterior descending coronary artery during cardiac surgery.
The aim was to investigate the phasic characteristics of normal human left coronary artery flow and velocity profiles across the vessel. The phasic characteristics of flow in the human left anterior descending coronary artery, the centreline flow velocities, and the velocity profiles were measured in 10 patients during corrective surgery for atrial septal defect after closure of the defect. None of these patients had any detectable coronary artery stenosis or left ventricular hypertrophy. Measurements were made with a 20 MHz 80 channel pulsed Doppler velocimeter. The velocity waveform displayed a diastolic-predominant pattern with a systolic to diastolic velocity ratio of 0.29(SD 0.17). Reverse flow was observed in early systole in five patients and in mid to late systole in six patients. The values of peak Reynolds number, unsteadiness parameter, and pulsatility index were 504(198), 2.5(0.6), and 5.9(4.4) respectively. The velocity profiles during diastole showed considerable variability in shape, ranging from symmetrical to skewed to M shaped patterns. The peak wall shear rate was 765(250) s-1 on the epicardial wall of the vessel and 712(301) s-1 on the myocardial wall; the difference was not statistically significant. The velocity waveform displayed a diastolic-predominant pattern. Considerable variability in shape of the velocity profile was found and was perhaps due to the time evolution of the velocity profile within the diastolic time period.


Rare Diagnostic and Clinical Manifestations in an Acute Hepatitis A Infection: A Case Report.
The hepatitis A virus (HAV) is a common cause of infectious hepatitis worldwide. In adults, clinical manifestations typically involve fever, nausea/vomiting, fatigue, abdominal pain, and jaundice, although rarer manifestations may be observed. Acute hepatitis A infection is detected via anti-HAV IgM antibodies, which are present in almost all patients at symptom onset. In this case, we present a patient who not only tested negative for acute HAV infection at symptom onset, but also presented with uncommon, extrahepatic manifestations including maculopapular skin rash and polyarthralgia. Wariness of such a presentation can facilitate the timely diagnosis of atypical cases of HAV infection. We report the case of a 51-year-old man who presented with fever, abdominal pain, headaches, and diarrhea for one week with elevated liver enzymes and leukocytosis. Workup consisting of viral hepatitis panels, various infectious studies, and rheumatologic antibody titers did not initially reveal an etiology for the patient's presentation. Computed tomography (CT) abdomen and pelvis, abdominal ultrasound, magnetic resonance cholangiopancreatography (MRCP), and hepatobiliary iminodiacetic acid (HIDA) scan did not reveal acute pathology. The patient's symptoms worsened over the following days, and he additionally developed bilateral wrist pain, digital arthralgias, paraspinal back pain, diffuse muscular weakness, and a pruritic maculopapular rash affecting the flanks and extremities. Eventually, viral hepatitis studies were repeated which revealed elevated levels of anti-HAV IgM antibodies, indicating acute hepatitis A infection. The patient was treated supportively while hospitalized with subsequent improvement of symptoms and lab abnormalities. Since discharge, the patient had not experienced persistent sequelae of the disease. This case of acute viral hepatitis A infection is notable for two reasons: (1) the patient experienced uncommon, delayed, extrahepatic manifestations of disease, and (2) the initial viral hepatitis studies revealed undetectable anti-HAV IgM levels despite having experienced symptoms of illness for several days. This case suggests that repeat viral hepatitis testing may be warranted in patients who continue to experience manifestations of the infection after initially testing negative. It also emphasizes the importance of recognizing potential atypical manifestations of acute hepatitis A infection.


Nucleoside transporters are critical to the uptake and antioxidant activity of 7,8-dihydroneopterin in monocytic cells.
7,8-Dihydroneopterin protects cells intracellularly from oxidative stress-induced death, but its mode of transport across the cell membrane is unknown. Nucleosides, such as guanosine, are transported via nucleoside transporters of the equilibrative and concentrative forms. Therefore, the objective of this study was to identify which membrane transporters are responsible for 7,8-dihydroneopterin transport in cells and whether this is necessary for protection against oxidative stress. Monocytic cell lines U937, THP-1 and human monocytes were incubated with varying concentrations of 7,8-dihydroneopterin with or without nucleoside transporter inhibitors nitrobenzylthioinosine (NBMPR; ENT1), dipyridamole (DP; ENT1 and ENT2) or indomethacin (INDO; CNT). Only DP inhibited 7,8-dihydroneopterin uptake in U937 cells, while NBMPR and DP inhibited 7,8-dihydroneopterin uptake in THP-1 cells. All three inhibitors limited 7,8-dihydroneopterin uptake in human monocytes at short time points only. When the cells were incubated with 10 mM of the peroxyl radical generator 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) a 50-80% loss of cell viability was measured. 7,8-dihydroneopterin protected all cell lines against AAPH-induced cell death, which was prevented with DP in U937 cells, NBMPR in THP-1 cells and a combination of all three nucleoside inhibitors in human monocytes. These data indicate 7,8-dihydroneopterin is transported across the cell membrane of monocytic cells via equilibrative and concentrative nucleoside transporters in a cell lineage-dependent manner. The data also indicate protection from peroxyl radical-generated cell death with 7,8-dihydroneopterin is intracellular and facilitated through nucleoside transporters in monocytic cells.


Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.
The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.


[Ventricular arrhythmia and late potentials in patients with hypertrophic cardiomyopathy].
Holter monitoring (48 h) and registration of signal-averaged late potentials (method of Simson, high pass filter 40 Hz) were performed in outpatiens with hypertrophic cardiomyopathy. A prevalence of spontaneous ventricular arrhythmias could be determined in 51 patients; the results of 45 patients not taking antiarrhythmic drugs are presented here. 96% of these showed ventricular premature beats, 76% had multiform extrasystoles, 27% showed pairs of ectopic beats and 20% had runs of ventricular tachycardia (more than 3 QRS complexes). Absolute counts of premature beats were low in most patients, but important interindividual differences could be observed: M = 34 extrasystoles/24 h (0-4943). Ventricular tachycardias were of short duration (maximum 11 QRS) with heart rate ranging from 120 to 200/min. All patients were asymptomatic during tachycardia. Signal-averaged late potentials could be registered in 30 patients, 28 of them without antiarrhythmic drug therapy. Mean QRS duration (QRSdur) was 108 +/- 12 ms, mean duration of low amplitude signals (less than 40 microV) in the terminal portion of the QRS (LAdur) was 27 +/- 13 ms, and mean amplitude of the last 40 ms of the filtered QRS (LAamp) was 65 +/- 43 microV. A patient was considered to show late potentials if two of the following criteria were present: QRSdur greater than 120 ms, LAdur greater than or equal to 40 ms, LAamp less than 20 microV. This was found in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of c-MYC SUMOylation by mass spectrometry.
The c-MYC transcription factor is a master regulator of many cellular processes and deregulation of this oncogene has been linked to more than 50% of all cancers. This deregulation can take many forms, including altered post-translational regulation. Here, using immunoprecipitation combined with mass spectrometry, we identified a MYC SUMOylation site (K326). Abrogation of signaling through this residue by substitution with arginine (K326R) has no obvious effects on MYC half-life, intracellular localization, transcriptional targets, nor on the biological effects of MYC overexpression in two different cell systems assessed for soft agar colony formation, proliferation, and apoptosis. While we have definitively demonstrated that MYC SUMOylation can occur on K326, future work will be needed to elucidate the mechanisms and biological significance of MYC regulation by SUMOylation.


Radiologic Features of Atlas Occipitalization and Its Clinical Implications.
Retrospective radiographic analysis. Evaluation of the anatomic features of the craniovertebral junction in patients with occipitalization with and without atlantoaxial dislocation (AAD). Atlas occipitalization is a common feature of congenital AAD and usually requires surgical intervention. However, not all instances of occipitalization necessarily lead to AAD. No study has specifically examined and compared the craniovertebral bony morphology in occipitalization with, and without, AAD. We reviewed computed tomography (CT) scans of 2500 adult outpatients. Occipitalization cases without AAD (ON) were selected. Meanwhile, a series of 20 inpatient occipitalization cases with AAD (OD) were obtained in parallel. Another 20 control cases without occipitalization were also included. Multi-directional reconstructed CT images of all cases were analyzed. A total of 18 adults with ON were found in all 2500 outpatients (0.7%). Both anterior height and posterior height of C1 lateral mass in the control group were significantly larger than those in both the ON and OD groups, whereas posterior height in the OD group was significantly less than that in the ON group. Three morphologic types of the occipitalized atlas posterior arch were identified: Type I, bilateral sides were unfused with opisthion; Type II, unilateral side was unfused with opisthion, whereas the other side was fused; and Type III, bilateral sides were fused with opisthion. In the ON group, three cases were type I (17%), six cases were type II (33%), and nine cases were type III (50%). In the OD group, all 20 cases were type III (100%). Atlas occipitalization with, and without, AAD results from a distinctly different bony morphology at the craniovertebral junction. The novel classification system based on reconstructed CT images may be useful in prognosticating AAD in the setting of atlas occipitalization.


Concurrent Fusarium chlamydosporum and Microsphaeropsis arundinis infections in a cat.
A 7-year-old cat was presented initially with multiple draining sinuses on the metatarsal region of its right hindlimb. Another lesion had appeared at the same time on the fifth proximal interphalangeal joint of the left forelimb. Histopathological examination of a biopsy from the right hindlimb lesion revealed chronic pyogranulomatous inflammation associated with yeast-like bodies and septate mycelia; a fungus was cultured on conventional media but not identified further. Culture of a swab collected from the left forelimb lesion demonstrated a pigmented fungus, also not characterised further. Although there was initially a favourable response to ketoconazole (Nizoral, Janssen-Cilag Pty. Ltd) and beta-lactam therapy, the infection in the hind limb relapsed subsequently, and Fusarium chlamydosporum was cultured from deep biopsy specimens. Clinical improvement followed debridement and itraconazole (Sporanox, Janssen-Cilag Pty. Ltd; 100 mg orally once daily), however amputation of the limb represented the best chance for a cure. The cat made an uncomplicated recovery following surgery and remained well for five months until the lesion on the left forelimb recurred. Amputation of the distal fourth digit was then performed, and the resected tissue submitted for culture. The dematiaceous fungus Microsphaeropsis arundinis was subsequently cultured. The cat remained well for several months, until a further F. chlamydosporum infection developed on the body wall. This was excised 7 months ago, and no lesions have recurred in this area. Importantly, this is the first reported case of M. arundinis infection in a mammalian host.


Effects of leukotrienes B4 (LTB4) and D4 (LTD4) on motility of isolated normodense human eosinophils and neutrophils.
The effects of exogenous leukotrienes B4 and E4 (LTB4, LTD4) on the under-agarose motility of isolated normodense human eosinophils and neutrophils were examined using a novel sampling strategy for quantitation of leukocyte migration distance and vectorial orientation. Eosinophil chemotaxis to LTD4 was evident at a 10(-10)M threshold. The selective peptide-LT antagonist, SK&F 104353, abolished LTD4-induced eosinophil migration, indicating pharmacological specificity of the response. Neutrophil chemotaxis was apparent only with a very high (10(-5)M LTD4 concentration. LTB4 was a potent eosinophil and neutrophil chemoattractant over a 10(-9)M to 10(-4)M dose range. Analysis of leukocyte orientations provided evidence that chemokinetic responses were not being interpreted as indications of chemotactic behavior. LTB4 and LTD4 significantly altered neutrophil vectorial orientation. Comparison of migration distance and orientation at the leading edge and at the periphery of the well seeded with cells suggested that cell polarization appeared to be the earliest response to chemoattractive LTs. These results indicate that chemoattractant responses to LTs may be identified by utilizing the under-agarose technique and computer assisted analysis of cell orientation.


Lewis Acid Catalyzed Displacement of Trichloroacetimidates in the Synthesis of Functionalized Pyrroloindolines.
The pyrroloindoline core is found in many natural products. These structures often differ at the C3a position, which may be substituted with an oxygen, nitrogen, or sp(3)- or sp(2)-hybridized carbon. Utilizing a trichloroacetimidate leaving group, a diversity-oriented approach to these structures has been developed. The trichloroacetimidate intermediate allows for the rapid incorporation of anilines, alcohols, thiols, and carbon nucleophiles. This method was applied in the synthesis of arundinine and a formal synthesis of psychotriasine.


Progressive dysphagia and dysphonia secondary to DISH-related anterior cervical osteophytes: A case report.
Dysphagia due to diffuse idiopathic skeletal hyperostosis (DISH)-related anterior cervical osteophytes is not uncommon. However, this rarely leads to dysphonia and/or dysphagia along with life- threatening airway obstruction requiring emergency tracheotomy. A 56-year-old male presented with progressive dysphagia and dysphonia secondary to DISH-related anterior osteophytes at the C3-C4 and C4-C5 levels. The barium swallow, X-ray, magnetic resonance imaging, and computed tomography scans confirmed the presence of DISH. Utilizing an anterior cervical approach, a large beak-like osteophyte was successfully removed, while preserving the anterior annulus. After clinic-radiological improvement, the patient was discharged with a soft cervical collar and nonsteroidal anti-inflammatory drug (NSAID). Large anterior osteophytes in Forestier disease/DISH may cause dysphagia and dysphonia. Direct anterior resection of these lesions yields excellent results as long as other etiologies for such symptoms have been ruled out.


Clonazepam for treatment of sleep disturbances associated with combat-related posttraumatic stress disorder.
Clonazepam is widely used for the treatment of posttraumatic stress disorder (PTSD)-related sleep disturbances despite very limited published data supporting its use for this indication. We conducted a pilot-controlled trial to provide more data on this clinical practice and lay the foundation for more definitive studies. The study was designed as a randomized, single-blind (ie, patient only), placebo-controlled, crossover clinical trial involving administration of clonazepam 1 mg at bedtime for one week followed by 2 mg at bedtime for one week. The following week served as a washout period before the alternate treatment was begun. Patients completed sleep diaries each morning upon awakening throughout the study. Parameters included quantity of sleep, quality of sleep, frequency and intensity of difficulty falling or staying asleep, and frequency and intensity of recurrent distressing dreams. Six patients with combat-related PTSD participated in the study. There were no statistically significant differences between clonazepam and placebo for any measure, although clonazepam therapy resulted in mild to moderate numeric improvements in difficulty falling or staying asleep. Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to receive further treatment with clonazepam at the conclusion of the trial. Clonazepam therapy was largely ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related PTSD. The small sample size was a significant limitation of this study, but the prospective design and single-blind, placebo-control parameters were strengths. Further studies are needed to further define the role of this widespread clinical practice.


Endoscopic transaxillary subpectoral breast augmentation.
The transaxillary approach to breast augmentation is an established technique that offers the advantage of a remote incision in an aesthetically acceptable area. The main disadvantage to this approach is the lack of visualization of the implant pocket, necessitating blind, blunt dissection of the pectoral muscle origins. Occasionally, this limitation may result in improper implant placement and poor aesthetic results. In order to address this shortcoming, we have explored the use of minimally invasive endoscopic techniques in transaxillary augmentation to allow division of the pectoral muscle origin under direct visualization, effectively lowering the inframammary crease. Initial dissections and instrument development were performed in five unpreserved female cadavers. Subsequently, 103 implants have been placed in 53 patients utilizing the endoscopic transaxillary approach. Follow-up ranges from 2 weeks to 20 months. There have been no hematomas, infections, capsular contractures, or other complications. Aesthetic results have been good, and patient acceptance is high. By providing predictable and reproducible control of the inframammary crease, endoscopic dissection has allowed us to expand our indications for the transaxillary approach to breast augmentation. Surgical technique and brief clinical experience are described.


An Easy Access to Organic Salt-Based Stimuli-Responsive and Multifunctional Supramolecular Hydrogels.
By exploiting orthogonal hydrogen bonding involving supramolecular synthons and hydrophobic/hydrophilic interactions, a new series of simple organic salt based hydrogelators derived from pyrene butyric acid and its β-alanine amide derivative, and various primary amines has been achieved. The hydrogels were characterised by microscopy, table-top rheology and dynamic rheology. FTIR, variable-temperature (1) H NMR and emission spectroscopy established the role of various supramolecular interactions such as hydrogen bonding and π-π stacking in hydrogelation. Single-crystal X-ray diffraction (SXRD) studies supported the conclusion that orthogonal hydrogen bonding involving amide-amide and primary ammonium monocarboxylate (PAM) synthons indeed played a crucial role in hydrogelation. The hydrogels were found to be stimuli-responsive and were capable of sensing ammonia and adsorbing water-soluble dye (methylene blue). All the hydrogelators were biocompatible (MTT assay in RAW 264.7 cells), indicating their suitability for use in drug delivery.


Epigenetic modification in diabetic kidney disease.
Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefore, novel therapeutic methods, targets and biomarkers are urgently needed to meet clinical requirements. In recent years, increasing attention has been given to the role of epigenetic modification in the pathogenesis of DKD. Epigenetic variation mainly includes DNA methylation, histone modification and changes in the noncoding RNA expression profile, which are deeply involved in DKD-related inflammation, oxidative stress, hemodynamics, and the activation of abnormal signaling pathways. Since DKD is reversible at certain disease stages, it is valuable to identify abnormal epigenetic modifications as early diagnosis and treatment targets to prevent the progression of end-stage renal disease (ESRD). Because the current understanding of the epigenetic mechanism of DKD is not comprehensive, the purpose of this review is to summarize the role of epigenetic modification in the occurrence and development of DKD and evaluate the value of epigenetic therapies in DKD.


Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging.
We report on the prevalence of dementia in Canadians age 85 years and older. The purpose of this study was to determine whether the prevalence of dementia continued to increase in the very old, and to define the types of dementia and their relative proportions in this age group. We collected data as part of the Canadian Study of Health and Aging (1990 to 1992), which consisted of a sample of 1,835 subjects from a population of 283,510 Canadians who were 85 years of age and older residing in the community or in institutions. The prevalence of dementia in the 85 years and older group was 28.5%, more than twice that of the 75- to 84-years cohort. The prevalence of dementia of 23% in the 85- to 89-years sample (n = 1,332) increased to 40% in the 90 to 94 years group (n = 371) and, in the 95 years and older sample (n = 104), reached 58%. Overall, Alzheimer's disease (AD; probable or possible) accounted for 75% of all dementias; a vascular etiology alone accounted for 13% of dementias. The proportion of clinically diagnosed AD cases to vascular dementia cases increased significantly after age 65 and was higher in the 85+ group than in a younger cohort (65 to 84 years).


2,3,7,8-Tetrachlorodibenzo-p-dioxin and diethylstilbestrol affect thymocytes at different stages of development in fetal thymus organ culture.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and estrogen induce thymic atrophy and alter thymocyte development. In the present study we investigate whether TCDD and the synthetic estrogen diethylstilbestrol (DES) alter intrathymic development by the same or different mechanisms. We compared the effects of TCDD and DES on thymocyte development in fetal thymus organ culture (FTOC) and found that both compounds caused a reduction in cell yield. TCDD- and DES-treated FTOCs yielded fewer CD4 + CD8+ double-positive cells. However TCDD treatment also led to a greater percentage of cells in the CD8+ single-positive compartment. At lower dioxin concentrations, our results demonstrated an actual increase in CD8+ cells, whereas DES-treated fetal thymocytes were mainly enriched in CD4-CD8- double-negative cells. More alpha beta-TCR+ positive cells were seen in TCDD- but not in DES-exposed cultures. Furthermore, in this study we found that TCDD and DES also alter intrathymic development at different stages in the CD4-CD8- double-negative compartment. TCDD induced a relative increase in c-kit + CD44 + CD25-HSA-thymocytes, while DES induced an relative increase in c-kit-CD44-CD25 + HSA+ cells. RT-PCR revealed that TCDD reduced RAG-1, RAG-2, and TdT gene expression in the CD4-CD8- double-negative thymocytes. Co-treatment by TCDD and DES in FTOC yielded a mixture of effects induced by each agent. Taken together, our results demonstrate that TCDD and DES affect thymocytes at different stages of development, suggesting distinct mechanisms for induction of thymic atrophy.


A current perspective on availability of tools, resources and networks for veterinary immunology.
There are many diseases of fish, livestock and companion animals that impact negatively on animal health, welfare and productivity and for which there are no effective vaccines. The development of new vaccines is reliant on the availability of well-characterised immunological tools and reagents to understand host-pathogen interactions and identify protective immune responses. Veterinary immunology has always lagged behind mouse and human immunology in terms of development and availability of tools and reagents. However, several initiatives are underway to address this. The Veterinary Immunology Committee (VIC) Toolkit was initiated 6 years ago at the sixth International Veterinary Immunology Symposium (IVIS) in Uppsala and in the intervening period there have been several notable developments that have advanced reagent development and information exchange. This review will discuss advances in veterinary reagent development, networks, databases and commercial availability with particular reference to the second VIC Toolkit workshop held at the eighth IVIS in Ouro Preto, Brazil on the 15th of August 2007.


Infrared spectroscopy of competitive interactions between liquid crystals, metal salts, and dimethyl methylphosphonate at surfaces.
We report the use of Fourier transform polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to characterize the influence of dimethyl methylphosphonate (DMMP) on the molecular interactions occurring within thin films of nitrile-containing liquid crystals supported on surfaces presenting metal perchlorate salts. Infrared spectra obtained using thin films of 4'-octyl-4-biphenylcarbonitrile (8CB) supported on copper(II) perchlorate salts reveal the nitrile groups of 8CB to be coordinated to the copper(II) on these surfaces, and subsequent exposure of the system to DMMP to result in the elimination of these coordinated nitrile groups. Concurrently, evidence of coordination of the phosphoryl group of DMMP with copper(II) is provided by measurement of a shift of the phosphoryl stretch from 1246 to 1198 cm(-1). In contrast, surfaces presenting nickel(II) perchlorate salts only weakly coordinate with DMMP [the phosphoryl peak shifts from 1246 to 1213 cm(-1) in the presence of nickel(II)], and exposure of 8CB to DMMP results in only partial loss of coordination of the nitrile groups of 8CB with nickel(II). These PM-IRRAS measurements and others reported in this article provide insights into the molecular origins of macroscopic ordering transitions that are observed when micrometer-thick films of nitrile-containing liquid crystals supported on copper(II) or nickel(II) perchlorate are exposed to DMMP: Upon exposure to DMMP, nematic phases of 4'-pentyl-4-biphenylcarbonitrile (5CB) supported on copper(II) perchlorate salts undergo ordering transitions, whereas 5CB supported on nickel(II) perchlorate salts do not. Our IR results support the hypothesis that these ordering transitions reflect the relative strengths of coordination interactions occurring between the 5CB, DMMP, and the metal salts at these interfaces.


Using the health belief model to explore nursing students' relationships between COVID-19 knowledge, health beliefs, cues to action, self-efficacy, and behavioral intention: A cross-sectional survey study.
Nursing educators should equip nursing students with sufficient knowledge about coronavirus disease 2019 (COVID-19), perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention in order to prevent the spread of COVID-19.The purpose of this study was to use the health belief model to elucidate nursing students' relationships between knowledge about COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention.A cross-sectional survey design was adopted and purposive sampling was utilized. A total of 361 nursing students participated in the study. Quantitative analysis was employed for all data analysis.The findings showed that the nursing students had the following mean scores on knowledge of COVID-19 9.43 [standard deviation (SD)1.19], perceived susceptibility 19.41 (SD2.68), perceived severity 20.31 (SD 4.09), perceived benefits 26.52 (SD 4.08), perceived barriers 15.17 (SD5.88), cues to action 3.30 (SD1.70), self-efficacy 17.68 (SD2.83), and behavioral intention 18.46 (SD2.33). Nursing students' demographic background, knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy explained 58.1% of the variance in behavioral intention (R2 = 0.581, F = 29.775, P < .001).Nursing educators can increase nursing students' knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy as effective means of health promotion to improve their behavioral intention to prevent the spread of COVID-19.


Enhanced glucose control for preventing and treating diabetic neuropathy.
There are two types of diabetes. Type 1 diabetes affects younger people and needs treatment with insulin injections. Type 2 diabetes affects older people and can usually be treated by diet and oral drugs. Diabetic neuropathy affects 10% of patients with diabetes mellitus at diagnosis and 40% to 50% after 10 years. Enhanced glucose control is the best studied intervention for the prevention of this disabling condition but there have been no systematic reviews of the evidence. To examine the evidence for enhanced glucose control in the prevention of distal symmetric polyneuropathy in people with type 1 and type 2 diabetes. We searched the Cochrane Neuromuscular Disease Group Specialized Register (30 January 2012), CENTRAL (2012, Issue 1), MEDLINE (1966 to January 2012) and EMBASE (1980 to January 2012) for randomized controlled trials of enhanced glucose control in diabetes mellitus. We included all randomized, controlled studies investigating enhanced glycemic control that reported neuropathy outcomes after at least one year of intervention. Our primary outcome measure was annual development of clinical neuropathy defined by a clinical scale. Secondary outcomes included motor nerve conduction velocity and quantitative vibration testing. Two authors independently reviewed all titles and abstracts identified by the database searches for inclusion. Two authors abstracted data from all included studies with a standardized form. A third author mediated conflicts. We analyzed the presence of clinical neuropathy with annualized risk differences (RDs), and conduction velocity and quantitative velocity measurements with mean differences per year. This review identified 17 randomized studies that addressed whether enhanced glucose control prevents the development of neuropathy. Seven of these studies were conducted in people with type 1 diabetes, eight in type 2 diabetes, and two in both types. A meta-analysis of the two studies that reported the primary outcome (incidence of clinical neuropathy) with a total of 1228 participants with type 1 diabetes revealed a significantly reduced risk of developing clinical neuropathy in those with enhanced glucose control, an annualized RD of -1.84% (95% confidence interval (CI) -1.11 to -2.56). In a similar analysis of four studies that reported the primary outcome, involving 6669 participants with type 2 diabetes, the annualized RD of developing clinical neuropathy was -0.58% (95% CI 0.01 to -1.17). Most secondary outcomes were significantly in favor of intensive treatment in both populations. However, both types of diabetic participants also had a significant increase in severe adverse events including hypoglycemic events. According to high-quality evidence, enhanced glucose control significantly prevents the development of clinical neuropathy and reduces nerve conduction and vibration threshold abnormalities in type 1 diabetes mellitus. In type 2 diabetes mellitus, enhanced glucose control reduces the incidence of clinical neuropathy, although this was not formally statistically significant (P = 0.06). However, enhanced glucose control does significantly reduce nerve conduction and vibration threshold abnormalities. Importantly, enhanced glucose control significantly increases the risk of severe hypoglycemic episodes, which needs to be taken into account when evaluating its risk/benefit ratio.


Field evidence that ecosystem service projects support biodiversity and diversify options.
Ecosystem service approaches to conservation are being championed as a new strategy for conservation, under the hypothesis that they will broaden and deepen support for biodiversity protection. Where traditional approaches focus on setting aside land by purchasing property rights, ecosystem service approaches aim to engage a much wider range of places, people, policies, and financial resources in conservation. This is particularly important given projected intensification of human impacts, with rapid growth in population size and individual aspirations. Here we use field research on 34 ecosystem service (ES) projects and 26 traditional biodiversity (BD) projects from the Western Hemisphere to test whether ecosystem service approaches show signs of realizing their putative potential. We find that the ES projects attract on average more than four times as much funding through greater corporate sponsorship and use of a wider variety of finance tools than BD projects. ES projects are also more likely to encompass working landscapes and the people in them. We also show that, despite previous concern, ES projects not only expand opportunities for conservation, but they are no less likely than BD projects to include or create protected areas. Moreover, they do not draw down limited financial resources for conservation but rather engage a more diverse set of funders. We also found, however, that monitoring of conservation outcomes in both cases is so infrequent that it is impossible to assess the effectiveness of either ES or BD approaches.


Single-chain semiconducting polymer dots.
This work describes the preparation and validation of single-chain semiconducting polymer dots (sPdots), which were generated using a method based on surface immobilization, washing, and cleavage. The sPdots have an ultrasmall size of ∼3.0 nm as determined by atomic force microscopy, a size that is consistent with the anticipated diameter calculated from the molecular weight of the single-chain semiconducting polymer. sPdots should find use in biology and medicine as a new class of fluorescent probes. The FRET assay this work presents is a simple and rapid test to ensure methods developed for preparing sPdot indeed produced single-chain Pdots as designed.


A case of simultaneous occurrence of acute myeloid leukemia and multiple myeloma.
Although the occurrence of acute myeloid leukemia (AML) after chemotherapy for multiple myeloma (MM) is common in clinical settings, the simultaneous occurrence of these malignancies in patients without previous exposure to chemotherapy is a rare event. Etiology, disease management, and clinical treatment remain unclear for this particular occurrence. To the best of our knowledge, this study is the first to report a case of simultaneous presentation of AML and MM after exposure to ultraviolet irradiation. We reported the case of a 73-year-old man (Han Chinese ethnicity) without previous medical history of AML and MM. The morphology and immunology of bone marrow cells confirmed the co-existence of AML and MM. Fluorescent in situ hybridization analysis of immunomagnetically separated abnormal plasma cells showed abnormal expression of the amplified RB-1, TP53, and CDKN2C (1p32). Cytogenetic analysis demonstrated Y chromosome deletion. After the patient was administered with bortezomib combined with cytarabine + aclarubicin + granulocyte colony-stimulating factor (CAG regimen), and evident curative effects were observed. The patient achieved and maintained complete remission for more than 6 months. Prior to the disease occurrence, the patient had received ultraviolet irradiation for 1 year and was detected with aberrant gene expression of RB-1, TP53, and CDKN2C (1p32). Nevertheless, the correlation of this phenomenon with the etiology of concurrent AML with MM remains unclear. This study discussed the case of a patient diagnosed with AML concurrent with MM, who has no previous exposure to chemotherapy. This patient was successfully treated by bortezomib combined with CAG regimen. This study provides a basis for clinical treatment guidance for this specific group of patients and for confirmation of the disease etiology.


Methicillin-resistant Staphylococcus aureus of the clonal lineage ST5-SCCmecII-t2460 was associated with high mortality in a Wuhan hospital.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that can cause serious infectious diseases. An emerging MRSA strain, ST5-SCCmecII spa-type-t2460 (SMRSA), has spread rapidly since its recent emergence in China, but little information is available about this lineage. In this study, 91 MRSA isolates were collected from patients treated in the Zhongnan Hospital, Wuhan University, from 2018 to 2019, and investigated for their molecular characteristics, antibiotic resistance profiles, and clinical characteristics. The predominant lineage, SMRSA, accounted for 37.4% (34/91) of the isolates, followed by ST239-SCCmecIII-t030 (19.8%, 18/91) and ST59-SCCmecIV-t437 (8.8%, 8/91). In contrast to the latter two non-SMRSA (nSMRSA) lineages, which are among the main MRSA found in Chinese settings, SMRSA exhibited small colony variant (SCV) phenotype and had extremely high resistance rates to erythromycin (100.0%), clindamycin (100.0%), levofloxacin (100.0%), tetracycline (97.1%), moxifloxacin (97.1%), and ciprofloxacin (100%), but was more susceptible to rifampicin (resistance rate 3%). The levels of white blood cells (WBC) and procalcitonin (PCT) and the 30-day mortality in patients infected with SMRSA were (12.54 ± 6.61) × 109/L, 0.66 ng/mL, and 52.9%, respectively, which were much higher than those in patients infected with nSMRSA. In addition, patients infected with SMRSA were more frequently admitted to the intensive care unit (ICU) and submitted to invasive procedures than those infected with nSMRSA. In conclusion, SMRSA showed SCV phenotype and exhibited multiple antibiotic-resistance profiles. In this study, SMRSA was associated with serious infections and poor prognosis. Compared with ST239, ST59, or other nSMRSA strains, patients infected with SMRSA strains have higher 30-day mortality, increased levels of inflammatory biomarkers, and more frequent ICU hospitalization and invasive procedures.


Treating Foot Injuries by Grafting Pedicled Distal Peroneal Artery Perforator Flaps.
Treating mid- and forefoot wounds is challenging. We share our clinical experience and describe the treatment of foreand midfoot wounds by grafting pedicled distal peroneal artery perforator (PNAP) flaps. The study enrolled 21 patients with fore- and midfoot injuries, who underwent grafting with a pedicled distal PNAP flap between August 2013 and May 2016. All of the flaps survived and were followed for 2 to 11 months. The appearance and texture of these flaps were good. The range of motion of the injured ankle was similar to the unaffected side. There were no complications, such as scar contracture, ulcer, or tenderness. The pedicled distal PNAP flaps can effectively extend the length of the flap pedicles and are better for repairing fore- and midfoot wounds than the traditional distally pedicled sural neuro-fasciocutaneous flaps.


Influence of filling procedures and the partial removal of filling on the seal of root canals filled with gutta-percha and glass ionomer cement.
The purpose of the present study was to investigate the apical seal of root canals filled with Ketac Endo glass ionomer cement with a single point or multiple points and partial removal of fillings using drills with or without water cooling. Ninety-six single-root teeth were instrumented and filled with Ketac Endo and gutta-percha. The single point procedure was used in 48 teeth and the multiple point procedure was used in the other 48 teeth, without lateral condensation. After 72 hours, 16 teeth were randomly selected from each of the two groups and the fillings were partially removed with drills without cooling. The fillings from an additional 16 teeth were partially removed with water spray cooled drills. The fillings in the remaining teeth were not removed. All the teeth were partially protected with nail varnish and then dipped in Indian ink and finally cleared. The maximum linear leakage was measured under a binocular microscope with a micrometric eyepiece. There were no significant differences in leakage between any of the study groups, the root canals filled with the multiple point procedure had a seal similar to those filled with a single point. There was no diference between canals with fillings removed with or without water cooling and they did not have any more leakage than the root canals whose fillings had not been removed. Using Ketak Endo as a sealant, the multiple point procedure without condensation achieves sealing similar to the single point procedure. Partial removal of the fillings from these teeth, with or without water-cooling does not affect the seal.


Spontaneous perirenal urinoma secondary to cervical carcinoma: diagnosis and management.
Formation of a urinoma secondary to obstruction by a tumour is rare. The authors report a case of perirenal urinoma secondary to cervical carcinoma; the urinoma was drained percutaneously. The diagnosis and management of this problem are reviewed.


BMI1'S maintenance of the proliferative capacity of laryngeal cancer stem cells.
In laryngeal squamous cell carcinoma (SCC), CD133+ cells were found to display cancer stem cell (CSC) characteristics. BMI1 is an oncogene that plays key roles in proliferation in CSCs. However, no published reports have examined the role of BMI1 in laryngeal CSCs. Immunofluorescence staining confirmed the coexpression of BMI1 and CD133. After sorting, real-time polymerase chain reaction (PCR) revealed BMI1 was differentially expressed in CD133+ cells. BMI1 was knocked down and proliferation, colony formation, and apoptosis assays were performed. The influence on CD133+ cells was determined by flow cytometry, sphere-formation assay, and quantitative PCR. Tumorigenicity assays were performed, and the impact on related genes was evaluated. BMI1 was highly enriched in CD133+ cells. BMI1 maintained CD133+ cell proliferation and prevented apoptosis. Gene expression analysis suggested BMI1 regulated alternate cellular pathways. BMI1 was required to maintain the proliferative capacity of laryngeal CSCs, which may be a molecular target to cure patients with laryngeal SCC.


Fortuitous discovery of an anomalous connection of the coronary arteries during an urgent coronary angiography: a case report.
Anomalous connection of the coronary arteries (ANOCOR) is a rare angiographic finding; although most ANOCORs are benign some are a risky condition that can lead to sudden death. Knowing their particularities is important to know how to manage them. With an angiographic prevalence averaging 1%, proximal anomalous connection of the Coronary arteries (ANOCOR) represents a diverse entity. The challenge is to distinguish the benign ANOCOR to reassure the patient from the high risk ANOCOR that may need surgical repair. We present a case of a 52-years-old man admitted to our cath lab for urgent coronary angiography after a non ST segment elevation myocardial infarction. At coronary angiography we found ectopic left anterior descending and circumflex arteries with a culprit lesion on the right non ectopic coronary artery. A computed tomography (CT) scan showed benign ectopic courses of the left anterior descending and circumflex arteries. No surgical repair was indicated.


A microfluidic-multiwell platform for rapid phase mapping of surfactant solutions.
Measurement of the phase behavior and (meta)stability of liquid formulations, including surfactant solutions, is required for the understanding of mixture thermodynamics, as well as their practical utilization. We report a microfluidic platform with a stepped temperature profile, imposed by a dual Peltier module, connected to an automated multiwell plate injector and optical setup, for rapid solution phase mapping. The measurement protocol is defined by the temperature step ΔT ≡ T1 - T2 (≲100 °C), volumetric flow rate Q ≡ ΔV/Δt (≲50 μl/min), which implicitly set the thermal gradient ΔT/Δt (≃0.1-50 °C/min), and measurement time (which must exceed the intrinsic timescale of the relevant phase transformation). Furthermore, U-shaped microchannels can assess the reversibility of such transformations, yielding a facile measurement of the metastable zone width of the phase diagram. By contrast with traditional approaches, the platform precisely controls the cooling and heating rates by tuning the flow rate, and the absolute temperature excursion by the hot and cold thermal profile, which remain stationary during operation, thus allowing the sequential and reproducible screening of large sample arrays. As a model system, we examined the transition from the micellar (L1) to the liquid crystalline lamellar phase (Lα), upon cooling, of aqueous solutions of sodium linear alkylbenzene sulfonate, a biodegradable anionic surfactant extensively employed in industry. Our findings are validated with quiescent optical microscopy and small angle neutron scattering data.


The Effect of Therapeutic Alliance on Attitudes Toward Psychiatric Medications in Schizophrenia.
The differential influence of therapeutic alliance with different health care professionals on patients' medication adherence has never been examined. Ninety-five stable outpatients (91 patients with schizophrenia and 4 patients with schizoaffective disorder) were recruited. Individual, clinical, and medication factors were assessed, along with drug attitude (10-item Drug Attitude Inventory). Comparison on these factors was made between outpatients who identified psychiatrists as the health care professional most involved in their care, as compared with other health care professionals. Older age, longer duration of illness, presence of medical comorbidities, lower levels of internalized stigma, higher levels of insight, higher levels of functioning, lesser severity of depressive symptoms, and positive symptoms were found to be significantly associated with greater levels of drug attitude (small to moderate associations). Only therapeutic alliance had a large correlation with drug attitude (ρ = 0.503, P < 0.001). The therapeutic alliance scores between the 2 health care professionals groups are not significantly different. However, participants who have identified psychiatrists as the health care professional that contributed the most to their recovery reported a significantly more positive attitude (μ = 6.18, SD = 3.42) toward psychiatric medication as compared with the other health care professionals group (μ = 3.11, SD = 5.32, P = 0.004). Only 2 factors, the Revised Helping Alliance Questionnaire (β = 0.424, P < 0.001) and Personal and Social Performance scale (β = 0.272, P = 0.006), were statistically significant predictors of drug attitude. Therapeutic alliance is found to be the lead factor associated with drug attitude in patients with schizophrenia. Identifying psychiatrists as the health care professional most involved in the patients' recovery can greatly increase patients' drug attitudes. Maintaining individuals' functioning also contributes to drug attitude.


Olfactory information processing in the Drosophila antennal lobe: anything goes?
When an animal smells an odor, olfactory sensory neurons generate an activity pattern across olfactory glomeruli of the first sensory neuropil, the insect antennal lobe or the vertebrate olfactory bulb. Here, several networks of local neurons interact with sensory neurons and with output neurons--insect projection neurons, or vertebrate mitral/tufted cells. The extent and form of information processing taking place in these local networks has been subject of controversy. To investigate the role of local neurons in odor information processing we have used the calcium sensor G-CaMP to perform in vivo recordings of odor-evoked spatiotemporal activity patterns in five genetically defined neuron populations of the antennal lobe of Drosophila melanogaster: three distinct populations of local neurons (two GABAergic and one cholinergic), as well as sensory neurons and projection neurons. Odor-specific and concentration dependent spatiotemporal response patterns varied among neuron populations. Activity transfer differed along the olfactory pathway for different glomerulus-odor combinations: we found cases of profile broadening and of linear and complex transfer. Moreover, the discriminability between the odors also varied across neuron populations and was maximal in projection neurons. Discriminatory power increased with higher odor concentrations over a wide dynamic range, but decreased at the highest concentration. These results show the complexity and diversity of odor information processing mechanisms across olfactory glomeruli in the fly antennal lobe.


The interplay between SARS-CoV-2 infected airway epithelium and immune cells modulates regulatory/inflammatory signals.
To assess the cross-talk between immune cells and respiratory tract during SARS-CoV-2 infection, we analyzed the relationships between the inflammatory response induced by SARS-CoV-2 replication and immune cells phenotype in a reconstituted organotypic human airway epithelium (HAE). The results indicated that immune cells failed to inhibit SARS-CoV-2 replication in the HAE model. In contrast, immune cells strongly affected the inflammatory profile induced by SARS-CoV-2 infection, dampening the production of several immunoregulatory/inflammatory signals (e.g., IL-35, IL-27, and IL-34). Moreover, these mediators were found inversely correlated with innate immune cell frequency (NK and γδ T cells) and directly with CD8 T cells. The enriched signals associated with NK and CD8 T cells highlighted the modulation of pathways induced by SARS-CoV-2 infected HAE. These findings are useful to depict the cell-cell communication mechanisms necessary to develop novel therapeutic strategies aimed to promote an effective immune response.


18F-FDG PET baseline radiomics features improve the prediction of treatment outcome in diffuse large B-cell lymphoma.
Accurate prognostic markers are urgently needed to identify diffuse large B-Cell lymphoma (DLBCL) patients at high risk of progression or relapse. Our purpose was to investigate the potential added value of baseline radiomics features to the international prognostic index (IPI) in predicting outcome after first-line treatment. Three hundred seventeen newly diagnosed DLBCL patients were included. Lesions were delineated using a semi-automated segmentation method (standardized uptake value ≥ 4.0), and 490 radiomics features were extracted. We used logistic regression with backward feature selection to predict 2-year time to progression (TTP). The area under the curve (AUC) of the receiver operator characteristic curve was calculated to assess model performance. High-risk groups were defined based on prevalence of events; diagnostic performance was assessed using positive and negative predictive values. The IPI model yielded an AUC of 0.68. The optimal radiomics model comprised the natural logarithms of metabolic tumor volume (MTV) and of SUVpeak and the maximal distance between the largest lesion and any other lesion (Dmaxbulk, AUC 0.76). Combining radiomics and clinical features showed that a combination of tumor- (MTV, SUVpeak and Dmaxbulk) and patient-related parameters (WHO performance status and age > 60 years) performed best (AUC 0.79). Adding radiomics features to clinical predictors increased PPV with 15%, with more accurate selection of high-risk patients compared to the IPI model (progression at 2-year TTP, 44% vs 28%, respectively). Prediction models using baseline radiomics combined with currently used clinical predictors identify patients at risk of relapse at baseline and significantly improved model performance. EudraCT: 2006-005,174-42, 01-08-2008.


N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fibrate combination.
The aim of this study was to study the effect of adding polyunsaturated fatty acid (PUFA) n-3 or placebo (containing oleic acid) to a combined statin-fibrate treatment on plasma lipoproteins, lipoperoxidation, glucose homeostasis, total homocysteine (tHcy) and microalbuminuria (MA) in patients with diabetic dyslipidemia (DDL). Twenty-four patients, who did not fulfill the recommended target lipid values with combined hypolipidemic therapy (pravastatin 20 mg+micronized fenofibrate 200 mg daily), were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo (olive oil) for the next 3 months. The concentrations of plasma lipids, fatty acid (FA) profiles of phosphatidylcholine (PC), cholesteryl esters (CE) and triglycerides (TG), tHcy levels, concentrations of conjugated dienes (CD) in low-density lipoprotein (LDL), and MA were determined in baseline state, after the PUFA n-3 and placebo treatment period. Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy (-29%, P < .01) and TG (-28%, P < .05) levels, as well as to a significant decrease in MA (-24%, P < .05). The decrease in MA correlated significantly with the increase in total PUFA n-3 (r = -.509, P < or = .05) and docosahexaenoic acid (r = -.52, P < .01) in TG. The concentrations of CD in LDL increased significantly (+15%, P < .05). The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA. It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression.


Endothelial injury, alarmins, and allograft rejection.
Allograft blood vessels are important targets of clinical allograft rejection. Perioperative allograft injury to graft vasculature, especially the endothelial cell (EC) lining, increases the risk of subsequent acute and chronic vascular rejection. We hypothesize that allograft EC injured by ischemia-reperfusion (I/R) during transplantation releases mediators, termed "alarmins," that alter and intensify the host antigraft adaptive immune response. We begin with a review of both perioperative I/R injury to graft endothelium and T-cell-mediated vascular rejection. We then describe several alarmins that may be released from injured allografts, including interleukin (IL)-1alpha, ATP, monosodium urate (MSU), and high mobility group protein B1 (HMGB1). These mediators have in common the ability to induce production of IL-1beta from mononuclear phagocytes, and both isoforms of IL-1 act on T cells to enhance destructive adaptive immune responses. Therefore, we propose that IL-1 is the key alarmin that communicates graft injury to the host's adaptive immune system, and we suggest that perioperative targeting of IL-1 represents a promising strategy to attenuate the strength of rejection reactions.


Comparison of clinical findings in 293 dogs with suspect acute pancreatitis: Different clinical presentation with left lobe, right lobe or diffuse involvement of the pancreas.
Pancreatitis is a common clinical condition seen in companion animals. The correlation of the region of the pancreas affected to the presentation of clinical signs has not been previously described. A retrospective study on the clinical findings in 293 client-owned dogs diagnosed with suspect pancreatitis based on history, clinical signs, laboratory testing and abdominal ultrasonography was performed. Based on ultrasonography, dogs were divided into three groups: group 1: 41 dogs with ultrasonographic changes consistent with pancreatitis within the left lobe of the pancreas; group 2: 105 dogs with ultrasonographic changes compatible with pancreatitis within the right lobe of the pancreas; and group 3: 147 dogs with ultrasonographic evidence of diffuse pancreatitis. No significant differences regarding age, breed and sex were evident. Furthermore, statistical significance was demonstrated with the presence of pain in group 3; poor appetite in groups 2 and 3; and vomiting and diarrhoea in group 3. Pain is expected to occur with a higher frequency in diffuse pancreatitis, but it is not a common clinical sign. This may represent a more severe form of the disease when the pancreas is diffusely affected. Vomiting was more common than diarrhoea with both clinical signs more prevalent in dogs with diffuse pancreatitis, and this could be ascribed to gastric and intestinal tract involvement. Poor appetite occurred more frequently in dogs with diffuse and right lobe pancreatitis. A possible explanation can be attributed to the fact that the duodenum has many receptors and is referred to as the 'organ of nausea'.


Review of Longitudinal Glaucoma Progression: 5 Years after the Shaffer Lecture.
In 2013, the senior author delivered the American Academy of Ophthalmology Robert N. Shaffer Lecture entitled "Glaucoma Changes-Reality Bites." This talk focused on describing the longitudinal structure-function relationships in glaucoma progression. The study was based on a 10-year longitudinal dataset created by calibrated measurements across multiple OCT generations with corresponding visual fields (VFs). The prior held observation was that functional damage follows structural damage. The lecture posited that structure and function change at similar times, but that current measurement technology limits our ability to detect functional abnormalities and change early in glaucoma, as well as to measure structural change late in the disease. The Shaffer lecture provided evidence that structure and function change concordantly and that any apparent discordance in the relationship was due to technologic limitations to measure glaucomatous change. Furthermore, we observed 5 longitudinal relationships of concordance and discordance that can exist with structure-function interactions. Concordance: (1) structure-structure progression, (2) structure-function tipping point, (3) structural floor tipping point. Discordance: (4) functional progression in a "stable" VF with structure-function correlation, (5) functional progression with "normal" structure. In this review article, we will review longitudinal glaucoma progression studies with long-term follow-up and discuss the clinical relevance of relationships of concordance and discordance that can exist with structure-function interactions.


Functional Outcomes of Isolated Medial Tibial Plateau Fractures.
Isolated medial tibial plateau injuries are uncommon and underdescribed in the literature. As such, the range of fracture severity and outcomes in comparison to more frequently described tibial plateau fractures are lacking. To assess outcomes of this rare injury, we compared two cohorts of patients. Overall, 27 patients who sustained 27 isolated medial plateau (Schatzker type IV) fractures and 81 patients with 81 split depression lateral plateau (Schatzker type II) fractures were compared. The outcomes were stratified by injury mechanism energy and assessed with radiographs, clinical and arthroscopic examinations, and functional status with the short musculoskeletal function assessment questionnaire (SMFA). Overall, 52% of Schatzker type IV fractures versus 71% of Schatzker type II were associated with high-energy injuries. Schatzker type IV fractures were more often nondisplaced and amenable to being managed, nonoperatively, 22 versus 6%, with excellent results. Schatzker type II fractures had a corresponding higher proportion of postoperative articular step off greater than 12 mm and poorer 12-month SMFA scores. Schatzker type IV fractures were more often treated with an external fixator than Schatzker type II fractures (22 vs. 1%). Within Schatzker type IV fractures, high- versus low-energy injuries did not differ significantly with regards to initial articular step off (4.2 vs. 5.1 mm), ligamentous and meniscal injury, or SMFA outcomes. Isolated medial plateau fractures had low- and high-energy patterns with differing management and outcomes. Schatzker type IV fractures overall were associated with lower energy mechanisms, less initial articular step off, and better functional outcomes than Schatzker II comparisons in this cohort. The level of evidence is 4.


Comparable long-term outcomes in patients undergoing total disc replacement or anterior cervical discectomy and noninstrumented fusion.
Anterior cervical discectomy and fusion (ACDF) is the leading surgical treatment for cervical radiculopathy. However, ACDF surgery has been suggested for to accelerate the degeneration of the adjacent cervical discs, which causes so-called adjacent segment disease (ASD). Over the past 2 decades, total disc replacement (TDR)/cervical disc arthroplasty (CDA) has become an increasingly common method for treating degenerative cervical diseases. The rationale is that a synthetic disc prosthesis may preserve motion at the operated level, which is expected to lead to reduced stress on the other cervical levels and thus decrease the risk of developing ASD. However, since the method was first introduced in the early 2000s, the long-term outcome after it is still not completely understood. Our goal was to compare the long-term outcomes of TDR and ACDF procedures. Retrospective case-control study. All patients who underwent TDR due to degenerative cervical disease at Helsinki University Hospital between 2006 and 2012 (38 patients) and matched control patients who underwent ACDF during this period (76 patients) for degenerative disc disease. The primary outcome measure was the rate of reoperations and further cervical surgeries. Secondary outcome measures included neck symptoms (Neck Disability Index, or NDI), health-related quality of life (EQ-5D-3L), satisfaction with the surgery, radiological outcomes, and employment status. The medical records of all patients who underwent TDR due to degenerative cervical disease at Helsinki University Hospital between 2006 and 2012 and those of the matched control patients were analyzed retrospectively. Questionnaires were sent to all available patients at the end of the follow-up (median 14 years) to evaluate their employment status, levels of satisfaction with the surgery, current neck symptoms, and health-related quality of life. Radiological outcomes were evaluated from the cervical plain radiographs, which were taken either at the end of the follow-up as a part of the present study or earlier on for other clinical reasons, but at least 2 years after index surgery. The total rate of reoperations and further cervical surgeries during the follow-up of a median of 14 years was 7/38 (18%) in the TDR group and 6/76 (8%) in the ACDF group (p=.096, ns.). Total disc replacement patients were reoperated earlier, and the 5-year reoperation rate was significantly higher in the TDR group (11% vs 1.3%, p=.026). None of the TDR patients underwent further cervical surgery more than 6 years after index surgery, whereas 5/6 (83%) of the reoperated ACDF patients were reoperated after that time. There were no significant differences in the NDIs between the patient groups. The employment rate and health-related quality of life were slightly higher in the TDR group, but the differences were statistically nonsignificant. TDR was significantly better at maintaining the angular range of motion at the operated level, and the fusion rate was significantly lower among this group. There were no significant differences in the long-term outcomes of ACDF and TDR when measured by reoperation rates, employment status, NDI, EuroQoL, and satisfaction with surgery. Reoperation rate and, on the other hand, employment rate and health-related quality of life, were higher in the TDR group, but the differences were statistically nonsignificant. However, TDR patients were reoperated earlier, and the 5-year reoperation rate was significantly higher in the TDR group. Randomized long-term studies in which these methods are compared are needed to further clarify the differences between them.


Incremental value of quantitative CMR including parametric mapping for the diagnosis of acute myocarditis.
Cardiac magnetic resonance (CMR) can visualize inflammatory tissue changes in acute myocarditis. Several quantitative image-derived parameters have been described to enhance the diagnostic value of CMR, but no direct comparison of these techniques is available. A total of 34 patients with suspected acute myocarditis and 50 control subjects underwent CMR. CMR protocol included quantitative assessment of T1 relaxation times using modified Look-Locker inversion recovery (MOLLI) and shortened MOLLI (ShMOLLI) acquisition schemes, extracellular volume fraction (ECV), T2 relaxation times, and longitudinal strain. Established Lake-Louise criteria (LLC) consisting of T2-weighted signal intensity ratio (T2-ratio), early gadolinium enhancement ratio (EGEr), and late gadolinium enhancement (LGE) were assessed. Receiver operating characteristics analysis was performed to compare diagnostic performance. Areas under the curve of native T1 (MOLLI: 0.95; ShMOLLI: 0.92) and T2 relaxation times (0.92) were higher compared with those of the other CMR parameters (T2-ratio: 0.71, EGEr: 0.71, LGE: 0.87, LLC: 0.90, ECV MOLLI: 0.77, ECV ShMOLLI: 0.80, longitudinal strain: 0.83). Combined with LGE, each native mapping technique outperformed the diagnostic performance of LLC (P < 0.01, respectively). A combination of native parameters (T1, T2, and longitudinal strain) significantly increased the diagnostic performance of CMR compared with LLC without need of contrast media application (0.99 vs. 0.90; P = 0.008). In patients suspected of having acute myocarditis, diagnostic performance of CMR can be improved by implementation of quantitative CMR parameters. Especially, native mapping techniques have the potential to replace current LLC. CLINICALTRIALS. NCT02299856.


Morphological and lipid analysis of the alveolar lining material in dog lung.
Endobronchial saline lavage was used to obtain acellular material and cells from the dog lung. The centrifuged lavage fluid yielded a sediment consisting of an upper white layer and a lower brown layer. The white layer was strongly surface-active. It consisted of a mixture of lipids and proteins; the composition of the lipid portion was the same in three dogs. The predominant lipids were phosphatidyl choline, cholesterol, and cholesteryl esters; 75-88% of the fatty acids in each phospholipid fraction were saturated. Electron microscopy showed a strong morphological resemblance between the white layer and alveolar lining material in situ.


[Basal-luminal epithelial cell differentiation in prostate cancer is associated with epithelial-mesenchymal transition and epithelium migration in the mesenchyme].
In patients with prostate cancer to trace the pathway of the malignant cells of the basal layer of the prostate epithelium during their differentiation into luminal cells and/or migration in the mesenchyme. We used histological and immunohistochemical staining of the markers of the basal layer of the prostate: cytokeratin 5 (CK5), E-cadherin and AMACR, and Western blot to assess the production of the same markers in epithelial and stromal compartments of malignant and normal prostate tissue in patients with prostate cancer. Our findings revealed that prostate cancer is associated with losing of the basal epithelial layer in the prostate tumor tissue, which is accompanied by a complete loss of CK5 secretion, increased levels of E-cadherin and AMACR in luminal epithelium and the emergence of cells producing E-cadherin and AMACR in the stromal compartment of the prostate. These findings suggest that in prostate cancer the transformation the basal layer of the epithelial cells is associated with their differentiation into luminal cells and migration into the surrounding mesenchyme due to epithelial-mesenchymal transition. Prostate cancer pathogenesis of associated with changes in epithelial cell pathways and the levels of the markers expression. Their assessment can be used for studying the disease mechanisms and seeking new diagnosis and treatment options.


DNA binding activity of the BarH1 homeodomain of Drosophila.
Using a series of deletion mutants of BarH1, a Drosophila homeobox gene required for eye morphogenesis, the DNA-binding region of the BarH1 protein was determined. Not only homeodomain but also its upstream sequence were found to be necessary for binding, whereas about a half of the conserved downstream sequence (Bar domain) was dispensable.