Combined effects of chemical, heat and ultrasound treatments to kill Salmonella and Escherichia coli O157:H7 on alfalfa seeds.
To determine the effectiveness of combined treatments with chemicals, heat and ultrasound in killing or removing Salmonella and Escherichia coli O157:H7 on alfalfa seeds intended for sprout production. Alfalfa seeds inoculated with Salmonella or E. coli O157:H7 were treated with ultrasound (38.5-40.5 kHz) in solutions containing 1% Ca(OH)(2), 1% Tween 80, 1% Ca(OH)(2) plus 1% Tween 80, 160 microg ml(-1) Tsunami 200 and 0.5% Fit at 23 and 55 degrees C for 2 and 5 min. Highest reductions were in chemical solutions at 55 degrees C, but seed viability was also reduced compared with treatment at 23 degrees C. Inactivation of Salmonella and E. coli O157:H7 was generally enhanced by simultaneous treatments with ultrasound, chemicals and heat. Ultrasound treatment, in combination with chemicals and heat, had a modest enhancing effect on the effectiveness of chemicals in killing or removing pathogens on alfalfa seeds. Overall, treatment with 1% Ca(OH)(2) was most effective in killing Salmonella and E. coli O157:H7. The use of 1% Ca(OH)(2) instead of 20,000 microg ml(-1) chlorine, which is currently recommended as a sanitizer for seeds intended for sprout production in the US, should be considered. Ultrasound treatment of alfalfa seeds containing Salmonella or E. coli O157:H7, in combination with chemical treatment, contributes to achieving greater reductions in populations of these pathogens, thereby reducing the risk of contamination and the presence of pathogens in sprouts produced from these seeds.


Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.
Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.


MR Imaging Enables Real-Time Monitoring of In Vitro Electrolytic Ablation of Hepatocellular Carcinoma.
To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.


Estimating insulin sensitivity from glucose levels only: Use of a non-linear mixed effects approach and maximum a posteriori (MAP) estimation.
Insulin Sensitivity is an important parameter for the management of Diabetes. It can be derived for a particular patient using data derived from some glucose challenge tests using measured glucose and insulin levels at various times. Whilst a useful approach, deriving insulin sensitivities to inform insulin dosing in other settings such as Intensive Care Units can be more challenging - especially as insulin levels have to be assayed in a laboratory, not at the bedside. This paper investigates an approach to measure insulin sensitivity from glucose levels only. Estimates of mean and between individual parameter variances are used to derive conditional estimates of insulin sensitivity. The method is demonstrated to perform reasonably well, with conditional estimates comparing well with estimates derived from insulin data as well.


Arthroscopic evaluation and management of rotator cuff tears.
The development of arthroscopic techniques has provided the shoulder surgeon with new opportunities to improve the chances of salvaging these difficult rotator cuff tears while generally avoiding the potential disastrous consequences attendant to the open procedures. The arthroscope can be used to review and document the status of the joint and cuff, assess the tear pattern, debride damaged tissues, and smooth the acromion. In addition, a trained shoulder arthroscopist can mobilize the available tissues and repair any viable tendon to bone, without damage to the overlying muscles, through small cosmetic incisions in an outpatient surgery setting. If there proves to be an irreparable injury, debridement and bone smoothing can be readily performed, avoiding iatrogenic injury to the remaining healthy tissues, especially the deltoid muscle. The patient and the surgeon must accept that the arthroscope is merely a helpful surgical tool, a convenient method to visualize the anatomy without damaging other tissues. When one attempts to repair a massive cuff tear, even with the aid of the arthroscope, there are no miracles or magic involved and often the results are less than perfect. Fortunately, once one can see the relevant anatomy, the opportunities to safely repair the tissues are then unprecedented.


Optimization of dose selection using multiple surrogates of toxicity as a continuous variable in phase I cancer trial.
In phase I trials, it is the top priority of clinicians to effectively treat patients and minimize the chance of exposing them to subtherapeutic and overly toxic doses, while exploiting patient information. Motived by this practical consideration, we revive the one parameter linear dose-finder developed in 1970s to accommodate a continuous toxicity response in the phase I cancer clinical trials, which is called the two parameters linear dose-finder (2PLD). The 2PLD is a fully Bayesian model that assumes a linear relationship between toxicity response and dose. We suggest a dose search algorithm based on the 2PLD to exploit the grades of toxicities from multiple adverse events to align with Common Toxicity Criteria for Adverse Events provided by the National Cancer Institute. The proposed search procedure suggests an optimal dose to each patient by using accrued patients' information while controlling the posterior probability of overdose. The heterogeneity of patients in dose reaction is addressed by making a fully Bayesian inference about the standard deviation of toxicity responses. The 2PLD can be an attractive tool for clinical scientists due to its parsimonious description of a toxicity-dose curve and medical interpretation as well as an automatic posterior computation. We illustrate the performance of this design using simulation data to identify the maximum tolerated dose.


Role of the gut microbiota in immunity and inflammatory disease.
The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. The collection of microbial populations that reside on and in the host is commonly referred to as the microbiota. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Conversely, pathogens have developed strategies to promote their replication in the presence of competing microbiota. Breakdown of the normal microbial community increases the risk of pathogen infection, the overgrowth of harmful pathobionts and inflammatory disease. Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.


Higher maximum doses of oxytocin are associated with an unacceptably high risk for uterine rupture in patients attempting vaginal birth after cesarean delivery.
The objective of the study was to more precisely estimate the effect of maximum oxytocin dose on uterine rupture risk in patients attempting vaginal birth after cesarean (VBAC) by considering timing and duration of therapy. A nested case-control study was conducted within a multicenter, retrospective cohort study of more than 25,000 women with at least 1 prior cesarean delivery, comparing cases of uterine rupture with controls (no rupture) while attempting VBAC. Time-to-event analyses were performed to examine the effect of maximum oxytocin dose on the risk of uterine rupture considering therapy duration, while adjusting for confounders. Within the nested case-control study of 804 patients, 272 were exposed to oxytocin: 62 cases of uterine rupture and 210 controls. Maximum oxytocin ranges above 20 mU/min increased the risk of uterine rupture 4-fold or greater (21-30 mU/min: hazard ratio [HR] 3.92, 95% confidence interval [CI], 1.06 to 14.52; 31-40 mU/min: HR 4.57, 95% CI, 1.00 to 20.82). These findings support a maximum oxytocin dose of 20 mU/min in VBAC trials to avoid an unacceptably high risk of uterine rupture.


An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease.
The deposition of aggregated tau in cytoplasmic inclusions is one of the common neuropathological features in various dementing neurodegenerative disorders. At present, it remains unclear whether tau inclusions exert neurotoxicity or they are simply the consequence of neurodegeneration. In our approach for the analysis of the composition of tau inclusions, we detected the intense binding of anti-diacylglycerol kinase-zeta (DGK-zeta) antibodies to Pick bodies (PBs), which represent tau inclusions in Pick's disease. The polyclonal antibodies were found to cross-react with a 21-kDa protein, but not with tau or ubiquitin, on Western blots of normal human brain extracts. Analysis of the 21-kDa protein by two-dimensional-gel electrophoresis and mass-spectrometry revealed that the protein is an N-terminal fragment of proSAAS (a human granin-like neuroendocrine peptide precursor). Our results suggest that sequestration of the N-terminal fragment of proSAAS in intracellular PBs may cause a functional disturbance of neurons in Pick's disease.


Observation of B0-->omega K0, B+-->eta pi+, and B+-->eta K+ and study of related decays.
We present measurements of branching fractions and charge asymmetries for seven B-meson decays with an eta, eta', or omega meson in the final state. The data sample corresponds to 89x10(6) BB pairs produced from e(+)e(-) annihilation at the Upsilon(4S) resonance. We measure the following branching fractions in units of 10(-6): B(B+-->eta pi(+))=5.3+/-1.0+/-0.3, B(B+-->eta K+)=3.4+/-0.8+/-0.2, B(B0-->eta K0)=2.9+/-1.0+/-0.2 (<5.2, 90% C.L.), B(B+-->eta(')pi(+))=2.7+/-1.2+/-0.3 (<4.5, 90% C.L.), B(B+-->omega pi(+))=5.5+/-0.9+/-0.5, B(B+-->omega K+)=4.8+/-0.8+/-0.4, and B(B0-->omega K0)=5.9(+1.6)(-1.3)+/-0.5. The charge asymmetries are A(ch)(B+-->eta pi(+))=-0.44+/-0.18+/-0.01, A(ch)(B+-->eta K+)=-0.52+/-0.24+/-0.01, A(ch)(B+-->omega pi(+))=0.03+/-0.16+/-0.01, and A(ch)(B+-->omega K+)=-0.09+/-0.17+/-0.01.


Femoral neck fractures.
Femoral neck fractures in the geriatric patient continue to represent a therapeutic challenge. Despite advances in surgical techniques and medical care, the risk of nonunion and osteonecrosis after fixation have not changed appreciably in the last 50 years. Considerable debate continues to occur with respect to the relative merits of internal fixation versus arthroplasty. The relative benefits and complications of unipolar and bipolar hemiarthroplasty, as well as total hip replacement, continue to be poorly understood. The next decade will bring advances in the prevention and treatment of osteoporosis that may finally decrease the incidence of these fractures. Advances in the use of bone graft substitutes may finally improve the outcome of internal fixation.


Discovery and pharmacodynamic evaluation of the novel butene lactone derivative M355 against influenza A virus in vitro and in vivo.
A new series of butene lactone derivatives were designed according to an influenza neuraminidase target and their antiviral activities against H1N1 infection of Madin-Darby canine kidney cells were evaluated. Among them, a compound that was given the name M355 was identified as the most potent against H1N1 (EC50 = 14.7 μM) with low toxicity (CC50 = 538.13 μM). It also visibly reduced the virus-induced cytopathic effect. Time-of-addition analysis indicated that H1N1 was mostly suppressed by M355 at the late stage of its infectious cycle. M355 inhibited neuraminidase in a dose-dependent fashion to a similar extent as oseltamivir, which was also indicated by a computer modeling experiment. In a mouse model, lung lesions and virus load were reduced and the expression of nucleoprotein was moderated by M355. The enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction analyses revealed that the levels of interferon-γ, interferon regulatory factor-3, Toll-like receptor-3, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8 were downregulated in the M355-treated groups, whereas the levels of IL-10 and IL-13 were upregulated. Similarly, IgG was found to be increased in infected mice plasma. These results demonstrate that M355 inhibit the expression of H1N1 in both cellular and animal models. Thus, M355 has the potential to be effective in the treatment of influenza A virus infection.


Catalysis by RNase P RNA: unique features and unprecedented active site plasticity.
Metal ions are essential cofactors for precursor tRNA (ptRNA) processing by bacterial RNase P. The ribose 2'-OH at nucleotide (nt) -1 of ptRNAs is known to contribute to positioning of catalytic Me2+. To investigate the catalytic process, we used ptRNAs with single 2'-deoxy (2'-H), 2'-amino (2'-N), or 2'-fluoro (2'-F) modifications at the cleavage site (nt -1). 2' modifications had small (2.4-7.7-fold) effects on ptRNA binding to E. coli RNase P RNA in the ground state, decreasing substrate affinity in the order 2'-OH > 2'-F > 2'-N > 2'-H. Effects on the rate of the chemical step (about 10-fold for 2'-F, almost 150-fold for 2'-H and 2'-N) were much stronger, and, except for the 2'-N modification, resembled strikingly those observed in the Tetrahymena ribozyme-catalyzed reaction at corresponding position. Mn2+ rescued cleavage of the 2'-N but also the 2'-H-modified ptRNA, arguing against a direct metal ion coordination at this location. Miscleavage between nt -1 and -2 was observed for the 2'-N-ptRNA at low pH (further influenced by the base identities at nt -1 and +73), suggesting repulsion of a catalytic metal ion due to protonation of the amino group. Effects caused by the 2'-N modification at nt -1 of the substrate allowed us to substantiate a mechanistic difference in phosphodiester hydrolysis catalyzed by Escherichia coli RNase P RNA and the Tetrahymena ribozyme: a metal ion binds next to the 2' substituent at nt -1 in the reaction catalyzed by RNase P RNA, but not at the corresponding location in the Tetrahymena ribozyme reaction.


Synthesis of selenium-containing amino acid analogues and their biological study.
Synthesis of selenium-containing amino acid analogues is described. These compounds were prepared in a concise and short synthetic route in good yields by nucleophilic substitution reaction of pyridineselenol and quinolineselenol derivatives with N-phthaloylglycyl chloride followed by hydrazinolysis. The newly synthesized compounds were screened against different strains of bacteria and fungi.


High-yield maize with large net energy yield and small global warming intensity.
Addressing concerns about future food supply and climate change requires management practices that maximize productivity per unit of arable land while reducing negative environmental impact. On-farm data were evaluated to assess energy balance and greenhouse gas (GHG) emissions of irrigated maize in Nebraska that received large nitrogen (N) fertilizer (183 kg of N · ha(-1)) and irrigation water inputs (272 mm or 2,720 m(3) ha(-1)). Although energy inputs (30 GJ · ha(-1)) were larger than those reported for US maize systems in previous studies, irrigated maize in central Nebraska achieved higher grain and net energy yields (13.2 Mg · ha(-1) and 159 GJ · ha(-1), respectively) and lower GHG-emission intensity (231 kg of CO(2)e · Mg(-1) of grain). Greater input-use efficiencies, especially for N fertilizer, were responsible for better performance of these irrigated systems, compared with much lower-yielding, mostly rainfed maize systems in previous studies. Large variation in energy inputs and GHG emissions across irrigated fields in the present study resulted from differences in applied irrigation water amount and imbalances between applied N inputs and crop N demand, indicating potential to further improve environmental performance through better management of these inputs. Observed variation in N-use efficiency, at any level of applied N inputs, suggests that an N-balance approach may be more appropriate for estimating soil N(2)O emissions than the Intergovernmental Panel on Climate Change approach based on a fixed proportion of applied N. Negative correlation between GHG-emission intensity and net energy yield supports the proposition that achieving high yields, large positive energy balance, and low GHG emissions in intensive cropping systems are not conflicting goals.


Intracellular processing of hapten-modified protein for MHC class I presentation: cytoplasmic delivery by pH-sensitive liposomes.
Phagocytic or endocytic uptake of pH-sensitive liposomes has been shown to result in the release of entrapped material into the cytosol. This system can therefore be applied to the targeted delivery of protein antigens into the MHC class I presentation pathway of antigen-processing cells. We have used trinitrophenyl (TNP)-modified chicken ovalbumin encapsulated in liposomes to examine the intracellular processing of haptenated proteins and the presentation of TNP-modified peptides to MHC class I-restricted hapten-specific CTL. Here, we demonstrate for the first time that hapten-modified proteins can undergo intracellular processing by macrophages, that similar peptides are produced in the form of unmodified or haptenated derivatives, and that TNP-peptides are transported to the cell surface and presented to class I-restricted CTL via the ER/Golgi pathway. This system can now be used to study T-cell responses to naturally processed hapten-conjugated peptides in vitro and in vivo.


Integrating Reproductive Health Services Into Opioid Treatment Facilities: A Missed Opportunity to Prevent Opioid-exposed Pregnancies and Improve the Health of Women Who Use Drugs.
: Opioid treatment programs (OTPs) are federally mandated to provide certain medical services to patients, and are often the only place where people with substance use disorders (SUD) obtain medical care. Just as medication for addiction treatment (MAT) should be part of comprehensive addiction care, so should reproductive health care be a part of comprehensive medical care. The most significant barrier that must be overcome is that the majority of OTPs believe that it is outside their scope of service to provide reproductive health services. Reproductive health care is basic medical care. It is imperative for the long-term health of women with SUD, their children and the community that they receive this care. OTPs can and should do better for their female clients.


The diversity of Odonata and their endophytic ovipositions from the Upper Oligocene Fossillagerstätte of Rott (Rhineland, Germany).
A commented list of fossil Odonata from the Oligocene outcrop of Rott is given, together with descriptions of new traces of oviposition in plant tissues, very similar to ichnotaxa already known from the early Eocene Laguna del Hunco floras of Patagonia. The joint presences of odonatan larvae and traces of oviposition demonstrate the autochthony of these insects in the palaeolake of Rott, confirming the existence of a diverse and abundant aquatic entomofauna, a situation strikingly different to that in the contemporaneous Oligocene palaeolake of Céreste (France).


Time course of AQP-2 and ENaC regulation in the kidney in response to PPAR agonists associated with marked edema in rats.
Peroxisome-proliferator-activated receptor (PPAR-gamma) agonists improve insulin sensitivity, but are associated with edema. Increased distal tubule sodium and water reabsorption through the epithelial sodium channel (ENaC) and aquaporin-2 (AQP-2) have been suggested to play mechanistic roles. To determine the molecular regulation of these proteins, we treated male, Sprague-Dawley rats daily by gavage with either vehicle, rosiglitazone (RGZ, 50mg/kg bw), or PD168 (a test compound causing marked edema, 10mg/kg bw), for 1, 3, or 5 days (n=6/treatment/time). On day 1, urine sodium excretion was significantly reduced by RGZ with a strong trend for PD168 (p-values 0.047 and 0.053, respectively) indicating early sodium retention. Blood pressure was lowered by RGZ- or PD168 treatment by 12h. Immunoblotting of whole kidney homogenates (WKHs) and a membrane-enriched fraction (MF) revealed increased band densities for AQP-2 in WKH (29 kDa and glycosylated bands) by both drugs at 1 day. However, at 5 days, the 29-kDa band was significantly decreased ( approximately 30% of vehicle). alpha-ENaC was increased by RGZ at 3 days; however both agents decreased alpha-ENaC by 5 days. In contrast, beta- and gamma-ENaC (85 kDa) were unchanged or decreased at all times by both agents. However, the 70-kDa band of gamma-ENaC (active band) in MF was increased in density (120-600%) by both agents on days 3-5. Overall, both agents resulted in early alterations in banding patterns for AQP-2 and ENaC subunits, many of which are described as activating changes. However, later reduction in AQP-2 and alpha-ENaC may represent an attempt to re-establish sodium and water balance.


Laparoscopic versus open renal procurement for pediatric recipients of living donor renal transplantation.
Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.


[Gastric mucosal cysts as a histomorphological equivalent to polypoid gastric mucosal lesions].
Report on a 57-year-old female patient with numerous polypoid lesions of the gastric mucosa. This aspect has been described only recently and it is not listed in the scheme of classification of gastric polyps, usual up to now. This clinical picture is histomorphologically characterized by multiple cysts of varying size within an otherwise intact and non-inflammatory glandular body of the corpus mucosa. No relation to the so-called cystic gastritis can be detected. Etiology and pathogenesis are unknown. A doubtful hamartoma or a functional secretory disorder are discussed.


Adverse drug reactions caused by methotrexate in Saudi population.
The aim of this study is to document adverse drug reactions (ARDs) of methotrexate (MTX) in Saudi patients. Cross sectional study of adult patients on MTX, attending rheumatology drug monitoring clinics in a university hospital, over a period of 24 weeks. Adverse drug reactions were sought by patient interview, files review and laboratory abnormalities. Data collected included patients' demographics, diagnoses, co-morbidities, MTX dose and duration, other medications, laboratory abnormalities and adverse reactions, their severity, preventability, and outcome. Out of a total of 593 patients screened, 186 (31.4%) using MTX were interviewed. Most of the patients were female (88.5%). Adverse drug reactions (ADRs) were detected in 61 patients (32.8%). Patients with ADRs took a mean dose of 12.9 mg (2.5-22.5 mg). Ten ADRs (16.4% of total reactions) were preventable; they ranged between severe, moderate and mild. The most common ADRs were gastrointestinal (GI) (52.5%), followed by anemia (8.2%) and chest tightness (6.6%). The duration of the reaction ranged from few hours to 4 years. In conclusion our patients with adverse reactions were younger, took less medications and had less co-morbidities. Our results were different from those published in the literature relating MTX toxicity.


The clinical and hemodynamic results of mitral balloon valvuloplasty for patients with mitral stenosis complicated by severe pulmonary hypertension.
Percutaneous balloon mitral valvuloplasty (PBMV) has become the procedure of choice for isolated, uncomplicated mitral stenosis (MS) with favorable morphology and may be a useful method for surgical high-risk conditions such as advanced age, the presence of severe tricuspid regurgitation, New York Heart Association (NYHA) class IV at presentation, and severe pulmonary hypertension (PH). The development of PH is a common and important sequela in patients with advanced mitral stenosis and is associated with hemodynamic and clinical decompensation. However, the influence of PBMV on patients with severe PH has seldom been evaluated. Our objective was to probe into the immediate and long-term effects of PBMV on patients with MS complicated by severe PH and to predict the factors that determine the prognosis of patients with severe PH. We included 44 patients with MS complicated by severe PH (systolic pulmonary pressure >80 mm Hg, group S) and 67 patients with MS complicated by mild PH (systolic pulmonary pressure <50 mm Hg, group M) in this study and we compared their immediate and late results after a follow-up period of 24 months after PBMV. Compared with group M, patients in group S were older, presented more frequently with NYHA III-IV class, valvular echo score >or=8, and more severe tricuspid regurgitation, and had a bigger left atrial diameter before PBMV. The successful rate and the incidence of severe complications from the PBMV procedure were similar in both groups. There were more cases of post-PBMV mitral valve area >or=1.5 cm(2) in group M than in group S, and the average mitral valve area in group M was somewhat larger than that of group S. After PBMV, NYHA class obviously improved in both groups, but there were more patients with NYHA<or=class II in group M than in group S at discharge. During the 24-month follow-up, 7 patients (10.5%) in group M and 11 (25.0%) in group S developed cardiac events (p<0.1). Cumulative event-free survival was 89.6% in group M and 75.0% in group S (p>0.05). NYHA class I or II was present for 80.6% in group M and 59.1% in group S (p<0.10). PBMV is a safe and effective procedure for patients with severe PH. It can remarkably improve clinical outcomes, although hemodynamic effects of PBMV on this subgroup are not complete. Pre-existing older age, more severe valvular lesion and tricuspid regurgitation, worse cardiac function, and bigger left atrial size in patients with severe PH may be important risk factors for the poor hemodynamic outcomes of PBMV.


Anti-inflammatory effect of trans-anethol in a rat model of myocardial ischemia-reperfusion injury.
Myocardial ischemia‑reperfusion injury (MI/R) is considered a main risk factor for global cardiac mortality and morbidity, for which no effective treatment exists. Both inflammation and epigenetic regulation play a pivotal role in the early stage of MI/R. The present study aimed at investigating the prospective anti-inflammatory role of trans-anethole (TNA) in targeting MI/R and its related mechanism in upregulating the expression of the inflammatory and cardiac-related gene (VAV3), and its epigenetic regulators (lncRNA-JRKL-AS1 and miR-1298) that were retrieved from in-silico data analysis in an ischemia/reperfusion (I/R) rat model. TNA was administered in 3 doses (50, 100, and 200 mg/kg), 15 min prior to coronary ligation in male Wistar rats. The left ventricular end-diastolic pressure and dP/dtmax were assessed. Histopathological, biochemical, and molecular analyses were performed to assess the effects of TNA pre-treatment on the I/R rats model. TNA alleviated the I/R-induced cardiac injury pathologically and improved the cardiac function tests and enzymes. At the molecular level, TNA upregulated the expression level of the retrieved RNA-based panel (VAV3 mRNA/miR-1298/lncRNA JRKL-AS1). At the protein level, TNA decreased the cardiac content of the pro-inflammatory cytokine TNF-α. TNA has demonstrated a potential ability to alleviate the cardiac injury and attenuate the inflammatory response following ischemia-reperfusion in the rat model through modulation of the expression of RNA panel (VAV3 mRNA/miR-1298/lncRNA JRKL-AS1) and TNF- α protein.


Placenta-specific 8 (PLAC8) mediates inflammation and mobility of the hPDLCs via MEK/ERK signaling pathway.
Placenta-specific 8 (PLAC8) is reported to regulate cellular functions in the progression of various diseases. However, its role in periodontitis is still unclear. Human periodontal ligament cells (hPDLCs) were treated with lipopolysaccharide of Porphyromonas Gingivalis (LPS-PG) to mimic periodontitis in vitro. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to measure the mRNA expression levels and western blot was for protein levels. Wound healing and transwell migration assays were performed to assess the cell mobility of hPDLCs. Both mRNA and protein levels of inflammatory cytokines including IFN-γ, IL-17, TNF-α, IL-4, IL-10 and IL-13 were accessed to evaluated process of periodontitis in vitro. Furthermore, the protein expressions of mitogen-activated protein kinase kinase (MEK), extracellular regulated protein kinase (ERK) and their phosphorylated products quantified by western blotting assay were determined to confirm the activation of the MEK/ERK signaling pathway. The microarray analysis results showed that PLAC8 was most significantly downregulated in periodontium samples of patients with periodontitis, which participates in blood coagulation and integrin-mediated signaling pathway. PLAC8 was also markedly downregulated in the LPS-PG-treated hPDLCs. Moreover, overexpression of PLAC8 ameliorated inflammation and promoted cell mobility of LPS-PG-treated hPDLCs, while inhibition of PLAC8 exhibited the opposite effects. MEK/ERK was selected based on analyses of the protein-protein interaction (PPI) network as the potential signaling pathway interacted with PLAC8, and PLAC8 showed regulatory function on activation of the MEK/ERK pathway. Additionally, U0126, the inhibitor of MEK, abrogated the effects of PLAC8 on inflammation and cell mobility of LPS-PG-treated hPDLCs. Overexpression of PLAC8 protected hPDLCs from dysfunction of inflammation and cell mobility via activating MEK/ERK pathway, indicating a novel therapeutic target for periodontitis.


Butaselen prevents hepatocarcinogenesis and progression through inhibiting thioredoxin reductase activity.
Hepatocellular carcinoma (HCC) accounts for most of primary liver cancer, of which five-year survival rate remains low and chemoprevention has become a strategy to reduce disease burden of HCC. We aim to explore the in vivo chemopreventive effect of an organoselenium-containing compound butaselen (BS) against hepatocarcinogenesis and its underlying mechanisms. Pre- and sustained BS treatment (9, 18 and 36mg/Kg BS) could dose-dependently inhibit chronic hepatic inflammation, fibrosis, cirrhosis and HCC on murine models with 24 weeks treatment scheme. The thioredoxin reductase (TrxR), NF-κB pathway and pro-inflammatory factors were activated during hepatocarcinogenesis, while their expression were decreased by BS treatment. BS treatment could also significantly reduce tumor volume in H22-bearing models and remarkably slow tumor growth. HCC cell lines HepG2, Bel7402 and Huh7 were time- and dose-dependently inhibited by BS treatment. G2/M arrest and apoptosis were observed in HepG2 cells after BS treatment, which were mediated by TrxR/Ref-1 and NF-κB pathways inhibition. BS generated reactive oxygen species (ROS), which could be reduced by antioxidant N-acetyl-L-cysteine (NAC) and NADPH oxidase inhibitor DPI. NAC could markedly increase HepG2 cells viability. TrxR activity of HepG2 cells treated with BS were significantly decreased in parallel with proliferative inhibition. The TrxR1-knockdown HepG2 cells also exhibited low TrxR1 activity, high ROS level, relatively low proliferation rate and increased resistance to BS treatment. In conclusion, BS can prevent hepatocarcinogenesis through inhibiting chronic inflammation, cirrhosis and tumor progression. The underlying mechanisms may include TrxR activity inhibition, leading to ROS elevation, G2/M arrest and apoptosis.


Retroperitoneal sarcomas.
Retroperitoneal sarcomas comprise a rare, heterogeneous group of neoplasms. Routine workup should include the patient's medical history, a physical examination, and helical CT of the abdomen and pelvis, with selective use of MRI and preoperative tissue sampling. The primary treatment is complete surgical resection with a rim of normal tissue. The role of adjuvant therapy is evolving and at present should not be used outside the investigational setting.


Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice.
Accumulation of amyloid-β peptide (Aβ) in the brain is closely associated with cognitive decline in Alzheimer's disease (AD). Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice, but more efficient and global delivery is necessary to treat the broadly distributed burden in AD. Here we developed an adeno-associated virus (AAV) vector capable of providing neuronal gene expression throughout the brains after peripheral administration. A single intracardiac administration of the vector carrying neprilysin gene in AD-model mice elevated neprilysin activity broadly in the brain, and reduced Aβ oligomers, with concurrent alleviation of abnormal learning and memory function and improvement of amyloid burden. The exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding Aβ oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary.


The relationship between laterality and numerical and spatial ability.
Hypotheses derived from right shift theory concerning the relationship between laterality and mathematical ability were investigated. This was done by dividing a group of 129 subjects into subgroups with presumably different distributions of the rs+ +, rs+ - and rs- - genotypes on the basis of their manual skills and then assessing their numerical and spatial abilities. No relationship was found between laterality and ability when the group as a whole were considered, but some marginal effects were found for numerical ability when data for a subgroup of 96 young female subjects were analysed separately. The results did not, however, conform to the predictions of right shift theory.


An aboral-dorsalization hypothesis for chordate origin.
Chordates originated from a common ancestor(s) shared with two other deuterostome groups, echinoderms and hemichordates, by creating a novel type of tadpole-like larva, which was characterized by a dorsal hollow neural tube and notochord. Recent molecular phylogeny supports the notion that echinoderms and hemichordates form a clade named the Ambulacraria and that, among the chordates, cephalochordates are more basal than urochordates and vertebrates. An aboral-dorsalization hypothesis is proposed to explain how the tadpole-type larva evolved. Embryological comparison of cephalochordates with nonchordate deuterostomes suggests that, because of limited space on the oral side of the ancestral embryo, morphogenesis to form the neural tube and notochord occurred on the aboral side of the embryo. Namely, the dorsalization of the aboral side of the ancestral embryo may have been a key developmental event that led to the formation of the basic chordate body plan.


Digital breast tomosynthesis (DBT)-guided biopsy of calcifications: pearls and pitfalls.
As digital breast tomosynthesis (DBT) is quickly becoming the standard of care in clinical practice, DBT-guided procedures are being more frequently utilized. DBT-guided biopsies of calcifications are efficient and easy to perform. As radiologists seek proficiency in these biopsies, there are some unique features of DBT-guided biopsies that they must consider. In this review, we provide a step-by-step guide on performing DBT-guided biopsies of calcifications, with a focus on pearls and pitfalls for problem solving in difficult biopsy cases.


Lung-Protective Ventilation.
Historically, mechanical ventilation of the lungs utilizing relatively large tidal volumes was common practice in the operating room and intensive care unit (ICU). The rationale behind this treatment strategy was to yield better patient outcomes, that is, fewer pulmonary complications, and a reduction in morbidity and mortality. As evidence-based practice has evolved, potential harmful effects of traditional, nonphysiological mechanical ventilation (ventilation with larger tidal volumes and the tolerance of high airway pressures) even in shortterm treatment have been shown to correlate with systemic inflammation and the development of ventilator-associated lung injury. Lung-protective ventilation principles using more physiological tidal volumes, avoiding high inspiratory plateau pressures, along with appropriate levels of positive end-expiratory pressure have been shown to decrease pulmonary complications and improve outcomes in patients with acute respiratory distress syndrome requiring ongoing ventilatory support in the ICU. In addition, current research is beginning to validate the benefit of providing more physiologic ventilator support in the operating room, particularly for high-risk patients undergoing major abdominal surgery, in minimizing acute lung injury. A review of lung-protective ventilation measures including benefits and potential side effects is presented. Additional treatment modalities and therapeutic considerations are offered for inclusion in optimal patient management.


Synchronous testicular seminoma and adrenocortical carcinoma: a case report.
We report a rare case of synchronous testicular seminoma and adrenocortical carcinoma. A 57-year-old man had a left testicular seminoma (clinical stage IIIB) with metastases to the lung and paraaortic lymph node. A complete response was obtained after 3 courses of chemotherapy with single-agent carboplatin. However, a left adrenal tumor was detected 1 2 months later and demonstrated a tumor volume doubling time of 2.1 months. Chemotherapy with bleomycin, etoposide and cisplatin failed to stop the tumor growth. A laparoscopic adrenalectomy was performed and pathology revealed an adrenocortical carcinoma. The patient has been free of recurrence for 42 months postoperatively.


Prevalence of non-strongyle gastrointestinal parasites of horses in Riyadh region of Saudi Arabia.
This study aimed to provide recent data on the occurrence of non-strongyle intestinal parasite infestation in horses in the Riyadh region of Saudi Arabia as a basis for developing parasite control strategies. We conducted necropsy for 45 horses from September 2006 to November 2007 in the Riyadh region, Saudi Arabia. 39 out of 45 horses were infected with intestinal parasites with an infestation rate of 86.6%. Infestations with seven nematode species and two species of Gasterophilus larva were found. The most prevalent parasites were Strongyloides westeri (64.4%) and Parascaris equorum (28.8%) followed by Habronema muscae (22.2%). Trichostrongylus axei and Oxyuris equi were less common at (11.1%) and (8.8%), respectively. Habronema megastoma and Setaria equine were found in two horses only (4.4%). Gasterophilus intestinalis larvae were recovered from 39 horses (86.6%) and Gasterophilus nasalis larvae were found in 17 horses (37.7%). Season had a significant effect on the prevalence of P. equorum and G. nasalis, while age of horses had a significant effect only on the prevalence of P. equorum. The husbandry in Saudi Arabia appears to be conductive to parasites transmitted in stables or by insects rather than in pasture.


Novel B2 mitogenomes from Continental southern Patagonia's Late Holocene: New insights into the peopling of the Southern Cone.
The main aim of this study is to discuss the migratory processes and peopling dynamics that shaped the genetic variability of populations during the settlement of the Southern Cone, through the analysis of complete mitogenomes of individuals from southern Patagonia. Complete mitogenomes were sequenced through massively parallel sequencing from two late Holocene individuals (SAC 1-1-3 and SAC 1-1-4) buried in the same chenque at Salitroso Lake Basin (Santa Cruz province, Argentina). To evaluate matrilineal phylogenetic affinities with other haplotypes, maximum likelihood and Bayesian phylogenetic reconstructions were performed, as well as a haplotype median-joining network. The mitogenomes were assigned to haplogroups B2 and B2b, exhibiting an average depth of 54X and 89X (≥1X coverage of 98.6% and 100%), and a high number of nucleotide differences among them. The phylogenetic analyses showed a relatively close relationship between the haplotype found in SAC 1-1-4 and those retrieved from a Middle Holocene individual from Laguna Chica (Buenos Aires province), and from a group of individuals from the Peruvian coast. For the SAC 1-1-3, no clear affiliations to any other haplotype were established. The large divergence between the haplotypes presented in this study suggests either a highly variable founder gene pool, or a later enrichment by frequent biological contact with other populations. Our results underline the persistence of genetic signals related to the first waves of peopling in South America, suggesting that the regional settlement of the southern end of the continent has been much more complex than initially thought.


Distribution and phytoavailability of heavy metal chemical fractions in artificial soil on rock cut slopes alongside railways.
Artificial soil is often sprayed onto cut slopes alongside railroad tracks to promote revegetation. This study evaluated the heavy metal content and the distribution of heavy metal chemical fractions in the soil, as well as the uptake of heavy metals by plants. The soil at four sites was determined to be considerably contaminated with Cd and Pb. The concentrations of Cd and Pb increased with the length of time the railway had been in use and decreased further away from the railway tracks. Pb primarily existed in reducible form but as residual fractions, whereas Cd was predominantly in exchangeable form. A correlation analysis indicated that pH, organic matter, and total phosphorus levels were important factors affecting the distribution of the heavy metal chemical fractions. The amounts of exchangeable Pb and Cd in the soil were highly correlated with their amounts in the plants sampled, indicating that the exchangeable fraction is a better indication of heavy metal phytoavailability than the total amount of heavy metals in the soil. Bioaccumulation and translocation factors indicated that Indigofera amblyantha had moderate tolerance and bioaccumulation capability for Pb, as did Leucaena leucocephala for Cd. These two plant species can serve as ideal slope remediation plants.


The influence of stereopsis on visual saliency in a proto-object based model of selective attention.
Some animals including humans use stereoscopic vision which reconstructs spatial information about the environment from the disparity between images captured by eyes in two separate adjacent locations. Like other sensory information, such stereoscopic information is expected to influence attentional selection. We develop a biologically plausible model of binocular vision to study its effect on bottom-up visual attention, i.e., visual saliency. In our model, the scene is organized in terms of proto-objects on which attention acts, rather than on unbound sets of elementary features. We show that taking into account the stereoscopic information improves the performance of the model in the prediction of human eye movements with statistically significant differences.


From genes to shape in leaf development and evolution.
Plant leaves display tremendous variation in shape. Here, we discuss how information obtained from genetics, live imaging and computational modeling has helped conceptualize the ways in which gene activity is translated into different leaf shapes. In this framework, the action of genes on leaf form can be captured as the sum of their effects on the amount, duration, and direction of cellular growth, which together produce leaf geometry. We use three different examples to illustrate this point. First, the emergence of complex versus simple leaves in eudicots, which arises from differences in organ-wide growth duration as well as local growth repression at the leaf margin. Second, the development of strap-shaped grass leaves with a broad sheathing base versus the typical eudicot leaves with a narrow petiole, where these features of grass leaves emerged through lateral expansion of the zone of leaf progenitor cells, coupled with later remodeling of growth of early domains of the leaf blade. Third, the formation of insect traps on carnivorous plants that arose through constrained directional growth that produced a 3D deformation. In all the above examples, changes in gene expression of different classes of homeobox genes have contributed to the altered growth patterns underlying these different aspects of leaf shape diversity.


Anti-Aβ antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology.
The brain pathology of Alzheimer's disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Aβ) peptide and hyperphosphorylated forms of the tau protein. Initial Aβ deposition is considered to trigger a sequence of deleterious events contributing to tau pathology, neuroinflammation and ultimately causing the loss of synapses and neurons. To assess the effect of anti-Aβ immunization in this context, we generated a mouse model by overexpressing the human tau protein in the hippocampus of 5xFAD mice. Aβ plaque deposition combined with human tau overexpression leads to an array of pathological manifestations including the formation of tau-positive dystrophic neurites and accumulation of hyperphosphorylated tau at the level of neuritic plaques. Remarkably, the presence of human tau reduces microglial clustering in proximity to the Aβ plaques, which may affect the barrier role of microglia. In this mouse model, continuous administration of anti-Aβ antibodies enhances the clustering of microglial cells even in the presence of tau. Anti-Aβ immunization increases plaque compaction, reduces the spread of tau in the hippocampal formation and prevents the formation of tau-positive dystrophic neurites. However, the treatment does not significantly reduce tau-induced neurodegeneration in the dentate gyrus. These results highlight that anti-Aβ immunization is able to enhance microglial activity around neuritic plaques, mitigating part of the tau-induced pathological manifestations.


Possible role of regional superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats.
Cd2+ (0.4 mg/kg) administration to growing rats (45 +/- 5 g) intraperitoneally, daily for 30 days was found to decrease the activity of superoxide dismutase (SOD) in all the brain regions, except hippocampus. The concentrations of lipid peroxides were significantly elevated in the cerebellum, cerebral cortex, corpus striatum and midbrain. A 100% inhibition in SOD activity was observed by 14 microM and 50 microM of Cd2+ in bovine blood and rat brain preparations, respectively. Cadmium-induced strong inhibitory effect on brain and purified bovine blood SOD suggested a direct effect of the metal on enzyme molecule. Furthermore, in vitro addition of a wide range of Cd2+ (1-100 microM) increased the rate of lipid peroxidation (LPO) reaction in fresh brain homogenate, however, did not affect boiled homogenate. The studies on LPO in reconstituted homogenate resulting from mixing of fresh and/or heated different subcellular fractions indicated the presence of some heat-labile Cd2+ -sensitive factor in 15000 x g pellet fraction. It is suggested that Cd2+ directly and indirectly through inhibition of SOD, increases the LPO of cell membranes and thus produces damage to the associated physiological functions leading to central nervous dysfunctions.


Bladder injuries after external trauma: 20 years experience report in a population-based cross-sectional view.
Report 20 years experience of bladder injuries after external trauma. Gender, age, mechanism/location of damage, associated injuries, systolic blood pressure (SBP), Revised Trauma Score (RTS), Injury Severity Score (ISS), Trauma Injury Severity Score (TRISS), complications, and length of stay (LOS) were analyzed in a prospective collected bladder injuries AAST-OIS grade ≥ II database (American Association for the Surgery of Trauma Organ Injury Scaling) from 1990 to 2009 in a trauma reference center. Among 2,575 patients experiencing laparotomy for trauma, 111 (4.3 %) presented bladder ruptures grade ≥ II, being 83.8 % (n = 93) males, mean age 31.5 years old (± 11.2). Blunt mechanism accounted for 50.5 % (n = 56)-motor vehicle crashes 47.3 % (n = 26), pedestrians hit by a car (29.1 %). Gunshot wounds represented 87.3 % of penetrating mechanism. The most frequent injury was grade IV (51 patients, 46 %). The mean ISS was 23.8 (± 11.2), TRISS 0.90 (± 0.24), and RTS 7.26 (± 1.48). Severity (AAST-OIS), mechanism (blunt/penetrating), localization of the bladder injury (intra/extraperitoneal, associated), and neither concomitant rectum lesion were related to complications, LOS, or death. Mortality rate was 10.8 %. ISS > 25 (p = 0.0001), SBP <90 mmHg (p = 0.0001), RTS <7.84 (p = 0.0001), and pelvic fracture (p = 0.0011) were highly associated with grim prognosis and death with hazard ratios of 5.46, 2.70, 2.22, and 2.06, respectively. Trauma scores and pelvic fractures impact survival in bladder trauma. The mortality rate has remained stable for the last two decades.


Bronchopulmonary dysplasia predicted at birth by artificial intelligence.
To develop a fast bedside test for prediction and early targeted intervention of bronchopulmonary dysplasia (BPD) to improve the outcome. In a multicentre study of preterm infants with gestational age 24-31 weeks, clinical data present at birth were combined with spectral data of gastric aspirate samples taken at birth and analysed using artificial intelligence. The study was designed to develop an algorithm to predict development of BPD. The BPD definition used was the consensus definition of the US National Institutes of Health: Requirement of supplemental oxygen for at least 28 days with subsequent assessment at 36 weeks postmenstrual age. Twenty-six (43%) of the 61 included infants developed BPD. Spectral data analysis of the gastric aspirates identified the most important wave numbers for classification and surfactant treatment, and birth weight and gestational age were the most important predictive clinical data. By combining these data, the resulting algorithm for early diagnosis of BPD had a sensitivity of 88% and a specificity of 91%. A point-of-care test to predict subsequent development of BPD at birth has been developed using a new software algorithm allowing early targeted intervention of BPD which could improve the outcome.


Endothelin and vasopressin activate low conductance chloride channels in aortic smooth muscle cells.
The non-contractile aortic smooth muscle cell line A7r5 was used to study the membrane events involved in the effect of vasoconstrictor peptides. Whole-cell voltage-clamp and membrane potential recording techniques were used to demonstrate the contribution of an increased Cl- conductance to the late depolarization induced by endothelin-1 and vasopressin. During cell-attached patch recording with N-methyl-D-glucamine in the pipette, bath application of endothelin or vasopressin induced single-channel inward currents in the following minutes. The current/potential (I/V) curve of the most frequently observed channel type--a small conductance Cl- (SCl) channel--reversed near the cell membrane potential and showed a single-channel conductance of 1.8 pS for inward currents. After patch excision in an extracellular solution containing CaCl2 (2 mM), the frequency of SCl channel openings increased. Patch excision in the absence of peptide stimulation also produced this channel activity. Replacement of CaCl2 by a Ca2+ chelator on the intracellular face of a patch reversibly inhibited the channel activity, indicating that these SCl channels are Ca(2+)-activated Cl- channels. The single-channel I/V characteristic showed outward rectification above +50 mV. An analysis of the gating kinetics of the SCl channel is given. Another channel type was recorded less frequently after peptide stimulation. It had a lower conductance (1.0-1.3 pS) and slower kinetics and was designated a very small conductance Cl- channel. It is concluded that activation of two types of Cl- channels (at least one of which is Ca2+ dependent) is involved in the late depolarization produced by vasoconstrictor peptides in vascular smooth muscle cells of the aortic cell line A7r5.


German guidelines on the diagnosis and treatment of neurosyphilis.
In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline. (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against Treponema pallidum. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count. The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).


Caulobacter zeae sp. nov. and Caulobacter radicis sp. nov., novel endophytic bacteria isolated from maize root (Zea mays L.).
Four bacterial strains designated 410T, 441, 695T and 736 were isolated from maize root in Beijing, P. R. China. Based on 16S rRNA gene phylogeny, the four strains formed two clusters in the genus Caulobacter. Since strain 441 was a clonal variety of strain 410T, only three strains were selected for further taxonomic studies. The whole genome average nucleotide identity (ANI) value between strains 410T and 695T was 94.65%, and both strains shared less than 92.10% ANI values with their close phylogenetic neighbors Caulobacter vibrioides DSM 9893T, Caulobacter segnis ATCC 21756T and Caulobacter flavus CGMCC 1.15093T. Strains 410T and 695T contained Q-10 as the sole ubiquinone and their major fatty acids were C16:0, 11-methyl C18:1ω 0, 11-methyl C18: 1ω7c, summed feature 3 (C16:1ω7c and/or C16:1ω 1ω7c and/or C16: 1ω6c) and summed feature 8 (C18:1ω7c and/or C18:1ω 1ω7c and/or C18: 1ω6c). Their major polar lipids consisted of glycolipids and phosphatidylglycerol, and phenotypic tests differentiated them from their closest phylogenetic neighbors. Based on the results obtained, it is proposed that the three strains represent two novel species, for which the names Caulobacter zeae sp. nov. (type strain 410T=CGMCC 1.15991=DSM 104304) and Caulobacter radicis sp. nov. (type strain 695T=CGMCC 1.16556=DSM 106792) are proposed.


Dopamine release rather than content in the caudate putamen is associated with behavioral changes in the iron rat model of Parkinson's disease.
The effects of intranigral iron injection on dopamine (DA) release and content in the caudate putamen (CPu) and their relationship to DA-related behavioral response were investigated in rats. Different concentrations of FeCl(3) (10, 20, and 40 microg) and saline were injected separately into the left substantia nigra. In some experiments, rats were pretreated with desferrioxamine or saline before iron injection. After 3 weeks, changes in behavioral response, DA release, and DA content in the CPu were determined. In all iron injection groups (10, 20, and 40 microg), DA content in the lesioned side of the brain was significantly decreased, showing a significant linear correlation (R(2) = 0.981, P = 0.01), and DA turnover ratio significantly increased (both P = 0.01, 0.01 and 0.001 vs unlesioned sides, respectively). However, injection dosages of 10 or 20 microg of iron did not lead to significant changes in DA release in the CPu or in behavioral response. At the 40-microg dosage, it was found that DA release in the lesioned side and rearing activity both were significantly reduced (all P = 0.01 vs unlesioned side or control) and apomorphine-induced rotation was observed. Pretreatment with desferrioxamine significantly inhibited the effect of iron on DA release and content. These results demonstrate that iron injection can damage dopaminergic neurons and suggest that DA release, rather than DA content, in the CPu is associated with DA-related behavioral changes in this PD model.


Impact of bent distortion on accuracy of measurement during transrectal ultrasonography for prostatic imaging: a preliminary study.
To evaluate the effect of bent distortion of the image of the prostate on the accuracy of 3-dimensional measurements during transrectal ultrasonography (TRUS). TRUS images were obtained prospectively from 60 patients with prostate cancer. The degree of rectal compression on the probe was varied in each case to obtain a typical bent distortion image (BDI) and a minimally bent image (MBI). Magnetic resonance imaging (MRI) served as the reference. Axial and midsagittal BDI, MDI, and MRI were selected. Three-dimensional prostate diameters (height, width, and length) and volume were obtained from all images by 2 independent observers. The data were analyzed by using a paired t test, intraclass correlation coefficients (ICCs), and Bland-Altman plots. The MBI and BDI diameters differed significantly (P <.001). All ICCs for the MBI diameters and volume and the ICCs for BDI length and volume exceeded 0.9, which indicates high measurement reliability. However, the ICCs for BDI height and width were below 0.9. When the difference in MBI or BDI relative to MRI was calculated for each variable, the MBI differences were all significantly smaller than the BDI differences (P <.001). Bent distortion during TRUS affects the accuracy of measurements. MBI is also morphologically more realistic than BDI. Therefore, to minimize prostatic image distortion, the rectal probe should be placed so that the posterior wall of the prostate is as flat as possible.


Differential human brain activity induced by two perceptually indistinguishable gentle cutaneous stimuli.
We examined differences in brain activity in response to two types of mechanical stimulation, which have been reported previously as being perceptually indistinguishable but having different impacts on autonomic reflexes. As an indicator of brain activity, glucose metabolism was evaluated by PET with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG). Twelve healthy, young adult men participated in the study. Two types of cutaneous stimulation tools, soft elastomer discs with microcones (microcone disc) or flat surfaces (flat disc), were used in a crossover, randomized double-blind manner. Each type of cutaneous stimulation tool was applied on the cheeks and F-FDG-PET scans were obtained. Greater F-FDG uptake was observed in the right anterior cingulate cortex during microcone disc stimulation compared with flat disc stimulation. However, F-FDG uptake during application of these two different stimuli was not different in the primary and secondary somatosensory cortices or insula. Stimulation using microcone discs and flat discs was noted by one and three participants, respectively, and there was no difference in the presence of perception between the stimulation tools. The results indicate that the right anterior cingulate cortex differentially responds to different types of cutaneous stimulation that are perceptually indistinguishable.


Does the distance between tumor and margin in radical prostatectomy specimens correlate with prognosis: relation to tumor location.
The posterior half of the prostate has a smooth well-defined edge unlike anteriorly. Often, tumor extends close to the posterior margin, where it is controversial whether pathologists should measure the distance between the tumor and the margin. There are no published data regarding the significance of a close margin factoring in the anatomical location within the radical prostatectomy (RP). We identified 158 RPs with 39 anterior-predominant carcinomas and 119 cases with posterior-predominant cancer. Distances between the tumor and inked margin were measured with an ocular micrometer. Eighty-seven cases had no progression with a minimum 6-year follow-up (median, 8; range, 6-9). Eighteen cases had progression with a median time to progression of 2 years with all men progressing within 6 years after RP. There was no statistically significant difference in the risk of progression relative to distance of tumor to the posterior margin (P=.09). The mean distance of tumor to the anterior margin for the cases that progressed was 0.6 mm (median, 0.5 mm; range, 0.05-1.18) compared to 1.9 mm (median, 1.1; range, 0.02-4) for the cases that did not progress (P=.02). Of 7 cases with anterior-predominant tumors that progressed, 5 had tumor located less than 1 mm from the anterior margin. In conclusion, if cancer is present less than 1 mm from the anterior margin, there is an increased tendency to recur, and this finding should be included in pathology reports. However, close margins posteriorly are not clinically significant and should not be reported.


[Rare localization of aneurysmal bone cyst in the sphenoid bone].
Aneurysmal bone cyst is a benign tumor that can affect all bones in the body. It rarely affects the base of the skull. It is usually located at the level of the long bones. We report the clinical case of a 44-year old man treated for a mass in the basisphenoid wrongly diagnosed as invasive prolactin-producing macroadenoma for which he was put under dopamine agonists over a period of 9 months. We adjusted the diagnosis by suggesting aneurysmal bone cyst in the sphenoid bone on the basis of its almost pathognomonic radiological aspect on MRI.


Carboxypeptidase A activity of cultured skin fibroblasts and relationship to cystic fibrosis.
Properties of carboxypeptidase A of cultured skin fibroblasts from control and cystic fibrosis patients were studied using alpha-N-carbobenzoxy-L-glutamyl-L-tyrosine as substrate. Carboxypeptidase A was inhibited by thiomersal, cyanide, iodoacetate and N-ethylmaleimide in a similar manner for control and cystic fibrosis fibroblasts. Both trypsin and dithiothreitol treatment activated the enzyme, but 1,10-phenanthroline inhibited only in the presence of dithiothreitol. Both Zn2+ and Co2+ reversed this inhibition. Trypsin treatment of carboxypeptidase A produced a form of the enzyme having a higher KM value for both control and cystic fibrosis fibroblasts. Dithiothreitol treatment of control fibroblasts resulted in a form with similar properties to the trypsin activated form, but cystic fibrosis fibroblasts yielded a variant form with even higher KM and Vmax values. Since other properties were similar, it seems likely that this difference reflected binding of a molecule to the enzyme rather than of a defect in the enzyme.


Detection and characterization of silver nanoparticles in aqueous matrices using asymmetric-flow field flow fractionation with inductively coupled plasma mass spectrometry.
Engineered nanomaterials (EN) may be released into the environment as a result of their use in various consumer products. Silver nanoparticles (nAg) are widely used as an antimicrobial agent in personal care and household products, and in textiles. Since there is high potential for nAg to be released into municipal wastewater and then discharged into the aquatic environment, there is a need to develop methods for the analysis of these materials in aqueous matrices. Asymmetric-flow field flow fractionation (AF4) with on-line detection by ultra violet-visible (UV-Vis) spectroscopy or inductively coupled plasma mass spectrometry (ICP-MS) was used to detect and characterize nAg in aqueous matrices. Analysis of a mixture of 20, 40 and 60 nm nAg standards suspended in water resulted in a well resolved fractogram. Retention times of nAg separated by AF4 were correlated with the particle sizes of the standards. The limit of detection (LOD) for analysis of nAg using the on-line AF4/ICP-MS method was 0.80 ng mL(-1). Two calibration approaches (i.e., external calibration and standard addition) were used to quantify nAg concentrations, and both methods gave similar results. Using the on-line AF4/ICP-MS analytical method, nano-sized Ag was detected and quantified in untreated wastewater (i.e., influent) collected from a wastewater treatment plant. The concentration and the modal size of nAg in the influent were 1.90 ng mL(-1) and 9.3 nm respectively.


Pyrethroid insecticides along the Southwestern Atlantic coast: Guiana dolphin (Sotalia guianensis) as a bioindicator.
The presence of pyrethroid compounds in hepatic tissue of Guiana dolphins (Sotalia guianensis) is reported for the first time. Twelve pyrethroids were determined in 50 animals from eight locations of the Brazilian coast. The highest average concentration of total pyrethroids (∑PYR) was 1166 ng.g-1 lw, with values ranging from 148 to 5918 ng.g-1 lw, in Ilha Grande Bay, Rio de Janeiro State, while the Espírito Santo State had the highest median, 568 ng.g-1 lw. Permethrin was the predominant compound in most areas, contributing for 42% to 81% of the ∑PYR, whereas cypermethrin was the most abundant compound in Guanabara and Sepetiba bays (79% and 81%, respectively), both located in Rio de Janeiro State. Biological factors were not correlated with pyrethroids concentration. Tetramethrin and es/fenvalerate compounds were negatively correlated to the age, suggesting degradation/metabolization capacity in these animals that increases throughout life. Despite being metabolized and excreted, the wide use of these pollutants is reflected in relevant concentrations found in Guiana dolphins. This is the first study evaluating pyrethroids in a representative number of hepatic samples and covering >2600 km of coast. The overall lack of information on pyrethroids in cetaceans highlights the importance of understanding the profile and distribution of these pollutants in dolphins which exclusively inhabit the Southwestern Atlantic coast.


Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle.
The aim of the present study was to investigate variation in the expression pattern of ornithine decarboxylase (ODC1), spermine (SPM), spermidine (SPD) and antizyme inhibitor (AZIN1) in hypothalamus, ovary and uterus during the estrous cycle of rats. Further, to understand any correlation between polyamines and GnRH I expression in hypothalamus; effect of putrescine treatment on GnRH I expression in hypothalamus and progesterone and estradiol levels in serum were investigated. The study also aims in quantifying all the immunohistochemistry images obtained based on pixel counting algorithm to yield the relative pixel count. This algorithm uses a red green blue (RGB) colour thresholding approach to quantify the intensity of the chromogen present. The result of the present study demonstrates almost similar expression pattern of polyamine and polyamine related factors, ODC1, SPD, SPM and AZIN1, with that of hypothalamic GnRH I, all of which mainly localized in the medial preoptic area (MPA) of the hypothalamus, during the proestrus, estrus and diestrus. This suggest that hypothalamic GnRH I expression is under regulation of polyamines. The study showed significant increase in hypothalamic GnRH I expression for both the doses of putrescine treatment to adult female rats. Further, it was shown that in ovary expression pattern of ODC1, SPM, SPD and AZIN1 were similar with that of steroidogenic factor, StAR during the estrous cycle, and putrescine supplementation increased significantly estradiol and progesterone levels in serum, all suggesting ovarian polyamines are involved in regulation of ovarian steroidogenesis. Localization of these factors in the theca and granulosa cells suggest involvement of polyamines in the process of folliculogenesis and luteinization; and ODC1, SPD, SPM and AZIN1 in oocyte further suggests polyamine role in maintenance of oocyte physiology. Finally, in uterus SPM and AZIN1 were localized throughout the estrous cycle, being comparatively more during the metestrus phase. There was intense immunostaining of SPD in the luminal and glandular epithelium during the metestrus and diestrus phases of the estrous cycle suggesting these all the three polyamines as such play important role in regulation of uterine physiology.


Spread of excitation in a myocardial volume: simulation studies in a model of anisotropic ventricular muscle activated by point stimulation.
The purpose of this study was to present simulations of excitation wavefronts spreading through a parallelepipedal slab of ventricular tissue measuring 6.5 x 6.5 x 1.0 cm. The slab incorporates the anisotropic properties of the myocardium including the transmural counterclockwise fiber rotation from epicardium to endocardium. Simulations were based on an eikonal model that determines excitation times throughout the ventricular wall, which is represented as an anisotropic bidomain. Excitation was initiated by delivering ectopic stimuli at various intramural depths. We also investigated the effect of a simplified Purkinje network on excitation patterns. Excitation wavefronts in the plane of pacing, parallel to epicardial-endocardial surfaces, were oblong with the major axis approximately oriented along the local fiber direction, with bulges and deformations due to attraction from rotating fibers in adjacent planes. The oblong intersections of the wavefront with planes at increasing distance from pacing plane rotated clockwise or counterclockwise, depending on pacing depth, but wavefront rotation was always less than fiber rotation in the same plane. For all pacing depths, excitation returned toward the plane of pacing. Return occurred in multiple, varying sectors of the slab depending on pacing depth, and was observed as close as 6 mm to the pacing site. Curvature of wavefronts and collision with boundaries of slab markedly affected local velocities. Shape and separation of epicardial isochrones and spatial distribution of epicardial velocities varied as a function of site and depth of pacing. When the Purkinje network was added to the model, epicardial velocities revealed the subendocardial location of the Purkinje-myocardial junctions. Considerable insight into intramural events could be obtained from epicardial isochrones. If validated experimentally, results may be applicable to epicardial isochrones recorded at surgery.


Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial.
The rapid worldwide spread of COVID-19 has caused a global health challenge with high mortality of severe or critically ill patients with COVID-19. To date, there is no specific efficient therapeutics for severe or critically ill patients with COVID-19. It has been reported that androgen is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide as an androgen receptor antagonist has shown potential treatment effects on COVID-19 patients. Thus, this trial is designed to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. This single-arm, open-label, single-center prospective exploratory trial is planned to recruit 64 severe or critically ill patients with COVID-19 in China. Recruitment started on 16 May 2022 and is foreseen to end on 16 May 2023. Patients will be followed-up until 60 days or death, whichever comes first. The primary outcome is the 30-day all-cause mortality. Secondary endpoints included 60-day all-cause mortality, rate of clinical deterioration within 30 days after administration, time to sustain clinical recovery (determined using an 8-point ordinal scale), mean change in the Acute Physiology and Chronic Health Evaluation II scores, change in oxygenation index, changes in chest CT scan, percentage of patients confirmed negative for SARS-CoV-2 by nasopharyngeal swab, change in Ct values of SARS-CoV-2 and safety. Visits will be performed on days 1 (baseline), 15 or 30, 22, and 60. The trial is the first to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. The findings of this study might lead to the development of better treatment for COVID-19 and provide convincing evidence regarding the efficacy and safety of proxalutamide. This study was registered on 18 June 2022 at the Chinese Clinical Trial Registry (ChiCTR2200061250).


Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial.
Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings. This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends. ClinicalTrials.gov NCT04141917 . Registered 28 October 2019. Trial sponsor: University of Washington.


Sequence analysis of LipL41 and LipL21: Prospective Outer Membrane Proteins (OMPs) in early diagnosing leptospirosis.
Leptospirosis is a zoonotic disease mostly occurring in tropical climate countries. The etiology of the disease is due to microbes from the genus Leptospira. Higher number of cases reported worldwide indicated the disease is not easily eradicated. Leptospirosis shares the most common febrile symptoms such as dengue, Zika and yellow fever thus making it difficult to differentiate the disease at an early stage. The widely used current detection via PCR, uses the bacterial outer membrane protein (OMP) as their target region. However, the heterogeneity and variation of the genome cause false negative results. Lipoprotein LipL41 is the third most abundant outer membrane lipoprotein among pathogenic species and it is surface exposed and expressed during infection thus making it a suitable candidate in identifying pathogenic Leptospira. LipL21 on the other hand is a potential candidate in identifying the intermediate species. The study aimed in designing suitable PCR primers in identifying pathogenic and intermediate species of Leptospira through bioinformatics analysis on the bacterial OMPs. LipL41 and LipL21 were chosen as the suitable target sequence to be used as PCR primers in detecting the pathogenic and intermediate species, respectively. The designed primers indicated positive feedback upon tested with their respective bacterial DNA extract. These lipoproteins may serve as potential PCR primers to be used with clinical samples in diagnosing leptospirosis.•The etiology of the illness is due to bacteria from the genus Leptospira.•PCR utilizes the bacterial external membrane protein (OMP) thus the heterogeneity and variety of the genome cause bogus adverse outcomes.•The suitable candidates are LipL41, the third most abundant outer membrane lipoprotein, whereas LipL21 is a potential candidate in identifying the intermediate species.


Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis.
To create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE). Fluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4-6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4-6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75-250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (Ktrans) and extracellular volume fraction (ve) were calculated from DCE-MR imaging along the lateral synovial regions of interest. The mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The Ktrans/ve values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed. A nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.


Free/total PSA ratio does not improve prediction of pathologic stage and biochemical recurrence after radical prostatectomy.
Despite several publications, the ability of the free/total (F/T) prostate-specific antigen (PSA) ratio to predict the pathologic extension of prostate cancer is still a matter of controversy. In addition, its ability to predict biochemical recurrence after radical prostatectomy has not yet been reported. Since January 6, 1996, the F/T PSA ratio was prospectively measured preoperatively in 343 patients undergoing radical prostatectomy as the first treatment for localized prostate cancer. The ability to predict organ-confined disease was measured by receiver operating characteristic analysis. The areas under the curve were 0.66 for PSA density, 0.61 for total PSA, 0.60 for Gleason score, and 0.587 for the F/T PSA ratio. In multiple logistic regression analyses, the F/T PSA ratio was not a relevant predictor of organ-confined disease (Wald statistic 0.345 for P = 0.55). Similar results were obtained in the subgroup of patients with a PSA level between 2.5 and 10 ng/mL. The biochemical survival for the 270 patients who did not receive adjuvant therapy was 86% at 61 months. Statistically significant univariate predictors (P <0.05) of PSA recurrence were pT stage (log-rank 18.2) and Gleason grade (log-rank 8.8). The F/T PSA ratio was not a significant predictor of recurrence in the univariate analysis (log-rank 3.6 for P = 0.314) and in multivariate analysis (Wald statistic 0.2 for P = 0.97). These results suggest that the F/T PSA ratio is not helpful for the prediction of organ-confined disease and PSA recurrence after radical prostatectomy.


Immuno-PCR for the early serological diagnosis of acute infectious diseases: the Q fever paradigm.
To reduce the delay in diagnosis of Q fever, we have adapted the ultrasensitive immuno-PCR method for the detection of Phase II IgM anti-Coxiella burnetii. We compared its performance to ELISA, IFA and PCR using 31 acute Q fever sera and 50 control sera. The best sensitivity was obtained by iPCR (27 out of 31) followed by PCR (18 out of 31), ELISA (12 out of 31) and IFA (10 out of 31). A specificity of 92% was found by iPCR (3 false positive out of 40), 92% for ELISA (3 false positive out of 40) whereas PCR and IFA exhibited a specificity of 100%. Among the 31 Q fever sera, we compared the four methods for the detection of the early sera sampled during the two first weeks after the onset of symptoms and found a sensitivity of 90% by iPCR, 55% for PCR, 35% for ELISA and 25% for IFA. The results presented in this study suggest that iPCR is a promising, sensitive and specific method that can be used for the early diagnosis of acute Q fever and more generally for acute infections where traditional methods lack sensitivity.


A portable integer FFT in FORTRAN.
A radix 2 integer fast Fourier transform is organised for compatibility among small computer systems by simulating binary fraction multiplications and bit reversal as functions in basic FORTRAN. After installation the efficiency can be improved by machine code replacement of some parts.


Mitral annular calcification is associated with atrial fibrillation and major cardiac adverse events in atrial fibrillation patients: A systematic review and meta-analysis.
The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients. We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC (random effects OR: 2.34; 95% CI: 1.24, 4.41; P = .009). MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events.


Accelerated aortic 4D flow MRI with wave-CAIPI.
The aim of this study was to investigate the acceleration potential of wave-CAIPI (controlled aliasing in parallel imaging) for 4D flow MRI, provided that image quality and precision of flow parameters are maintained. The 4D flow MRIs with acceleration factor R = 2 were performed on 10 healthy volunteers, using both wave-CAIPI and standard Cartesian/2D-CAIPI sampling for reference. In addition, 1 patient with known aortic valve stenosis was examined. The flow rate ( Q ), net flow ( Qnet ), peak velocity vmax , and net average through-plane velocity ( v¯⊥ ) were calculated in eight analysis planes in the ascending and descending aorta. The acquisitions were retrospectively undersampled (R = 6), and deviations of flow parameters and hemodynamic flow patterns were evaluated. Flow parameters measured with an undersampled wave-CAIPI trajectory showed considerably smaller deviations to the references than the 2D-CAIPI images. For vmax , the mean absolute differences were 6.02±2.08 cm/s versus 14.36±5.68 cm/s; for Qnet , the mean absolute differences were 3.67±1.40 ml versus 5.87±1.91 ml for wave-CAIPI versus 2D-CAIPI, respectively. Noise calculations indicate that the 2D-CAIPI sampling exhibits a 43±38% higher average noise level than the wave-CAIPI technique. Qualitative discrepancies in hemodynamic flow patterns, visualized through streamlines, particle traces and flow velocity vectors, could be reduced by using the undersampled wave-CAIPI trajectory. Use of wave-CAIPI instead of 2D-CAIPI sampling in retrospectively 6-fold accelerated 4D flow MRI enhances the precision of flow parameters. The acquisition time of 4D flow measurements could be reduced by a factor of 3, with minimal differences in flow parameters.


An Overview of Liver Directed Locoregional Therapies.
An overview of all liver-directed locoregional therapies, including surgical resection for melanoma liver metastases (MLMs), is provided. MLM patients are divided by their primary melanoma location; cutaneous, uvea (eye), and mucosal melanoma. If patients with isolated cutaneous MLMs are considered for surgical resection, treatment with systemic therapy should be part of the treatment course. For uveal MLMs, complete surgical or ablative treatment of all MLMs suggests superior results compared with other liver-directed or systemic therapies, based on current evidence, no recommendations for any liver-directed regional therapy in the treatment of mucosal MLMs can be made.


Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.
The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.


Behaviour of aluminium in forest soils with different lithology and herb vegetation cover.
The aim of this study was to determine the content, distribution and behaviour of Al in soils under beech forest with different parent rock, and to assess the role of herbaceous vegetation on soil Al behaviour. We hypothesize that the contents of elements in the soil sorption complex (Al etc.) are strongly influenced by vegetation cover. Also, low molecular mass organic acids (LMMOA) can be considered as an indicator of soil organic matter (SOM) decomposition and vegetation litter turnover. Speciation of LMMOA, nutrition content (PO43-, Ca2+, K+) and element composition in aqueous extracts were determined by means of ion chromatography and inductively coupled plasma - optical emission spectrometry (ICP-OES) respectively. Active and exchangeable pH, sorption characteristics and exchangeable Al (Alex) were determined in BaCl2 extracts by ICP-OES. Elemental composition of parent rocks was assessed by means of X-ray fluorescence spectroscopy. Herb-poor localities showed lower pH, less nutrients (PO43-, Ca2+, K+), less LMMOA, a larger stock of SOM and greater cation exchange capacity. There was also lower mobilisation of Al in organic horizons, which explains the larger pools of Al. Generally, we can conclude that LMMOA, and thus soil vegetation cover, play an important role in the Al soil cycle.


Selective adsorption of anions on hydrotalcite-like compounds derived from drinking water treatment residuals.
Most drinking water treatment residuals (DWTRs) with rich metal resources are landfilled directly without treatment, which results in wasted Al/Fe resources. This work proposes a new method of preparing Mg-Al-Fe Hydrotalcite-like compounds (MAF-HTCLs) by recycling DWTRs as the raw material to selectively adsorb anions in the waste water. In this study, MAF-HTCLs were prepared by the coprecipitation method with recycled DWTRs. The characterizations and adsorption of MAF-HTCLs were studied for the selective adsorption of P, Cr, F, and Br. The adsorption capacity was increasing as the value of pH decreased. For kinetic adsorption, the pseudo-second-order model fit better, and two isotherm models (the Langmuir and Freundlich models) described the isotherm results well. According to the Langmuir model, the maximum adsorption capacities of P, Cr, F, and Br were 55.2, 34.9, 16.84, and 13.9 mg/g, respectively. Based on the results of characterizations before and after adsorption, adsorption mechanisms of Cr, F, and Br were proposed, including physicochemical adsorption, surface complexation, and ion exchange, in which ion exchange was dominant. Finally, we determined that the selective adsorption mechanisms of P on MAF-HTCLs included strong ion exchange and surface chemical precipitation by analyzing the results of X-ray photoelectron spectroscopy.


Tolerability of prostate transrectal biopsies using gel and local anesthetics: results of a randomized clinical trial.
To evaluate the role of intrarectal EMLA, a new topical anesthetic cream, and lidocaine gel as local anesthesia during transrectal prostate biopsy and to observe whether gel temperature can improve pain control. A series of 210 consecutive patients were randomized. Group 1 (N = 60) underwent intrarectal instillation of EMLA cream, group 2 (N = 50) 2.5% lidocaine gel, group 3 (N = 40) placebo, and group 4 (N = 60) no treatment. Patients in groups 2 and 3 were subdivided into subgroups according to instillation of warm or cooled gel. Pain control was assessed by a 10-point visual analog scale. The median pain scores were 2.6 in group 1, 3.8 in group 2, 3.9 in group 3, and 3.6 in group 4. In 16 patients (7.6%), the procedure was suspended because of pain: none group 1, 6.0% in group 2, 10% in group 3, and 15% ing group 4. The temperature of the lidocaine gel did not affect tolerability. Intrarectal instillation of EMLA cream is a simple, safe, and effective method of local anesthesia during transrectal prostate biopsy, superior to lidocaine gel, placebo, and no treatment.


Covalent linkage of 125I-insulin to a cytosolic insulin-degrading enzyme.
Cytosol extracts high in insulin-degrading activity were cross-linked to 125I-insulin with the bifunctional cross-linker disuccinimidyl suberate. With cytosols from either rat muscle, liver, kidney or brain or human erythrocytes, only a single protein (Mr = 110,000) was specifically labeled. Three different lines of evidence indicated that this labeled protein is insulin-degrading enzyme, a cysteine protease which accounts for most of the insulin-degrading activity in cell extracts. Firstly, the cross-linking of 125I-insulin to this protein is inhibited by unlabeled insulin over the same concentration range of insulin which inhibits degradation. Separated insulin A and B chain were less potent at inhibiting cross-linking, whereas bovine serum albumin and cytochrome c were without effect. Secondly, antibodies to purified insulin-degrading enzyme precipitated the labeled protein in parallel with their ability to precipitate the insulin-degrading activity of the extracts. Thirdly, when the insulin-degrading activity was purified 40,000-fold from erythrocytes, this Mr 110,000 protein co-purified. These results indicate that cross-linking 125I-insulin may be a convenient method for labeling the insulin-degrading enzyme.