An overview of neonicotinoids: biotransformation and biodegradation by microbiological processes.
Neonicotinoids are a class of pesticides widely used in different phases of agricultural crops. Similar to other classes of pesticides, they can damage human and environmental health if overused, and can be resistent to degradation. This is especially relevant to insect health, pollination, and aquatic biodiversity. Nevertheless, application of pesticides is still crucial for food production and pest control, and should therefore be carefully monitored by the government to control or reduce neonicotinoid contamination reaching human and animal feed. Aware of this problem, studies have been carried out to reduce or eliminate neonicotinoid contamination from the environment. One example of a green protocol is bioremediation. This review discusses the most recent microbial biodegradation and bioremediation processes for neonicotinoids, which employ isolated microorganisms (bacteria and fungi), consortiums of microorganisms, and different types of soils, biobeds, and biomixtures.


Autoimmune hepatitis in patients aged 70 years or older: Disease characteristics, treatment response and outcome.
Autoimmune hepatitis (AIH) affects both sexes and all age groups. However, very few studies have focused specifically on the characteristics and outcome of AIH in patients aged 70 y or older. 25/234 patients with well-established AIH and disease onset at ≥70-y (median: 73-y) were analysed and compared to the rest patients (median: 47 y). Treatment response was assessed in all patients from both groups who were eligible for treatment (n = 202). Disease presentation was mainly insidious in both groups (19/25, 76% vs. 134/209, 64.1%; P = .313). At diagnosis, older patients had lower alaninoaminotrasferase (101[433] vs. 199[441] IU/L, P < .05) but were more frequently cirrhotic (12/25, 48% vs. 57/209, 27.3%; P = .03). Importantly, similar rates of on-treatment response (16/18, 89% vs. 154/184, 84%; P = .565), corticosteroid withdrawal (10/16, 62.5% vs. 113/154, 73.4%; P = .355) and complete withdrawal of immunosuppression (1/16, 6.3% vs. 40/154, 26%; P = .122) were achieved in both groups. Treatment-related adverse events were evenly observed between groups (6/18, 33% vs. 54/184, 29%; P = .724). In treated patients, the age ≥70 y was only associated with the overall mortality (HR 8.3 [95% CI: 2.1-36.4], P = .003), but not with the liver-related mortality (HR 3.4 [95% CI: 0.4-30.0], P = .268). AIH should be seriously considered in patients ≥70 y with unexplained impaired liver function tests as the disease is not infrequent in this group and seems to bear an increased risk for advanced disease stage at diagnosis. However, if immunosuppression is started promptly, it seems as safe and effective as in younger patients.


[Interaction between calcium antagonists and digoxin].
Therapeutic uses of calcium antagonists have expanded to include not only ischemic heart disease but arrhythmias, systemic hypertension, congestive heart failure and various pulmonary and gastrointestinal diseases. Many patients receiving calcium antagonists concomitantly receive digoxin. Although the potential interactions between these agents have frequently been investigated, literature reports are confusing and inconsistent. The pharmacokinetics and mechanisms of interaction are summarized in order to help clinicians to evaluate the potential calcium antagonist digoxin interaction. From the investigations to date, changing the digoxin dosage prior to initiating calcium antagonist therapy is, however, not justifiable. The best approach would be to monitor pharmacodynamic values, SDC, and the patient's clinical status.


Injectable depot corticosteroid therapy in hay fever.
Forty-two patients with stable hay fever were treated with injections of long-acting corticosteroids. They were randomly assigned to either 2 ml of betamethasone dipropionate + betamethasone phosphate (Diprospan) or 2 ml of methylprednisolone acetate (Depomedrol). Eye and nose symptoms were evaluated according to a four-step scale of weekly intervals. Both steroids were highly efficacious in reducing the symptoms with maximal effect one week after injection and slow diminution during subsequent weeks. However, Diprospan showed a significantly better effect than Depomedrol on all symptoms. It is concluded that depot injectable formulations of corticosteroids are a useful therapeutical alternative in hay fever.


Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.
In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514. Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups. There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed. Kiniksa Pharmaceuticals.


A single step reversed-phase high performance liquid chromatography separation of polar and non-polar lipids.
This paper reports a simple chromatographic system to separate lipids classes as well as their molecular species. By the use of phenyl coated silica as stationary phase in combination with a simple mobile phase consisting of methanol and water, all tested lipid classes elute within 30 min. Furthermore, a method to accurately predict retention times of specific lipid components for this type of chromatography is presented. Common detection systems were used, namely evaporative light scattering detection (ELSD), charged aerosol detection (CAD), electrospray mass spectrometry (ESI-MS), and UV detection.


Effects of exercise on transmitral gradient and pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study.
Doppler echocardiography was used to determine changes in transmitral gradient and pulmonary artery pressure after exercise in 12 patients with mitral stenosis and 11 patients with a prosthetic mitral valve. The mean transmitral gradient in the mitral stenosis group was 9 +/- 7 mm Hg at rest and increased to 17 +/- 8 mm Hg after exercise. In patients with a prosthetic mitral valve, exercise resulted in an increase in mean transmitral gradient from 5 +/- 2 to 8 +/- 3 mm Hg. Calculated pulmonary artery systolic pressure increased with exercise from 41 +/- 19 to 70 +/- 32 mm Hg in the mitral stenosis group and from 28 +/- 8 to 39 +/- 15 mm Hg in patients with a prosthetic valve. Exercise Doppler echocardiographic evaluation of changes in transmitral gradient and pulmonary artery systolic pressure was found to be technically simple and an important addition to the noninvasive evaluation of patients with mitral valve disease.


Discriminating between simultaneous audible alarms is easier with auditory icons.
When more than one audible alarm is heard simultaneously, discrimination may be compromised. This experiment compares near-simultaneous clinical alarms in two styles, the first are the tonal 'melodies' from the 2012/2006 version of a global medical device safety standard (IEC 60601-1-8) and the second are the auditory-icon-style recommended in the 2020 version of the same standard. Sixty-six participants were required to identify the meaning and priority of four different clinical alarms for one of the two styles of alarm (between-subjects). Alarms sounded both singly and in pairs (within-subjects). Results showed that the auditory icon alarms outperformed the tonal alarms on all measures except one, both for overall accuracy (recognizing both priority and function) and for partial accuracy (recognizing priority or function but not both). The results add to the growing body of evidence supporting the use of auditory icon alarms in clinical environments.


Development of a nomogram for predicting nasogastric tube-associated pressure injuries in intensive care unit patients.
Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.


Effect of organosilicone and mineral silicon fertilizers on chemical forms of cadmium and lead in soil and their accumulation in rice.
Cadmium (Cd) and lead (Pb) pollution in soil and their accumulation in edible parts possess a worldwide eco-environmental and health risk, especially in developing countries. Recently, organosilicone fertilizer (OSiF) has been reported to reduce uptake of heavy metals, but the effectiveness has not been verified and its associated mechanisms are not fully understood. This work investigated whether and how OSiF and mineral silicon fertilizer (MSiF) affect mitigation of Cd and Pb stress in rice (Oryza sativa). Both soil incubation and pot experiments were conducted to assess the effect of OSiF and MSiF on bioavailability of Cd and Pb in soil and their accumulation in rice. Additionally, a hydroponic experiment was conducted to study whether Si in rice can alleviate Cd stress. We found that both Si fertilizers could increase soil pH, induce the transformation of the acid soluble and reducible fractions of Cd and Pb to the oxidizable and residual fractions in soil, decreasing their bioavailability and the uptake of Cd and Pb in rice. However, Si in OSiF was not phyto-available, but Si in MSiF was available since available Si in soil and Si in plant increased in MSiF treatments but not in OSiF treatments. Meanwhile, rice grain yields significantly increased and the Cd and Pb content of brown rice reduced in MSiF treatments but not in OSiF treatments. In addition, Si was found to be able to alleviate Cd stress by improving the antioxidant capacity of rice. These results suggested that the decreased Cd and Pb accumulation in OSiF-treated rice was due to Cd and Pb immobilization in soil simply with pH increase, but in MSiF-treated rice Cd and Pb immobilization in soil (ex planta effect) and Si-conferred inhibitory effect of root-to-shoot Cd and Pb transport (in planta effect) contribute to the lower accumulation in rice.


Effects of kinesiology taping and core stability exercise on clinical variables in patients with non-specific chronic low back pain: A randomized controlled trial.
Properly-designed exercises and use of different physiotherapeutic modalities have been shown to be useful in the management of patients with non-specific chronic low back pain (NSCLBP). This research examined the effects of Kinesiology taping (KT) and Core-stabilization exercises (CSE) on pain intensity, lumbar range of motion, functional disability, depression, anxiety, sleep disturbance and Kinesiophobia in patients with NSCLBP. Randomized controlled trial. Two tertiary health facilities. Thirty-five patients (28 males and 7 females) with NSCLBP were allocated into three groups (KT + CSE, CSE and KT only). Pain intensity, functional disability, psychological status, sleep disturbance, kinesiophobia and lumbar range of motion (LROM) were assessed. The results revealed reduction in pain intensity, improved functional ability, psychological status (Depression and Anxiety), kinesiophobia, decreased sleep disturbance and increased LROM (P < 0.001) within each of the groups post-intervention. All participants had improved clinical outcomes. However, KT + CSE group had better result in all the clinical outcomes. PACTR201807604459572.


Visual servoing for a US-guided therapeutic HIFU system by coagulated lesion tracking: a phantom study.
Applying ultrasound (US)-guided high-intensity focused ultrasound (HIFU) therapy for kidney tumours is currently very difficult, due to the unclearly observed tumour area and renal motion induced by human respiration. In this research, we propose new methods by which to track the indistinct tumour area and to compensate the respiratory tumour motion for US-guided HIFU treatment. For tracking indistinct tumour areas, we detect the US speckle change created by HIFU irradiation. In other words, HIFU thermal ablation can coagulate tissue in the tumour area and an intraoperatively created coagulated lesion (CL) is used as a spatial landmark for US visual tracking. Specifically, the condensation algorithm was applied to robust and real-time CL speckle pattern tracking in the sequence of US images. Moreover, biplanar US imaging was used to locate the three-dimensional position of the CL, and a three-actuator system drives the end-effector to compensate for the motion. Finally, we tested the proposed method by using a newly devised phantom model that enables both visual tracking and a thermal response by HIFU irradiation. In the experiment, after generation of the CL in the phantom kidney, the end-effector successfully synchronized with the phantom motion, which was modelled by the captured motion data for the human kidney. The accuracy of the motion compensation was evaluated by the error between the end-effector and the respiratory motion, the RMS error of which was approximately 2 mm. This research shows that a HIFU-induced CL provides a very good landmark for target motion tracking. By using the CL tracking method, target motion compensation can be realized in the US-guided robotic HIFU system.


Fluorescence lifetime and polarization-resolved imaging in cell biology.
Fluorescence lifetime imaging (FLIM) and fluorescence polarization imaging are complementary techniques that can be used to extract information about macromolecules from biological samples. Owing to the sensitivity of fluorescence to the physicochemical environment, and nanometer-scale interactions via Förster resonance energy transfer (FRET), FLIM has been implemented in many laboratories for numerous applications in the life sciences and beyond. This review seeks to provide a brief overview of some of the recent advances in the techniques and more pertinently their applications in cell and tissue imaging. The particular merits of polarization-resolved fluorescence measurements are highlighted, including the unique ability to elucidate the occurrence of homo-FRET.


Thyroid cancer. Survival in 148 cases followed for 10 years or more.
One hundred forty-eight patients with differentiated carcinoma of the thyroid treated between May 1954 and April 1973 are presented. There were 89 papillary and 59 follicular carcinomas. They were classified according to Woolner criteria. Treatment consisted of surgery I-131 and thyroid hormone. Recurrences occurred in 8.7% of the patients, and lethality at the end of the observation period was 3.3%. The impact of histologic type, extent of the primary, and age of the patient at the time of treatment on prognosis were studied. The data were submitted to statistical analysis. This study revealed that these factors are determinant on prognosis. Best survival rates were observed in patients 40 years of age or younger at the time of treatment, in patients with intrathyroid papillary carcinomas, and in patients with noninvasive follicular carcinomas.


Effect of a trans fatty acid-enriched diet on mitochondrial, inflammatory, and oxidative stress parameters in the cortex and hippocampus of Wistar rats.
Previously showed that dietary trans fatty acids (TFAs) may cause systemic inflammation and affect the central nervous system (CNS) in Wistar rats by increased levels of cytokines in the cerebrospinal fluid (CSF) and serum (Longhi et al. Eur J Nutr 56(3):1003-1016, 1). Here, we aimed to clarifying the impact of diets with different TFA concentrations on cerebral tissue, focusing on hippocampus and cortex and behavioral performance. Wistar rats were fed either a normolipidic or a hyperlipidic diet for 90 days; diets had the same ingredients except for fat compositions, concentrations, and calories. We used lard in the cis fatty acid (CFA) group and PHSO in the TFA group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO), and (4) high partially hydrogenated soybean oil (HPHSO). Mitochondrial parameters, tumor necrosis factor alpha (TNF-α), 2'7'-dichlorofluorescein (DCFH) levels in brain tissue, and open field task were analyzed. A worse brain tissue response was associated with oxidative stress in cortex and hippocampus as well as impaired inflammatory and mitochondrial parameters at both PHSO concentrations and there were alterations in the behavioral performance. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. Partially hydrogenated soybean oil impaired cortical mitochondrial parameters and altered inflammatory and oxidative stress responses, and the hyperlipidic treatment caused locomotor and exploratory effects, but no differences on weight gain in all treatments. These findings suggest that quality is more important than the quantity of fat consumed in terms of CFA and TFA diets.


A two-stage prediction model for heterogeneous effects of treatments.
Treatment effects vary across different patients, and estimation of this variability is essential for clinical decision-making. We aimed to develop a model estimating the benefit of alternative treatment options for individual patients, extending a risk modeling approach in a network meta-analysis framework. We propose a two-stage prediction model for heterogeneous treatment effects by combining prognosis research and network meta-analysis methods where individual patient data are available. In the first stage, a prognostic model to predict the baseline risk of the outcome. In the second stage, we use the baseline risk score from the first stage as a single prognostic factor and effect modifier in a network meta-regression model. We apply the approach to a network meta-analysis of three randomized clinical trials comparing the relapses in Natalizumab, Glatiramer Acetate, and Dimethyl Fumarate, including 3590 patients diagnosed with relapsing-remitting multiple sclerosis. We find that the baseline risk score modifies the relative and absolute treatment effects. Several patient characteristics, such as age and disability status, impact the baseline risk of relapse, which in turn moderates the benefit expected for each of the treatments. For high-risk patients, the treatment that minimizes the risk of relapse in 2 years is Natalizumab, whereas Dimethyl Fumarate might be a better option for low-risk patients. Our approach can be easily extended to all outcomes of interest and has the potential to inform a personalized treatment approach.


Structure activity relationship in β-carboline derived anti-malarial agents.
Malaria, even though an avoidable and treatable disease, can be fatal if ignored. Artemisinin Combination Therapy (ACT) and RTS, S/AS01 vaccine (Mosquirix™) are the only modest means available with humans to overcome malaria, a lethal affliction wreaking havoc across the globe. Employment of ACT is associated with problems such as 'Artemisinin Resistance' and the 'Hypnozoite conundrum' that hinder the complete eradication of malaria. In this view, the natural products specifically comprising β-carboline scaffold have shown good antiplasmodial responses against different strains of malaria. Taking these observations forward, researchers have performed structure-activity relationship (SAR) studies around three different β-carboline skeletons (tetrahydro β-carbolines, dihydro β-carbolines, β-carbolines) to design new β-carboline derived heterocyclic structures or modified naturally occurring derivatives. In addition, different approaches such as dimerization and linkage to other moieties have also been adopted to enhance the antimalarial activity. The present review describes a comprehensive SAR study encapsulating various natural and synthetic β-carbolines to elaborate upon the utility of these skeletons in designing drugs to subdue this deadly disease.


Serotonin 5-HT1C receptors are expressed at high density on choroid plexus tumors from transgenic mice.
Choroid plexus tumors develop spontaneously in adult transgenic mice carrying integrated copies of SV40 early region genes. In this communication, we report that these tumors exhibit the highest density of serotonin receptors (6600 fmol/mg protein) found in any tissue. 125I-LSD binding to choroid plexus tumors displays a pharmacological profile that matches the properties of 5-HT1C receptors in normal choroid plexus tissue. Autoradiographic localization of 125I-LSD binding in brain sections from transgenic mice shows high levels of labelling in the tumors, in correlation with immunohistochemical staining for SV40 large T antigen expression. Choroid plexus tumors from these transgenic mice provide an excellent model system for the study of serotonin 5-HT1C receptors.


A randomized, controlled, double-blind trial comparing two loading doses of aminophylline.
To compare 8 mg/kg and 6 mg/kg loading doses of aminophylline. Sixty-one preterm infants weighing <1500 g were enrolled once a decision to administer intravenous aminophylline was made. A standard maintenance dose was used. Serum levels of theophylline were drawn 8 hours after the loading dose and before the fifth maintenance dose. After the initial loading dose, the 8 mg/kg group achieved recommended serum theophylline levels (7-12 microg/ml) more frequently than the 6 mg/kg group (39% vs 3%, p=0.002). Subsequent levels were similar between the groups. There were no increases in side effects with the higher loading dose. If a clinical decision to start intravenous aminophylline therapy in preterm infants has been made, the use of an 8 mg/kg loading dose appears to be a better and safe way to quickly achieve serum theophylline levels within the recommended range.


Characterization of a latent cysteine proteinase from ascitic fluid as a high molecular weight form of cathepsin B.
The latent cysteine proteinase present in ascitic fluid of patients with neoplasia and released from ascites cells in culture has been partially purified and the enzyme after pepsin activation was shown to be immunologically related to the lysosomal proteinase, cathepsin B. The latent form was characterized as a single chain of Mr 40 000 as determined by SDS-polyacrylamide gel electrophoresis under reducing conditions followed by Western blotting and immune staining with an antiserum to human cathepsin B. Using the same techniques the enzyme after pepsin activation gave a single band of Mr 33 000. Analysis by isoelectric focusing showed that the latent enzyme before and after pepsin treatment is composed of several acidic isoenzymes. These findings suggest that this latent proteinase represents a precursor form of cathepsin B which is released extracellularly rather than being processed and directed to the lysosome.


The kinin system in hypertensive pathophysiology.
Cardiovascular diseases are the prime cause of death in the world. The kallikrein-kinin system has been implicated in the pathophysiology of the vascular smooth muscle and cardiac dysfunctions. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction and left ventricular hypertrophy, have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular-related diseases. The cardioprotective actions of the angiotensin-converting enzyme inhibitors are primarily dependent on protecting the kinin-forming components, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.


Mercury speciation in mine tailings amended with biochar: Effects on mercury bioavailability, methylation potential and mobility.
Biochar is a low-cost and environmentally friendly amendment with strong ability for adsorption of mercury (Hg) from aqueous solutions, contaminated soils, and sediments. In the present study, six biochars were prepared from the pyrolysis of cocoa pod husk, sugarcane bagasse and banana pseudostem at 400 and 600 °C in order to use them as an organic amendment and to evaluate their capacities to reduce the bioavailability, methylation potential, and mobility of Hg present in mine tailings without environmental treatment. To quantify the effects of each variety of biochar, incubation experiments of soil were established by mixing mine tailings with 5% by weight of biochar for 90 days. Once the incubation time concluded, sequential extraction procedures were carried out to determine the fractionation of the Hg species. Speciation analysis results indicated that the remedial effects of biochar depended on the source of organic matter and pyrolysis temperature. The bioavailable and organic Hg fractions decreased respectively by up to 75 and 79%, indicating a methylation potential reduction. Immobile Hg fraction increased to 76% with respect to the control. Adsorption and stabilization to HgS from the soluble forms of Hg reduce the percentage of bioavailable Hg. The organic Hg fraction reduction was correlated with the decrease of the bioavailable Hg fraction and with direct adsorption processes in the biochar structure. Highly porous biochars developed at high temperature, with large contents of superficial polar functional groups (H/C), and high pH, electrical conductivity, ash percentage and cation exchange capacity values favor the stabilization and adsorption of Hg in mine tailings. In summary, the application of biochar could be an effective method for the remediation of Hg-contaminated mine tailings, transforming the Hg species into less toxic, soluble, reactive, and bioavailable forms.


Delayed degeneration of the optic tract and neurons in the superior colliculus after forebrain ischemia.
Neuronal damage induced by 15-min forebrain ischemia was investigated in adult rats 1-5 days (short-term group) and 1-5 months (long-term group) after the initial ischemic attack. In addition to the vulnerable areas reported previously, we observed that the optic tract was also very susceptible. Degeneration of the optic tract and subsequent transsynaptic cell death in the superior colliculus developed slowly and was observed only in the long-term group. The delayed, progressive neuronal damage in this sensory system may serve as a suitable model to investigate the mechanisms of long-term changes in the injured brain.


Pancreatic carcinosarcoma in a cat.
A 10-year-old female American shorthair cat was presented for evaluation of weight loss. An intra-abdominal mass was found on ultrasonography and laparotomy was performed. The mass was located in the left uterine horn and further masses were found in the pancreas, greater omentum and diaphragm. Microscopical examination revealed that the pancreatic mass had epithelial and mesenchymal components, which on immunohistochemistry expressed cytokeratin and vimentin, respectively. In addition, some spindle cells expressed vimentin and E-cadherin, which might suggest epithelial to mesenchymal transition. In contrast, the uterine, omental and diaphragmatic masses had only mesenchymal composition. The pancreatic lesion is proposed to be a primary carcinosarcoma with metastasis of only the mesenchymal component to distant sites. This the first report of pancreatic carcinosarcoma in a cat.


Method of choice for urinary diversion in surgical treatment of bladder carcinoma.
Evidence is presented concerning 94 patients with malignancy of bladder in whom diversion of urine was performed after cystectomy for exclusion of the bladder. There were 80 men and 14 women, ages ranging from 30 to 81 years. In 35 of these 94 cases ureterosigmoidoanastomosis, in 38 cases ureterocutaneostomy, in 15 Portilla's operation, in 2 Bricker's method and in 4 nephro-pyelostomy were performed. For the prevention of bleeding cystectomy was preceded by bilateral ligation of the internal iliac artery in 14 cases. Continuous postoperative follow-up of the patients (from a few months to 14 years) and analysis of the early and late results allow to regard the combined technique of Coffey II-Nesbit-Goodwin as the method of choice having the slightest risk of peritonitis, intestinoureteral reflux and other complications inherent in other procedures. Of the existing methods of ureterocutaneostomy the authors have chosen Le Dentu's method with some modifications. They consider ureterostomy to be the simplest and quickest method owing to the higher location of ureterostoma. Portilla's method is no longer used because of its unfavourable long-term results. Of 94 patients with cancer of the bladder, who had been subjected to different methods of urinary diversion in the years 1954-1974, 16 have survived up till now. There are 10 survivors after ureterosigmoidoanastomosis, 5 after ureterocutaneostomy and 1 after Bricker's operation.


Potentiating activity of Norfloxacin by synthetic chalcones against NorA overproducing Staphylococcus aureus.
Staphylococcus aureus is responsible for a series of infections occurring in both human and animal hosts. S. aureus SA1199B is a strain resistant to hydrophilic fluoroquinolone due to overproduction of the NorA efflux pump that has been used as a microbial model to evaluate if a compound act as efflux pump inhibitor. Finding substances from natural or synthetic origin able to reverse resistance mechanisms like those of efflux pumps is a challenge. The use of Chalcones and their derivatives is of great chemical and pharmacological interest, as they present a simple structure and several pharmacological activities. This study aims to evaluate the antibacterial potential of 4 synthetic chalcones, as well as to evaluate their action in the modulation of Norfloxacin resistance against the strain SA1199B strain. Microdilution assays were performed for evaluation of the antimicrobial activity. For evaluation of the modulating effect on resistance to Norfloxacin or EtBr, MIC values of these compounds were determined in the absence or presence of subinhibitory concentrations used of each chalcone. MICs values of both Norfloxacin and EtBr were significantly reduced in the presence of all tested chalcones, indicating that inhibition of the active efflux of these compounds by NorA could be a possible mechanism of action of the chalcones. These results show that the compounds studied have a high potential as a NorA inhibitor, with the best modulating effect verified for the compound 3. Pharmacokinetic and toxicity predictive studies indicated a high intestinal absorption and good volume of distribution for chalcones by oral administration, activity in the central nervous system and ease to be transported between biological membranes. Emphasizing that analogs 1 and 4 were easily metabolized by CYP3A4 enzyme, constituting a pharmacological active ingredient without toxic risk due to metabolic activation. These chalcones combined with Norfloxacin could be a promise technological strategy to be applied in the treatment of infections caused by S. aureus overproducing NorA.


The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring.
The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria. We extracted data on immune outcomes and methodological characteristics, and assessed the risk of bias. The descriptive summary showed that most studies reported an absence of effect, with an equal number of studies reporting an increase or decrease in the immune mediator being studied. Meta-analysis showed increased IL-6 concentrations in the offspring of poly(I:C) exposed mothers. This effect appeared larger prenatally than post-weaning. Furthermore, poly(I:C) administration during mid-gestation was associated with higher IL-6 concentrations in the offspring. Maternal poly(I:C) induced changes in IL-1β, Il-10 and TNF-α concentrations were small and could not be associated with age of offspring, gestational period or sampling location. Finally, quality of reporting of potential measures to minimize bias was low, which stresses the importance of adherence to publication guidelines. Since neurodevelopmental disorders in humans tend to be associated with lifelong changes in cytokine concentrations, the absence of these effects as identified in this systematic review may suggest that combining the model with other etiological factors in future studies may provide further insight in the mechanisms through which maternal immune activation affects neurodevelopment.


'Nano-immuno test' for the detection of live Mycobacterium avium subspecies paratuberculosis bacilli in the milk samples using magnetic nano-particles and chromogen.
Early rapid detection of Mycobacterium avium subspecies paratuberculosis (MAP) bacilli in milk samples is the major challenge since traditional culture method is time consuming and laboratory dependent. We report a simple, sensitive and specific nano-technology based 'Nano-immuno test' capable of detecting viable MAP bacilli in the milk samples within 10 h. Viable MAP bacilli were captured by MAP specific antibody-conjugated magnetic nano-particles using resazurin dye as chromogen. Test was optimized using true culture positive (10-bovine and 12-goats) and true culture negative (16-bovine and 25-goats) raw milk samples. Domestic livestock species in India are endemically infected with MAP. After successful optimization, sensitivity and specificity of the 'nano-immuno test' in goats with respect to milk culture was 91.7% and 96.0%, respectively. Whereas, it was 90.0% (sensitivity) and 92.6% (specificity) with respect to IS900 PCR. In bovine milk samples, sensitivity and specificity of 'nano-immuno test' with respect to milk culture was 90.0% and 93.7%, respectively. However, with respect to IS900 PCR, the sensitivity and specificity was 88.9% and 94.1%, respectively. Test was validated with field raw milk samples (goats-258 and bovine-138) collected from domestic livestock species to detect live/viable MAP bacilli. Of 138 bovine raw milk samples screened by six diagnostic tests, 81 (58.7%) milk samples were positive for MAP infection in one or more than one diagnostic tests. Of 81 (58.7%) positive bovine raw milk samples, only 24 (17.4%) samples were detected positive for the presence of viable MAP bacilli. Of 258 goats raw milk samples screened by six diagnostic tests, 141 (54.6%) were positive for MAP infection in one or more than one test. Of 141 (54.6%) positive raw milk samples from goats, only 48 (34.0%) were detected positive for live MAP bacilli. Simplicity and efficiency of this novel 'nano-immuno test' makes it suitable for wide-scale screening of milk samples in the field. Standardization, validation and re-usability of functionalized nano-particles and the test was successfully achieved in field samples. Test was highly specific, simple to perform and easy to read by naked eyes and does not require laboratory support in the performance of test. Test has potential to be used as screening test to estimate bio-load of MAP in milk samples at National level.


Improving the selectivity of cancer treatments by interfering with cell response pathways.
The cellular response to the stress induced by treatment with anticancer agents is a key determinant of drug activity. A pivotal role in this response is played by checkpoint proteins that control the normal passage of cells through the cell cycle. There is evidence that cancer cells often have defects in one checkpoint control that makes them more vulnerable to inhibition of a second checkpoint, thereby enhancing the overall response to treatment. The G1 and G2 checkpoints are particularly crucial for the decision of a cell to arrest in the cell cycle after damage. The checkpoints are used to try to allow the repair of any damage, or to activate the apoptotic (programmed cell death) machinery. Inhibition of both G1 and G2 checkpoints in cancer cells is therefore likely to result in an induction of the death response in cancer cells. Similarly, an increasing knowledge of the molecular mechanisms that form the basis of apoptotic pathways has helped to define why cancer cells have a reduced propensity to undergo apoptosis following the activation of apoptotic inhibitory pathways or the inhibition of pro-apoptotic pathways. Therefore, the possibility to modulate these pathways is likely to result not only in the increased activity of anticancer agents, but also in an increase in their specificity.


New secondary metabolites with immunosuppressive and BChE inhibitory activities from an endophytic fungus Daldinia sp. TJ403-LS1.
Five new acetylenic phenol derivatives (1-4 and 7), one new benzofuran derivative (8), one new naphthol derivative (9), and two known analogues (5 and 6), were isolated and identified from an endophytic fungus Daldinia sp. TJ403-LS1 that was isolated from the medicinally valuable plant Anoectochilus roxburghii. Their structures were elucidated by means of extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. In addition, compound 1 exhibited remarkable immunosuppressive activity against LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with the same IC50 values of 0.06 μM and BChE inhibitory activity with an IC50 value of 6.93 ± 0.71 μM, and compounds 6, 8 and 9 showed excellent BChE inhibitory activity with IC50 values of 16.00 ± 0.30, 23.33 ± 0.55, and 15.53 ± 0.39 μM, respectively (positive drug neostigmine, IC50 = 49.60 ± 6.10 μM), highlighting the promising potentials to be designed and developed as immunosuppressive and BChE inhibitory agents.


The effect of vitamin B12 on synaptic plasticity of hippocampus in Alzheimer's disease model rats.
Hippocampus cells, responsible for learning and memory, are disturbed in Alzheimer's disease (AD), resulting in production of several inflammatory markers, such as neurexin 1 -neuroligin, cyclooxygenase-2 (COX-2), and caspase-3 proteins, used in measurement of AD's severity and development. Vitamin B12, which plays a role in brain functioning, has anti-inflammatory properties and its impairment is associated with apoptosis in Alzheimer's disease. This study aimed to investigate the effect of vitamin B12 on restoration of Synaptic Plasticity on scopolamine-induced AD in rats. To simulate AD, Rats, except the control group were i.p. injected with 3 mg/kg scopolamine. Before scopolamine the pretreatment group vitamin B12 (0.5, 2, and 4 mg/kg) was injected every day for the next 14 days. After 24 h, sectioning the rats' brains, the concentration of postsynaptic density protein 95 (PSD-95), neurexin 1-neurolgin, COX-2, and caspase-3 proteins in hippocampus were measured using immunoblotting. B12 significantly enhanced molecular balance. PSD-95 and neurexin 1 and neuroligin concentrations were significantly reduced, whereas COX-2 and activated caspase-3 were enhanced in the hippocampus of scopolamine-injected subjects. Their alterations were decreased after B12 administration. Vitamin B12 protected scopolamine-injected rats and inhibited hippocampal inflammation and apoptosis and preserved pre- and post-synaptic proteins and possibly synaptic integrity in hippocampus route.


ARCHAEA-ExPRESs targeting of alpha-tubulin 4 mRNA: a model for high-specificity trans-splicing.
Effectiveness of trans-splicing-mediated mRNA reprogramming depends on specificity and efficiency. We have previously developed a new strategy (ARCHAEA-ExPRESs) that uses a tRNA endonuclease derived from Archaea and its natural substrate, the bulge-helix-bulge (BHB) structure. ARCHAEA-ExPRESs provides increased specificity in functional targeting. In fact, this system is based on a double check, the base pairing and the formation of a BHB structure between the target mRNA and the targeting RNA. In this study, we demonstrate the high specificity of ARCHAEA-ExPRESs by tagging the endogenous alpha-tubulin 4 via trans-splicing. Alpha-tubulin 4 belongs to a gene family sharing high degree of nucleotide sequence homology. The formation of a perfect BHB structure between targeting RNAs and the isotype alpha-tubulin 4 enables selective trans-splicing. Most important, ARCHAEA-ExPRESs functionality is conserved in vivo following transient expression of archaeal tRNA endonuclease in mouse liver. Production of the recombinant protein is strictly dependent on the expression of the archaeal endonuclease, and the efficiency of the system depends on the relative amount of the target and targeting mRNAs. These data prove the effectiveness of ARCHAEA-ExPRESs in an endogenous highly demanding context and disclose the possibility to utilize this system in a variety of technological or therapeutic applications.


Cell fusion for reprogramming pluripotency: toward elimination of the pluripotent genome.
Embryonic stem cell (ESC) technology should enable the generation of specific cell types for the study and treatment of human diseases. Therapeutic cloning provides a way to generate ESCs genetically matched to diseased individuals through nuclear reprogramming of the somatic genome. However, practical and ethical limitations associated with therapeutic cloning are calling for the development of oocyte- and-embryo-free alternatives for obtaining of autologous pluripotent cells for transplantation therapy. An alternative approach to reprogram the somatic genome involves fusion between somatic and pluripotent cells. Potential fusion partners with reprogramming activities include embryonal carcinoma cells, embryonic germ cells, and ESCs. Experimental evidence is now available, which demonstrates that mouse and human somatic cells can be reprogrammed by fusion to form pluripotent hybrid cells. Recent progress infusion-based reprogramming is reviewed with reference to the developmental potency of hybrid cells as well as genetic and epigenetic correlates of reprogramming. However, hybrid cells lack therapeutic potential because of their abnormal ploidy and the presence of nonautologous genes from the pluripotent parent. We discuss the potential of fusion-based reprogramming for the generation of diploid, autologous pluripotent cells using two alternative routes: the enucleation of ESCs and the fusion of such cytoplasts to somatic cell karyoplasts or intact somatic cells, and the selective elimination of the pluripotent genome following fusion to the somatic partner. Finally, these approaches are discussed in the light of recent progress showing that overexpression of embryonic transcription factors can restore a state of pluripotency to somatic cells.


Vertebrate segmentation: snail counts the time until morphogenesis.
During segmentation of vertebrate embryos, unsegmented mesenchymal mesoderm is divided into epithelial segments called somites. This process is governed by oscillating gene expression of the somite clock. A recent paper identifies the transcription factor Snail as a link between the somite clock and the control of somite morphogenesis.


Effects of an 8-week meditation program on the implicit and explicit attitudes toward religious/spiritual self-representations.
Explicit self-representations often conflict with implicit and intuitive self-representations, with such discrepancies being seen as a source of psychological tension. Most of previous research on the psychological effects of mindfulness-meditation has assessed people's self-attitudes at an explicit level, leaving unknown whether mindfulness-meditation promotes changes on implicit self-representations. Here, we assessed the changes in implicit and explicit self-related religious/spiritual (RS) representations in healthy participants following an 8-week mindfulness-oriented meditation (MOM) program. Before and after meditation, participants were administered implicit (implicit association test) and explicit (self-reported questionnaires) RS measures. Relative to control condition, MOM led to increases of implicit RS in individuals whit low pre-existing implicit RS and to more widespread increases in explicit RS. On the assumption that MOM practice may enhance the clarity of one's transcendental thoughts and feelings, we argued that MOM allows people to transform their intuitive feelings of implicit RS as well as their explicit RS attitudes.


Cellular Digital Fibroma: A Comprehensive Review of a CD34-Positive Acral Lesion of the Distal Fingers and Toes.
Cellular digital fibroma is a benign fibrous lesion that typically occurred on either a finger or a toe. Cellular digital fibroma was introduced as a distinctive cluster of differentiation 34 (CD34)-positive lesion in July 2005. Cellular digital fibroma has been described in 20 patients: 12 men and 8 women. The patients ranged in age from 27 to 83 years old (median, 52 years old) at diagnosis. The tumor had been present from 2 months to 2 years (median, 11 months) prior to seeking medical attention. The cellular digital fibroma was usually slowly growing and asymptomatic; there has been no prior history of trauma at the tumor site. The lesion typically presented as either an erythematous or a flesh-colored, solitary papule of 5 mm or smaller. It frequently occurred on either the dorsal, lateral or ventral side of a digit. Yet, some of the lesions were located on the nail fold of the digit. Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis; diffuse and strongly positive CD34 staining is present throughout the entire tumor. There is no erosion by the tumor of the bony phalanx. Other acral tumors, such as superficial acral fibromyxoma (which also has diffuse strongly positive CD34 staining) and acquired digital fibrokeratoma (which is either CD34-negative or only focal CD34 positive), are in the clinical and pathologic differential diagnosis of cellular digital fibroma. Conservative complete excision is the treatment of cellular digital fibroma; however, even for tumors that have only been partially removed during biopsy, recurrence has not been observed. In conclusion, cellular digital fibroma is a unique CD34-positive acral lesion of the distal fingers and toes whose diagnosis requires correlation of the clinical morphology and the pathologic features of the tumor.


The ESTRO Breur lecture. Cellular sensitivity to low dose-rate irradiation focuses the problem of tumour radioresistance.
This paper emphasises the radiobiology of human tumour cells irradiated at the relatively low dose rate of 1 Gy/h (i.e.1-2 cGy/min), described here as the "Regaud dose rate". Continuous irradiation at this dose rate is approximately isoeffective with fractionated radiotherapy using 2 Gy/fractions. At the Regaud dose rate, cell survival curves are approximately exponential and they appear to extrapolate the initial slope of the high dose rate survival curve. Little recovery occurs after such treatments since it has largely taken place during irradiation. At the Regaud dose rate human tumour cell lines show a wide range of radiosensitivities, differing by a factor of around 7. This may well be the most clinically-relevant way of describing the radiosensitivity of tumour cells. Current models of radiation cell killing envisage a component of damage that increases linearly with dose. It is this component that dominates the slope of the Regaud survival curve. It may be produced by DNA damage due to clusters of ionisation events, or perhaps by damage to hypersensitive parts of the genome. The steepness of this component of damage may be modified by exogenous inhibitors of DNA damage repair.


Optimal mutation sites for PRE data collection and membrane protein structure prediction.
Nuclear magnetic resonance paramagnetic relaxation enhancement (PRE) measures long-range distances to isotopically labeled residues, providing useful constraints for protein structure prediction. The method usually requires labor-intensive conjugation of nitroxide labels to multiple locations on the protein, one at a time. Here a computational procedure, based on protein sequence and simple secondary structure models, is presented to facilitate optimal placement of a minimum number of labels needed to determine the correct topology of a helical transmembrane protein. Tests on DsbB (four helices) using just one label lead to correct topology predictions in four of five cases, with the predicted structures <6 Å to the native structure. Benchmark results using simulated PRE data show that we can generally predict the correct topology for five and six to seven helices using two and three labels, respectively, with an average success rate of 76% and structures of similar precision. The results show promise in facilitating experimentally constrained structure prediction of membrane proteins.


Medical approach to pituitary tumors.
Transsphenoidal surgery and medical treatment are the cornerstones of the management of pituitary adenomas. However, the optimal therapy should be chosen based on the type of tumor, the patient, and the tumor characteristics. For nonfunctional adenomas surgery is still the first-line treatment. However, for prolactinomas surgery has been replaced by medical treatment. In the other functional pituitary adenomas a more balanced approach is needed to decide between surgery and medical therapy as first-line treatment. In the majority of cases a combination of treatment modalities is needed. In acromegaly and TSH-secreting adenomas medical treatment has a more prominent role than in Cushing's disease. In this chapter the efficacy and side-effects of the different medical therapies is discussed according to adenoma type.


Pyroptosis Markers in Human Primary Specimens: Quantification of Intracellular ASC Specks by Imaging Flow Cytometry and Extracellular Oxidized Mitochondrial by ELISA.
Pyroptosis is an immunological response to infection and cellular stresses initiated by inflammasome oligomerization resulting in the release of pro-inflammatory factors including cytokines and other immune stimuli into the extracellular matrix. In order to understand the role of inflammasome activation and subsequent pyroptosis in human infection and disease pathogenesis and to explore markers of these signaling events as potential disease or response biomarkers, we must utilize quantitative, reliable, and reproducible assays to readily investigate these pathways in primary specimens. Here, we describe two methods using imaging flow cytometry for evaluation of inflammasome ASC specks in homogeneous peripheral blood monocytes and in bulk, heterogeneous peripheral blood mononuclear cells. Both methods can be applied to assess speck formation as a biomarker for inflammasome activation in primary specimens. Additionally, we describe the methods for quantification of extracellular oxidized mitochondrial DNA from primary plasma samples, serving as a proxy for pyroptosis. Collectively, these assays may be utilized to determine pyroptotic influences on viral infection and disease development or as diagnostic aids and response biomarkers.


Polymorphisms in BMP2/BMP4, with estimates of mean lung dose, predict radiation pneumonitis among patients receiving definitive radiotherapy for non-small cell lung cancer.
Single nucleotide polymorphisms (SNPs) in TGFβ1 can predict the risk of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) after definitive radiotherapy. Here we investigated whether SNPs in TGFβ superfamily members BMP2 and BMP4 are associated with RP in such patients. In total, we retrospectively analyzed 663 patients given ≥ 60 Gy for NSCLC. We randomly assigned 323 patients to the training cohort and 340 patients to the validation cohort. Potentially functional and tagging SNPs of BMP2 (rs170986, rs1979855, rs1980499, rs235768, rs3178250) and BMP4 (rs17563, rs4898820, rs762642) were genotyped. The median of mean lung dose (MLD) was 17.9 Gy (range, 0.15-32.74 Gy). Higher MLD was strongly associated with increased risk of grade ≥ 2 RP (hazard ratio [HR]=2.191, 95% confidence interval [CI] = 1.680-2.856, P < 0.001) and grade ≥ 3 RP (HR = 4.253, 95% CI = 2.493-7.257, P < 0.001). In multivariate analyses, BMP2 rs235768 AT/TT was associated with higher risk of grade ≥ 2 RP (HR = 1.866, 95% CI = 1.221-2.820, P = 0.004 vs. AA) both in training cohort and validation cohort. Similar results were observed for BMP2 rs1980499. BMP2 rs3178250 CT/TT was associated with lower risk of grade ≥ 3 RP (HR = 0.406, 95% CI = 0.175-0.942, P = 0.036 vs. CC) in the pooled analysis. Adding the rs235768 and rs1980499 SNPs to a model comprising age, performance status, and MLD raised the Harrell's C for predicting grade ≥ 2 RP from 0.6117 to 0.6235 (P = 0.0105). SNPs in BMP2 can predict grade ≥ 2 or 3 RP after radiotherapy for NSCLC and improve the predictive power of MLD model. Validation is underway through an ongoing prospective trial.


Molecular Analyses of Chorionic-Type Intermediate Trophoblastic Lesions: Atypical Placental Site Nodules are Closer to Placental Site Nodules Than Epithelioid Trophoblastic Tumors.
Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSNs, the World Health Organization classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which diagnostic criteria remain unclear, leading to a risk of overdiagnosis and difficulties in patient management. We retrospectively studied 8 PSNs, 7 APSNs, and 8 ETTs to better characterize this new entity and performed immunohistochemical analysis (p63, human placental lactogen, Cyclin E, and Ki67), transcriptional analysis using the NanoString method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression among the 3 groups (P = .476), whereas the Ki67 index was significantly (P < .001) higher in ETT samples than in APSN and PSN samples. None of the APSN samples harbored the LPCAT1::TERT fusion transcripts, in contrast to 1 of 6 ETT samples, as previously described in 2 of 3 ETT samples. The transcriptomic analysis allowed robust clustering of ETTs distinct from the APSN/PSN group but failed to differentiate APSNs from PSNs. Indeed, only 7 genes were differentially expressed between PSN and APSN samples; CCL19 upregulation and EPCAM downregulation were the most distinguishing features of APSNs. In contrast, 80 genes differentiated ETTs from APSNs, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETTs and APSNs. These results suggested that APSN might not represent a distinct entity but rather a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of cases that need further clinical investigations.


Cross-Cultural Validation of Quebec User Satisfaction with Assistive Technology 2.0 for Spanish Population (QUEST-2.0 ES).
Assistive technologies (ATs) are resources to promote the independence and participation of people with a disability. The use of standardized tools, based on outcome measures, is essential for guaranteeing high-quality rates. The Quebec User Evaluation of Satisfaction with AT-2.0 (QUEST) is a scale to assess the satisfaction of people using any AT. To translate and culturally validate the QUEST-2.0 for the Spanish population (QUEST 2.0-ES). A validation cross-design and descriptive study. The test-retest reliability, validity, and internal consistency of QUEST 2.0-ES were studied. It was divided into two phases: Sample 1 was formed by 26 persons; in sample 2, 30 persons participated. The conditions included neurological conditions, amputations, rare diseases, and deafness. Thirty-five men and 21 women participated in total. The majority of AT used were those for mobility. QUEST 2.0-ES analysis showed internal consistency values between the test (α = 0.87) and retest versions (α = 0.89). The internal consistency was high for AT (test, α = 0.83; retest, α = 0.87) and Service (test, α = 0.80; retest, α = 0.80). The temporal reliability (1-2 weeks) for test-retest was 0.88. QUEST 2.0-ES showed good psychometric properties in terms of validity and test-retest reliability, and it is a good tool to assess the user's satisfaction with ATs and services.


Myocardial metabolism and haemodynamic responses during high-dose fentanyl anaesthesia for coronary patients.
Fentanyl (mean dose 109 micrograms X kg-1) and oxygen were given to ten patients having coronary vein grafts. Serial studies were done before, during and after operation, of central and mean arterial pressures (MAP), cardiac index (CI) and coronary sinus flow (CBF) by thermodilution, myocardial oxygen consumption (MVO2) and lactate extraction (MLE). On induction CI and stroke work index decreased, but heart rate and MAP were unchanged as systemic resistance increased. Mean MAP and heart rate remained at the awake levels. Mean CBF remained unchanged along with stable MAP and coronary resistance. Oxygen content of CS blood increased on induction and remained elevated until the incision; it was above the awake level early postoperatively. MVO2 was low normal when the patients were awake and remained so. Normal MLE continued with a few exceptions. High-dose fentanyl did not uniformly abolish autonomic reflexes. Heavy premedication, complete beta adrenergic blockade and a high initial doses of fentanyl plus its continued infusion, aided in retaining a hypodynamic circulation and myocardial oxygenation.


The nature of the product of the cys B gene of Escherichia coli.
Amber and temperature-sensitive mutations have been isolated in the cys B gene of Escherichia coli. Their existence suggests that the gene codes for a protein.


The establishment of the gut microbiota in 1-year-aged infants: from birth to family food.
With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named "A.MA.MI." (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Forty-five fecal samples were collected at 12 months of infants' age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith's PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life.


Occupational exposure to polycyclic aromatic hydrocarbons in Korean adults: evaluation of urinary 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene using Second Korean National Environmental Health Survey data.
Polycyclic aromatic hydrocarbons (PAHs) are occupational and environmental pollutants generated by the incomplete combustion of organic matter. Exposure to PAHs can occur in various occupations. In this study, we compared PAH exposure levels among occupations based on 4 urinary PAH metabolites in a Korean adult population. The evaluation of occupational exposure to PAHs was conducted using Second Korean National Environmental Health Survey data. The occupational groups were classified based on skill types. Four urinary PAH metabolites were used to evaluate PAH exposure: 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenanthrene (1-OHPHE), and 2-hydroxyfluorene (2-OHFLU). The fraction exceeding the third quartile of urinary concentration for each PAH metabolite was assessed for each occupational group. Adjusted odds ratios (ORs) for exceeding the third quartile of urinary PAH metabolite concentration were calculated for each occupational group compared to the "business, administrative, clerical, financial, and insurance" group using multiple logistic regression analyses. The "guard and security" (OR: 2.949; 95% confidence interval [CI]: 1.300-6.691), "driving and transportation" (OR: 2.487; 95% CI: 1.418-4.364), "construction and mining" (OR: 2.683; 95% CI: 1.547-4.655), and "agriculture, forestry, and fisheries" (OR: 1.973; 95% CI: 1.220-3.191) groups had significantly higher ORs for 1-OHP compared to the reference group. No group showed significantly higher ORs than the reference group for 2-NAP. The groups with significantly higher ORs for 1-OHPHE than the reference group were "cooking and food service" (OR: 2.073; 95% CI: 1.208-3.556), "driving and transportation" (OR: 1.724; 95% CI: 1.059-2.808), and "printing, wood, and craft manufacturing" (OR: 2.255; 95% CI: 1.022-4.974). The OR for 2-OHFLU was significantly higher in the "printing, wood, and craft manufacturing" group (OR: 3.109; 95% CI: 1.335-7.241) than in the reference group. The types and levels of PAH exposure differed among occupational groups in a Korean adult population.


External Evaluation of Population Pharmacokinetic Models for Precision Dosing: Current State and Knowledge Gaps.
Predicting drug exposures using population pharmacokinetic models through Bayesian forecasting software can improve individual pharmacokinetic/pharmacodynamic target attainment. However, selecting the most adapted model to be used is challenging due to the lack of guidance on how to design and interpret external evaluation studies. The confusion around the choice of statistical metrics and acceptability criteria emphasises the need for further research to fill this methodological gap as there is an urgent need for the development of standards and guidelines for external evaluation studies. Herein we discuss the scientific challenges faced by pharmacometric researchers and opportunities for future research with a focus on antibiotics.


Adversarial Argument, Belief Change, and Vulnerability.
When people argue, they are vulnerable to unwanted and costly changes in their beliefs. This vulnerability motivates the position that belief involuntarism makes argument inherently adversarial (Casey, Informal Log 40:77-108, 2020), as well as the development of alternatives to adversarial argumentation such as "invitational rhetoric" (Foss and Griffin, Commun Monogr 62:2-18, 1995). The emphasis on involuntary belief change in such accounts, in our perspective, neglects three dimensions of arguing: the diversity of arguer intentions, audience agency, and the benefits of belief change. The complex impact of arguments on both audiences and arguers involves vulnerabilities related to various forces of argument, not just the intellectual force of premise-conclusion complexes. Shifting emphasis from adversariality to vulnerability, we propose a more holistic understanding of argument, in which vulnerability reveals various sources of strength and opportunity in addition to risk.


Cancer Biology of the Endoplasmic Reticulum Lectin Chaperones Calreticulin, Calnexin and PDIA3/ERp57.
The lectin chaperones calreticulin (CALR) and calnexin (CANX), together with their co-chaperone PDIA3, are increasingly implicated in studies of human cancers in roles that extend beyond their primary function as quality control facilitators of protein folding within the endoplasmic reticulum (ER). Led by the discovery that cell surface CALR functions as an immunogen that promotes anti-tumour immunity, studies have now expanded to include their potential uses as prognostic markers for cancers, and in regulation of oncogenic signaling that regulate such diverse processes including integrin-dependent cell adhesion and migration, proliferation, cell death and chemotherapeutic resistance. The diversity stems from the increasing recognition that these proteins have an equally diverse spectrum of subcellular and extracellular localization, and which are aberrantly expressed in tumour cells. This review describes key foundational discoveries and highlight recent findings that further our understanding of the plethora of activities mediated by CALR, CANX and PDIA3.


Are we getting the best from breastfeeding?
Different breastfeeding methods (traditional ⁄ scheduled, demand or baby-led) influence lactation physiology by either supporting or interfering with the let-down reflex, by an autocrine effect in the breast, and indirectly via infant appetite. Postnatal breast morphological changes and neonatal osmoregulation are also susceptible to breastfeeding method. Feed length is important: short feeds from both breasts (employed in traditional methods) optimize breast morphological changes and neonatal osmoregulation, condition the let-down reflex, limit autocrine inhibition, stimulate the infant's appetite and are associated with a plentiful supply of milk. However, the limited evidence available on prolonged feeds and those from only one breast (both often seen with the baby-led method), suggests interference with lactation because of a compromised let-down reflex and autocrine inhibition, resulting in a reduced milk supply. Regular short feeds from both breasts encourage a plentiful milk supply and successful breastfeeding: these are best reflected by a modified traditional breastfeeding method.


The Psyche Magnetometry Investigation.
The objective of the Psyche Magnetometry Investigation is to test the hypothesis that asteroid (16) Psyche formed from the core of a differentiated planetesimal. To address this, the Psyche Magnetometer will measure the magnetic field around the asteroid to search for evidence of remanent magnetization. Paleomagnetic measurements of meteorites and dynamo theory indicate that a diversity of planetesimals once generated dynamo magnetic fields in their metallic cores. Likewise, the detection of a strong magnetic moment ( > 2 × 10 14 Am 2 ) at Psyche would likely indicate that the body once generated a core dynamo, implying that it formed by igneous differentiation. The Psyche Magnetometer consists of two three-axis fluxgate Sensor Units (SUs) mounted 0.7 m apart along a 2.15-m long boom and connected to two Electronics Units (EUs) located within the spacecraft bus. The Magnetometer samples at up to 50 Hz, has a range of ± 80 , 000 nT , and an instrument noise of 39 pT axis - 1 3 σ integrated over 0.1 to 1 Hz. The two pairs of SUs and EUs provide redundancy and enable gradiometry measurements to suppress noise from flight system magnetic fields. The Magnetometer will be powered on soon after launch and acquire data for the full duration of the mission. The ground data system processes the Magnetometer measurements to obtain an estimate of Psyche's dipole moment.


Energy partitioning in laser-induced millimeter-sized spherical cavitation up to the fourth oscillation.
To investigate the energy partitioning up to the fourth oscillation of a millimeter-scale spherical cavitation bubble induced by laser, we used nanosecond laser pulses to generate highly spherical cavitation bubbles and shadowgraphs to measure the radius-time curve. Using the extended Gilmore model and considering the continuous condensation of the vapor in the bubble, the time evolution of the bubble radius, bubble wall velocity, and pressure in the bubble is calculated till the 4th oscillation. Using Kirkwood-Bethe hypothesis, the evolution of velocity and pressure of shock wave at the optical breakdown, the first and second collapses are calculated. The shock wave energy at the breakdown and bubble collapse is directly calculated by numerical method. We found the simulated radius-time curve fits well with experimental data for the first four oscillations. The energy partition at the breakdown is the same as that in previous studies, the ratio of shock wave energy to bubble energy is about 2:1. In the first collapse and the second collapse, the ratio of shock wave energy to bubble energy is 14.54:1 and 2.81:1 respectively. In the third and fourth collapses, the ratio is less, namely than 1.5:1 and 0.42:1 respectively. The formation mechanism of the shock wave at the collapse is analyzed. The breakdown shock wave is mainly driven by the expansion of the supercritical liquid resulting from the thermalization of the energy of the free electrons in the plasma, and the collapse shock wave is mainly driven by the compressed liquid around the bubble.


[Effect of oxidizing and reducing agents on the rate of water proton relaxation in the chloroplasts of beans and particles of photosystem 2].
The change of longitudinal proton relaxation rate, 1/T1, in the native and shocked chloroplasts, PS2 chloroplasts' particles and exogenous complexes Mn2+--PPCI (pigment--protein complex of PSI), Mn2+--PPCII in the presence of the PS2 donors and acceptors and at different pH change were studied. It has been shown that 1/T1 increases in chloroplasts and PS2 particles in the presence of the PS2 donors and decreases in the presence of the acceptors in contrast to untreated preparations. The 1/T1 change of exogenous complexes is not specific. The results suggest that the manganese pool of the chloroplasts PS2 may be the main factor responsible for the chloroplasts' proton relaxation rate. The change of the manganese valency in the presence of donors and of acceptors may result in changing 1/T1.


Molecular characterization and functional analysis of CD209E from Nile Tilapia (Oreochromis Niloticus) involved in immune response to bacterial infection.
CD209 plays significant roles in pathogen recognition, innate and adaptive immunity, and cell-cell interactions. In the present study, a CD209 antigen-like protein E from Nile tilapia (Oreochromis niloticus) (designated as OnCD209E) was identified and characterized. OnCD209E contains an open reading frame (ORF) of 771 bp encoding a 257 amino acid protein, as well as the carbohydrate recognition domain (CRD). Multiple sequence analysis exhibits that the amino acid sequence of OnCD209E was relatively high homologous to that of partial fish, especially the highly conserved CRD, in which four conserved disulfide-bonded cysteine residues, WIGL conserved motif and two Ca2+/carbohydrate-binding sites (EPD and WFD motifs) were founded. Quantitative real-time PCR and Western Blot revealed that OnCD209E mRNA/protein is generally expressed in all tissues examined, but with wealth in head kidney and spleen tissues. The mRNA expression of OnCD209E was significantly increased in brain, head kidney, intestine, liver, and spleen tissues in response to the stimulation with polyinosinic-polycytidylic acid, Streptococcus agalactiae and Aeromonas hydrophila in vitro. Recombinant OnCD209E protein exhibited detectable bacterial binding and agglutination activity against different bacteria as well as inhibited the proliferation of tested bacteria. Subcellular localization analysis revealed that OnCD209E was mostly localized in the cell membrane. Moreover, overexpression of OnCD209E could activate nuclear factor-kappa B reporter genes in HEK-293T cells. Collectively, these results demonstrated that CD209E may potentially involve in immune response of Nile tilapia against bacterial infection.


Aldosterone and angiotensin II profiles in young black and white women using different hormonal contraceptives: the African-PREDICT study.
Exogenous estrogens and progestins may affect the components of the renin-angiotensin-aldosterone system (RAAS). Changes in ventricular blood volume are associated with increased secretion of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), which may also be affected by hormonal contraceptives. In this study, we aimed to compare components of the RAAS and NT-proBNP between groups using different hormonal contraceptives, including the combination pill, the injection or implant, and controls (no contraception) in black and white women of fertile age (20 - 30 years). Secondly, we determined whether blood pressure and NT-proBNP are associated with the RAAS components. We included 397 black and white women not using contraceptives, 120 using the combination pill, and 103 receiving an injection/implant. RAAS Triple-A analysis was carried out with LC-MS/MS quantification, and blood pressure measurements (ABPM) taken over 24 h. We found that serum aldosterone was higher (475.7 vs. 249.2 pmol/L; p < 0.001) in the combination pill group than in the no contraception group of white women. The aldosterone-angiotensin II ratio (AA2) was higher (5.4 vs. 2.5; p < 0.001) in the combination pill group than in the no contraception group. In the black women using the combination pill, we found a borderline-positive and borderline-negative association between 24-h systolic blood pressure and NT-proBNP with equilibrium (eq) Ang II, respectively. In white women using the combination pill, only CRP contributed positively and independently to NT-proBNP. To conclude, activation of RAAS by different hormonal contraceptives may increase future risk for the development of hypertension in young black and white women.


Inhibition of mammalian collagenases by thiol-containing peptides.
The following thiol-containing peptide analogues of the carboxyl side of the collagenase-sensitive bond of collagen were synthesized and tested as inhibitors of collagenases partially purified from homogenates of rabbit V-2 tumor and culture medium of pig synovium: HSCH2CH(CH3)CO-Ala-OEt (I), HSCH2CH(CH2Ph)CO-Ala-OEt (II), HSCH2CH[CH2CH(CH3)2]CO-Ala-OEt (III); HSCH2 CH-[CH2CH(CH3)2]CO-Ala-Gly-OEt (IV); HSCH2CH[CH2CH(CH3)2]CO-Ala-Gly-Gln (V). The compounds are listed in order of their inhibitory potency when assayed with nonfibrillar-acid-soluble calf skin collagen at pH 7.6, 35 degrees C. The best inhibitor (III) gave 50% inhibition between 1 and 4 microM. II was a competitive inhibitor with a Ki value of 75 microM. The enzymes preferred an isobutyl side chain at the 2-carbon position, and, where tested (III, IV), did not discriminate strongly between stereoisomers at the chiral 2-carbon. Increasing the length of the inhibitor did not markedly increase potency.


[Clinical studies of renal pelvic and ureteral tumors: an analysis of 611 registered cases and progress of treatment].
A review of 611 cases of renal pelvic or ureter tumor registered in Tokai Urological Tumor Registry for the past 10 years from 1980 and comparison of results between the first and latter half was made. The number of renal pelvis tumor was 347 and that of ureter tumors was 264. Clinical stages and pathological grades of the tumor were as follows; Ta, 11.9; T1, 31.8; T2, 14.4; T3, 24.3; T4, 17.6% and G1, 10.5; G2, 49.3; G3, 33.0%. Higher stages and grades were observed in the recent 5 years. Of 409 cases (66.9% in total cases) treated by total nephroureterectomy, 28.3% of the first and 49.0% of the latter half were treated adjunctively by chemotherapy. Five years relative survival rates of these two groups were 49.4 and 47.3%, respectively, suggesting no improved results. A new treatment strategy such as neoadjuvant chemotherapy or lymphadenectomy is expected to improve the prognosis.


Critical limb ischemia.
Critical limb ischemia (CLI), the most advanced form of peripheral artery disease (PAD), carries grave implications with regard to morbidity and mortality. Within 1 year of CLI diagnosis, 40% to 50% of diabetics will experience an amputation, and 20% to 25% will die. Management is optimally directed at increasing blood flow to the affected extremity to relieve rest pain, heal ischemic ulcerations, avoid limb loss, and prevent cardiovascular events. This management is achieved by guideline-directed medical therapy and risk factor modification, whereas the mainstay of therapy remains revascularization by endovascular or surgical means for patients who are deemed potential candidates.


Updated but not outdated "Gliadin": A plant protein in advanced pharmaceutical nanotechnologies.
For many years, natural products have been considered as the backbone of medical therapy. Recently, different extracted active moieties of these botanical plants were employed as innovative drug delivery vehicles. Protein-based nanocarriers have acquired great engrossment as colloidal vehicles for delivering different therapeutic agents, anticancer, anti-inflammatory, vitamins, or even biomedical devices. Gliadin is a natural protein, accounts for 80-85% of the total wheat protein, and forms a vital part in the quality and nutritional value of flour. Gliadin is not just a dietary protein, its properties created a novel and surprising applications in medical fields, pharmaceutical, biomedical devices, and drug delivery. Gliadin is safe, biocompatible, and superior over synthetic proteins. The current review highlights the nature, characteristics, quantitation, and extraction of gliadin moreover sheds the light on its different applications. The high bioadhesive ability endorsed its interaction with gastric mucosa facilitating the delivery of various drug molecules, its structure, and the disulfide bonds expanded the encapsulation of lipophilic molecules, vitamins, and enzymes. Add on this its antimicrobial film capability and its flexibility as fibers. Gliadin is applied extensively in food and its safety to the patient with celiac disease, and cytotoxicity to normal cells has not been fully elaborated.


Cell-to-substratum adhesion of dissociated embryonic cells of the sea urchin,Pseudocentrotus depressus.
Some plant lectins, Concanavalin agglutinin (Con A), succinyl Con A and wheat germ agglutinin (WGA) increased the adhesion of dissociated embryonic cells of the sea urchin,Pseudocentrotus depressus, to the substratum (plastic and glass surface) in vitro. Other plant lectins,Ulex europeus agglutinin (UEA) andDolichos biflorus agglutinin (DBA) had no effect on the cell-to-substratum interaction. A specific monocarbohydrate inhibitor of lectins, α-methyl-D-mannoside, inhibited the Con A-induced cell-to-substratum adhesion of dissociated embryonic cells. This observation suggests that the Con A-induced cell-to-substratum adhesion may be attributed to the Con A-carbohydrate interaction. In Millipore-filtered sea water (MPFSW) containing Con A (0.1 mg/ml), dissociated embryonic cells adhered to the substratum for more than 6 h at 18°C, while in MPFSW as control, almost all the dissociated cells were released from the substratum after 1 h. A scanning electron microscopic study showed that dissociated embryonic cells adhered to the substratum were surrounded by an extracellular fibrous material, when the cells were cultured in MPFSW containing Con A. The induction of the extracellular fibrous material by Con A was inhibited by α-methyl-D-mannoside. The appearance of this material may be related to the cell-to-substratum adhesion of dissociated cells. Sequential extractions of Con A-treated dissociated cells with Triton X 100 and urea solubilized most of the cellular components, leaving the fibrous material on the surface. Biochemical conponents of the isolated fibrous material included sea urchin fibronectin, Con A and minor components (88 and 140 kilodalton proteins). Fibronectin preformed in the cells was excreted after the dissociation, while the 88 and 140 kilodalton proteins were synthesized and released to the extracellular space.


Failure of rapport: why psychotherapeutic engagement fails in the treatment of Asian clients.
The extent to which relatively unassimilated Asian clients can utilize traditional psychotherapy is likely to depend upon the ability of therapists to understand cultural differences and to adapt their clinical styles accordingly. Common errors made by non-Asian therapists attempting to engage Asians in psychotherapy are identified and appropriate therapeutic strategies are suggested.


Empowering the visually impaired by customized Braille prescription and thus reducing medication errors.
To assess the use of routine Braille prescription in reducing medication errors in visually impaired patients. This observational, questionnaire-based study was conducted in 100 blind or visually impaired patients who were Braille literate (aged ≥18 years). We initiated our Braille prescription from January 2017 to March 2018. The questionnaire consisted of 8 items that captured patient details on the medication management process in addition to a face-to-face interview with them. It was administered twice to each patient at baseline and at the end. Braille prescription included details regarding all medicines, their dosages, instructions, expiry dates, and major side effects. The prescription was developed easily and quickly with an average turnaround time of 1 hour. It was seen that most of the study patients aged between 30-40 years (n = 80) and majority were men (78%). At baseline, 73% of our respondents faced challenges when self-administering medications as compared to 17.5% at endline. After using Braille prescription, only 5% reported of taking a wrong dosage compared to 46.2% at baseline. Patients missing a dosage significantly reduced after using routine Braille prescription (43.7% vs. 7.5% respectively, P < 0.05). Our study successfully has rolled out Braille prescription as an efficacious method in addressing the key issues to medication safety with the visually impaired.


Dynamic phosphocreatine imaging with unlocalized pH assessment of the human lower leg muscle following exercise at 3T.
To develop a high temporal resolution imaging method that measures muscle-specific phosphocreatine (PCr) resynthesis time constant (τPCr ) and pH changes in muscles of the lower leg following exercise on a clinical 3T MRI scanner. We developed a frequency-selective 3D non-Cartesian FLORET sequence to measure PCr with 17-mm nominal isotropic resolution (28 mm actual resolution) and 6-s temporal resolution to capture dynamic metabolic muscle activity. The sequence was designed to additionally collect inorganic phosphate spectra for pH quantification, which were localized using sensitivity profiles of individual coil elements. Nineteen healthy volunteers were scanned while performing a plantar flexion exercise on an in-house developed ergometer. Data were acquired with a dual-tuned multichannel coil array that enabled phosphorus imaging and proton localization for muscle segmentation. After a 90-s plantar flexion exercise at 0.66 Hz with resistance set to 40% of the maximum voluntary contraction, τPCr was estimated at 22.9 ± 8.8 s (mean ± standard deviation) with statistical coefficient of determination r2 = 0.89 ± 0.05. The corresponding pH values after exercise were in the range of 6.9-7.1 in the gastrocnemius muscle. The developed technique allows measurement of muscle-specific PCr resynthesis kinetics and pH changes following exercise, with a temporal resolution and accuracy comparable to that of single voxel 31 P-MRS sequences. Magn Reson Med 79:974-980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Secretome analysis of differentially induced proteins in rice suspension-cultured cells triggered by rice blast fungus and elicitor.
Secreted proteins were investigated in rice suspension-cultured cells treated with rice blast fungus Magnaporthe grisea and its elicitor using biochemical and 2-DE coupled with MS analyses followed by their in planta mRNA expression analysis. M. grisea and elicitor successfully interacted with suspension-cultured cells and prepared secreted proteins from these cultures were essentially intracellular proteins free. Comparative 2-D gel analyses identified 21 differential protein spots due to M. grisea and/or elicitor over control. MALDI-TOF-MS and microLC-ESI-MS/MS analyses of these protein spots revealed that most of assigned proteins were involved in defense such as nine chitinases, two germin A/oxalate oxidases, five domain unknown function 26 (DUF 26) secretory proteins, and beta-expansin. One chitin binding chitinase protein was isolated using chitin binding beads and strong enzymatic activity was identified in an in-gel assay. Interestingly, their protein abundance correlated well at transcript levels in elicitor-treated cultures as judged by semi-quantitative RT-PCR. Each identified differentially expressed protein group was compared at transcript levels in rice leaves inoculated with incompatible (KJ401) and compatible (KJ301) races of M. grisea. Time-course profiling revealed their inductions were stronger and earlier in incompatible than compatible interactions. Identified secreted proteins and their expression correlation at transcript level in suspension-cultured cells and also in planta suggest that suspension-cultured cells can be useful to investigate the secretome of rice blast-pathogen interactions.


Fendosal (HP 129): a potent anti-inflammatory and analgesic compound.
Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.4 times greater than does aspirin in carrageenan-induced rat paw edema. Fendosal is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation. The analgesic activity of fendosal is considered to be superior to that of aspirin, with the advantage of a prolonged duration of action. The gastric-irritating properties of fendosal are very low in comparison with those of aspirin. Fendosal has a much wider separation of effective and gastric-irritating doses than does aspirin.


Uncommon case of chronic myeloid leukemia with multiple myeloma.
We describe a 72-year-old woman who was diagnosed with asymptomatic multiple myeloma (MM) while being treated for Philadelphia (Ph)-positive chronic myeloid leukemia (CML) with imatinib mesylate (400 mg/day). The diagnosis of CML was based on the presence of the Ph chromosome and chimeric BCR-ABL messenger RNA. Three months after starting imatinib mesylate treatment, the patient achieved a complete cytogenetic response. However, bone marrow analysis at that time demonstrated plasmacytosis, and paraprotein (IgG, kappa-type) was also detected. Hypercalcemia, renal failure, anemia, and bone lesions were not observed, which suggested that asymptomatic MM had developed. The coexistence of CML and MM is an extremely uncommon event that has only been reported in 12 cases. We discuss the relationship between CML and MM.


Congenital midureteral stricture in children diagnosed with antenatal hydronephrosis.
Antenatal hydronephrosis is the most common genitourinary pathologic finding during gestational ultrasonography. Congenital midureteral strictures are an unusual cause of prenatal hydronephrosis, with 13 total previously reported and only 1 diagnosed as a result of antenatal ultrasonography. We present 4 cases of midureteral strictures as the cause of antenatal hydronephrosis and review the published data on congenital midureteral obstruction. All midureteral strictures in our series and in the published reports were treated surgically after varying periods of observation. Retrograde pyelography was diagnostic in all cases. This atypical cause of antenatal hydronephrosis may provide additional insight into the controversy regarding preoperative retrograde pyelography before surgical intervention for ureteropelvic junction obstruction. Given the typical misdiagnosis of ureteropelvic junction obstruction in the setting of midureteral stricture disease, we believe that the threshold for retrograde pyelography should be very low.


[Evolution of stents for the treatment of femoral artery lesions].
Endovascular treatment and stent implantation in the superficial femoral artery have been proposed for over 20 years. However, the first experiments with stainless stents were relatively disappointing. The first improvement consisted in the introduction of nitinol self-expanding stents. This technology allowed an initial improvement of clinical performances, but the first generation of nitinol stents demonstrated a relatively high rate of fractures. Better knowledge of the femoral artery biomechanics and advances in technology allowed to propose a second generation of nitinol stents with improved flexibility, which decreased the rates of fracture. In-stent restenosis related to neointimal hyperplasia has also led to the development of new concepts to improve patency rates after stenting of the femoral artery: drug-eluting stents (coated-stents), biodegradable stents, and covered stents. These technologies will help to treat more complex lesions of the femoral artery in the future, with comparable results to those obtained with femoropopliteal bypasses, but we are still waiting for results of ongoing studies.


Inductive expression and characterization analysis of Paralichthys olivaceus pigment epithelium-derived factor in a virally infected cell line.
Pigment epithelium-derived factor (PEDF) is acknowledged to be a non-inhibitory member of the serine protease inhibitor (serpin) superfamily, with antiangiogenesis, and neuroprotective and immunoregulatory function, mainly in the tissues of nervous system. Here, A PEDF gene homolog, Paralichthys olivaceus PEDF (PoPEDF), was isolated from flounder embryonic cells (FEC) treated with UV-inactivated Grass carp hemorrhage virus (GCHV) and subsequently identified as a differentially expressed gene. The full length of PoPEDF cDNA is 1803bp with an open reading frame of 1212bp encoding a 403-amino-acid protein. This deduced protein contains an N-terminal signal peptide, a glycosylation site, a consensus serpin motif, and a 34-mer and a 44-mer fragment, all of which are very conserved in the PEDF family. PoPEDF gene exhibits a conserved exon-intron arrangement with 8 exons and 7 introns. This conserved evolutionary relationship was further confirmed by a phylogenetic analysis, where fish PEDFs and mammalian members formed a well-supported clade. Constitutive expression of PoPEDF was widely detected in many tissues. In response to UV-inactivated GCHV or poly(I:C), PEDF mRNA was upregulated in FEC cells with time. This is the first report on the transcriptional induction of PEDF in virally infected cells.


Tunable Photocontrolled Motions Using Stored Strain Energy in Malleable Azobenzene Liquid Crystalline Polymer Actuators.
A new strategy for enhancing the photoinduced mechanical force is demonstrated using a reprocessable azobenzene-containing liquid crystalline network (LCN). The basic idea is to store mechanical strain energy in the polymer beforehand so that UV light can then be used to generate a mechanical force not only from the direct light to mechanical energy conversion upon the trans-cis photoisomerization of azobenzene mesogens but also from the light-triggered release of the prestored strain energy. It is shown that the two mechanisms can add up to result in unprecedented photoindued mechanical force. Together with the malleability of the polymer stemming from the use of dynamic covalent bonds for chain crosslinking, large-size polymer photoactuators in the form of wheels or spring-like "motors" can be constructed, and, by adjusting the amount of prestored strain energy in the polymer, a variety of robust, light-driven motions with tunable rolling or moving direction and speed can be achieved. The approach of prestoring a controllable amount of strain energy to obtain a strong and tunable photoinduced mechanical force in azobenzene LCN can be further explored for applications of light-driven polymer actuators.


A molecular epidemiological study of rabies in Puerto Rico.
The mongoose is the principal reservoir for rabies on the island of Puerto Rico. This report describes a molecular epidemiological study of representative rabies viruses recovered from the island in 1997. Two closely related but distinct variants circulating in regionally localised parts of the island were identified. The lack of a monophyletic relationship of these viruses suggests that two independent incursions of rabies onto the island have occurred. Both of these Puerto Rican variants were closely related to a variant, known as the north central skunk strain, currently circulating in North American skunk populations and all are members of the cosmopolitan rabies lineage spread during the colonial period. However, the Puerto Rican viruses are clearly distinct from those presently circulating in mongooses in Cuba and which are epidemiologically closely linked to the Mexican dog rabies virus. This study clearly establishes the distinct origins of the rabies viruses now circulating on these two Caribbean islands.


Unmutated immunoglobulin M can protect mice from death by influenza virus infection.
To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza virus on mice deficient of activation-induced cytidine deaminase (AID), which is absolutely required for CSR and SHM. In the primary infection, AID deficiency caused no significant difference in mortality but did cause difference in morbidity. In the secondary infection with a lethal dose of influenza virus, both AID-/- and AID+/- mice survived completely. However, AID-/- mice could not completely block replication of the virus and their body weights decreased severely whereas AID+/- mice showed almost complete prevention from the reinfection. Depletion of CD8+ T cells by administration of an anti-CD8 monoclonal antibody caused slightly severer body weight loss but did not alter the survival rate of AID-/- mice in secondary infection. These results indicate that unmutated immunoglobulin (Ig)M alone is capable of protecting mice from death upon primary and secondary infections. Because the titers of virus-neutralizing antibodies were comparable between AID-/- and AID+/- mice at the time of the secondary infection, a defect of AID-/- mice in protection of morbidity might be due to the absence of either other Ig classes such as IgG, high affinity antibodies with SHM, or both.