Synergistic Effect of Zinc-Chitosan Nanoparticles and Hydroxychloroquine to Inhibit Buffalo Coronavirus.
Zinc ions can hinder the synthesis of proteins required for accomplishing several stages of the viral life cycle. The intracellular zinc concentration can be increased by using zinc ionophores which transport zinc ions into the cells and hinder viral replication. (Hydroxy)chloroquine is an example of a zinc ionophore, but both zinc and (hydroxy)chloroquine can be toxic to the host organism. The nanocarriers may serve as camouflage to evade the adverse effects of drugs, chemicals, and nanoparticles on the host. We formulated ZnO nanoparticles with flower-like morphology (ZnONFs). It was further decorated with chitosan along with hydroxychloroquine (as a zinc ionophore) (CHCZnO NPs). We have chosen the cationic polymer chitosan since it is biocompatible, biodegradable and binds easily with the cells, and enhances the transport of drugs across cell membranes. The formulation was investigated for size, shape, surface charge, and interaction of chemicals used. We evaluated the formulations for cytotoxicity, and biocompatibility in embryonated chicks and their efficacy against bovine coronavirus (BCoV) isolated from a buffalo calf, and pneumo-enteric coronaviruses isolated from a buffalo calf with promising results in comparison to ZnONFs/hydroxychloroquine alone. Furthermore, we elucidate the mechanism underlying the lysosomotropic effect of various formulations on Vero cells infected with the buffalo coronavirus.


Absence of pyrimidine salvage and prevention of thymineless radiosensitization in Escherichia coli thyA cells fed dihydrothymine or thymine glycol.
Little information is available concerning the metabolic fate of radiation-induced thymine base damage products once they have been excised from DNA. The present study was an attempt to determine whether or not thymine-requiring mutants of Escherichia coli could grow on dihydrothymine (DHT) and thymine glycol (TG) by "salvaging" the altered thymines. A second test of thymine product utilization was prevention of thymineless radiosensitization. Results showed that very low growth of Thy- cells on DHT or TG could be explained by the presence of less than or equal to 1% contaminating thymine in the mixtures. Radiation dose-modification factors (DMFs) for thyA cells fed DHT or TG for 3 h were 1.38 +/- 0.28 and 1.26 +/- 0.24, respectively, whereas the DMF for 3 h thymine-starved cells was 1.63 +/- 0.05. The small (approximately 25%) amelioration of thymineless radiosensitization observed in DHT- or TG-fed cells could probably be explained by contaminating thymine in the medium. Although DHT is a normal metabolite in some cells, neither DHT nor TG could be used efficiently by thymine-requiring cells in the protocol presented.


Prognostic importance of postbypass regional wall-motion abnormalities in patients undergoing coronary artery bypass graft surgery. SPI Research Group.
Regional wall motion abnormalities (RWMA) detected by intraoperative transesophageal echocardiography (TEE) are thought to be sensitive markers of myocardial ischemia. To assess the prognostic significance of RWMA as compared with other less costly technologies such as electrocardiography (ECG) and hemodynamic measurements [blood pressure (BP) and pulmonary artery (PA) pressure], 50 patients were prospectively studied who were undergoing elective coronary artery bypass graft (CABG) surgery using continuous TEE, ECG (Holter), and hemodynamic measurements during the prebypass, postbypass, and early postoperative intensive care unit (ICU) periods (first 4 h). Echocardiographic and ECG evidence of ischemia was characterized during each of these three periods and related to adverse clinical outcomes (postoperative myocardial infarction, ventricular failure, and cardiac death). Clinicians were blinded to the TEE and ECG information. The prevalence of myocardial ischemia during the perioperative periods was as follows: prebypass, 20% (TEE) versus 7% (ECG); postbypass, 36% (TEE) versus 25% (ECG); ICU 25% (TEE) versus 16% (ECG). Neither prebypass TEE ischemia nor ECG ischemia occurring in any of the three periods predicted adverse outcome. In contrast, postbypass TEE ischemia was predictive of outcome: six of 18 patients with postbypass TEE ischemia had adverse outcomes versus 0 of 32 without TEE ischemia (P = 0.001). Seventy-three percent of the echocardiographic ischemic episodes occurred without acute change (+/- 20% of control) in heart rate, BP, or PA pressure. The authors conclude that: 1) prebypass myocardial ischemia was relatively uncommon, 2) the incidence of ECG and TEE ischemia was highest in the postbypass period, and 3) postbypass RWMA were related to adverse clinical outcome.


Characterization of flow reduction properties in an aneurysm due to a stent.
We consider a lattice Boltzmann simulation of blood flow in a vessel deformed by the presence of an aneurysm. Modern clinical treatments involve introducing a stent (a tubular mesh of wires) into the cerebral artery in order to reduce the flow inside the aneurysm and favor its spontaneous reabsorption. A crucial question is to design the stent with suitable porosity so as to produce the most effective flow reduction. We propose a stent positioning factor as a characterizing tool for stent pore design in order to describe the flow reduction effect and reveal the several flow reduction mechanisms using this effect.


A role for Pak protein kinases in Schwann cell transformation.
Neurofibromatosis type 1 (NF1), a common autosomal dominant disorder caused by loss of the NF1 gene, is characterized clinically by neurofibromas and more rarely by neurofibrosarcomas. Neurofibromin, the protein encoded by NF1, possesses an intrinsic GTPase accelerating activity for the Ras proto-oncogene. Through this activity, it is a negative regulator of Ras. The Pak protein kinase is a candidate for a downstream signaling protein that may mediate Ras signals because it is activated by Rac and Cdc42, two small G proteins required for Ras signaling. Here, we use Pak mutants to explore the role of Pak in Ras signaling in Schwann cells, the cells affected in NF1. Whereas an activated Pak mutant does not transform cells, dominant negative Pak mutants are potent inhibitors of Ras transformation of rat Schwann cells and of a neurofibrosarcoma cell line from an NF1 patient. Although activated Pak stimulated jun-N-terminal kinase, inhibition of Ras transformation by dominant negative Pak did not require inhibition of jun-N-terminal kinase. Instead, the Pak mutants appeared to inhibit transformation by preventing Ras activation of the ERK/mitogen-activated protein kinase cascade. These results have implications for our understanding of NF1 because a neurofibrosarcoma cell line derived from a patient with NF1 was reverted by stable expression of the Pak dominant negative mutants.


Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines.
Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly used in APS patients, but contradictory guidelines recommendations on their use do exist. We performed a systematic review of literature including studies investigating the role of DOACs in APS patients. At this aim, PubMed and Cochrane databases were searched according to PRISMA guidelines. We identified 14 studies which investigated the use of DOACs in patients with APS, of which 3 randomized clinical trials (RCTs), 1 post-hoc analysis of 3 RCTs, 7 case series and 3 cohort studies (2 prospective and 1 retrospective). Among DOACs, rivaroxaban was the most used (n = 531), followed by dabigatran (n = 90) and apixaban (n = 46). Regarding guidelines indications, the 2019 European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients. The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance provided more detailed indications stating that warfarin should be the first-choice treatment but DOACs may be considered in patients (1) already on a stable anticoagulation with a DOAC, (2) with low-quality anticoagulation by warfarin, (3) unwilling/unable to undergo INR monitoring, (4) with contraindications or serious adverse events under warfarin. Patients with arterial APS or triple positivity should be treated with warfarin while venous APS with single or double positivity may be candidate to DOACs, but high-quality studies are needed.


Recent Advancements of Graphene-Based Materials for Zinc-Based Batteries: Beyond Lithium-Ion Batteries.
Graphene-based materials (GBMs) possess a unique set of properties including tunable interlayer channels, high specific surface area, and good electrical conductivity characteristics, making it a promising material of choice for making electrode in rechargeable batteries. Lithium-ion batteries (LIBs) currently dominate the commercial rechargeable battery market, but their further development has been hampered by limited lithium resources, high lithium costs, and organic electrolyte safety concerns. From the performance, safety, and cost aspects, zinc-based rechargeable batteries have become a promising alternative of rechargeable batteries. This review highlights recent advancements and development of a variety of graphene derivative-based materials and its composites, with a focus on their potential applications in rechargeable batteries such as LIBs, zinc-air batteries (ZABs), zinc-ion batteries (ZIBs), and zinc-iodine batteries (Zn-I2 Bs). Finally, there is an outlook on the challenges and future directions of this great potential research field.


Adrenoleukodystrophy: cortical hypoperfusion demonstrated with 99mTc-HMPAO SPECT.
Regional cerebral blood flow was investigated in an 8-year-old boy with adrenoleukodystrophy by single photon emission computed tomography. The use of 99mTc-hexamethylpropylene amine oxime revealed markedly reduced blood flow in the occipital, parietal, and temporal cortical gray matter, in addition to the anticipated reduction in white matter. The area with a decreased blood flow was more extensive than that detected by x-ray computed tomography.


Cost Comparison of Rodent Soiled Bedding Sentinel and Exhaust Air Dust Health-Monitoring Programs.
Rodent vivaria have traditionally used soiled bedding sentinel (SBS) health-monitoring programs to detect and exclude adventitious pathogens that could affect research results. Given the limitations of SBS, a likely reduction in animal usage, and a decrease in animal care staff labor, exhaust air dust (EAD) health monitoring has been evaluated by several groups for its efficacy in detecting pathogens when used as a complete replacement for traditional SBS health-monitoring programs. Compared with SBS, EAD has also been shown to provide increased sensitivity for the detection of multiple pathogens. After implementing EAD at our institution, we conducted an analysis to compare the annual costs of the 2 health-monitoring programs. The EAD program was found to be 26% less expensive than SBS. In addition to these cost savings, EAD decreased the amount of time spent by the staff on heath-monitoring activities. For veterinary technicians, this decrease in time was calculated as a savings of 150 h annually, almost 3 h each week. Finally, the EAD program replaced the use of live sentinel animals, decreasing the associated yearly usage from 1,676 animals to zero.


Identification and in vitro cytotoxicity of ochratoxin A degradation products formed during coffee roasting.
The mycotoxin ochratoxin A is degraded by up to 90% during coffee roasting. In order to investigate this degradation, model heating experiments with ochratoxin A were carried out, and the reaction products were analyzed by HPLC-DAD and HPLC-MS/MS. Two ochratoxin A degradation products were identified, and their structure and absolute configuration were determined. As degradation reactions, the isomerization to 14-(R)-ochratoxin A and the decarboxylation to 14-decarboxy-ochratoxin A were identified. Subsequently, an analytical method for the determination of these compounds in roasted coffee was developed. Quantification was carried out by HPLC-MS/MS and the use of stable isotope dilution analysis. By using this method for the analysis of 15 coffee samples from the German market, it could be shown that, during coffee roasting, the ochratoxin A diastereomer 14-(R)-ochratoxin A was formed in amounts of up to 25.6% relative to ochratoxin A. The decarboxylation product was formed only in traces. For toxicity evaluations, first preliminary cell culture assays were performed with the two new substances. Both degradation products exhibited higher IC50 values and caused apoptotic effects with higher concentrations than ochratoxin A in cultured human kidney epithelial cells. Thus, these cell culture data suggest that the degradation products are less cytotoxic than ochratoxin A.


An exploratory examination of the Spiritual Well-Being Scale among incarcerated black and white male drug users.
A number of studies have examined the link between criminality and religiosity. However, only a limited number of studies have examined the relationship between spirituality and criminality. Because spirituality has been identified as a fundamental attribute of the personalities of Blacks, studies examining differences in the association between spirituality by ethnicity could provide information to understand the disparity of incarceration rates among Blacks and Whites. For this study, data were collected from 661 male prisoners with prior histories of drug use to examine spirituality that was assessed using two factors from a modified version of the Spiritual Well-Being Scale: relationship with a higher power and satisfaction with oneself in the world. Analyses revealed that White men reported significantly higher scores on both factors than Black men. The unexpected findings are discussed in light of the existing literature that identifies the significance of spirituality in the personality and coping style of Blacks.


Application of interactive, computer technology to adolescent substance abuse prevention and treatment.
This article provides an overview of several interactive, computer-based substance abuse-prevention and -treatment interventions that we have developed for adolescents, including an interactive substance abuse-prevention multimedia program for middle school-aged youth and a customizable program focused on prevention of HIV, hepatitis, and sexually transmitted infections among youth in substance abuse treatment. The content in these programs is grounded in a scientific understanding of the types of skills and information that are critical to effective prevention. The programs also use several evidence-based informational technologies that have been shown to be critical in effectively training key skills and information. Our evaluations to date have underscored the effectiveness of these programs in producing desired health-behavior change. Applying information technologies to the delivery of science-based interventions may allow for unique opportunities to provide widespread dissemination of cost-effective interventions with consistency and in a manner that is engaging and acceptable to youth.


[Quality control in aspiration biopsy cytology].
Comparison and quality control of our experience of thyroid cytology (784 samples) and breast cytology (1,202 samples) were reported. False positive rate and other parameters were superior in breast cytology than thyroid. It may be due to the fact that cytological diagnostic criteria for follicular thyroid carcinoma from follicular adenoma is not established yet. More suspicious diagnosis in thyroid than breast also give low incidence of malignancy in thyroid suspicious diagnosis. As recommended by a guideline for both thyroid and breast cytology from the Papanicolaou society et al, conservative handling and protective diagnosis may help to reduce false positive and false negative rates.


[Intestinal hemorrhage from diverticulosis of the jejunum: a case report].
The diagnosis of intestinal diverticulosis is difficult to achieve preoperatively because the clinical symptoms are usually non-specific. Intestinal bleeding is a rare complication of jejunal diverticulosis. Its diagnosis and treatment can be difficult and an emergency laparotomy is often needed. We report a case of massive intestinal bleeding from jejunal diverticulosis. The correct diagnosis was first suggested by CT and then confirmed at laparotomy. The treatment was a segmental jejunal resection with primary anastomosis.


Palliative treatment of malignant dysphagia with self-expanding metal stents: a 12-year experience.
The incidence of oesophageal cancer is increasing but the prognosis is still very poor. Around 50% of patients have advanced disease when diagnosed. Stenting using expandable metal stents is primarily aimed at palliation. The purpose of this study was to evaluate factors influencing morbidity, procedure-related mortality and symptom relief for dysphagia in patients with unresectable oesophageal cancer treated with self-expanding metal stents. We conducted a retrospective observational clinical study of consecutive patients treated with self-expanding metal stents in the Department of Surgery, Danderyd Hospital, Sweden, between January 1993 and May 2005. One hundred and seventy-four stents were placed in 149 patients. The procedure-related mortality was 3% and the complication rate 26%. Pre- and post-treatment dysphagia could be evaluated in 139 stent placements, and showed significant improvement of dysphagia symptoms in 70% of subjects (p<0.0001). Tumour length, tumour location, histology, age, gender or prior dilatation did not affect the outcome regarding procedure-related morbidity or symptom relief. Palliation of malignant dysphagia with self-expanding metal stents is safe and confers almost immediate improvement of dysphagia in the majority of patients. Tumour-related and demographic factors do not seem to influence the outcome.


Ring-System-Based Exhaustive Structure Generation for Inverse-QSPR/QSAR.
Inverse-QSPR/QSAR aims to solve the inverse problem of chemical structure generation based on QSPR/QSAR models, once the properties or activities are specified. To efficiently solve this problem, an exhaustive ring-system-based structure generation methodology was developed. The concept of the applicability domain (AD) is automatically acknowledged within the proposed strategy. The local AD is considered by introducing the probability distribution of a given data set, and the universal AD is considered using ring-system-based fragments in the training data set. Structures with desired properties or activities are enumerated by assembling fragments, including atomic elements, in a tree-like way. The usefulness of the proposed method is demonstrated through a case study of ligand design for the human alpha 2A adrenergic receptor (ADR2A_HUMAN). We succeeded in generating structures focusing only on a pre-defined region in chemical space, resulting in structures whose desired activity has a high likelihood being efficiently generated. In addition, the limitations of our proposed method and future challenges are discussed.


[UNDIFFERENTIATED CARCINOMA OF THE URETER WITH FETAL CLINICAL COURSE: A CASE REPORT].
Undifferentiated carcinoma of ureter is rare neoplastic lesion, and the natural history of undifferentiated carcinoma of ureter has not been known well yet. We hereby presented an autopsy case of undifferentiated carcinoma of the ureter with rapid progression from the initial stage. A 62-year-old male visited the local urologist complaining of asymptomatic gross hematuria. Cystoscopy revealed the outflow of hematuria from the right ureteral orifice. Abdominal CT showed the right hydronephrosis with atrophic change of the renal parenchyma and the stenosis of upper ureter. He was referred to our hospital on suspicion of a right ureteral tumor. Magnetic resonance imaging and retrograde ureterography did not reveal a tumor in the right ureter. He complained of low back pain 4 months after the initial hematuria, and CT revealed the diffuse enlargement of the right kidney, swelling of the abdominal lymph nodes, and lung nodules. Renal biopsy was done, and only undifferentiated cells were revealed histopathologically without any specific findings to diagnose the primary organ. The tumor increased progressively, and he died about 6 months after the initial gross hematuria. Autopsy was performed, and urothelial carcinoma was found in the right ureter as the primary lesion. The ureteral tumor infiltrated to the right kidney, right adrenal gland, liver, duodenum, and pancreas with undifferentiation. Undifferentiated tumor cells were also found in distant metastatic lesion including the abdominal lymph nodes, left adrenal gland, liver, lung, pleura, and peritoneum.


Board Network and CSR Decoupling: Evidence From China.
This paper investigates the influence of board network centrality on corporate social responsibility (CSR) decoupling. CSR decoupling refers to the gap between corporate internal and external actions in CSR practices. Specifically, we measure CSR decoupling as the difference between corporate social disclosure (CSD) and corporate social performance (CSP). This paper uses a sample of Chinese A-share listed firms during 2009-2018, takes the technical dimension score (T-score) and content dimension score (C-score) of RKS ratings as proxies of CSD and CSP, and obtains CSR decoupling as the difference between CSD and CSP. Our results show that (1) board network centrality is positively related to over-decoupling in the pre-adoption period (2009-2014) of the new environmental law but negatively related to over-decoupling in the post-adoption period (2015-2018) and (2) centrality is not related to under-decoupling in the pre-adoption period but a significantly positive related in the post-adoption period. Our finding reveals a complex role of the board network in CSR practices in China.


Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome.
In order to estimate the contribution of mutations at the fibrillin-1 locus (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic differences between patients with an FBN1 mutation vs. without, a comprehensive molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the clinical diagnosis of MFS according to the Ghent nosology was performed. The initial mutation screening by CSGE/SSCP allowed identification of an FBN1-mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11 mutation-negative patients, while in nine others, DHPLC was used. This allowed identification of seven and five additional mutations, respectively. Southern blot analysis revealed an abnormal hybridization pattern in one more patient. A total of 23 out of the 85 mutations identified here are reported for the first time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs. premature termination mutations revealed significant differences in ocular and skeletal involvement. The phenotype of the eight patients without proven FBN1 mutation did not differ from the others with respect to the presence of major cardiac, ocular, and skeletal manifestations or positive familial history. Most likely, a portion of FBN1-mutations remains undetected because of technical limitations. In conclusion, the involvement of the FBN1-gene could be demonstrated in at least 91% of all MFS patients (85/93), which strongly suggests that this gene is the predominant, if not the sole, locus for MFS.


Characterization of oxygen-linked glucuronides by laser desorption mass spectrometry.
A laser desorption time-of-flight mass spectrometer is used for structural confirmation of several acyl- and ether-linked glucuronides. Abundant molecular ion species are produced, as well as fragmentation reflecting both the molecular structure and the stability of the conjugates. The major ions are produced by cationization, and detection limits are as low as 1.6 ng (5.0 pmol).


Unilateral acute angle closure glaucoma.
A 52-year-old gentleman presented with 1-week history of severe right-sided headache associated with reduced vision in his right, amblyopic eye. Examination revealed raised intraocular pressure at 64 mm Hg. The anterior chamber (AC) was shallow and there was a dense cataract with no red reflex or fundal view. The contralateral eye had a deep anterior chamber with normal pressure and a clear lens. He was treated initially for acute angle closure glaucoma. The anterior chamber remained shallow and the intraocular pressure uncontrolled, despite maximum medical therapy. Owing to the absent fundal view and unilateral AC shallowing, further imaging was performed and a choroidal mass was found to be responsible for anterior displacement of the lens and shallowing of the angle. He went on to have an enucleation of the right eye, and histological examination confirmed the diagnosis of choroidal melanoma.


'I didn't know so many people cared about me': support for patients who interrupt drug-resistant TB treatment.
Early interventions for patients who interrupt their treatment for drug-resistant tuberculosis (DR-TB) are rarely reported and assessed. A novel, patient-centred intervention for patients at risk of loss to follow-up (LTFU) from DR-TB treatment was implemented in Khayelitsha, South Africa, in September 2013. To explore the experiences and perceptions of patients, key support persons, health care workers (HCWs) and programme managers of a patient-centred model. This was a qualitative study consisting of 18 in-depth interviews with patients, key support persons, HCWs, key informants and one focus group discussion with HCWs, between July and September 2017. Data were coded and thematically analysed. The model was well perceived and viewed positively by patients, care providers and programme managers. 'Normalisation' and tolerance of occasional treatment interruptions, tracing, tailored management plans and peer support were perceived to be beneficial for retaining patients in care. Although the model was resource-demanding, health workers were convinced that it 'needs to be sustained,' and proposed solutions for its standardisation. An intervention based on early tracing of patients who interrupt treatment, peer-delivered counselling and individualised management plans by a multidisciplinary team was considered a beneficial and acceptable model to support patients at risk of LTFU from DR-TB treatment.


The effect of acute lithium and rubidium pretreatment on apomorphine-induced pecking in pigeons.
The effects of different doses of lithium (5-320 mg/kg intramuscularly) and rubidium (0.25 32 mg/kg intramuscularly) on apomorphine-induced pecking were investigated in pigeons. These two cations did not induce pecking by itself. Intramuscular administration of apomorphine (a mixed D1/D2 dopamine receptors agonist, 0.1-1.6 mg/kg) induced pecking in a dose-dependent manner. SCH 23390 (D1 dopamine receptor antagonist, 0.02-0.08 mg/kg) and sulpiride (D2 dopamine receptor antagonist, 25-100 mg/kg) decreased apomorphine-induced pecking dose-dependently. Combination of SCH 23390 (0.04 mg/kg) with sulpiride (50 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both D1 and D2 dopamine receptors are involved in apomorphine-induced pecking. The response induced by apomorphine (0.2-0.8 mg/kg) was decreased in animals pretreated with lithium and rubidium. In these conditions, SCH 23390 and sulpiride produced a larger inhibitory effect on the apomorphine response, suggesting that acute lithium and rubidium pretreatment inhibit pecking by interfering with dopaminergic mechanisms.


Redox behavior of uranium at the nanoporous aluminum oxide-water interface: implications for uranium remediation.
Sorption-desorption experiments show that the majority (ca. 80-90%) of U(VI) presorbed to mesoporous and nanoporous alumina could not be released by extended (2 week) extraction with 50 mM NaHCO(3) in contrast with non-nanoporous α alumina. The extent of reduction of U(VI) presorbed to aluminum oxides was semiquantitatively estimated by comparing the percentages of uranium desorbed by anoxic sodium bicarbonate between AH(2)DS-reacted and unreacted control samples. X-ray absorption spectroscopy confirmed that U(VI) presorbed to non-nanoporous alumina was rapidly and completely reduced to nanoparticulate uraninite by AH(2)DS, whereas reduction of U(VI) presorbed to nanoporous alumina was slow and incomplete (<5% reduction after 1 week). The observed nanopore size-dependent redox behavior of U has important implications in developing efficient remediation techniques for the subsurface uranium contamination because the efficiency of in situ bioremediation depends on how effectively and rapidly U(VI) bound to sediment or soil can be converted to an immobile phase.


Unilateral hydronephrosis and hydroureter by foreign body in urinary bladder: a case report.
Foreign bodies inserted through the urethra are often found in the urinary bladder. We presently report the first case of hydronephrosis and hydroureter due to direct compression in the urinary bladder by silicon, which had been introduced by the patient himself 2 yr prior to presentation with severe right flank pain. Computed tomography indicated a convoluted, high-attenuation mass in the urinary bladder; unilateral hydronephrosis and hydroureter were also present due to direct compression by the mass. The foreign body was removed using a cystoscope. This foreign body was proven to be silicon.


ERG induces taxane resistance in castration-resistant prostate cancer.
Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.


Reversible Navier-Stokes equation on logarithmic lattices.
The three-dimensional reversible Navier-Stokes (RNS) equations are a modification of the dissipative Navier-Stokes (NS) equations, first introduced by Gallavotti [Phys. Lett. A 223, 91 (1996)0375-960110.1016/S0375-9601(96)00729-3], in which the energy or the enstrophy is kept constant by adjusting the viscosity over time. Spectral direct numerical simulations of this model were performed by Shukla et al. [Phys. Rev. E 100, 043104 (2019)2470-004510.1103/PhysRevE.100.043104] and Margazoglou et al. [Phys. Rev. E 105, 065110 (2022)10.1103/PhysRevE.105.065110]. Here we consider a linear, forced reversible system obtained by projecting RNS equations on a log lattice rather than on a linearly spaced grid in Fourier space, as is done in regular spectral numerical simulations. We perform numerical simulations of the system at extremely large resolutions, allowing us to explore regimes of parameters that were out of reach of the direct numerical simulations of Shukla et al. Using the nondimensionalized forcing as a control parameter, and the square root of enstrophy as the order parameter, we confirm the existence of a second-order phase transition well described by a mean-field Landau theory. The log-lattice projection allows us to probe the impact of the resolution, highlighting an imperfect transition at small resolutions with exponents differing from the mean-field predictions. Our findings are in qualitative agreement with predictions of a 1D nonlinear diffusive model, the reversible Leith model of turbulence. We then compare the statistics of the solutions of RNS and NS, in order to shed light on an adaptation of the Gallavotti conjecture, in which there is equivalence of statistics between the reversible and irreversible models, to the case where our reversible model conserves either the enstrophy or the energy. We deduce the conditions in which the two are equivalent. Our results support the validity of the conjecture and represent an instance of nonequilibrium system where ensemble equivalence holds for mean quantities.


A biphasic tumor in posterior cranial fossa and the pineal region in young adult.
Biphasic tumors of the central nervous system are rarely described and mainly consisted out of the glial and mesenchymal component. The tumor originated out of both astrocytes and pinealocytes, best to our knowledge, has not been described. We present a case of a brain tumor consisted out of pilocytic astrocytoma (PA) and pineocytoma as components situated in the pineal region and posterior cranial fossa in young adult. We present a 21-year-old patient with a history of intermittent headache, followed by nausea and vomiting, double vision, and dextropulsion. Magnetic resonance imaging revealed an extensive cystic-solid expansive formation in the posterior cranial fossa with a solid part in the area of the pineal gland. The patient underwent surgical resection. The pathohistological analysis showed two types of tumor cells; the major part of tumor showed features of PA, while minor part corresponded to pineocytoma. PA accounts for 5% of all gliomas and is most common in children and young adults. It usually occurs in the cerebellum, the optic pathway, third ventricular region, etc. Pineocytomas are rare, accounting up to 1% of all intracranial tumors. Since tumors origin is different, there must be complex molecular events or mutations that can lead to cell rearrangements and generation of two histologically different tissues in the same tumor mass. The course of treatment options is different for PA and pineocytoma; therefore, the case of brain mass consisted out of two different tissues can be helpful when deciding about the treatment of tumors in posterior cranial fossa and pineal region.


Detection of P210bcr-abl in mature granulocytes from Ph1-positive chronic myelogenous leukemia patients by an immunoblotting method.
Previously, p210bcr-abl has been detected in Philadelphia-chromosome-positive chronic myelogenous leukemia (CML) blast crisis and established cells originating from blasts. It has not been detected in mature granulocytes in the chronic phase. Protein degradation tends to occur during protein extraction, due to the activities of protease and phosphatase within these cells. Protein was, therefore, extracted in a cell lysis buffer containing alpha 1-antitrypsin and a high concentration of Na3VO4 as inhibitors. In mature granulocytes in the chronic phase, p210bcr-abl was detected and the level of tyrosine phosphorylation estimated by immunoblotting, using the enzyme-labeled antibody method with anti-c-abl and anti-phosphotyrosine antibodies. p210bcr-abl was phosphorylated on tyrosine residues in blast crisis cells and K562 cells derived from CML blast crisis, whereas it was dephosphorylated in mature granulocytes from chronic phase CML patients. This suggests that p210bcr-abl in mature granulocytes has no tyrosine kinase activity, or it is extremely weak, and dephosphorylation of p210bcr-abl is associated with differential maturation of immature cells in the chronic phase of CML.


Recognizing megatsunamis in Mediterranean deep sea sediments based on the massive deposits of the 365 CE Crete event.
The Mediterranean Sea hosts two subduction systems along the convergent Africa-Eurasia plate boundary that have produced strong ground shaking and generated tsunamis. Based on historical descriptions and sedimentary records, one of these events, in 365 CE, impacted a broad geographical area, including tsunami evidence for distances of 700-800 km from the source event, qualifying it as a 'megatsunami'. Understanding how megatsunamis are produced, and where they are more likely, requires a better understanding of the different secondary processes linked to these events such as massive slope failures, multiple turbidity current generation, and basin seiching. Our sedimentary records from an extensive collection of cores located in distal and disconnected basins, identify turbidites which are analyzed using granulometry, elemental (XRF), micropaleontological, and geochemical data in order to reconstruct their coastal or marine source. The results show that the 365 CE basin floor sediments are a mixture of inner shelf and slope materials. The tsunami wave produced multiple far-field slope failures that resulted in stacked basal turbidites. It also caused transport of continent-derived organic carbon and deposition over basal turbidites and into isolated basins of the deep ocean. The composition of sediment in isolated basins suggests their deposition by large-scale sheet like flows similar to what has been caused by the Tohoku earthquake associated tsunamis. This is significant for rectifying and resolving where risk is greatest and how cross-basin tsunamis are generated. Based on these results, estimates of the underlying deposits from the same locations were interpreted as possible older megatsunamis.


Activation of MMPs in Macrophages by Mycobacterium tuberculosis via the miR-223-BMAL1 Signaling Pathway.
An interaction between Mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on M. tuberculosis-triggered organ lesions. In this study, we focused on the regulation of the expression of matrix metalloproteinases (MMPs), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following M. tuberculosis infection. Female BALB/c mice were intravenously injected with the M. tuberculosis strain H37Rv at 0 h zeitgeber time (ZT0) or 12 h zeitgeber time (ZT12). The expression and activity of MMP-1, -2, -3, and -9 in lungs and spleens were then evaluated. In vitro, peritoneal macrophages were harvested at ZT0 or at ZT12 and infected with 10 MOI M. tuberculosis. The expression of MMPs, microRNA-223 and BMAL1 was analyzed by qRT-PCR and/or Western blot. The binding of BMAL1 3'-UTR by miR-223 was confirmed by luciferase activity assay. Additionally, wild-type BMAL1 or NLSmut BMAL1 plasmids were transfected to evaluate the effect of BMAL1 on MMPs. The results showed a differential expression of MMPs in mice tissues infected at different times. M. tuberculosis infection caused enhanced MMP-1, -9, and miR-223 expression, with inhibited BMAL1 expression. MiR-223 modulated BMAL1 expression via the direct binding of BMAL1 3'-UTR. Furthermore, wild-type BMAL1 other than NLSmut BMAL1 attenuated MMPs expression in M. tuberculosis-infected macrophages. Overall, this study demonstrated a potential involvement of circadian rhythm in MMP activation by M. tuberculosis in macrophages. J. Cell. Biochem. 118: 4804-4812, 2017. © 2017 Wiley Periodicals, Inc.


Extended Plant Metarhizobiome: Understanding Volatile Organic Compound Signaling in Plant-Microbe Metapopulation Networks.
Plant rhizobiomes consist of microbes that are influenced by the physical, chemical, and biological properties of the plant root system. While plant-microbe interactions are generally thought to be local, accumulating evidence suggests that topologically disconnected bulk soil microbiomes could be linked with plants and their associated rhizospheric microbes through volatile organic compounds (VOCs). While several studies have focused on the effect of soil physicochemical properties for VOC movement, it is less clear how VOC signaling is affected by microbial communities themselves when VOCs travel across soils. To gain a better understanding of this, we propose that soil microbe-plant communities could be viewed as "metarhizobiomes," where VOC-mediated interactions extend the plant rhizobiome further out through interconnected microbial metapopulation networks. In this minireview, we mainly focus on soil microbial communities and first discuss how microbial interactions within a local population affect VOC signaling, leading to changes in the amount, type, and ecological roles of produced VOCs. We then consider how VOCs could connect spatially separated microbial populations into a larger metapopulation network and synthesize how (i) VOC effects cascade in soil matrix when moving away from the source of origin and (ii) how microbial metapopulation composition and diversity shape VOC-signaling between plants and microbes at the landscape level. Finally, we propose new avenues for experimentally testing VOC movement in plant-microbe metapopulation networks and suggest how VOCs could potentially be used for managing plant health in natural and agricultural soils.


[Genomic changes in primary lesion and lymph node metastases of esophageal squamous cell carcinoma].
Local lymph node and blood metastasis could occur at early stage of esophageal squamous cell carcinoma (ESCC), which may be the key factors of its recurrence and poor prognosis. However, the mechanism of ESCC metastasis is unclear. This study was to analyze the genetic changes in primary lesion and lymph node metastases of ESCC, to screen for and locate ESCC metastasis-related genes. Genomic alterations in 15 pairs of primary lesions and matched metastatic lymph nodes of ESCC were analyzed by comparative genomic hybridization (CGH). In the 15 pairs of tissues, the most common chromosomal alterations were the gains of 3q, 8q, 6p, 20p, 5p, 18p, 2p, 2q and 1q, and the losses of 10p, 10q, 17p, 18q, 4p and 13q. Of these changes, the most significant finding was the gain of 6p with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions, and the gain of 20p with a frequency of 73% in metastatic lymph nodes and 33% in primary lesions. The second interesting finding was the loss of 10p with a frequency of 53% in metastatic lymph nodes and 13% in primary lesions, and the loss of 10q with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions. The gains of 6p and 20p and the losses of 10p and 10q are common genomic alterations in primary lesion and lymph node metastases of ESCC, which may code ESCC metastasis-related genes.


Tissue factor-mediated activation of the prothrombin complex concentrate (PCC) is differently inhibited by dabigatran, rivaroxaban, and apixaban: potential clinical implication.
Currently, several newer oral anticoagulants namely dabigatran (anti-IIa), rivaroxaban (anti-Xa), and apixaban are available for various clinical implications. Another oral anti-Xa edoxaban is under development. A parenteral anti-Xa drug namely otamixaban is also under development for cardiovascular interventions. Bleeding complications have been reported in the new oral anticoagulants and have been managed by conventional approaches with limited success. Prothrombin complex concentrates (PCCs) are reported to neutralize the anticoagulant activity of these agents. The PCCs are also able to generate endogenous factor Xa and IIa along with other proteases that are capable of neutralizing the circulating anti-Xa or anti-IIa activities of the newer anticoagulants. The generation of Xa and IIa is also dependent on the type of tissue factor available for their activation. These reported studies suggest that different tissue factors differentially activate a PCC namely Profilnine SD. Furthermore, dabigatran differs from rivaroxaban and other factor Xa inhibitors in its inhibitory profile.


Epigenetic tailoring for the production of anti-infective cytosporones from the marine fungus Leucostoma persoonii.
Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B (1, 360%), C (2, 580%) and E (3, 890%), as well as the production of the previously undescribed cytosporone R (4). Cytosporone E was the most bioactive, displaying an IC(90) of 13 µM toward Plasmodium falciparum, with A549 cytotoxicity IC(90) of 437 µM, representing a 90% inhibition therapeutic index (TI(90) = IC(90) A459/IC(90)P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 µM and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 µM).


Three new alkaloids from the seeds of Nigella glandulifera.
Three new alkaloids namely 8-(4-hydroxyphenyl)-6-methoxy-3,4-dihydroisoquinolin-1(2H)-one (1), 4-aminonigellidine (2), and N-[(4-hydroxy-2-isopropyl-5-methyl)]phenylurea (3), along with six known ones (4-9), were isolated from the seeds of Nigella glandulifera. The structures of 1-3 were determined through spectroscopic analyses (HRESIMS, 1D/2D NMR). Compound 1 was a rare isoquinolinone alkaloid with phenyl substituted at C-8.


Non-redox metal ion promoted oxygen transfer by a non-heme manganese catalyst.
This work demonstrates that non-redox metal ions as Lewis acids can sharply improve the oxygen transfer efficiency of a manganese(II) catalyst having a non-heme ligand. In the absence of Lewis acid, oxidation of a manganese(II) complex will generate the known di-μ-oxo-bridged dinuclear Mn2(III,IV) core which is very sluggish for olefin epoxidation. Adding non-redox metal ions causes the dissociation of the dinuclear core, leading to sharp improvement in its oxygen transfer efficiency.


Experiencing the Surge: Report From a Large New York Radiation Oncology Department During the COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic is affecting all aspects of life and changing the practice of medicine. Multiple recommendations exist on how radiation oncology practices should deal with this crisis, but little information is available on what actually happens when the COVID-19 surge arrives. New York City experienced the first surge of COVID-19 in the United States and is now the epicenter of the global pandemic. This study reviews how COVID-19 has affected aspects of medicine, nursing, radiation therapy, and administration in a hospital system in New York. A retrospective review was conducted of the department of radiation oncology in a single health system in New York from March 1, 2020, to April 1, 2020. Collaboration was obtained from physicians, nurses, radiation therapy staff, and administration to recall their policies and effect on specific duties. A timeline was reconstructed to chronicle significant events. Numbers were obtained for patients on treatment, treatment breaks, and COVID-19 infections among staff and patients. The COVID-19 surge has had a tremendous effect on the health system, such as cessation of all of surgeries, including oncologic surgery, and transfer of all inpatient oncology services to makeshift outpatient facilities. Radiation oncology has made aggressive efforts to reduce the number of patients in treatment to protect patients and staff and to reallocate staff and space for more acute clinical needs. Patients on-beam were reduced by 27% from 172 to 125 by April 1. Almost all visits were changed to telemedicine within 2 weeks. Infection rates and quarantine were quite low among staff and patients. The majority of residents were deployed into COVID-19 clinical settings. Although we "planned for the worst," our health system was able to make necessary changes to still function at a reduced capacity. Our experience will give other departments a concrete experience to help them make their own policies and manage expectations.


Necessity of a two-stage process for the production of azadirachtin-related limonoids in suspension cultures of Azadirachta indica.
The effect of major nutrients on growth and azadirachtin-related limonoids (AZRL) production in plant cell culture of Azadirachta indica (neem) was studied with the objective to increase the yield of AZRL, one of the major group of pesticidal compounds found in intact neem trees. We report the novel online monitoring of plant cell respiration activities in a new parallel shake flask measuring device. Results obtained using three standard plant cell culture media showed non-growth-associated production characteristics for AZRL. These findings were supported by the oxygen uptake rate data. Further investigations on AZRL production in a modified MS medium with different concentrations of nitrogen and phosphorus sources resulted in 0.25 mg.g(-1) dry weight of AZRL, compared to no detectable AZRL production in standard MS media. These characteristics suggest the necessity of a two-stage process for the production of AZRL in plant cell culture. Compared to the single-stage process, an almost twofold increase in the volumetric productivity of AZRL was achieved using the two-stage process.


The role of macrophage polarization on fibroblast behavior-an in vitro investigation on titanium surfaces.
This study investigated the effect of smooth and rough titanium surface topographies on macrophage polarization and their influence on gingival fibroblast behavior cultured on titanium surfaces. RAW 264.7 macrophages were seeded on smooth (pickled titanium (PT)) and rough Sand-blasted with Large grit particles followed by Acid-etching (SLA) titanium surfaces and first investigated for macrophage polarization towards tissue-inflammatory M1 macrophages or wound-healing M2 macrophages. Thereafter, culture media collected from macrophages on both surfaces were cultured with gingival fibroblasts seeded on their respective topographies. All experiments were performed in triplicate with three independent experiments. Macrophages seeded on SLA surfaces polarized towards tissue-inflammatory M1 macrophages at early time points. Immunofluorescent staining and RT-PCR analysis demonstrated higher levels of iNOS and gene expression of IL-1β, IL-6, and TNF-alpha on SLA surfaces at 3 days when compared to both tissue culture plastic (TCP) and PT surfaces (p < 0.001). Very little differences were found between smooth PT surfaces and TCP. Interestingly, proliferation assay (CCK-8) suggested that conditioned media (CM) from macrophages seeded on SLA surfaces drastically inhibited gingival fibroblast proliferation at 3 and 5 days (p < 0.001). Meanwhile, CM from macrophages cultured on SLA surfaces also significantly reduced collagen 1 synthesis on SLA surfaces at 14 days as assessed by immunofluorescent staining (p < 0.001). The results from this study demonstrate that the polarization of macrophages towards a pro-inflammatory (M1) phenotype on SLA surfaces may have a negative impact on gingival fibroblast behavior on titanium surfaces. Future strategies to better modulate macrophage polarization should be investigated to support a favorable immune response and encourage tissue integration. As SLA surfaces have a potential to shift macrophages towards tissue-inflammatory M1 macrophages, this might be a negative impact for soft tissue healing. Therefore, SLA surfaces should be kept within the bone, as when in contact with soft tissue, they are prone to support a lack of soft tissue integration leading to inflammation.


L-DOPA and 5-HTP modulation of air-stepping in newborn rats.
In newborn rats, L-DOPA increases the occurrence of air-stepping activity without affecting movement characteristics. L-DOPA administration increases the spinal content of dopamine in a dose-dependent manner. Injection of 5-HTP increases the spinal serotonin content but does not trigger air-stepping. 5-HTP counteracts the pro-locomotor action of L-DOPA. Less dopamine and serotonin are synthesized when L-DOPA and 5-HTP are administered as a cocktail. The catecholamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is a well-established pharmacological agent for promoting locomotor action in vertebrates, including triggering air-stepping activities in the neonatal rat. Serotonin is also a well-known neuromodulator of the rodent spinal locomotor networks. Here, using kinematic analysis, we compared locomotor-related activities expressed by newborn rats in response to varying doses of L-DOPA and the serotonin precursor 5-hydroxytryptophan (5-HTP) administered separately or in combination. L-DOPA alone triggered episodes of air-stepping in a dose-dependent manner (25-100 mg/kg), notably determining the duration of locomotor episodes, but without affecting step cycle frequency or amplitude. In contrast, 5-HTP (25-150 mg/kg) was ineffective in instigating air-stepping, but altered episode durations of L-DOPA-induced air-stepping, and decreased locomotor cycle frequency. High performance liquid chromatography revealed that L-DOPA, which was undetectable in control conditions, accumulated in a dose-dependent manner in the lumbar spinal cord 30 min after its administration. This was paralleled by an increase in dopamine levels, whereas the spinal content of noradrenaline and serotonin remained unaffected. In the same way, the spinal levels of serotonin increased in parallel with the dose of 5-HTP without affecting the levels of dopamine and noradrenaline. When both precursors are administrated, they counteract each other for the production of serotonin and dopamine. Our data thus indicate for the first time that both L-DOPA and 5-HTP exert opposing neuromodulatory actions on air-stepping behaviour in the developing rat, and we speculate that competition for the production of dopamine and serotonin occurs when they are administered as a cocktail.


Irisin ameliorates myocardial ischemia-reperfusion injury by modulating gut microbiota and intestinal permeability in rats.
Recently, myocardial ischemia-reperfusion (I/R) injury was suggested associated with intestinal flora. However, irisin has demonstrated beneficial effects on myocardial I/R injury, thus increasing interest in exploring its mechanism. Therefore, whether irisin interferes in gut microbiota and gut mucosal barrier during myocardial I/R injury was investigated in the present study. Irisin was found to reduce the infiltration of inflammatory cells and fracture in myocardial tissue, myocardial enzyme levels, and the myocardial infarction (MI) area. In addition, the data showed that irisin reverses I/R-induced gut dysbiosis as indicated by the decreased abundance of Actinobacteriota and the increased abundance of Firmicutes, and maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the production of proinflammatory cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Based on the results, irisin could be a good candidate for ameliorating myocardial I/R injury and associated diseases by alleviating gut dysbiosis, endothelial dysfunction and anti-inflammatory properties.


Familial Mediterranean fever (FMF) mutations occur frequently in the Greek-Cypriot population of Cyprus.
Familial Mediterranean Fever (FMF) is an autosomal recessive disease of high prevalence within Mediterranean countries and particularly common in four ethnic populations: Arabs, non-Ashkenazi Jews, Armenians, and Turks. The responsible gene MEFV has been assigned to chromosome 16p13.3. Our aim was to establish the frequencies of the most common mutations in Greek-Cypriots. We found that 1 in 25 is a carrier of one of three mutations. V726A, M694V, and F479L. In 68 Grek-Cypriot FMF chromosomes analyzed, we found V726A (25%), F479L (20.6%), M694V (17.6%), and others (36.8%). Mutation F479L, relatively common in this population, is very rare elsewhere. Our study indicates that FMF is not a rare condition in Cyprus and that, because of the significant morbidity associated with this disorder, which is often diagnosed only after unnecessary surgeries, a newborn screening program to detect affected in this population may be warranted.


Geospatial assistive technologies for wheelchair users: a scoping review of usability measures and criteria for mobile user interfaces and their potential applicability.
Background: Wheelchair users are increasingly using route planners and navigation systems to help them get around the city. The absence of a list of usability criteria for wheelchair user-centred design and recommending geospatial assistive technologies creates uncertainty about the choices to be made by rehabilitation clinicians and geographic information systems specialists. The aim of this study was to compile such a list by identifying usability criteria from standardized questionnaires linked to user interfaces and geospatial assistive technologies (GATs).Material and methods: We conducted a scoping review in ACM Digital Library, Inspec/Compendex and PsycINFO for the period 2005-2016 using keyword strategies. From 84 articles identified, after screening and exclusion procedures, 15 articles were selected. Data were extracted from them and reported in table 1 (relevant questionnaires listed in alphabetical order, type of user interface, population studied, psychometric properties, type of measurement scale and information about the construct, number of subscales and items) and in table 2 (usability criteria up to 20 items for the questionnaires, scales or constructs, pointing criteria as gold standard in physical rehabilitation and as in geographic information).Results: We identified 87 usability criteria in 12 standardized questionnaires in 15 articles (with at least two types of psychometric properties). There are 54 usability criteria that could be used in clinical situations concerning their potential applicability to GATs for wheelchair users: 20 are familiar to rehabilitation clinicians who recommend assistive technologies, 21 are generic to GATs while 13 are specific to mobile applications or voice recognition systems. It remains 34 criteria that are not actually familiar to clinicians: actual use, content (including content-clarity, content-color, content-consistency, content-credibility, content-legibility, content-relevance, content-trustworthy, and content-understandable), control-obviousness, customer service behavior, delivery format, design-application, ease of navigation, entry-point type, everyday words, fingertip-size controls, font, functions-expected, functions-integration, gestalt, graphics, habit, hierarchy, input, network externality, speech characteristics, structure, subtle animation, time spent waiting, transition, user goal orientation and verbosity.Conclusions: More research is needed to develop a questionnaire specific to geospatial assistive technologies for wheelchair users linked with mobile applications and information content.Implications for rehabilitationFor manual wheelchair users paired with geospatial assistance technology, "effectiveness, efficiency, learnability and satisfaction" are essential criteria for route planning and navigation task.Clinicians can optimize the selection of a geospatial assistance technology considering 16 criteria: appearance, assistance-human support, comfort, ease of holding, ease of use, emotional aspect, endurance, facilitating conditions, intention to use, minimal memory load, physical effort, price value, simplicity, social influence, training and usefulness.Clinicians should have in mind that WC users want to plan a route with as few obstacles as possible. Information on the screen should be accessible to WC users (text, contrast, symbols, graphics, photos, voice, vibration, route views). Hands are occupied with the hand rims, WC users would prefer "listen to verbal" instructions to continue their route instead of looking on their electronic device. 34 criteria are specific for route planning and navigation task.


Evaluation of a cleavable stable isotope labeled synthetic peptide for absolute protein quantification using LC-MS/MS.
Protein cleavage coupled with isotope dilution mass spectrometry (PC-IDMS) has the potential to provide the absolute concentration of a specific protein, or multiple proteins, in complex mixtures. However, PC-IDMS differs from standard IDMS since the internal standard is a different molecule than the analyte at the start of the experiment, more specifically, the internal standard is a peptide and the analyte is a protein prior to cleavage. It is not until after the cleavage process that the stable isotope labeled synthetic peptide has the same physicochemical behavior as the peptide cleaved from the protein. The work presented here evaluates the use of tryptic cleavage sites incorporated into the internal standard synthetic peptide in an attempt to create an internal standard that has cleavage characteristics more similar to the protein being quantified. Results presented here suggest that an internal standard synthetic peptide incorporating internal cleavage sites does not improve the accuracy and precision of the values obtained when performing PC-IDMS.


Common sense dermatological drug suggestions for women who are breast-feeding.
Use of medications by breast-feeding mothers is not uncommon. When prescribing a medication to a nursing mother, the physician must weigh the potential risk of exposing the infant to the medication or the risks of not breast-feeding against the benefits of the medication to the mother. Information regarding the safety of common dermatological medications during lactation will be reviewed. Based on this information, treatment recommendations will be made.


Serum chitotriosidase levels in cancer patients undergoing high dose chemotherapy and stem cell transplantation.
Human chitotriosidase (ChT) is an active chitinase expressed by activated phagocytes. Increased ChT activity has been reported in systemic Candida albicans infections and in Gram-negative and Gram-positive bacterial infections, indicating that an increase in ChT activity reflects phagocyte activation. The aim of this study was to determine the changes in serum ChT activity in patients who underwent high dose chemotherapy (HDC) and stem cell transplantation (SCT), who are at an increased risk for fungal and bacterial infections due to depression of the immune system during the neutropenic period. A total of 55 SCT patients were included in the study. Serum ChT activity was determined before the initiation of HDC and during the neutropenic period after hematopoietic stem cell reinfusion on post-transplant first, fifth and tenth days. Chitotriosidase levels before transplantation were significantly lower than the results at first, fifth and tenth days post-hematopoietic stem cell reinfusion. Although the number of neutrophils was low, ChT enzyme activity was high in newly produced granules of neutrophils. Chitotriosidase may be supplemented as a drug for preventing and treating infections in the near future.


A gain-of-function mutant of Munc18-1 stimulates secretory granule recruitment and exocytosis and reveals a direct interaction of Munc18-1 with Rab3.
Munc18-1 plays a crucial role in regulated exocytosis in neurons and neuroendocrine cells through modulation of vesicle docking and membrane fusion. The molecular basis for Munc18 function is still unclear, as are the links with Rabs and SNARE [SNAP (soluble N-ethylmaleimide-sensitive factor-attachment protein) receptor] proteins that are also required. Munc18-1 can bind to SNAREs through at least three modes of interaction, including binding to the closed conformation of syntaxin 1. Using a gain-of-function mutant of Munc18-1 (E466K), which is based on a mutation in the related yeast protein Sly1p, we have identified a direct interaction of Munc18-1 with Rab3A, which is increased by the mutation. Expression of Munc18-1 with the E466K mutation increased exocytosis in adrenal chromaffin cells and PC12 cells (pheochromocytoma cells) and was found to increase the density of secretory granules at the periphery of PC12 cells, suggesting a stimulatory effect on granule recruitment through docking or tethering. Both the increase in exocytosis and changes in granule distribution appear to require Munc18-1 E466K binding to the closed form of syntaxin 1, suggesting a role for this interaction in bridging Rab- and SNARE-mediated events in exocytosis.


[Differential expression profile of miRNAs in amniotic fluid exosomes from fetuses with Down syndrome].
To investigate the role of miRNAs in amniotic fluid exosomes in growth and development of fetuses with Down syndrome (DS). Amniotic fluid were collected from 20 fetuses with DS and 20 normal fetuses (control) to extract amniotic exosome miRNA. MicroRNA sequencing technique was used to identify the differentially expressed miRNAs between the two groups, for which gene ontology (GO) and pathway analysis was performed. Three differentially expressed miRNAs with the strongest correlation with DS phenotype were selected for qPCR verification. Dual luciferase reporter assay was used to verify the activity of let-7d-5p for targeted regulation of BACH1. We identified 15 differentially expressed miRNAs in DS as compared with the control group, among which 7 miRNAs were up-regulated and 8 were down-regulated. Target gene prediction results showed that the differentially expressed miRNAs targeted 17 DS-related genes. GO analysis revealed that the main functions of the target genes involved protein binding, protein transport, ATP binding, transferase activity and synapses. Pathway analysis revealed that the functional pathways were closely related with the development of the nervous system. qPCR results showed that the expression levels of miR-140-3p and let-7d-5p were significantly lower in DS group than in the control group (P < 0.05), as was consistent with miRNA sequencing results; the expression level of miR-4512 was significantly higher in DS group than in control group (P < 0.05), which was contrary to miRNA sequencing results. The results of double luciferase reporter gene assay confirmed that let-7d-5p was capable of targeted regulation of BACH1 expression. Let-7d-5p in amniotic fluid exosomes may promote oxidative stress events in the brain of fetuses with DS by regulating BACH1 expression.


Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.
People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review. To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 24 June 2016. All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was no significant difference between treatment groups in: forced expiratory volume in one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48, moderate quality evidence); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16, low quality evidence); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13, low quality evidence); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42, low quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96, moderate quality evidence). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08, moderate quality evidence), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33, moderate quality evidence). The included trials did not report antibiotic resistance patterns or quality of life. Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.


Change in nasal congestion index after treatment in patients with chronic rhinosinusitis with nasal polyposis.
The management of chronic rhinosinusitis with nasal polyposis (CRSwNP) involves both surgical and medical approaches, and remains a controversial subject. The objective of this prospective, randomized, controlled trial was to compare the medical and surgical treatments of CRSwNP in terms of their effect on the nasal congestion index (NCI). Forty-eight patients with CRSwNP were randomized either to medical or surgical therapy. Pretreatment and 3- and 6-month posttreatment assessments of the visual analog scale score, the 20-Item Sino-Nasal Outcome Test, saccharine clearance time, nasal endoscopy, and NCI measurement with acoustic rhinometry were performed. Forty-one subjects were included in the analysis. Both the medical and surgical interventions for CRSwNP resulted in significant improvement in the visual analog scale score, 20-Item Sino-Nasal Outcome Test, saccharine clearance time, and nasal endoscopic examination scores. There was no difference between the two groups in terms of the percentage change from baseline for any of the parameters at the 6-month posttreatment assessment. NCI showed no significant difference from baseline. Similarly, no significant difference was found between the medical and surgical groups in terms of their effect on the NCI (p > 0.05). Because NCI does not correlate with standard subjective measures in outcomes for this group of patients, it cannot be used as an outcome measurement of treatment of subjects with CRSwNP. Results of this prospective randomized study did not find any additional benefit of surgical therapy over medical therapy in subjects with CRSwNP.


Income-related disparities in kidney transplant graft failures are eliminated by Medicare's immunosuppression coverage.
Beginning January 1, 2000, Medicare extended coverage of immunosuppression medications from 3 years to lifetime based on age >65 years or disability. Using United States Renal Data System (USRDS) data for Medicare-insured recipients of kidney transplants between July 1995 and December 2000, we identified four cohorts of Medicare-insured kidney transplant recipients. Patients in cohort 1 were individuals who were both eligible and received lifetime coverage. Patients in cohort 2 would have been eligible, but their 3-year coverage expired before lifetime coverage was available. Patients in cohort 3 were ineligible for lifetime coverage because of youth or lack of disability. Patients in cohort 4 were transplanted between 1995 and 1996 and were ineligible for lifetime coverage. Incomes were categorized by ZIP code median household income from census data. Lifetime extension of Medicare immunosuppression was associated with improved allograft survival among low-income transplant recipients in the sense that the previously existing income-related disparities in graft survival in cohort 2 were not apparent in cohort 1. Ineligible individuals served as a control group; the income-related disparities in graft survival observed in the early cohort 4 persisted in more recent cohort 3. Multivariate proportional hazards models confirmed these findings. Future work should evaluate the cost effectiveness of these coverage increases, as well as that of benefits extensions to broader patient groups.


Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.
Developing multiple cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the clinical genetic testing outcomes of these patients. We compared cancer index patients with ≥2 primary malignancies versus 1 primary cancer who underwent clinical evaluation and testing with multi-gene panels comprising up to 49 genes from 1998-2016. Among 1191 cancer index patients, 80.6%, 17.2%, and 2.2% respectively had 1, 2, and ≥3 primary malignancies. For patients with 2 primary cancers (n=205), the most common cancer pairs were bilateral breast (37.5%), breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231 (47.6%) with multiple malignancies. Pathogenic variants were found more frequently in younger patients, in those with a family history of cancer related to the suspected syndrome, and a trend towards significance in those with multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%), BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic mutations were in other moderate- to high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53. Patients with multiple cancers were more likely to carry pathogenic mutations than those with single cancer. About three-quarters of deleterious mutations in patients with multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi-gene panel testing facilitated the detection of mutations in another 6 genes and is warranted in this high-risk population.


Heparin binding affinity of normal and genetically modified antithrombin III measured using a monoclonal antibody to the heparin binding site of antithrombin III.
The inhibitory activity of the plasma serine proteinase inhibitor antithrombin III (AT III) is enhanced about 1000-fold upon binding to heparin. We have determined the dissociation constants, Kd, of 48.8 nM for the heparin-AT III interaction, of 175 nM for the specific pentasaccharide-AT III interaction, and of 13 microM for the low-affinity heparin-AT III interaction, using a binding assay based on a monoclonal antibody (MAb) that recognizes an epitope at or close to the heparin binding site of AT III. The heparin binding affinities and proportions of normal and variant AT III in plasma from patients with mutations of AT III have been quantitated for the first time using the binding assay. Substitution mutations in three regions of AT III have been investigated: (i) mutations in the reactive site loop affecting Ala382, Arg393, and Ser394 have no discernible effect on heparin binding; (ii) mutations in the previously identified N-terminal heparin binding region, affecting Arg47, Leu99, and Arg129, produce variant AT III molecules with heparin affinities reduced 11-924-fold, the largest reduction being observed for the substitution mutation Arg47-Cys in Padua 2, which has an affinity of 65.6 microM; (iii) mutations in the hydrophobic regions around strand 1C of the C terminus, affecting Phe402, Ala404, Asn405, Pro407, and Pro429, have pleiotropic effects that include the production of reduced amounts of low-affinity AT III with dissociation constants from 6 to 43 microM.(ABSTRACT TRUNCATED AT 250 WORDS)


Shearing particle monolayers: strain-rate frequency superposition.
We report surface shear rheological measurements on monolayers of silica nanoparticles at the air-water interface. We have used the method of strain-rate frequency superposition (SRFS) to characterize the structural relaxation. We show that the rheological properties of the layers have the same universal linear and nonlinear behavior as three-dimensional soft materials. We also discuss the original healing properties of these monolayers.


The Influence of Living Situations on Family Therapy Involvement Among Youth Adjudicated of a Sexual Crime.
Clinical and research professionals working with youth who have sexually offended have increasingly advocated for community-based care. However, other scholars have noted the appropriateness of residential placements for many youth. Research is inconclusive concerning the degree to which youth with sexually harmful behaviors receive family services, particularly family therapy in either community-based care settings or residential settings, and has yet to thoroughly identify how placement influences family therapy involvement. This study reviews the files of youth who have been adjudicated of a sexual crime (N = 85) to quantitatively identify how living situations influence family therapy involvement. Using bivariate estimations, findings reveal that youth living out of the home and those who change placements were more involved in family therapy than those treated in their own communities or homes. Implications and future research directions are considered.


Graphene Films: Synthesis of Graphene Films on Copper Foils by Chemical Vapor Deposition (Adv. Mater. 29/2016).
Synthesis of graphene films on copper foils is discussed by X. Li, L. Colombo, and R. S. Ruoff on page 6247. Graphene can grow on metal substrates by chemical vapor deposition of hydrocarbons. Hydrocarbons crack on a metal surface, nucleate, grow, and finally merge to form a continuous graphene film. Copper is one of the best candidates for graphene growth due to the advantages of good control over the graphene thickness, the growth of high-quality graphene, and the ease for graphene transfer, and has been widely used for production of large-area graphene films in both academia and industry.


Effects of Epigallocatechin-3-Gallate-Palmitate (EC16) on In Vitro Norovirus Infection.
Norovirus is the world-leading cause of acute gastroenteritis associated with severe symptoms and deaths. However, vaccines against norovirus are currently not available, and medications that specifically target human norovirus infection are still under development. The current study evaluated the virucidal and antiviral activities of epigallocatechin-3-gallate-palmitate (EC16), a compound derived from green tea polyphenols, against murine norovirus (MNV S99, a surrogate for human norovirus). Initially, formulation suitability tests were conducted to compare EGCG (epigallocatechin-3-gallate), EC16 and tea polyphenol-palmitate in alcohol solution and hand hygiene formulations. The virucidal activity of EC16 was then tested in hand sanitizer gel and hand sanitizer foam formulations using a TCID50 time-kill suspension assay. In vitro treatment and prevention tests were performed using a 1-hour incubation of EC16 or EGCG with RAW264.7 cells, either post-infection or pre-infection with MNV. Statistical analysis employed two-tailed student t test (alpha=0.05). Unlike EC16, both EGCG and tea polyphenol-palmitate showed auto-oxidation (color change) and precipitation in alcohol solution and hand hygiene formulations, and thus less suitable for potential hand hygiene product or new drug development. The time-kill suspension test results demonstrated that EC16 in both sanitizer gel and foam formulations reduced MNV by >99.99% (>log10 4) after 60 sec direct contact. One-hour incubation of EC16 with RAW264.7 cells either before or after MNV infection (i.e., without direct contact with MNV), resulted in >99% (>log10 2) reduction of MNV infectivity. EC16 is a candidate for use as a virucidal and antiviral compound to prevent and treat norovirus infection, with potential to be developed as a new drug against norovirus, pending in vivo and clinical tests.


1H- and 15N-NMR assignment and solution structure of the chemotactic Escherichia coli Che Y protein.
Che Y is a 129-residue parallel alpha/beta protein involved in bacterial chemotaxis. We have used this protein as a model to study the folding reaction of parallel alpha/beta proteins. As a first step we carried out the complete assignment of the 1H and 15N spectra from Escherichia coli Che Y protein on the basis of two-dimensional 1H homonuclear and 1H-15N heteronuclear experiments by using sequence-specific methods. Our assignments differ from the preliminary assignments made by Kar et al. [Kar, L., Matsumura, P. & Johnson, M.E. (1992) Biochem. J. 287, 521-531] of aromatic residues obtained by comparison of NOEs with short proton-proton distances in the crystal structure of Che Y. The analysis of the extension of the secondary elements, as well as a preliminary calculation of the three-dimensional structure, indicate that the solution structure is closely coincident with the single crystal structure determined by X-ray diffraction.


Experimental investigation of halogen-bond hard-soft acid-base complementarity.
The halogen bond (XB) is a topical noncovalent interaction of rapidly increasing importance. The XB employs a `soft' donor atom in comparison to the `hard' proton of the hydrogen bond (HB). This difference has led to the hypothesis that XBs can form more favorable interactions with `soft' bases than HBs. While computational studies have supported this suggestion, solution and solid-state data are lacking. Here, XB soft-soft complementarity is investigated with a bidentate receptor that shows similar associations with neutral carbonyls and heavy chalcogen analogs. The solution speciation and XB soft-soft complementarity is supported by four crystal structures containing neutral and anionic soft Lewis bases.


Tyr(less) kinase signaling during mitosis.
Tyrosine phosphorylation is rare, representing only about 0.5% of phosphorylations in the cell under basal conditions. While mitogenic tyrosine kinase signaling has been extensively explored, the role of phosphotyrosine signaling across the cell cycle and in particular during mitosis is poorly understood. Two recent, independent studies tackled this question from different angles to reveal exciting new insights into the role of this modification during cell division. Caron et al. 1 exploited mitotic phosphoproteomics data sets to determine the extent of mitotic tyrosine phosphorylation, and St-Denis et al. 2 identified protein tyrosine phosphatases from all subfamilies as regulators of mitotic progression or spindle formation. These studied collectively revealed that tyrosine phosphorylation may play a more prominent and active role in mitotic progression than previously appreciated.


Authentic learning in healthcare education: A systematic review.
The increasing complexity of the clinical environment demands a higher level of clinical performance competency. New pedagogical authentic learning methods have been developed to meet this need by bridging the gap between knowledge and practice. This systematic review aimed to examine authentic learning methods and their effects in healthcare education. Systematic review. Data were obtained from a literature search of Embase, PubMed, MEDLINE, CINAHL, PsycINFO, and Korean databases (e.g., KoreaMed) for studies published until May 2021. This review selected research papers documenting RCTs or quasi-experimental studies targeting undergraduate students training to become healthcare professionals. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The risk of bias assessment utilized the Joanna Briggs Institute (JBI) critical checklist. Of 20 selected studies, 12 studies were randomized controlled trials, while 8 had quasi-experimental designs with a control group. Simulation was identified as an effective educational method for authentic learning. Through authentic learning, undergraduate students cultivated their knowledge and learning motivation. However, divergent conclusions were shown for performance skills. Authentic pedagogical methodologies effectively enhanced learners' competencies in the cognitive, psychomotor, and affective domains. Integrating technological applications, e.g., e-learning or web-based approaches, facilitated education across academic boundaries. Further studies on combining technology with authentic learning approaches should be conducted to construct realistic educational environments for learners. CRD42021229350.


Sortase-Mediated High-Throughput Screening Platform for Directed Enzyme Evolution.
Sortase-catalyzed ligations have emerged as powerful tools for the site-specific ligation of peptides and proteins in material science and biocatalysis. In this work, a directed sortase evolution strategy (SortEvolve) has been developed as a general high-throughput screening (HTS) platform to improve activity of sortase A (application 1) and to perform directed laccase evolution through a semipurification process in 96-well microtiter plate (MTP) (application 2). A semipurification process in polypropylene MTP (PP-MTP) is achieved through the anchor peptide LCI, which acts as adhesion promoter. To validate the SortEvolve screening platform for both applications, three site-saturation mutagenesis (SSM) libraries of sortase A (Sa-SrtA) from Staphylococcus aureus (application 1) and two SSM libraries of the copper efflux oxidase (CueO laccase) from Escherichia coli (application 2) were generated at literature reported positions. After screening and rescreening, an array of Sa-SrtA variants (including the previously reported P94S, D160N, and D165A) and CueO variants (including the previously reported D439A and P444A) were identified. Further recombinant Sa-SrtA variant P94T/D160L/D165Q and CueO variant D439V/P444V were characterized with 22-fold and 103-fold improvements in catalytic efficiency compared with corresponding wild-types, respectively. An important advantage of the SortEvolve screening platform in comparison to many MTP-based screening systems is that the background noise was minimized (decreased 20-fold; application 2) due to the employed semipurification process. In essence, SortEvolve provides a universal surface-functionalized screening platform for sortases and enzymes in which especially background activity can be minimized to enable successful directed evolution campaigns.


Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography.
Five different morphological types of Maytenus ilicifolia of the same age and harvested under the same conditions showed distinct accumulations of some friedo-nor-oleananes. A rapid, sensitive and reliable reverse-phase HPLC method (employing an external standard) was used for the determination of the cytotoxic triterpenoids, 20 alpha-hydroxymaytenin, 22 beta-hydroxymaytenin, maytenin, celastrol and pristimerin in each of the five types. Well resolved peaks with good detection response and linearity in the range 1.0-100 micrograms/mL were obtained.


The effect of laparoscopy on intracranial pressure as measured by optic nerve sheath diameter: A review.
Laparoscopic surgery has many benefits over open surgery including lower complication rates, and shorter duration and lower cost of hospitalization. However, recent human literature suggests laparoscopy and carbon dioxide insufflation can result in intracranial hypertension. Invasive monitoring of intracranial pressure is not routinely performed in veterinary medicine, and ultrasonographic evaluation of the optic nerve sheath has been employed as an indirect measure of intracranial pressure in many species. The optic nerve sheath is continuous with the meninges of the brain and becomes distended with intracranial hypertension. Optic nerve sheath diameter is a reliable and consistent measure of intracranial pressure and has been utilized in humans to evaluate patients for intracranial hypertension secondary to laparoscopy and capnoperitoneum. No thorough evaluation of the effects of laparoscopy on intracranial pressure has been performed in dogs. Ultrasonographic evaluation of the optic nerve sheath is a safe, non-invasive, and inexpensive procedure that may allow for the evaluation of intracranial pressure without the need for invasive monitoring systems. As laparoscopic procedures are performed increasingly often, this review aims to inform the reader on the effects of capnoperitoneum and to facilitate appropriate patient selection, anesthetic considerations, and surgical planning.


Influence of surface roughness of universal shade resin composites on color adjustment potential.
This study aimed to determine the influence of surface roughness of the color adjustment potential restoration of universal resin composites. A structural colored resin composite (Omnichroma, OC) and a pigment-employed universal shade resin composite (Beautifil Unishade, BU) were used. Each resin composite was placed in a cavity to determine its ability to match the color of artificial teeth. The surface of the resin composites was polished with #800- or #2000-grit SiC paper before performing color measurements. One-way analysis of variance and Tukey post hoc tests were performed (α=0.05). The color difference (ΔE*ab) ranged from 2.5-3.9 for OC and 1.8-8.7 for BU. OC has a more stable color adjustment than BU. The color adjustment potential of universal resin composites was affected by the surface roughness of the restorations.


Antibodies with specificities against a dispase-produced 15-kilodalton hexon fragment neutralize adenovirus type 2 infectivity.
During the entrance of adenovirus type 2 into cells, it has been suggested that the virion undergoes a conformational change. In this investigation, we have further characterized the hypothetical conformational change, which the structural protein hexon undergoes in response to low pH. From pH 5.0 to pH 6.0, the proteolytic enzyme dispase cleaved the hexon into a few distinct fragments with a dominating low-molecular-weight fragment with a molecular weight of 15,000 (15K peptide), whereas between pH 6.5 and pH 8.0, the cleavage of the hexon was negligible. The degradation of the hexon with dispase at low pH was not due to an increased activity or alteration of the active site of dispase at low pH. The 15K fragment was identified as a segment of the N-terminal part of the hexon polypeptide beginning at amino acid residue 5. An immune serum produced in response to acid-treated and glutaraldehyde-fixed hexons contained a small amount of antibodies directed towards the 15K fragment, as judged by Western immunoblotting. An anti-15K antibody fraction was isolated by affinity chromatography by removing antibodies recognizing the hexon in the alkaline configuration. Such antibodies displayed a higher relative titer at pH 5.0 than at pH 7.5 in an enzyme-linked immunosorbent assay. The isolated antibodies showed a specific neutralizing capacity five times higher than that of the corresponding unfractionated polyclonal anti-hexon serum; however, the neutralizing ability was independent of pH. The neutralization of adenovirus type 2 infection by the isolated anti-15K antibodies implies that the N-terminal end of the hexon may play a critical role in the early steps of the virion-cell interaction.


[MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration].
Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNA molecules, which regulate the gene expression at the post-transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease.


Evidence for alpha-2 adrenoreceptor modulation of arterial chemoreflexes in the caudal solitary nucleus of the rat.
The caudal region of the nucleus of the solitary tract (cNTS) is the primary central termination site for arterial chemoreceptor afferents originating from the carotid body. The purpose of the present study was to investigate the role of endogenous activation of alpha-2 adrenoreceptors in the cNTS on arterial chemoreflex function. Arterial chemoreflex responses to intravenous injections of potassium cyanide (KCN; 75 microg/kg) were recorded before and following blockade of alpha-2 adrenoreceptors in the cNTS of urethane-anesthetized rats. KCN alone elicited a reflex increase in arterial pressure, renal sympathetic nerve activity, and respiration. After bilateral cNTS microinjection of alpha-2 receptor antagonists (2 nmol idazoxan or 0.2 nmol yohimbine), arterial chemoreflex responses were markedly attenuated. Attenuation of chemoreflex function was not accompanied by any significant change in resting blood pressure or respiratory rate. The results suggest that the endogenous activation of alpha-2 adrenoreceptors facilitates central processing of chemoreceptor afferent inputs in the cNTS of the rat.


Stimulation of carbohydrate metabolism reduces hypothermia-induced calcium load in fatty acid-perfused rat hearts.
In the present study we examined the impact of glycolysis and glucose oxidation on myocardial calcium control and mechanical function of fatty acid-perfused rat hearts subjected to hypothermia rewarming. One group (control) was given glucose (11.1 mM) and palmitate (1.2 mM) as energy substrates. In a second group glycolysis was inhibited by iodoacetate (IAA, 100 microM) and replacement of glucose with pyruvate (5 mM), whereas in the third group glucose oxidation was stimulated by administration of dichloroacetate (DCA, 1 mM) and insulin (500 microU/ml). All groups showed a rise in myocardial calcium ([Ca]total in response to hypothermia (10 degrees C). However, [Ca]total was significantly lower both in IAA- and DCA-treated hearts, as compared to controls (2.20 +/- 0.22 and 2.94 +/- 0.20 v 3.83 +/- 0.29 nmol/mg dry wt., P < 0.025). The reduced calcium load in the treated hearts was correlated with higher levels of high energy phosphates. Following rewarming control and DCA-treated hearts still showed elevated [Ca]total, whereas IAA-treated hearts [Ca]total was not different from the pre-hypothermic value. All groups showed a reduction in cardiac output following rewarming. Furthermore, the control group, in contrast to both IAA- and DCA-treated hearts, showed a significant reduction in systolic pressure. These results show that hypothermia-induced calcium uptake in glucose and fatty acid-perfused rat hearts was reduced by two different metabolic approaches: (1) inhibition of glycolysis by IAA while simultaneously by-passing the glycolytic pathway by exogenous pyruvate: and (2) stimulation of glucose oxidation by DCA. Thus, glycolytic ATP is not an essential regulator of sarcolemmal calcium transport under the present experimental conditions. Instead, we suggest that a change in oxidative substrate utilization in favour of carbohydrates may improve myocardial calcium homeostasis during hypothermia and rewarming.