Ocular residual astigmatism (ORA) does not seem to correlate with baseline refractive error among refractive surgery candidates.
Ocular residual astigmatism (ORA) is defined as the difference between refractive astigmatism and anterior corneal astigmatism. A high ORA may be correlated with poorer results in patients undergoing corneal-based laser surgery. Is a high baseline refractive error related to a higher degree of ORA? This was a retrospective analytical study including 181 right eyes of an equal number of refractive surgery candidates. Manifest subjective refraction was measured, along with a Pentacam AXL Wave corneal tomography. Via a vector analysis with this methodology, subjective cylinder was translated into the corneal plane and a vectorial subtraction was performed in order to measure ORA. Spearman's rank order test, one-way ANOVA and Chi-square were used to determine whether different levels of baseline refractive error correlate with different levels of ORA. Mean age was 28.33 ± 4.71 years with a female preponderance (65.7%). Mean ORA was 0.74 ± 0.39 D, with 33.1% of eyes having an ORA ≥ 0.90 D. There was not a correlation between ORA and level of myopia (rho = - 0.022; p = 0.764), nor between ORA and spherical equivalent (rho = 0.009; p = 0.903). Refractive astigmatism did not demonstrate to be correlated with ORA level either (rho = 0.078; p = 0.329). One-way ANOVA tests failed to demonstrate an association between different classifications of refractive error and level of ORA. In the studied population, ORA is not correlated with baseline refractive error. Every patient presenting for possible corneal-based laser refractive surgery should be evaluated for a possible high level of ORA, irrespective of their baseline ametropia level.


Hybridization-based aptamer labeling using complementary oligonucleotide platform for PET and optical imaging.
Aptamers are promising next-generation ligands used in molecular imaging and theragnosis. Aptamers are synthetic nucleic acids that can be held together with complementary sequences by base-pair hybridization. In this study, the complementary oligonucleotide (cODN) hybridization-based aptamer conjugation platform was developed to use aptamers as the molecular imaging agent. The cODN was pre-labeled with fluorescent dye or radioisotope and hybridized with a matched sequence containing aptamers in aqueous conditions. The cODN platform-hybridized aptamers exhibited good serum stability and specific binding affinity towards target cancer cells both in vitro and in vivo. These results suggest that the newly designed aptamer conjugation platform offers great potential for the versatile application of aptamers as molecular imaging agents.


Pre-operative variables including fitness associated with complications after oesophagectomy.
Oesophagectomy is a technically-demanding operation associated with a high level of morbidity. We analysed the association of pre-operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02-1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre-operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37-0.80), p = 0.002 and 0.89 (0.82-0.96), p = 0.004, respectively. Survival was associated with the ratio of expected-to-observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03-0.91), p = 0.039 and 0.96 (0.90-1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17-1.63), p < 0.0001.


Neurofibroma and epidermoid cyst: unexpected findings after first foreskin retraction.
We report here 2 unusual cases of tumor of the glans penis in children. Abnormal findings were found on a 12-year-old and a 13-year-old boy soon after their first foreskin retraction. Initial medical examination suggested inclusions of smegma and they were referred to our Department of Pediatric Urology. Complete resection was performed under general anesthesia. Histologic examination revealed an epidermoid cyst in the first patient and a solitary neurofibroma in the second. These patients represent respectively the third and the second cases of such entities described in the pediatric age group. Cautious examination is required for persistent inclusions of smegma.


Production of fertile transgenic wheat plants via tissue electroporation.
Electroporation has been used effectively to deliver DNA into the tissue of intact wheat immature embryos. Transformed plantlets have been recovered after electroporation using field strengths of 275 and 750 V/cm, 960-µF capacitor and 50 µg/ml of linear plasmid DNA, containing bar and uidA genes. The field strength of 750 V/cm proved to be more effective for DNA delivery (estimated by transient GUS expression) and for recovery of transformed plants (two transgenic plants were recovered with an efficiency of 0.4%). After application of a field strength of 275 V/cm there was no visual evidence of transient GUS expression, but one transgenic plant was recovered with an efficiency of 0.2%, based on the number of electroporated embryos. This indicates that the amount of DNA delivered into the cells was too low for visual identification of transient GUS expression and that GUS expression may not provide an appropriate assessment of the efficiency of DNA delivery. Southern blot hybridisation has revealed a low copy number of transgene integration with some rearrangements in integrated loci. None of the transgenic plants has shown any visual GUS expression, although we could amplify the transcript of the uidA gene in T(0) progeny using RT-PCR. This may indicate that suppression of uidA expression occurred at the post-transcriptional level. The efficiency of tissue electroporation is still dependent on the quality of the plant material which is used but the transformation events were reproducible from one group of experiments to another. At present, this technique is dependent on a combination of factors including pretreatments of the recipient tissue, quality of tissue culture and optimisation of electroporation conditions.


Uptake and release of p-dichlorobenzene in early life stages of Salmo gairdneri.
Early life stages of Salmo gairdneri from eggs to alevins were exposed to p-dichlorobenzene (p-DCB) in a series of short-term uptake and release studies and in a long-term continuous test at three different concentrations from 3 to 79 micrograms/liter. Water concentration was frequently checked and the concentration of p-DCB in eggs and alevins was determined by gas chromatographic analysis of hexane extracts. Total and neutral lipids in the different stages were also determined. Neither macroscopic malformations nor histological changes were observed at hatching. The highest concentration (about 1/10th of the incipient lethal level for alevins of S. gairdneri) did not show any significant difference in mortality compared to the control. Bioconcentration factors (BCF) experimentally determined on alevins agreed with the theoretical ones, calculated on the basis of water solubility, whereas higher contents of p-DCB up to one order of magnitude were observed in some stages before the hatching. The hypothesis relating accumulation to lipid content was tested; higher concentration factors (CF) of p-DCB were found in stages with higher lipid levels, particularly eggs. Metabolic modifications, occurring during the hatching, on the other hand, increase the rate of release in spite of the still high lipid content at this stage. Kinetic constants of uptake and release were determined for eggs and alevins. It is concluded that more attention has to be paid to compounds with medium theoretical BCF to evaluate the effective accumulation potential of early life stages as in general compounds with very high BCF have a slow rate of uptake.


Roles and mechanisms of renalase in cardiovascular disease: A promising therapeutic target.
Cardiovascular disease (CVD) is prevalent worldwide and remains a leading cause of death. Although substantial progress has been made in the diagnosis and treatment of CVD, the prognosis remains unsatisfactory. Renalase is a newly discovered cytokine that is synthesized by the kidney and then secreted into blood. Numerous studies have suggested the efficacy of renalase in treating CVD by metabolizing catecholamines in the circulatory system. As a new biomarker of heart disease, renalase is normally recognized as a signalling molecule that activates cytoprotective intracellular signals to lower blood pressure, protect ischaemic heart muscle and promote atherosclerotic plaque stability in CVD, which subsequently improves cardiac function. Due to its important regulatory role in the circulatory system, renalase has gradually become a potential target in the treatment of CVD. This review summarizes the structure, mechanism and function of renalase in CVD, thereby providing preclinical evidence for alternative approaches and new prospects in the development of renalase-related drugs against CVD.


Attitudes and access to resources and strategies to improve quality of radiotherapy among US radiation oncologists: A mixed methods study.
We aimed to assess contouring-related practices among US radiation oncologists and explore how access to and use of resources and quality improvement strategies vary based on individual- and organization-level factors. We conducted a mixed methods study with a sequential explanatory design. Surveys were emailed to a random 10% sample of practicing US radiation oncologists. Participating physicians were invited to a semi-structured interview. Kruskal-Wallis and Wilcoxon rank-sum tests and a multivariable regression model were used to evaluate associations. Interview data were coded using thematic content analysis. Survey overall response rate was 24%, and subsequent completion rate was 97%. Contouring-related questions arise in ≥50% of clinical cases among 73% of respondents. Resources accessed first include published atlases (75%) followed by consulting another radiation oncologist (60%). Generalists access consensus guidelines more often than disease-site specialists (P = 0.04), while eContour.org is more often used by generalists (OR 4.3, 95% CI 1.2-14.8) and younger physicians (OR 1.33 for each 5-year increase, 95% CI 1.08-1.67). Common physician-reported barriers to optimizing contour quality are time constraints (58%) and lack of access to disease-site specialists (21%). Forty percent (40%, n = 14) of physicians without access to disease-site specialists indicated it could facilitate the adoption of new treatments. Almost all (97%) respondents have formal peer review, but only 43% have contour-specific review, which is more common in academic centres (P = 0.02). Potential opportunities to improve radiation contour quality include improved access to disease-site specialists and contour-specific peer review. Physician time must be considered when designing new strategies.


Synthesis and biological activity of organothiophosphoryl polyoxotungstates.
Organothiophosphoryl polyoxotungstates R(contains)XW(infinityinfinity)O(contains exists) (/-) , R(contains) P(contains)W(infinity),O(infinity) (/-), R(contains)PW( exists)O(contains) (Delta) (-)(X = P, Si, Ge, B or Ga; R = PhP(S), C(6)H(11)P(S)) have been prepared from lacunary polyoxoanions and PhP(S). The products were characterized by elemental analysis, IR, and NMR spectroscopy. According to spectroscopic observations, the hybrid anions consist of a lacunary anion framework on which are grafted two equivalent or groups through P-O-W bridges. Some of the title compounds showed the antigerm activity.


Potential role of entactin in hemostasis. Specific interaction of entactin with fibrinogen A alpha and B beta chains.
The interactions between the endothelial basement membrane, platelets, and coagulation factors play essential roles in hemostasis. Entactin is an integral and ubiquitous component of the basement membrane. Experiments were designed to study the interactions between entactin and blood coagulation factors. We have demonstrated, for the first time, that entactin interacts with fibrinogen in a specific manner. Entactin binding sites have been localized to the A alpha and B beta chains of fibrinogen. The binding of entactin to either the A alpha chain or the B beta chain was divalent cation-independent. The binding of 35S-labeled entactin to the immobilized fibrinogen A alpha or B beta chain was concentration-dependent and saturable and could be inhibited by unlabeled entactin, soluble fibrinogen, anti-entactin antiserum, or anti-fibrinogen antiserum. In addition, we have provided evidence that entactin can be cross-linked to itself, and probably also to fibrin(ogen), by transglutaminase. These novel properties, together with its cell binding, chemotactic, and phagocytic promoting activities and ubiquitous distribution in basement membranes, suggest that entactin may play important roles in hemostasis and wound healing.


5-HT4 receptor mediated stimulation of gastric emptying in rats.
It is well documented that certain substituted benzamides, such as cisapride, and benzimidazolones, such as BIMU 8, enhance gastric emptying in rats. As these compounds possess 5-HT3 antagonistic and 5-HT4 agonistic properties, the precise mechanisms (5-HT3 or 5-HT4) underlying their gastroprokinetic effects is still unclear. In the present study, we used SC 49518 (a benzamide and selective 5-HT4 receptor agonist) and two selective 5-HT4 receptor antagonists (RS 23597-190 and SB 204070) to elucidate the role of 5-HT4 receptors in gastroprokinesis. SC 49518 (1-316 micrograms/kg; ip) produced significant and dose-dependent stimulation of gastric emptying in rats (ED50 = 2.3 micrograms/kg; ip). SC 49518 also produced dose-dependent inhibition of bradycardia induced by 2-methyl 5-HT (von Bezold-Jarisch reflex) but with a 156 fold lower potency (ID50 = 0.36 mg/kg; ip). The gastroprokinetic effects of SC 49518 (3-316 micrograms/kg; ip) were significantly antagonized by the selective 5-HT4 receptor antagonist RS 23597-190 (0.1 mg/kg/min; iv). SB 204070 (0.003-1 mg/kg; ip), another selective 5-HT4 receptor antagonist, produced dose-dependent inhibition of the gastroprokinetic effects of SC 49518 (10 micrograms/kg; ip), the inhibition attaining statistical significance at the dose of 0.1 mg/kg; ip. RS 23597-190 had no effects on gastric emptying per se whereas SB 204070 significantly increased gastric emptying by itself at 1 mg/kg; ip but not at 0.1 mg/kg; ip. These findings show, for the first time, that SC 49518, a selective 5-HT4 receptor agonist, produces potent stimulation of gastric emptying in rats via a mechanism involving activation of 5-HT4 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in function and morphology of normal human skin: evaluation using optical coherence tomography.
Optical coherence tomography (OCT) is a noninvasive morphological method for investigating human skin. It allows high-resolution in vivo imaging of inflammatory skin diseases and tumours. Because it is a newly developed method, systematic studies on standardization and on evaluation of factors influencing the representation of the skin have not yet been performed. In this study, normal human skin was treated with various external stimuli which induce changes of function and morphology. Changes in stratum corneum thickness as well as changes induced by pigmentation, oedema and erythema were investigated using OCT. Healthy skin of human volunteers was treated with tape stripping, ultraviolet A irradiation, water, histamine, nicotinic acid and various ointments. In the tape stripping experiment, the thickness of the horny layer was quantified and monitored. Pigmentation increased the light attenuation of the tissue, whereas hydration and erythema led to a slight decrease of scattering. Topical treatment of the skin gave a nonspecific increase of penetration depth of the light due to the lower reflectivity of the surface. There are various physiological conditions which influence optical properties of the skin. These parameters should be considered when performing standardized OCT studies.


Value of Neutrophil to Lymphocyte Ratio and Its Trajectory in Patients Hospitalized With Acute Heart Failure and Preserved Ejection Fraction.
The neutrophil to lymphocyte ratio (NLR) has been proposed as a simple and routinely obtained marker of inflammation. This study sought to determine whether the NLR on admission as well as NLR trajectory would be complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score in patients hospitalized with acute heart failure with preserved ejection fraction (HFpEF).Using the Stanford Translational Research Database, we identified 443 patients between January 2002 and December 2013 hospitalized with acute HFpEF and with complete data of NLR both on admission and at discharge. The primary endpoint was all-cause mortality. Mean age was 77 ± 16 years, 58% were female, with a high prevalence of diabetes mellitus (35.4%), coronary artery disease (58.2%), systemic hypertension (96.6%) and history of atrial fibrillation (57.5%). Over a median follow-up of 2.2 years, 121 (27.3%) patients died. The median NLR on admission was 6.5 (IQR 3.6 - 11.1); a majority of patients decreased their NLR during the course of hospitalization. On multivariable Cox modeling, both NLR on admission (HR 1.18 95% CI (1.00 - .38), p = 0.04) and absolute NLR trajectory (HR 1.26 95% CI (1.10 - 1.45), p = 0.001) were shown to be incremental to GWTG-HF risk score (p < 0.05) for outcome prediction. Adding the NLR or absolute NLR trajectory to the GWTG-HF risk score significantly improved the area under the operator-receiver curve and the reclassification up to 3 years after admission.This simple, readily available marker of inflammation may be useful when stratifying the risk of patients hospitalized with HFpEF.


Irreversible inhibition of aldolase by a phosphorylated alpha-dicarbonyl compound.
The preparation of a phosphorylated alpha-dicarbonyl compound designed to specifically react with arginine residues of enzymes accepting phosphorylated compounds as effectors is reported, and shown to inhibit rabbit muscle aldolase in a time-dependent and irreversible manner. This irreversible inhibition occured in a buffer devoid of borate ions, suggesting that the presence of the phosphate moiety contributes in the stabilization of the adduct formed with arginine residues. Under the same conditions, the metalloenzyme iron superoxide dismutase, in which an arginine is known to be critical for the catalytic function, is not significantly inhibited.


Flurbiprofen and immunosuppression of Trypanosoma brucei infection in the goat.
Goats infected with Trypanosoma brucei and treated with the non-steroidal anti-inflammatory agent flurbiprofen, showed a marked increase in parasitaemia, followed in one of the four goats by death. The in vitro response to mitogens of peripheral blood lymphocytes and separated T- and B-lymphocytes from healthy goats treated with flurbiprofen was normal when compared with non-treated animals. T. brucei-infected goats, not treated with flurbiprofen, showed a marked immunosuppression which was mainly localized in the B-enriched lymphocyte fraction. A combination of T. brucei infection and treatment with flurbiprofen led to even more suppression, because the T-lymphocyte function was also suppressed. It is concluded that flurbiprofen first causes a rise in the parasitaemia and that this high parasitaemia is responsible for the observed immunosuppression.


Pulmonary Manifestations of Primary Immunodeficiency Disorders.
Pulmonary disease, ranging from infectious pneumonia, lung abscess, and empyema to structural lung diseases to malignancy, significantly increase morbidity and mortality in primary immune deficiency. Treatment with supplemental immunoglobulin (intravenous or subcutaneous) and antimicrobials is beneficial in reducing infections but are largely ineffective in preventing noninfectious complications, including interstitial lung disease, malignancy, and autoimmune disease. A low threshold for suspecting pulmonary complications is necessary for the early diagnosis of pulmonary involvement in primary immunodeficiency disorders, before irreversible damage is done, to improve patient outcomes.


Rapid dimethyl sulfoxide-modified acid-fast stain of Cryptosporidium oocysts in stool specimens.
A rapid dimethyl sulfoxide modification of an acid-fast technique was applied to direct fecal smears to monitor cryptosporidiosis in nonhuman primates. Brilliantly stained pink oocysts against a pale green background demonstrated well-preserved internal morphology and facilitated rapid, simple, noninvasive diagnosis without fluorescent or phase-contrast microscopy.


Clinical added value of interictal automated electrical source imaging in the presurgical evaluation of MRI-negative epilepsy: A real-life experience in 29 consecutive patients.
During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.


Neural systems underlying reward and approach behaviors in childhood and adolescence.
Transitions into and out of adolescence are critical developmental periods of reward-seeking and approach behaviors. Converging evidence suggests that intriguing reward-related behavioral shifts are mediated by developmental changes in frontostriatal circuitry. This chapter explores how the conceptual frameworks and empirical studies in the field of developmental cognitive neuroscience have contributed to understanding reward-related behavior across development.The chapter concludes with some implications for adaptive and maladaptive behaviors that arise from these behaviors as children transition from childhood to adolescence.


RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group.
Autologous stem cell transplantation (ASCT) combined with novel agents is the standard treatment for transplant-eligible, newly diagnosed myeloma (NDMM) patients. Lenalidomide is approved for maintenance after ASCT until progression, although the optimal duration of maintenance is unknown. In this trial, 80 patients with NDMM received three cycles of lenalidomide, bortezomib, and dexamethasone followed by ASCT and lenalidomide maintenance until progression or toxicity. The primary endpoint was the proportion of flow-negative patients. Molecular response was assessed if patients were flow-negative or in stringent complete response (sCR). By intention to treat, the overall response rate was 89%. Neither median progression-free survival nor overall survival (OS) has been reached. The OS at 3 years was 83%. Flow-negativity was reached in 53% and PCR-negativity in 28% of the patients. With a median follow-up of 27 months, 29 (36%) patients are still on lenalidomide and 66% of them have sustained flow-negativity. Lenalidomide maintenance phase was reached in 8/16 high-risk patients but seven of them have progressed after a median of only 6 months. In low- or standard-risk patients, the outcome was promising, but high-risk patients need more effective treatment approach. Flow-negativity with the conventional flow was an independent predictor for longer PFS.


Contrast echocardiography: evidence for clinical use.
The failure of echocardiography to give diagnostically useful information in a significant proportion of patients has led to the development of specific contrast agents to enhance imaging. Suitable contrast media must have the ability to modify ultrasound characteristics, be capable of crossing the pulmonary capillary bed, show stability over the duration of a procedure, offer low blood solubility with low toxicity and be rapidly eliminated. The current generation of ultrasound contrast agents comprises microbubbles of a high molecular-weight gas encapsulated in a shell of phospholipid or protein. A review of the clinical evidence shows that these agents are clinically effective in enhancing echocardiographic imaging. They enable the rescue of failed procedures, often sparing patients from invasive tests, but appear not to add to the burden of side effects. Indeed, the benefits of using contrast agents in stress echocardiography have been recommended in recently published American Society of Echocardiography guidelines. Myocardial contrast echocardiography has now developed to the stage where assessment of myocardial perfusion for the detection of coronary artery disease is possible with the same diagnostic accuracy as radionuclide imaging. However, in comparison with the latter technique, it is less expensive, is more portable, and avoids the use of ionizing radiation. It is precisely the ability of myocardial contrast echocardiography to simultaneously assess function and perfusion at the bedside that has given it a unique role in clinical practice. This review provides an overview of the clinical evidence supporting the efficacy of contrast echocardiography in the assessment of myocardial structure, function, and perfusion.


Production of l-ribose from l-arabinose by co-expression of l-arabinose isomerase and d-lyxose isomerase in Escherichia coli.
l-Ribose is an important pharmaceutical intermediate that is used in the synthesis of numerous antiviral and anticancer drugs. However, it is a non-natural and expensive rare sugar. Recently, the enzymatic synthesis of l-ribose has attracted considerable attention owing to its considerable advantages over chemical approaches. In this work, a new strategy was developed for the production of l-ribose from the inexpensive starting material l-arabinose. The l-arabinose isomerase (l-AIase) gene from Alicyclobacillus hesperidum and the d-lyxose isomerase (d-LIase) gene from Thermoflavimicrobium dichotomicum were cloned and co-expressed in Escherichia coli, resulting in recombinant cells harboring the vector pCDFDuet-Alhe-LAI/Thdi-DLI. The co-expression system exhibited optimal activity at a temperature of 70 °C and pH 6.0, and the addition of Co2+ enhanced the catalytic activity by 27.8-fold. The system containing 50 g L-1 of recombinant cells were relatively stable up to 55 °C. The co-expression system (50 g L-1 of recombinant cells) afforded 20.9, 39.7, and 50.3 g L-1 of l-ribose from initial l-arabinose concentrations of 100, 300, and 500 g L-1, corresponding to conversion rate of 20.9%, 13.2%, and 10.0%, respectively. Overall, this study provides a viable approach for producing l-ribose from l-arabinose under slightly acidic conditions using a co-expression system harboring l-AIase and d-LIase genes.


Ageing of patients on chronic dialysis: effects on mortality--a 12-year study.
During the last few decades the mean age of subjects on chronic dialysis (CD) significantly increased. The effects of these changes on mortality rates, causes of death, early and long-term predictors for mortality have not yet been clarified. We analysed this issue through a study performed over a period of 12 years. We studied 8977 patients enrolled on the Lazio Dialysis Registry (Italy) in 1995-2006. We analysed annual mortality rates, causes of death, probability and determinants of the survival. The overall mortality rate was 14.6 deaths (95% CI: 14.2-14.9) per 100 person-years on CD, remaining essentially unchanged over the 12-year period, despite a 5-year increase in the median age. A reduction in mortality was found for patients >74 years from 29.8 (95% CI: 24.8-34.9) in 1995 to 22.5 (95% CI: 20.0-25.1) in 2006. No statistically significant differences were found over time in annual mortality rates by cause of death. The probability of survival was 0.86 1 year after starting dialysis and 0.33 after 12 years. We found a higher association between haematocrit levels, serum albumin, self-sufficiency and survival within 1 year of dialysis and between diabetes and survival after 1 year. The finding that the mortality rate of CD patients did not change over the last 12 years, despite concomitant and significant ageing of patients, supports the public health policy of providing CD to very old subjects. The identification of the clinical factors that predict survival underlines the role of clinicians in preventing and treating these conditions after the start of CD.


Hsa_circ_0003098 promotes bladder cancer progression via miR-377-5p/ACAT2 axis.
Accumulating evidence has proven that circRNAs play vital roles in tumor progression. Nevertheless, the mechanisms underlying circRNAs in bladder cancer (BCa) remain largely unknown. The purpose of this study was to identify the role and investigate the potential molecular mechanisms of hsa_circ_0003098 in BCa. We confirmed that hsa_circ_0003098 expression was significantly upregulated in BCa tissues, of which expression was remarkably associated with poor prognosis. Functionally, overexpression of hsa_circ_0003098 promoted BCa cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. Mechanistically, hsa_circ_0003098 promoted upregulation of ACAT2 expression and induced cholesteryl ester accumulation via acting as a sponge for miR-377-5p. Thus, hsa_circ_0003098 plays an oncogenic role in BCa and may serve as a potential biomarker and therapeutic target for BCa.


Exploring public attitudes toward live-streaming fitness in China: A sentiment and content analysis of China's social media Weibo.
Live-streaming fitness is perceived by the Chinese government as an invaluable means to reduce the prevalence of physical inactivity amid the COVID-19 pandemic. This study aims to investigate the public altitudes of the Chinese people toward live-streaming fitness and provide future health communication strategies on the public promotion of live-streaming fitness accordingly. This study collected live-streaming fitness-related microblog posts from July 2021 to June 2022 in Weibo, the Chinese equivalent to Twitter. We used the BiLSTM-CNN model to carry out the sentiment analysis, and the structured topic modeling (STM) method to conduct content analysis. This study extracted 114,397 live-streaming fitness-related Weibo posts. Over 80% of the Weibo posts were positive during the period of the study, and over 85% were positive in half of the period. This study finds 8 topics through content analysis, which are fitness during quarantine; cost reduction; online community; celebrity effect; Industry; fitness injuries; live commerce and Zero Covid strategy. It is discovered that the public attitudes toward live-streaming fitness were largely positive. Topics related to celebrity effect (5-11%), fitness injuries (8-16%), live commerce (5-9%) and Zero Covid strategy (16-26%) showed upward trends in negative views of the Chinese people. Specific health communication strategy suggestions are given to target each of the negative topics.


Effects of caffeine intake and smoking on neurocognition in schizophrenia.
Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.


The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis.
Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran's Q test and I2 statistics. A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.


Fatigue in multiple sclerosis: interrelations between fatigue complaints, cerebral MRI abnormalities and neurological disability.
Although fatigue is a frequent complaint of patients with multiple sclerosis (MS), little is known about the origins of multiple-sclerosis-associated fatigue. Our primary focus was to study if the extent of cerebral abnormalities, as shown on magnetic resonance imaging (MRI), had any relation with the frequency and intensity of fatigue complaints of patients with a definite diagnosis of MS. Fatigue severity was rated by the patients with the use of a 2-week diary and a fatigue questionnaire, while conventional T1- and T2-weighted MRI provided several measures for cerebral abnormalities. In total, 72% of 45 patients reported to be seriously fatigued at least several times a week over the last 3-month period. Fatigue severity was not related to the total extent of cerebral abnormalities, or to MRI-based atrophy measures. Regional lesion load did not differ between fatigued and non-fatigued subjects. Although neurological disability, as measured by the Expanded Disability Status Scale (EDSS) and Neurological Rating Scale (NRS), did correlate significantly with most MRI measures, it showed no relation with fatigue severity. Neurological progression rates and number of exacerbations in the 2-year period prior to assessment were not significantly associated with the fatigue measures. Therefore, our findings suggest that differences in levels of self-reported fatigue in patients with multiple sclerosis cannot merely be explained by the degree of clinical disease activity, neurological disability or the extent of MRI abnormalities. These results are compared to other research findings and the possible role of alternative factors influencing fatigue in multiple sclerosis are discussed.


Erratum to "Risk factors for morbidity in 1- to 9-day-old dairy calves following caustic paste disbudding" (JDS Commun. 2:376-380).
[This corrects the article DOI: 10.3168/jdsc.2021-0121.].


Green synthesis of quaternized chitosan/silver nanocomposites for targeting mycobacterium tuberculosis and lung carcinoma cells (A-549).
Lung cancer (LC) is the most-deadly type of cancer representing a major public health problem worldwide. Tuberculosis TB is another infectious disease influencing lungs that causes death especially in developing countries. The present study is the first to report antimycobacterial activity of TMC/Ag nanocomposite. It aims to solve the case of lung cancer and its most associative pathogen. The current study reports one pot green biosynthesis of silver nanocomposite in presence of biodegradable biopolymer (N,N,N-trimethyl chitosan chloride, TMC) as both reducing and stabilizing agent. The structure of TMC/Ag nanocomposite was characterized with different analysis tools including TEM, XRD and UV-vis spectrophotometer techniques. TEM images showed that Ag nanoparticles were well distributed spheres and their diameter ranged from 11 to17.5 nm. While, XRD pattern of TMC/Ag nanocomposite showed diffraction peaks related to the crystalline nature of Ag nanoparticles. In addition, UV-vis spectrum revealed a broad absorption peak at 400 nm attributing to the surface Plasmon resonance (SPR) of Ag. TMC/Ag nanocomposite exhibited a promising in vitro antimycobacterial activity with MIC of 1.95 μg/mL. On the other hand, The antitumor activity results of nanocomposites against both lung carcinoma cells (A-549) and normal lung cells (WI 38) revealed that nanocomposite cytotoxicity against A-549 cells with IC50 of 12.3 μg/mL, whereas the IC50 value against normal WI 38 cells was 357.2 μg/mL.


Design and synthesis of a novel class of PDE4 inhibitors with antioxidant properties as bifunctional agents for the potential treatment of COPD.
It is well known that chronic obstructive pulmonary disease (COPD) patients are always trapped in the vicious circle of inflammation and oxidative stress, therefore anti-inflammatory and antioxidant bifunctional agents may interrupt this vicious cycle in COPD. Phosphodiesterase 4 (PDE4) inhibitors, as anti-inflammatory drugs, have been used for COPD treatment in clinical, and the PDE4 inhibitors with antioxidant properties may be a good strategy to design bifunctional agents for COPD. Sappanone A was the first PDE4 inhibitor with antioxidant properties we identified from natural products in our previous study, which was used by us as a hit compound to design new bifunctional agents for COPD in this study. 27 derivatives of sappanone A including homoisoflavonoids, aurones and chalcones were designed and synthesized by innovatively fusing the antioxidant pharmacophore of catechol from polyphenols and the pharmacophore of catechol ether abstracted from the PDE4 inhibitors of the catechol ether class such as rolipram, roflumilast and apremilast respectively. All the compounds were assayed for the PDE4 inhibitory and radical scavenging against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) activities in vitro. Herein we obtained a series of bifunctional compounds with better PDE4 inhibitory activity than sappanone A, and their free radical scavenging activities were superior to edaravone in vitro. In addition, they can reduce tumour necrosis factor-alpha (TNF-α) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and malondialdehyde (MDA) production induced by Fe2+ in mouse lung homogenate. Meanwhile, it showed outstanding abilities in reducing Fe3+ and complexing Fe2+. 6o, as the candidate anti-inflammatory and antioxidant bifunctional compound, exhibited good drug-likeness, ADME (Absorption, Distribution, Metabolism, Excretion) properties and human liver microsomal stability. In vivo, 6o (50 mg/kg and 100 mg/kg, i. p.) distinctly prevented LPS-induced serum levels of TNF-α in mice. In conclusion, the preliminary investigation provided a novel class of PDE4 inhibitors with antioxidant properties as bifunctional agents for the potential treatment of COPD, which can interrupt the vicious cycle of chronic inflammation and oxidative stress in COPD.


Thrombin induces the rapid formation of inositol bisphosphate and inositol trisphosphate in human platelets.
Human platelets prelabeled with [3H]inositol were exposed to thrombin. The aqueous soluble inositol phosphates were separated by anion exchange column chromatography, paper chromatography or high-performance liquid chromatography, and identified by cochromatography with authentic standard substances. Thrombin immediately induces the rapid formation of inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate. Accumulation of inositol-1-monophosphate and inositol-2-monophosphate occurs later after a time lag of 10 sec. The results indicate that the phospholipase C induced polyphosphoinositide hydrolysis rather than the phosphatidylinositol hydrolysis is the triggering event for platelet activation, and support the concept of inositol 1,4,5-trisphosphate as putative second messenger.


Effect of splenectomy on the humoral immune response in the lizard, Scincus scincus.
Adult splenectomy in the lizard, Scincus scincus, did not affect humoral immune response to rat erythrocytes until 30 days post-immunization, but severely depressed subsequent antibody production.


Eco-innovations and sustainability in solid waste management: An indian upfront in technological, organizational, start-ups and financial framework.
Technological interventions and eco-innovative solutions are necessary to cope with the adverse environmental impacts of waste accumulation. The notion to consider "waste as a resource and recycling of the same for getting the value of the waste" has truly transformed the approach towards solid waste management (SWM). Technological eco-innovations rely on the automation of waste segregation, collection, route optimization, digital apps for creating communication (enhanced efficiency by 40-85%) and treatment technologies. The regulatory framework with amendments in rules, new policies, schemes, smart city missions are responsible for the implementation of "Tech-innovations" at the ground level and has shown societal benefits. India has significantly shown progress in sustainable development goals (SDGs) score from 50.93 to 60.23 (year 2000-2019). The innovative and sustainable waste management practices in India have increased contribution to renewable energy (approx. 2554 MW/annum), 15-billion-USD business opportunity by the circular economy, 25-30% resale profit from processed E-waste, increased co-operative collaborations, trailblazing start-ups, improved SDG 3,7,8,9,11,12,13, improved market for green products and services, brilliant institutional and regional innovations addressing the issue of climate change. The present article critically reviews the exemplary eco-innovations (technological and non-technological) including resource recovery and viable technologies for SWM in India. The review also illustrates the lacunae (in awareness, bioproducts adoption and advanced technologies), recommendations based on findings and future research areas. The paper can also assist researchers, entrepreneurs and the policy makers for improving the status of SWM in India as well as other developing countries with the same societal and economic status.


Larval descriptions of Annitella esparraguera (Schmid 1952) and Annitella iglesiasi González & Malicky 1988 (Trichoptera: Limnephilidae), two endemic species from Southern Europe.
Descriptions of the previously unknown larvae of Annitella esparraguera and A. iglesiasi, two European endemic species from the southern Iberian Peninsula are presented. The most important diagnostic features are illustrated and some taxonomic, zoogeographical and ecological notes are given. In addition, a previous key is modified to include these two new Iberian Limnephilidae larvae.


Therapeutic Plasma Exchange in Guillain-Barre Syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.
Therapeutic plasma exchange (TPE) has been used as a treatment modality in many autoimmune disorders, including neurological conditions, such as Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The American Society for Apheresis (ASFA) publishes its guidelines on the use of therapeutic apheresis every 3 years based on published evidence to assist physicians with both the medical and technical aspects of apheresis consults. The ASFA Guidelines included the use of TPE in both GBS and CIDP as an acceptable first-line therapy, either alone and/or in conjunction with other therapeutic modalities. In this article, we briefly reviewed GBS and CIDP, discussed the role of apheresis in these conditions as well as various technical aspects of the TPE procedure, such as apheresis calculation, number of volume exchange, replacement fluid, and management of potential complications.


Delayed high-grade atrioventricular block requiring pacemaker implantation in a multiple sclerosis patient treated with fingolimod.
Fingolimod is a sphingosine-1-phosphate 1 (S1P1) modulator which retains lymphocytes in secondary lymphoid organs and is approved for the treatment of relapsing multiple sclerosis (MS). The decrease of heart rate and AV block are reversible side-effects of treatment initiation. We report a case of persistent high-grade atrioventricular (AV) block 450 days after start of fingolimod and permanent pacemaker requirement in late-onset relapsing multiple sclerosis (MS). We discuss emerging risk factors for cardiac conduction deficits including the recently discovered vagomimetic effects of S1P1 modulation, structural brain and spinal cord damage, ageing and comorbidities.


Adaptation in motor strategies for postural control associated with sensory reweighting.
The purpose of this study was to identify and differentiate the motor strategies associated with sensory reweighting adapted during specific sensory integration tasks by healthy young adults. Thirty-six subjects (age range: 21-33 years) performed standing computerized dynamic posturography balance tasks across progressively increasing amplitudes of visual (VIS), somatosensory (SOM) and both (VIS+SOM) systems perturbation conditions. Adaptation in the motor strategy was measured as changes in electromyographic (EMG) activities and joint angles. The contribution of the perturbed sensory input in maintaining postural stability was calculated to determine the sensory reweighting. A multivariate design was used to model a linear combination of motor adaptation variables that discriminates specific sensory integration tasks. Results showed a significant progressive decrease in postural sway per unit amplitude of sensory perturbation in each condition, indicating dynamic sensory reweighting. Linear discriminant function analysis indicated that the adaptation in motor strategy during the VIS condition was associated with increased activity of EMG and joint angles in the upper body compared to the lower body. Conversely, during the SOM and VIS+SOM conditions, the adaptation in motor strategy was associated with decreased activity of EMG and joint angles in the lower body compared to the upper body. Therefore, the adaptation in motor strategies associated with sensory reweighting were different for different sensory integration tasks.


Single-Molecule Nanomechanical Genotyping with DNA Origami-Based Shape IDs.
Atomic force microscopy (AFM)-based nanomechanical imaging provides a sub-10-nm-resolution approach for imaging biomolecules under ambient conditions. Here we describe how to generate a set of DNA origami-based shape IDs (triangular and cross shape, with and without streptavidin) to site-specifically label target genomic DNA sequences containing two single-nucleotide polymorphisms (SNPs). Adjacent labeling sites separated by only 30 nucleobases (~10 nm) can be differentiated under AFM imaging. We can directly genotype single molecules of human genomic DNA.


Investigating the use of titanium dioxide (TiO2) nanoparticles on the amount of protection against UV irradiation.
In this study, three samples of commercial titanium dioxide nanoparticles (TiO2) in different sizes were used to investigate their effect on the formulation of sunscreen creams. The aim was to evaluate their role in the performance of sunscreens (i.e. SPF, UVAPF, and critical wavelength). Then the particle size of these samples was determined by photon correlation spectroscopy methods. As a result, the size of primary particles was reduced by using milling and homogenization methods at different times. The results showed that the particle size of samples TA, TB, and TC in the ultrasonic homogenizer decreased from 966.4, 2745.8, and 2471.6 nm to 142.6, 254.8, and 262.8 nm, respectively. These particles were used in the pristine formulation. Then the functional characteristics of each formulation were determined by standard methods. TA had the best dispersion in cream compared to other samples due to its smaller size (i.e. 142.6 nm). For each formulation, two important parameters, including pH and TiO2 dosage, were investigated in different states. The results showed that the formulations prepared with TA had the lowest viscosity compared to formulations containing TB and TC. SPSS 17 statistical software analysis of variance showed that the performance of SPF, UVAPF and λc in formulations containing TA had the highest levels. Also, the sample containing TAU with the lowest particle size values had the highest protection against UV rays (SPF). According to the photocatalytic functionality of TiO2, the photodegradation of methylene blue in the presence of each nanoparticle of TiO2 was studied. The results showed that smaller nanoparticles (i.e. TA) had more photocatalytic activity under UV-Vis irradiation during 4 h (TA (22%) > TB (16%) > TC (15%)). The results showed that titanium dioxide can be used as a suitable filter against all types of UVA and UVB rays.


Evaluating the effect of different irrigation activation techniques on the dentin tubules penetration of two different root canal sealers by laser scanning confocal microscopy.
The aim of this study is to evaluate the effect of different irrigation activation techniques on the dentin tubules penetration of two different sealers by confocal laser scanning microscope (CLSM). A hundred premolar teeth were used in this study. The root canals were shaped and irrigated with 5% NaOCl and 17% EDTA using the following final irrigation activation techniques in each group; Group1: Conventional Syringe Irrigation (CSI), Group2: Passive Ultrasonic Irrigation (PUI), Group3: Apical Negative Pressure (EndoVac), Group4: Er:YAG laser and Group5: Er,Cr:YSGG laser. Then the teeth were separated two subgroups according to sealers (AH-Plus and Totalfill-BC). Horizontal sections were obtained at 2, 5, 8 mm distance of apex. Images were obtained with CLSM and the penetration areas of sealers were calculated with four different dentin tubule penetration assessment techniques. The data were statistically analyzed with Kruskal Wallis and Mann Whitney U tests. No significant difference was observed between the sealers (p > .05). EndoVac, Er:YAG and Er,Cr:YSGG laser activation groups were observed to have a significantly higher mean penetration depth, penetration percentage and penetration area than the Control group. There was a significant difference between all regions in all penetration parameters (p < .05). While the use of resin or bioceramic-based root canal sealers did not affect dentin tubule penetration, the use of activation techniques positively affect the dentin tubule penetration. The average tubule penetration and penetration area assessment techniques are suitable methods for the investigation of dentinal tubule penetration. It can be stated that the use of resin or bioceramic based root canal sealers does not affect dentin tubule penetration and the use of irrigation activation techniques during removal of the smear layer positively affects dentinal tubule penetration. In addition, it has been determined that the average tubule penetration and penetration area assessment techniques are suitable methods for the investigation of dentinal tubule penetration.


Improvements in the production of Aspergillus oryzae β-galactosidase crosslinked aggregates and their use in repeated-batch synthesis of lactulose.
Aspergillus oryzae β-galactosidase was immobilized by aggregation and crosslinking, obtaining catalysts (CLAGs) well-endowed for lactulose synthesis. Type and concentration of the precipitating agent were determinants of immobilization yield, specific activity and thermal stability. CLAGs with specific activities of 64,007, 48,374 and 44,560 IUH g-1 were obtained using 50% v/v methanol, ethanol and propanol as precipitating agents respectively, with immobilization yields over 90%. Lactulose synthesis was conducted at 50 °C, pH 4.5, 50% w/w total sugars, 200 IUH g-1 of enzyme and fructose/lactose molar ratio of 8 in batch and repeated-batch operation. Lactulose yields were 0.19 g g-1 and 0.24 g g-1 for fructose to lactose molar ratios of 4 mol mol-1 and 8 mol mol-1 while selectivities were 3.3 mol mol-1 and 6.6 mol mol-1 respectively for CLAGs obtained by ethanol and propanol precipitation. Based on these results, both CLAGs were selected for the synthesis in repeated-batch mode. The cumulative mass of lactulose in repeated-batch was higher with CLAGs produced by ethanol and propanol precipitation than with the free enzyme. 86 and 93 repeated-batches could have been respectively performed with those CLAGs considering a catalyst replacement criterion of 50% of residual activity, as determined by simulation.


Relation between the ventriculographic silhouette and topography of thoracic potential in coronary artery disease.
The body surface potential map obtained within 30 days of cardiac catheterization was examined in 180 patients with coronary artery disease. Radii to the systolic and diastolic boundaries of the right anterior oblique ventriculogram were measured at 18 degrees intervals; isointegral voltages were tabulated for early and late halves of the QRS complex at 35 definitive electrode sites. Multivariate analysis showed all ray lengths depended on all 70 voltage values. Linear transformation matrices to predict ray length from voltage distribution were calculated for a training set which was successively expanded from 80 to 160 at increments of 20 patients. Training set expansion led to a progressive decrease in the error of reproduction of the ray lengths for patients outside the training set. There is a strong relation between ventriculographic contours in patients with coronary artery disease and body surface potential values during early and late QRS complexes. Even in simplified linear formulation, the relation is detectable throughout a large population despite interindividual variations in anatomic geometry.


Sesquiterpene lactones from Lychnophora species: Antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout.
Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1β cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1β and TNF-α concentrations, and SOD and CAT activities. Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities. Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro-inflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.


In vitro metabolism of 4-androstene-3,17-dione and testosterone by rat submaxillary gland.
Tritiated 4-androstene-3,17-dione and testosterone were incubated with submaxillary gland homogenates of male and female rats. The metabolism was predominately reductive. In 15 and 180 min incubations submaxillary tissue converted 4-androstene-3,17-dione chiefly to androsterone. Less testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one, 5 alpha-androstane-3,17-dione, 5 alpha-androstane-3 alpha, 17 beta-diol, and 4-androstene-3 alpha, 17 beta-diol were also identified. Testosterone was converted to the same products plus 4-androstene-3,17-dione. 5 alpha-Androstane-3 alpha, 17 beta-diol was the major testosterone metabolite. Qualitatively the metabolism by male and female submaxillary gland was similar.


Modulation of arachidonic acid metabolism by phenols: relation to their structure and antioxidant/prooxidant properties.
The effects of substituted catechols (3-methylcatechol, 4-methylcatechol, 4-nitrocatechol, and guaiacol) and trihydroxybenzenes (pyrogallol, propyl gallate, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) on the synthesis of prostaglandin (PG)E2 and leukotriene (LT)B4 were tested in human A23187-stimulated polymorphonuclear leukocytes. The effects were related to their peroxyl-radical-scavenging (antioxidant), superoxide-scavenging (antioxidant), and superoxide-generating (prooxidant) properties. In general, compounds with hydroxyl groups in the ortho position increased PGE2/LTB4 ratio, and compounds with hydroxyl groups in the meta position decreased PGE2/LTB4 ratio. Catechols, which have hydroxyl groups in the ortho position, were the most potent peroxyl radical and superoxide anion scavengers. Trihydroxybenzenes (pyrogallol, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) generated superoxide, whereas dihydroxybenzenes did not. Thus, the positions and number of hydroxyl groups seem to be the most important properties determining the action of phenolic compounds on PGE2/LTB4 ratio and their antioxidant/prooxidant activities.


Thermal conductivity of Fe-Si alloys and thermal stratification in Earth's core.
Light elements in Earth's core play a key role in driving convection and influencing geodynamics, both of which are crucial to the geodynamo. However, the thermal transport properties of iron alloys at high-pressure and -temperature conditions remain uncertain. Here we investigate the transport properties of solid hexagonal close-packed and liquid Fe-Si alloys with 4.3 and 9.0 wt % Si at high pressure and temperature using laser-heated diamond anvil cell experiments and first-principles molecular dynamics and dynamical mean field theory calculations. In contrast to the case of Fe, Si impurity scattering gradually dominates the total scattering in Fe-Si alloys with increasing Si concentration, leading to temperature independence of the resistivity and less electron-electron contribution to the conductivity in Fe-9Si. Our results show a thermal conductivity of ∼100 to 110 W⋅m-1⋅K-1 for liquid Fe-9Si near the topmost outer core. If Earth's core consists of a large amount of silicon (e.g., > 4.3 wt %) with such a high thermal conductivity, a subadiabatic heat flow across the core-mantle boundary is likely, leaving a 400- to 500-km-deep thermally stratified layer below the core-mantle boundary, and challenges proposed thermal convection in Fe-Si liquid outer core.


Naloxone accessibility without an outside prescription from U.S. community pharmacies: A systematic review.
Recent evidence has identified limited naloxone accessibility in community pharmacies. To summarize current literature regarding naloxone accessibility without an outside prescription from U.S. community pharmacies and discuss implications on community pharmacists' ability to mitigate the opioid overdose epidemic. A systematic review was developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed was searched up to May 12, 2022. References from articles chosen for inclusion were subsequently reviewed to identify additional relevant studies. Peer-reviewed publications reporting new data regarding the accessibility of naloxone from U.S. community pharmacies without an outside prescription (e.g., standing order, protocol) were included. Review articles and articles written in a non-English language were excluded. Individual study data were reported, along with a qualitative discussion of limitations of individual studies and in aggregate. When possible, naloxone accessibility data were also pooled and reported as overall accessibility and further stratified by chain versus independent pharmacies and urban versus rural settings. Thirty studies were included. Naloxone was in stock in 6867 of 10,934 (62.8%) pharmacies, though this varied greatly between studies (range, 26.4%-96.1%). Chain pharmacies were more likely to stock naloxone than independents (69.7% [range, 35.4%-89.1%] vs. 36.4% [range, 19.1%-89.7%], P < 0.0001). Stocking did not significantly differ between urban and rural locations. A total of 5660 of 8999 (62.9%; range, 23.5%-97%) pharmacies audited were willing to dispense without a prescription, with chain (67.4% vs. 22.2%, P < 0.0001) and rural (69.3% vs. 40.7%, P < 0.0001) pharmacies more likely than independent and urban, respectively. Key access barriers identified included naloxone not stocked, high naloxone cost, and pharmacist misinformation or stigma. Though limited by study heterogeneity, analysis of thirty U.S. studies revealed naloxone was available without a prescription in less than two-thirds of community pharmacies. Availability varied significantly by study and pharmacy type.


Uric acid is an independent risk factor for carotid atherosclerosis in a Japanese elderly population without metabolic syndrome.
Carotid intima-media thickness (IMT) is an useful surrogate marker of cardiovascular disease. Associations between uric acid (UA), metabolic syndrome (MetS) and carotid IMT have been reported, but findings regarding the relationship have been inconsistent. A total of 1,579 Japanese elderly subjects aged ≥65 years {663 men aged, 78 ± 8 (mean ± standard deviation) years and 916 women aged 79 ± 8 years} were divided into 4 groups according to UA quartiles. We first investigated the association between UA concentrations and confounding factors including MetS; then, we assessed whether there is an independent association of UA with carotid IMT and atherosclerosis in participants subdivided according to gender and MetS status. Carotid IMT was significantly increased according to the quartiles of UA in both genders without MetS and women with MetS. Multivariate logistic regression analysis showed that odds ratio (OR) {95% confidence interval (CI)} in men for carotid atherosclerosis was significantly increased in the third (OR, 1.75; 95% CI, 1.02-3.02), and fourth quartiles (OR, 2.01; 95% CI, 1.12-3.60) of UA compared with that in the first quartile of UA, and the OR in women was significantly increased in the fourth quartile (OR, 2.10; 95% CI, 1.30-3.39). Similarly, the ORs were significantly associated with increasing quartiles of UA in both genders without MetS, but not necessarily increased in those with MetS. UA was found to be an independent risk factor for incidence of carotid atherosclerosis in both genders without MetS.


Genotoxicity and molecular response of silver nanoparticle (NP)-based hydrogel.
Since silver-nanoparticles (NPs) possess an antibacterial activity, they were commonly used in medical products and devices, food storage materials, cosmetics, various health care products, and industrial products. Various silver-NP based medical devices are available for clinical uses, such as silver-NP based dressing and silver-NP based hydrogel (silver-NP-hydrogel) for medical applications. Although the previous data have suggested silver-NPs induced toxicity in vivo and in vitro, there is lack information about the mechanisms of biological response and potential toxicity of silver-NP-hydrogel. In this study, the genotoxicity of silver-NP-hydrogel was assayed using cytokinesis-block micronucleus (CBMN). The molecular response was studied using DNA microarray and GO pathway analysis. The results of global gene expression analysis in HeLa cells showed that thousands of genes were up- or down-regulated at 48 h of silver-NP-hydrogel exposure. Further GO pathway analysis suggested that fourteen theoretical activating signaling pathways were attributed to up-regulated genes; and three signal pathways were attributed to down-regulated genes. It was discussed that the cells protect themselves against silver NP-mediated toxicity through up-regulating metallothionein genes and anti-oxidative stress genes. The changes in DNA damage, apoptosis and mitosis pathway were closely related to silver-NP-induced cytotoxicity and chromosome damage. The down-regulation of CDC14A via mitosis pathway might play a role in potential genotoxicity induced by silver-NPs. The silver-NP-hydrogel induced micronuclei formation in cellular level and broad spectrum molecular responses in gene expression level. The results of signal pathway analysis suggested that the balances between anti-ROS response and DNA damage, chromosome instability, mitosis inhibition might play important roles in silver-NP induced toxicity. The inflammatory factors were likely involved in silver-NP-hydrogel complex-induced toxic effects via JAK-STAT signal transduction pathway and immune response pathway. These biological responses eventually decide the future of the cells, survival or apoptosis.


Clinical evaluation of the APAS® Independence: Automated imaging and interpretation of urine cultures using artificial intelligence with composite reference standard discrepant resolution.
This study reports the outcome of the first evaluation of the APAS® Independence for automated reading and preliminary interpretation of urine cultures in the routine clinical microbiology laboratory. In a 2-stage evaluation involving 3000 urine samples, two objectives were assessed; 1) the sensitivity and specificity of the APAS® Independence compared to microbiologists using colony enumeration as the primary determinant, and 2) the variability between microbiologists in enumerating bacterial cultures using traditional culture reading techniques, performed independently to APAS® Independence interpretation. Routine urine samples received into the laboratory were processed and culture plates were interpreted by standard methodology and with the APAS® Independence. Results were compared using typical discrepant result resolution and with a composite reference standard, which provided an alternative assessment of performance. The significant growth sensitivity of the APAS® Independence was determined to be 0.919 with a 95% confidence interval of (0.879, 0.948), and the growth specificity was 0.877 with a 95% confidence interval of (0.827, 0.916). Variability between microbiologists was demonstrated with microbiologist bi-plate enumerations in agreement with the consensus 88.6% of the time. The APAS® Independence appears to offer microbiology laboratories a mechanism to standardise the processing and assessment of urine cultures whilst augmenting the skills of specialist microbiology staff.


On the relationship between cortical excitability and visual oscillatory responses - A concurrent tDCS-MEG study.
Neuronal oscillations in the alpha band (8-12Hz) in visual cortex are considered to instantiate 'attentional gating' via the inhibition of activity in regions representing task-irrelevant parts of space. In contrast, visual gamma-band activity (40-100Hz) is regarded as representing a bottom-up drive from incoming visual information, with increased synchronisation producing a stronger feedforward impulse for relevant information. However, little is known about the direct relationship between excitability of the visual cortex and these oscillatory mechanisms. In this study we used transcranial direct current stimulation (tDCS) in an Oz-Cz montage in order to stimulate visual cortex, concurrently recording whole-brain oscillatory activity using magnetoencephalography (MEG) whilst participants performed a visual task known to produce strong modulations of alpha- and gamma-band activity. We found that visual stimuli produced expected modulations of alpha and gamma - presenting a moving annulus stimulus led to a strong gamma increase and alpha decrease - and that this pattern was observable both during active (anodal and cathodal) tDCS and sham tDCS. However, tDCS did not seem to produce systematic alterations of these oscillatory responses. The present study thus demonstrates that concurrent tDCS/MEG of the visual system is a feasible tool for investigating visual neuronal oscillations, and we discuss potential reasons for the apparent inability of tDCS to effectively change the amplitude of visual stimulus induced oscillatory responses in the current study.


Mirror, mirror on the wall, how does my brain recognize my image at all?
For decades researchers have used mirrors to study self-recognition. However, attempts to identify neural processes underlying this ability have used photographs instead. Here we used event related potentials (ERPs) to compare self-face recognition in photographs versus mirrors and found distinct neural signatures. Measures of visual self-recognition are therefore not independent of the medium employed.


Monogenoidea Communities Differ Between Male Morphotypes of Bluegill Sunfish (Lepomis macrochirus).
Bluegill sunfish (Lepomis macrochirus) are a North American sport fish that exhibit two different male morphotypes. Alpha-males are large, colorful, territorial, and have significant parental investment, while β-males are small, drab, and have two reproductive phenotypes, neither of which involves parental investment. Due to the two different reproductive strategies, the level of interaction between congenerics varies, which may impact parasites that are spread via close contact, such as Monogenoidea that infect the gills. Monogeneans are ectoparasites on the gills and skin of fish hosts that may cause significant pathology in high numbers and be an indicator of host behavior and interaction between hosts. In this study, 328 L. macrochirus (106 α-males, 92 β-males, and 130 females) were necropsied from 8 lakes and ponds in northwestern Virginia to identify and enumerate monogenean parasites from the gills. Alpha-males had a significantly greater parasite abundance and species richness compared to β-males. This may be due to the increased size and surface area of gills in α-males, increased interaction with females during mating, and stationary behavior when guarding nests, which enhanced the chances of α-males contracting the parasites. This also led to significant differences in the monogenean communities infecting the two morphotypes, which were also significantly influenced by the size of the hosts. It is important in future studies regarding parasitism that behavioral morphotypes within a sex, such as α-male and β-male L. macrochirus in this study, be treated separately as behavioral and morphometric differences between them can potentially lead to differences in parasitism.


Studies on Limulus amoebocyte lysate II. Purification of the coagulogen and the mechanism of clotting.
A coagulogen in Limulus lysate has been purified to apparent homogeneity as judged by sodium dodecyl sulfate-gel electrophoresis. The purified coagulogen identified by its ability to clot with either trypsin or the purified Limulus clotting enzyme (Tai, J.Y., and Liu, T. Y. (1976) Fed. Proc. 35, 1486) has a molecular weight of 24,500. It consists of a single polypeptide chain of about 220 amino acids with glycine and serine as its NH2- and COOH-terminal residues; respectively. When acted upon by the Limulus clotting enzyme, the coagulogen releases a soluble C-peptide of about 45 amino acids and an insoluble coagulin of about 170 amino acids. The latter interacts in a noncovalent fashion to form the clot. Amino acid analyses together with the results of NH2- and COOH-terminal analyses suggest that the clot formation involves the cleavage of an--Arg--Lys--bond. Trypsin acts on the coagulogen to cause clotting by splitting the same peptide bond.


Unaccustomed high mileage compared to intensity training-related neuromuscular excitability in distance runners.
The influence of a 4-week unaccustomed average 103% mileage increase (ITV, increase in training volume; n = 8; average baseline mileage 85.9 km.week-1, final mileage 174.6 km.week-1) on performance and neuromuscular excitability (NME) was tested in experienced distance runners and controlled 1 year later by a 4-week unaccustomed average 152% increase in tempo-pace and interval-runs (ITI, increase in training intensity; n = 9; baseline 9 km.week-1 final 22.7 km.week-1) with an average total mileage of 61.7 km.week-1 (week 1) to 84.7 km.week-1 (week 4). Seven athletes participated in ITV as (week 4). Seven athletes participated in ITV as well as in ITI. During incremental treadmill test performance at a lactate concentration of 2 mmol.1-1 (2 LP) increased, and at 4 mmol.1-1 (4 LP) performance did not change, whereas total running distance (TD) during the incremental test decreased in ITV compared to an increase in 2 LP, 4 LP and TD during ITI which may indicate that there was an ITV-related overtraining. The NME of the reference muscles vastus medialis and rectus femoris deteriorated in ITV (day 28 compared to 0) compared to constant values during ITI, reflecting an ITV-related overload of neuromuscular structures.


5-Fluoro-1H-indole-3-carb-oxy-lic acid.
In the title compound, C(9)H(6)FNO(2), the carboxyl group is twisted slightly away from the indole-ring plane [dihedral angle = 7.39 (10)°]. In the crystal, carboxyl inversion dimers linked by pairs of O-H⋯O hydrogen bonds generate R(2) (2)(8) loops and N-H⋯O hydrogen bonds connect the dimers into (10[Formula: see text]) sheets.


Valorization of full-scale waste aerobic granular sludge for biogas production and the characteristics of the digestate.
Despite the dynamic development of aerobic granular sludge (AGS) technology in wastewater treatment, there is limited data on how the different properties of AGS and activated sludge (AS) translate into differences in waste sludge management. Waste sludge generated in both AGS and AS technology is the biggest waste stream generated in wastewater treatment plants (WWTPs). This study aimed to assess biogas production from waste AGS from a full-scale system. Additionally, the properties of the digestate were investigated in terms of its management in line with the assumptions of a circular economy. Both aspects are important because the characteristics of AGS differ from those of AS. Its dense, extracellular-polymer-rich granule structure makes the susceptibility of AGS to anaerobic stabilization lower than that of AS. Given the advantages of AGS for sustainable wastewater treatment and its increasing popularity, waste AGS management will pose a serious challenge for WWTP operators. Therefore, AGS from a full-scale municipal WWTP was valorized for biogas production by increasing the accessibility of the organics in the sludge by homogenization or ultrasound pretreatment. Ultrasound pretreatment released about an order of magnitude more organics from the biomass than homogenization and significantly improved the production of methane-rich biogas (455 L/kg VS, about 66% of CH4). The digestion time of pretreated AGS was reduced by 25% in comparison with that of untreated AGS making anaerobic digestion of AGS a feasible solution for sludge management. The AGS digestate was rich in Ca (77.0 g/kg TS), Mg (10.9 g/kg TS), N (35.1 g/kg TS) and P (32.4 g/kg TS), whereas its heavy metal levels and biochemical methane potential were low. AGS digestate is not only environmentally safe, but it can serve as a rich source of organics and elements essential for soil fertility and stability.


The role of the corpus callosum in the development of interocular eye alignment and the organization of the visual field in the cat.
In young cats, the posterior portion of the corpus callosum was sectioned 13--29 days after birth. The animal's eyes were photographed at weekly intervals for six months using the pupil-reflex method. From the corneal reflection evident in the photographs the degree of alignment for the optical axes of each cat was estimated (Sherman, 1972). The 17 experimental cats all showed a significant tendency toward permanent divergent strabismus, as compared to six normal cats. The limits of the visual field were determined for both groups of cats using a perimetry technique similar to that of Sprague and Meikle (1965) and Sherman (1973). With one eye open normal cats responsed from 90 degrees ipsilateral to 45 degrees past the vertical midline into the contralateral visual field. With either eye the experimental cats responsed from 90 degrees ipsilateral to approximately the vertical midline. The loss of visual responsiveness is within the contralateral region of the normally binocular zone. Three cats received the same operation at 9, 13, or 20 months old. Eye alignment and visual field perimetry were unaffected by the surgery. It is not known whether the observed abnormalities result from arrested development, or disruption of intrinsically determined ocular alignment.


MiR-29a function as tumor suppressor in cervical cancer by targeting SIRT1 and predict patient prognosis.
Cervical cancer is the second most frequently malignant tumors in females and metastasis is a challenge of the treatment of cervical cancer. MiR-29a is usually low expressed in several tumors and its functions in cervical cancer remain unclear. The quantitative real-time polymerase chain reaction was employed to assess the expression of miR-29a and the Sirtuin-1 (SIRT1). Cell metastatic ability was assessed using Transwell and Western blot assays. The dual-luciferase reporter assay was performed to verify that miR-29a targeted to the 3'-untranslated region (UTR) of SIRT1 mRNA. MiR-29a was low expressed in cervical cancer and downregulation of miR-29a was associated with poor outcome. MiR-29a regulated the expression of SIRT1 by targeting to its 3'-UTR of mRNA in HeLa cells. SIRT1 was upregulated in cervical cancer tissues and cells in comparison with the non-tumor tissues and normal cells. Upregulation of SIRT1 predicted worse outcome of cervical cancer patients. MiR-29a was participated in the migration, invasion and epithelial-mesenchymal transition (EMT) in cervical cancer through directly targeting to the 3'-UTR of SIRT1 mRNA. SIRT1 reversed partial roles of miR-29a on metastasis in cervical cancer. miR-29a suppressed migration, invasion and EMT by directly targeting to SIRT1 in cervical cancer. The newly identified miR-29a/SIRT1 axis provides novel insight into the pathogenesis of cervical cancer.


Can a liveable city be a healthy city, now and into the future?
City planning and infrastructure can influence the social determinants of health, the liveability of cities and the physical and mental health of city residents. This article defines these concepts and discusses how city planning can help in mitigating COVID-19 transmission, and support health by accommodating active transport (i.e. walking and cycling) and emerging technologies (i.e. autonomous and electric vehicles).


Familiarisation of novice and experienced treadmill users during a running session: Group specific evidence, time and individual patterns.
The elimination of familiarisation effects is a recurring topic in biomechanical testing during treadmill running among different experience levels. The two aims of this study were (i) to calculate familiarisation times of novice and experienced treadmill runners on a group level and (ii) to examine individual familiarisation patterns in order to classify those with similar characteristics. Twenty runners participated in this study by performing a treadmill running session with 3D motion capture. Familiarisation times for 9 kinematic variables among both groups (novices and experienced treadmill runners) were statistically analysed. Additionally a qualitative clustering process (supported by quantitative criteria) provided individual familiarisation patterns for all participants and variables. Group mean familiarisation times were inconsistent across variables (ranging from 3 to 14 min), with no general tendency for decreased familiarisation time in experienced compared to novice treadmill runners. The analysis of individual familiarisation patterns revealed that 30.5% were not stable after 15 min. Substantial changes compared to the initial state were observed in data sets with detected familiarisation pattern. Treadmill running experience does not affect familiarisation patterns since this process is highly individual and variable-specific. Consequently, no generalised familiarisation time can be provided and the elimination of familiarisation in biomechanical testing a priori does not seem to be possible in the first 15 min for approximately one third of the individual patterns studied. In conclusion, the common practice of collecting data subsequent to a pre-defined generalised familiarisation time ought to be replaced by measurements at several points in time during trials. This required procedure would allow for checking familiarisation patterns and fluctuations in order to exclude inappropriate data sets in future treadmill studies.


Lived experiences of parents caring for a child with a life-limiting condition in Australia: A qualitative study.
Experiential studies in paediatric palliative care are needed to enable an ongoing international agenda which supports the development of responsive family supports. To provide an in-depth exploration of the prevalent lived experiences of parents who are currently providing care for a child with a life-limiting condition in Australia. Cross-sectional, prospective, qualitative study guided by an advisory group and reported according to the consolidated criteria for reporting qualitative studies. Transcripts were subjected to a thematic analysis, underpinned by an interpretative phenomenological framework. Purposively sampled parents (n = 14) recruited from a statewide paediatric hospice who self-identified as a 'primary caregiver' for one or more children and/or adolescents (⩽18 years) with a life-limiting condition. Four key themes represented the prevalent experiences of parents: (1) trapped inside the house, (2) the protector, (3) living with the shadow and (4) travelling a different pathway. They describe parents' physical and social isolation, exclusion from the workforce, pervasive grief and associated impacts to their health and well-being. Limited professional and diminished social supports resulted in full ownership of care responsibility. Yet, parents embraced their role as 'protector', reporting acquired meaning and purpose. This study builds upon the growing body of evidence available in paediatric palliative care internationally. The key themes highlight the substantial demand for both physical and emotional support beyond what is currently offered and call for the implementation of carefully planned support services and other societal initiatives which seek to alleviate the broad health impacts to caregivers.


Conversion of a lumboperitoneal shunt to a lumboatrial shunt through femoral catheterization: technical note.
A new technique for the diversion of the peritoneal end of a lumboperitoneal shunt into the right atrium through femoral vein catheterization is presented. As an alternative to a ventriculoatrial shunt, this is a promising technique for the treatment of patients with communicating hydrocephalus when the peritoneal cavity is not suitable for placing the distal end of the shunt.


Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules.
To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance. We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry. All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094-0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243-0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238-0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients. This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.


The mechanism by which ATP regulates alcoholic steatohepatitis through P2X4 and CD39.
Alcoholic liver disease caused by chronic excessive drinking has become one of the most common types of liver disease. Alcohol-induced inflammatory immune responses play a central role in the development of alcohol-associated steatohepatitis. The content and expression of ATP and P2X4 in the livers of alcoholic steatohepatitis mice are significantly increased. The content of ATP increased by 20 percent and the expression of P2X4 receptor protein was 1.3 times higher than that in the livers of normal mice. Treatment with 5-BDBD, a P2X4 receptor-specific inhibitor, significantly reduced alcohol-induced liver inflammation and lipid deposition. In RAW264.7 cell experiments, 5-BDBD inhibited the expression of P2X4 and alleviated alcohol-induced inflammation, while the CD39-specific inhibitor POM-1 reduced extracellular ATP degradation and promoted the expression of P2X4, thereby exacerbating inflammation. After treatment with 5-BDBD, P2X4 receptor protein expression decreased by 0.2 times and after treatment with POM-1, P2X4 receptor protein expression increased by 0.1 times compared to the alcohol-stimulated group. In addition, inhibition of P2X4 expression in RAW264.7 cells reduced calcium influx in RAW264.7 cells. P2X4 may induce the activation of NLRP3 inflammasomes by mediating calcium influx, thus exacerbating the inflammatory response, and inhibition of P2X4 expression can effectively block this process. Conclusion: These results suggest that the ATP-P2X4 signaling pathway promotes the inflammatory response in alcoholic steatohepatitis and that CD39 may play a protective role in regulating P2X4 expression by hydrolyzing ATP. In conclusion, the CD39 and ATP-P2X4 signaling pathways may be potential therapeutic targets for alcoholic steatohepatitis.


Cervical cytology in Western Australia. Frequency, geographical and socioeconomic distributions and providers of the service.
Basic data were obtained from the records of 16,069 women who had smears taken for cervical cytological examination in Western Australia during an eight-week period in 1983. The peak smear rate was 340.7 per 1000 at 25-29 years of age and fell thereafter with age. The estimated peak frequency of smears that were designated as "screening" smears was 178.3 per 1000 at 30-34 years of age. Screening smears comprised 39% to 66% of the total number of smears, depending on age. After correction for the estimated prevalence of past hysterectomy, only in the age range 20-34 years did the rate of all smears approach the rate of screening smears that would be obtained under a recommended frequency of once every three years. The frequency of screening smears was 20% less in rural areas of Western Australia than in the capital city, Perth. In Perth it fell with decreasing socioeconomic status. General practitioners took 62.4% of all smears and 70.3% of screening smears. On average, female general practitioners took twice as many smears than did male general practitioners.


Isolation and identification of androstanediol glucuronide from human plasma.
[3H]Dihydrotestosterone (50 microCi) was infused into normal men and women for 8 h. It was previously shown that this was sufficient time for this material to reach a steady state. Venous plasma was obtained at 6 and 8 h, pooled, and the unconjugated steroids removed by ether extraction. The remaining plasma was adjusted to pH 4.9 and the steroid conjugate was extracted first with ethyl acetate and then with an ether-ethanol mixture. The extracts were combined and taken to dryness. Steroid sulfates were solvolyzed using dioxane, and the mixture partitioned between ether and 1% NaOH. The aqueous phase was acidified and added to an XAD-2 column, washed with water, and the glucuronide fraction eluted with methanol. The solvent was concentrated and the methanol extract was passed through a C18 Sep-Pak, filtered through an Acrodisc CR and then subjected to gradient high performance liquid chromatography [HPLC] (Nova-Pak C18, KH2PO4, pH 3, and methanol). The fractions containing steroid glucuronides were collected and esterified with diazomethane and then acetylated with acetic anhydride in pyridine. The glucuronide triacetyl methyl ester (GAME) derivatives were then run in a second HPLC system (3 Lichrosorb 5 mu columns, 4 mm x 25 cm) using a gradient of ethanol-heptane and heptane. We clearly established that this system separates 3 alpha-diol GAME conjugated at the 17 and 3 positions (44 vs 50 min) with authentic samples previously synthesized in our laboratory. We concluded that the pooled plasma contained only the 17-GAME conjugate. No significant activity of the 3-glucuronide was detected. The natural compound in circulation, therefore, is 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide.


Hepatic microsomal alcohol-oxidizing system. Affinity for methanol, ethanol, propanol, and butanol.
Oxidation of methanol, ethanol, propanol, and butanol by the microsomal fraction of rat liver homogenate is described. This microsomal alcohol-oxidizing system is dependent on NADPH and molecular oxygen and is partially inhibited by CO, features which are common for microsomal drug-metabolizing enzymes. The activity of the microsomal alcohol-oxidizing system could be dissociated from the alcohol peroxidation via catalase-H2O2 by differences in substrate specificity, since higher aliphatic alcohols react only with the microsomal system, but not with catalase-H2O2. Following solubilization of microsomes by ultrasonication and treatment with deoxycholate, the activity of the microsomal alcohol-oxidizing system was separated from contaminating catalase by DEAE-cellulose column chromatography, ruling out an obligatory involvement of catalase-H2O2 in the activity of the NADPH-dependent microsomal alcohol-oxidizing system. In intact hepatic microsomes, the catalase inhibitor sodium azide slightly decreased the oxidation of methanol and ethanol, but not that of propanol and butanol, indicating a facultative role of contaminating catalase in the microsomal oxidation of lower aliphatic alcohols only. It is suggested that the microsomal alcohol-oxidizing system accounts, at least in part, for that fraction of hepatic alcohol metabolism which is independent of the pathway involving alcohol dehydrogenase activity.


A nonribosomal peptide synthetase gene tzw1 is involved in zwittermicin A biosynthesis in Bacillus thuringiensis G03.
A 4.20-kb SspI fragment from Bacillus thuringiensis G03 was cloned and sequenced. Sequencing analysis revealed two complete open reading frames (ORF; tzw1 and tzw2), and one incomplete ORF (tzw3) (GenBank accession no. EU293887). Tzw1 encodes a putative nonribosomal peptide synthetase with thiolation and condensation domains localized at the C-termini, whereas tzw2 and tzw3 encode acyl carrier protein and Acyl-CoA dehydrogenase, respectively. To investigate the function of tzw1 in zwittermicin A (ZA) biosynthesis, an in-frame deletion of 1,461 bp within tzw1 was constructed. The mutant abolished ZA production. Complementation of the mutant with cloned tzw1 restored ZA productivity. These results revealed that tzw1 is required for ZA biosynthesis in B. thuringiensis G03.


Aspergilloma in a patient with an occult congenital pulmonary airway malformation.
We describe the case of a 14-year-old male who presented with a right upper lobe aspergilloma forming in a previously occult congenital pulmonary airway malformation. This is the first case describing an aspergilloma forming within a CPAM.