Relationship between the weight of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.
Secondary hyperparathyroidism is one of the common and important abnormalities of mineral metabolism in hemodialysis patients. In this study we investigated the relationship between the weight of individual parathyroid glands (PTG) and their secretion of parathyroid hormone (PTH). Sixty-four PTGs in 16 patients undergoing parathyroidectomy (PTx) at our hospital were included in this study. Patients' ages ranged from 34 to 68 years (60.3 +/- 6.6 years). They were undergoing maintenance dialysis therapy for 81-256 months (175.3 +/- 56.0 months). The cause of end-stage renal failure was chronic glomerulonephritis in all patients. We measured whole PTH (wPTH) levels before PTx and 15 min after the resection of each individual gland (Delta whole PTH). A positive correlation was found between the weight of individual gland and ultrasonography (US) size of individual PTG (r = 0.91, P < 0.001, N = 53). A positive correlation was found between the total mass of the gland and the total volume of PTG on US (r = 0.896, P < 0.001, N = 16). A positive correlation was found between the mass of each individual gland and Delta whole PTH (r = 0.625, P < 0.001, N = 64); however, massive PTGs did not secrete more whole PTH per unit mass (0.01 g). Determination of the volume of PTGs by US is a good indicator of their weight. Larger PTGs secrete more whole PTH per gland, whereas these PTGs did not have the ability to secrete more PTH per unit volume.


Antibody-Dependent Cell-Mediated Inhibition (ADCI) of Plasmodium falciparum: One- and Two-Step ADCI Assays.
The ADCI assay aims to measure the ability of parasite-specific antibodies, which by triggering blood monocytes, control P. falciparum parasite density. The assay relies on three easily accessible components: blood monocytes, immunoglobulins, and P. falciparum in vitro culture. Yet the reliability of results depends on the quality of the three above components, and therefore great care must be taken with each of them. We describe here different protocols for successfully carrying out the ADCI assay with emphasis on procedures and validation criteria necessary to ensure meaningful results.


Occurrence and characteristics of methicillin-resistant and -susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci from Japanese retail ready-to-eat raw fish.
Staphylococci are not part of the normal fish microflora. The presence of staphylococci on fish is an indication of (a) post-harvest contamination due to poor personnel hygiene, or (b) disease in fish. The aim of this study was to determine the prevalence, molecular genetic characteristics, antibiotic resistance and virulence factors of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) isolated from 200 samples of retail ready-to-eat raw fish (sashimi) collected from the Japanese prefecture of Hiroshima. We characterized 180 staphylococcal strains. A majority of the grocery stores surveyed (92%, 23/25) contained fish contaminated with Staphylococcus species. We recovered 175 S. aureus isolates from 174 (87%, 174/200) samples, with 170 isolates of MSSA. For the MRSA and MR-CoNS, 10 isolates were obtained from 10 samples (5%, 10/200) collected from 10 shops (40%, 10/25) belonging to four supermarket chains. SCCmec typing revealed the presence of a type IV.1 SCCmec cassette in S. warneri isolates, a type II.1 SCCmec cassette in S. haemolyticus isolates and a cassette in methicillin-resistant S. aureus (MRSA) isolates that could not be typed. Molecular typing of two MRSA isolates by spa sequencing and multilocus sequence typing (MLST) identified t1767 and ST8, respectively. Antibiotic resistance genes that confer resistance to aminoglycosides, tetracyclines, β-lactams, macrolides, lincosamides and streptogramin B (MLS(B)) antibiotics were detected. Genes encoding one or more of the following virulence factors: staphylococcal enterotoxins (seb, and sed), toxic shock syndrome toxin 1 (tst), exfoliative toxin (etaA) were detected in 14.2% (25/175) of S. aureus isolates. The accessory gene regulator (agr) typing of S. aureus isolates revealed that agr type 1 was most prevalent (96.5%, 169/175) followed by type 2 (2.2%, 4/175) and type 3 (1.1%, 2/175). None of the S. aureus isolates carried the Panton-Valentine leucocidin (PVL) encoding genes, lukF-PV and lukS-PV. To the best of our knowledge, this is the first report to show MRSA and MR-CoNS isolated from retail ready-to-eat food in Japan. Our results showed that sashimi is a likely vehicle for transmission of multidrug-resistant and toxigenic staphylococci.


The use of continuous low-dosage copper sulfate as a molluscicide on an irrigation scheme in Kenya.
On a developing irrigation scheme in Kenya where there was a potential danger of Schistosoma mansoni transmission, copper sulfate at a concentration of between 0.125 p.p.m. and 0.25 p.p.m. was introduced as soon as water started flowing into the canals; there was no pre-sulfation at a higher concentration and mechanical barriers were not used.It was hoped that if this method proved successful it could be adopted for the routine control of bilharziasis, but as it proved impossible to provide day-to-day supervision, no definite conclusions as to the efficacy of the method can be made. The available data, however, indicated that at an average of 0.25 p.p.m. a barrier was created which was lethal to snails which passed through it, but that at an average of 0.125 p.p.m. results were indeterminate.Further trials to obtain more precise data on the mechanism of chemical barriers are recommended.


Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs.
Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients' benefit-risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients' preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.


Postoperative recurrence in hepatocellular carcinoma: Comparison between percutaneous ethanol injection and radiofrequency ablation.
Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.


Reliability and validity of home-visit nursing quality indicators for children with medical complexity in Japan.
This study aims to examine the reliability and validity of Home-visit Nursing Quality Indicators for Children (HNQIC) with medical complexity in Japan that will enable measuring the quality of services provided by home-visit nursing agencies (HNA) for children with medical complexity (CMC) and their families. This study employed a model that measures medical quality as proposed by Donabedian in a conceptual framework. The HNQIC is comprised of a total of 42 items with responses in 5-point Likert scale: 8 items in "Structure", 24 items in "Process", and 10 items in "Outcome". A self-rating questionnaire survey was administered and responses from 57 home-visit nursing agencies were analyzed. An exploratory factor analysis was performed to examine the validity of the construct, and a covariance structure analysis was performed to examine the structural validity of the model that measures medical quality. The "Structure" and "Process" sections included 28 items in 5 factors, and the "Outcome" section included 7 items in 3 factors. The Cronbach's α coefficient for all of the items of "Structure" and "Process" was 0.93, and that of "Outcome" was 0.76. As a result of a covariance structure analysis, we obtained following goodness-of-fit indices: χ2 / df = 1.41, GFI = .897, AGFI = .794, CFI = .926, and for the coefficient of determination .14 ≤ R2 ≤ .68. As the statistical validity of the HNQIC was confirmed, we determined the goodness-of-fit indices of the model to be acceptable. The findings suggested that the HNQIC can be used as a quality indicator to access care effects objectively to provide better support.


A dual cytotoxic and anti-angiogenic water-soluble gold(III) complex induces endoplasmic reticulum damage in HeLa cells.
The water-soluble gold(III) complex [Au(III)(butyl-C^N)biguanide]Cl (butyl-HC^N = 2-(4-n-butylphenyl)pyridine, BCN) displays cytotoxicity through S-phase cell cycle arrest and endoplasmic reticulum (ER) damage in HeLa cells, and shows a promising anti-angiogenic effect at sub-cytotoxic concentrations.


[Behavior of various blood constituents (glucose, fructose, insulin, lactate, pyruvate, free fatty acids, inorganic phosphate) and half-life of monosaccharides in the plasma after i.v. infusion of glucose, fructose, galactose and invert sugar solutions in ruminants. 1. Studies in calves and heifers].
Studies into the half-life of monosaccharides as well as into the effects of intravenous infusion of sugar solutions (0.5 g/kg body weight of glucose, fructose, galactose, and invert sugar) on the concentration of various blood components were undertaken with six calves and five heads of young cattle. Half-life values of glucose and galactose were of nearly identical magnitude over the first weeks of age, whereas that of fructose was much longer on account of slower conversion. Infusion of invert sugar solution, therefore, cannot be recommended for calves during the first three weeks of age. Infusion of the above monosaccharides led to more or less strongly pronounced rise of insulin levels in the blood serum. More or less strongly marked pyruvate increase took place following infusion, if the pyruvate concentration in the blood plasma had been low before infusion. Lactate levels in the blood usually underwent little change, whereas the levels of free fatty acids and inorganic phosphate in the blood plasma usually were reduced.


Aspirin for prevention of preeclampsia and adverse perinatal outcome in twin pregnancies: a systematic review and meta-analysis.
This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies. Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched. The search and selection criteria were restricted to the English language. The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48-0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low. The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies.


Eyelash growth in subjects treated with bimatoprost: a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study.
Bimatoprost 0.03% is associated with increased growth and prominence of eyelashes. We sought to compare the safety and efficacy of once-daily bimatoprost 0.03% versus vehicle in increasing eyelash length, thickness, and darkness after topical administration to upper eyelid margins. In this 5-month study, subjects were randomized to receive once-daily bimatoprost 0.03% (n = 137) or vehicle (n = 141). The primary end point was eyelash prominence assessed by the investigator global eyelash assessment scale. Secondary efficacy measures included eyelash length, thickness, and darkness measured by digital image analysis and patient-reported outcomes. Safety data included adverse event monitoring and ophthalmic examinations. A higher percentage of subjects treated with bimatoprost 0.03% (78.1%) versus vehicle (18.4%) demonstrated at least a 1-grade increase in global eyelash assessment score at week 16 (P < .0001). Subjects in the bimatoprost 0.03% group also had statistically significantly greater increases in eyelash length, thickness, and darkness (P < .0001) than those in the vehicle group. For adverse events, only conjunctival hyperemia occurred at a statistically significant higher incidence rate in the bimatoprost 0.03% versus the vehicle group (P = .03). Short-term duration of the trial was a limitation; black subjects were not enrolled secondary to technical requirements of digital image analysis. Bimatoprost 0.03% was found to be effective at enhancing eyelashes in adults with a very good safety profile.


Perinatal hypoxic-ischemic brain injury affects the glutamatergic signal transduction coupled with neuronal ADP-ribosyl cyclase activity.
Agonists of glutamate ionotropic (NMDA) and metabotropic receptors (mGluRI and mGluRIII) had the regulatory effect on ADP-ribosyl cyclase/CD38 activity in cerebellar granular cells of newborn rats. Perinatal hypoxic-ischemic brain injury was followed by dysregulation of this mechanism.


Antioxidant properties and phenolic profile of the most widely appreciated cultivated mushrooms: a comparative study between in vivo and in vitro samples.
The present study reports a comparison of the antioxidant properties and phenolic profile of the most consumed species as fresh cultivated mushrooms and their mycelia produced in vitro: Agaricus bisporus (white and brown), Pleurotus ostreatus (oyster), Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake). The antioxidant activity was evaluated through reducing power (Folin-Ciocalteu and Ferricyanide/Prussian blue assays), free radical scavenging activity (DPPH assay) and lipid peroxidation inhibition (β-carotene/linoleate and TBARS assays). The analysis of phenolic compounds was performed by HPLC/PAD. The mushroom species with the highest antioxidant potential was Agaricus bispous (brown). However, concerning to the species obtained in vitro, it was L. edodes that demonstrate the highest reducing power. Generally, in vivo samples revealed higher antioxidant properties than their mycelia obtained by in vitro techniques. About the phenolic compounds researched, they were detected both in mushrooms and mycelia without any particular abundance. Results showed that there is no correlation between the studied commercial mushrooms and the corresponding mycelia obtained in vitro. Nevertheless, this study contributes to the rise of data relatively to the species consumed as fresh mushrooms and the possibility of their in vitro production as a source of bioactive compounds.


Mycorrhizal networks: des liaisons dangereuses?
Mycorrhizal associations, by which most land plants receive mineral nutrition, are diffuse and often non-specific. A common mycorrhizal network is formed when fungal mycelia colonize and link together the roots of two or more plants, sometimes of different species. Here, we discuss recent work showing how, under realistic ecological conditions, such networks can affect the physiology and ecology of plants by facilitating interplant nutrient exchange, acting as inoculum reservoirs for seedlings and altering plant competitive abilities. Although mechanisms for their evolutionary emergence remain unclear, investigating mycorrhizal networks profoundly modifies our understanding of plant communities.


Mo2: functional properties of antigen-bearing cells.
Mo2 is a membrane antigen whose expression is associated with human cells enriched for monocytes and macrophages. Anti-Mo2 monoclonal antibody in the presence of rabbit complement causes an inhibition of the proliferative response of human peripheral blood leukocytes (PBL) to soluble antigens, that can be restored by the addition of fresh monocytes. Fluorescence-activated cell sorting (FACS) of PBL on the basis of Mo2 expression results in a population of Mo2+ cells (morphologically monocytes) that is selectively active in phagocytosis and cytolysis of antibody-sensitized human erythrocytes, and a population of Mo2- cells (morphologically lymphoid cells) that is nonphagocytic but selectively active in natural killing. These experiments indicate that expression of Mo2 is a useful marker for cells possessing the morphological and functional properties of monocytes.


Digoxin use after diagnosis of colorectal cancer and survival: a population-based cohort study.
Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer-specific mortality. A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality. Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response. In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in colorectal cancer patients.


Catching HPV in the Homologous Recombination Cookie Jar.
To replicate, the human papillomaviruses (HPVs) that cause anogenital and oropharyngeal malignancies must simultaneously activate DNA repair pathways and avoid the cell cycle arrest that normally accompanies DNA repair. For years it seemed that HPV oncogenes activated the homologous recombination pathway to facilitate the HPV lifecycle. However, recent developments show that, although homologous recombination gene expression and markers of pathway activation are increased, homologous recombination itself is attenuated. This review provides an overview of the diverse ways that HPV oncogenes manipulate homologous recombination and ideas on how the resulting dysregulation and inhibition offer opportunities for improved therapies and biomarkers.


Squamous cell carcinoma in a tuatara (Sphenodon punctatus).
A mature male tuatara was presented with a history of recurrent cloacal prolapse. The prolapsed tissue included a 12 mm diameter mass, which histologically showed cords and nodules of neoplastic epithelial cells. The mass was diagnosed as a squamous cell carcinoma with ulceration of the overlying stratified squamous epithelium and diffuse inflammation of the surrounding dermis. This case presented a rare opportunity to investigate squamous cell carcinoma in a long-lived lower vertebrate species. Future recurrence or metastasis of the mass may add useful information to the current base of knowledge of the behaviour of malignant neoplasms in reptiles.


Genes and plays: bringing ELSI issues to life.
Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal, and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To illuminate these enduring concerns, we explore how perceptions and relationships have influenced-and been influenced by-genetics as portrayed through dramatic vignettes. We build on the legacy of using case vignettes as a clinical teaching modality, and believe similar value exists within the research ethics domain. The selection of dialogue discussed encompasses abbreviated excerpts from two existing and one original vignette that we staged at the ELSI 2011 Congress and various academic and health institutions.


Correction to: Antiretroviral treatment indications and adherence to the German-Austrian treatment initiation guidelines in the German ClinSurv HIV Cohort between 1999 and 2016.
In this article the cooperating partners of the ClinSurv HIV cohort were not listed in the acknowledgements. The correct paragraph appears below.


Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice.
The involvement of glucocorticoid response in the hippocampal changes in aged SAMP8 mice after removal of their upper molar teeth (molarless condition) was examined using biochemical, morphological and behavioral techniques. Molarless mice showed plasma corticosterone levels to be significantly greater than those in molar-intact control mice. Pretreatment with metyrapone, which suppresses the stress-induced rise in plasma corticosterone levels, prevented the molarless condition-induced increase in plasma corticosterone levels, reduction in CA1 pyramidal neuron numbers, and impairment of spatial learning. The results suggest a link between the molarless condition and the glucocorticoid response, which may be involved in spatial learning deficits and hippocampal neuronal death in aged SAMP8 mice.


Plasma levels of cathepsins L, K, and V and risks of abdominal aortic aneurysms: a randomized population-based study.
Cathepsin L (CatL), cathepsin K (CatK), and cathepsin V (CatV) are potent elastases implicated in human arterial wall remodeling. Whether plasma levels of these cathepsins are altered in patients with abdominal aortic aneurysms (AAAs) remains unknown. Plasma samples were collected from 476 male AAA patients and 200 age-matched male controls to determine CatL, CatK, and CatV levels by ELISA. Student's t-test demonstrated significantly higher plasma CatL levels in AAA patients than in controls (P < 0.0001), whereas CatK and CatV levels were lower in AAA patients than in controls (P = 0.052, P = 0.025). ROC curve analysis confirmed higher plasma CatL levels in AAA patients than in controls (P < 0.001). As potential confounders, current smoking and use of angiotensin-converting enzyme (ACE) inhibitors, aspirin, clopidogrel, and statins associated with significantly increased plasma CatL. Pearson's correlation test demonstrated that plasma CatL associated positively with CatS (r = 0.43, P < 0.0001), body-mass index (BMI) (r = 0.07, P = 0.047) and maximal aortic diameter (r = 0.29, P < 0.001), and negatively with lowest measured ankle-brachial index (ABI) (r = -0.22, P < 0.001). Plasma CatL remained associated positively with CatS (r = 0.43, P < 0.0001) and aortic diameter (r = 0.212, P < 0.001) and negatively with ABI (r = -0.10, P = 0.011) after adjusting for the aforementioned potential confounders in a partial correlation analysis. Multivariate logistic regression analysis indicated that plasma CatL was a risk factor of AAA before (odds ratio [OR] = 3.04, P < 0.001) and after (OR = 2.42, P < 0.001) the same confounder adjustment. Correlation of plasma CatL levels with aortic diameter and the lowest ABI suggest that this cysteinyl protease plays a detrimental role in the pathogenesis of human peripheral arterial diseases and AAAs.


Advanced oxidative degradation of acetaminophen by carbon catalysts: Radical vs non-radical pathways.
Two representative carbon catalysts, granular activated carbon (GAC) and carbon nanotube (CNT) were selected for the degradation of acetaminophen (ACT) by persulfate (PS) activation. In this study, the materials characterization study indicated that the surface functional groups and surface area of the GAC were more abundant and larger, respectively, than the CNT. Whereas the contribution of sp2 and CO groups of the CNT was superior to the GAC; the structural defect levels and surface charging characteristics (pHPZC) were similar in both. The mass-based pseudo-first-order reaction rate constant of the CNT was 1.5 m-1 g-1, which was 50 times higher than that of the GAC (0.03 m-1 g-1). Radical and non-radical pathways were evaluated for catalytic reactions by the GAC/PS and CNT/PS systems, respectively. Experimental results using scavenger tests, linear voltammetry, and electron spin resonance (ESR) showed that the radical pathway was dominant in the GAC/PS system, whereas the non-radical pathway was dominant in the CNT/PS systems. To confirm this, the influence of affecting factors such as initial ACT concentration, the dosage of oxidant (PS), and initial pH were also investigated and compared for the two systems. The results showed that the catalytic activity of the GAC/PS system was highly dependent on initial concentrations of ACT and PS, while these were less influential in the CNT/PS system. The removal efficiency of ACT was not affected under a pH of 3-7 in both systems. Reusability experiments were conducted five times, and both the CNT/PS and GAC/PS systems demonstrated that the removal rate of ACT did not notably decrease with the number of experiment repetitions. This means that the application of a carbon catalyst to treat pharmaceutical contaminants in wastewater is effective.


Hyperuricemia, Gout, and the Brain-an Update.
This review aims to summarize recent evidence regarding the complex relationship between uric acid (UA), gout, and brain diseases. Observational studies have suggested that patients with hyperuricemia or gout might have a decreased risk of neurodegenerative diseases. Conversely, they may be at increased risk of cerebrovascular disease. Mendelian randomization (MR) studies use a genetic score as an instrumental variable to address the causality of the association between a risk factor (here, UA or gout) and an outcome. So far, MR analyses do not support a causal relationship of UA or gout with Alzheimer's disease and dementia, and of UA with Parkinson's disease or stroke. Observation studies indicate a U-shaped association between UA and brain diseases, but MR studies do not support that this association is causal. Further studies should address the causal role of gout as well as the impact of urate-lowering therapy on these outcomes.


Polycystic kidney disease increases the stoke incidence in Taiwan: A retrospective population-based cohort study using National Health Insurance Database.
Few studies documented incidence rates of different types of stroke among patients with polycystic kidney disease (PKD). We conducted a retrospective cohort study based on the National Health Insurance (NHI) Database of Taiwan. The PKD cohort comprised patients aged≥20 years diagnosed with PKD using inpatient claims from 1998 to 2011, excluding prior stroke. The reference cohort was established by inpatients without PKD using 1:4 frequency-matched with age, gender, and baseline comorbidities. The two cohorts were followed-up until stroke hospitalization, death, withdrawal from the NHI program, or the end of 2012. To account for competing risks of death, we used multivariable competing risks regression models to estimate sub-distribution hazard ratio (SHR) adjusted for age, gender, baseline comorbidities and end stage renal disease. 7837 PKD patients and 31,211 reference subjects were followed up through 2012. A total of 955 cases of stroke were identified in the PKD cohort, including 441 ischemic stroke (IS), 289 intracranial hemorrhage (ICH), 73 subarachnoid hemorrhage (SAH) and 232 other stroke. The incidence rates of overall stroke, IS, ICH, and SAH were 21.3, 10.2, 6.8, and 1.7 per 1000 person-years, respectively. The SHR for overall stroke was 1.39 [95% confidence interval (CI) 1.28-1.50]. SAH had the highest SHR, 4.55 [95% CI 3.26-6.37], followed by ICH (1.84), other stroke (1.24), and IS (1.22). This study illustrated the incidence rates of stroke among inpatient of PKD. The PKD patients had a significantly increased risk of all kinds of stroke after adjusting baseline comorbidities.


Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and progression-free survival in intracranial PCNSL.
To compare the Nordic and the Memorial Sloan-Kettering Cancer Center (MSKCC) chemotherapy protocols for Overall Survival (OS) and Progression-Free Survival (PFS) for intracranial primary CNS lymphoma (PCNSL). A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014). Overall, 79 patients with PCNSL were identified, of whom 57 received chemotherapy. MSKCC with Rituximab (RTX) was used in 18 patients (32%) who had median OS of 46.3 months [9.8-131.9] and median PFS of 34.6 months [6.4-131.9]. The Nordic protocol was used in 14 patients (25%) who had median OS of 30.9 months [2.7-106.3] and PFS of 14.3 months [0.0-106.3]. The MSKCC was used without RTX in 25 patients (44%) who had OS of 15.2 months [0.7-136.5] and PFS of 12.0 months [0.0-117.0]. MSKCC with RTX had a significantly longer median OS (p < 0.05) compared to the other regimens in univariate analysis. In multivariate analysis, the only prognostic factor for OS and PFS of significance was deep brain involvement (p < 0.005). In univariate analysis, the MSKCC with RTX achieved significantly longer median OS compared to the Nordic protocol. However, in multivariate analysis, the only prognostic factor for survival of statistical significance was deep brain involvement.


Rapid quantitative determination of hydrogen peroxide by oxidation decolorization of methyl orange using a Fenton reaction system.
In this study, a sensitive and rapid method for hydrogen peroxide (H(2)O(2)) determination has been developed with the aid of oxidation decolorization of methyl orange (MO) by using Fenton reactions, because the decolorization extent of MO solution (at the maximum absorption wavelength of 507 nm) is proportion to the concentration of H(2)O(2). Under optimum conditions, this spectrophotometric method for the H(2)O(2) analysis yields a dynamic range of H(2)O(2) concentration from 5.0 x 10(-7) to 1.0 x 10(-4) mol L(-1) (r=0.997) and a detection limit (3 sigma/k) of 2.0 x 10(-7) mol L(-1). This method for the determination of H(2)O(2) (0.04 mmol L(-1)) is able to tolerate the interference from NaCl (0-5.0 mmol L(-1)), Na(2)SO(4) (0-5.0 mmol L(-1)), MgCl(2) (0-5.0 mmol L(-1)), sodium humate (0-0.1 mmol L(-1)), benzene (0-0.2 mmol L(-1)), toluene (0-0.2 mmol L(-1)), chlorobenzene (0-0.2 mmol L(-1)) and chloroform (0-0.2 mmol L(-1)). The analysis results for practical rainwater samples are in good agreement with the classical N,N-diethyl-p-phenylenediamine (DPD) method for H(2)O(2) determination.


Immobilization of Candida rugosa lipase on glass beads for enantioselective hydrolysis of racemic naproxen methyl ester.
Candida rugosa lipase (CRL) was immobilized on glutaraldehyde-activated aminopropyl glass beads by using covalent binding method or sol-gel encapsulation procedure and improved considerably by fluoride-catalyzed hydrolysis of mixtures of RSi(OCH3)3 and Si(OCH3)4. The catalytic properties of the immobilized lipases were evaluated into model reactions, i.e. the hydrolysis of p-nitrophenylpalmitate (p-NPP). It has been observed that the percent activity yield of the encapsulated lipase was 166.9, which is 5.5 times higher than that of the covalently immobilized lipase. The enantioselective hydrolysis of racemic Naproxen methyl ester by immobilized lipase was studied in aqueous buffer solution/isooctane reaction system and it was noticed that particularly, the glass beads based encapsulated lipases had higher conversion and enantioselectivity compared to covalently immobilized lipase. In short, the study confirms an excellent enantioselectivity (E>400) for the encapsulated lipase with an ee value of 98% for S-Naproxen.


Ascorbate-induced hyperoxalaemia has no significant effect on lactate generation or erythrocyte 2,3,diphosphoglycerate in dialysis patients.
To examine the possible effects of hyperoxalaemia on anaerobic metabolism and erythrocyte pyruvate kinase activity, we induced a rise in plasma oxalate in 11 dialysis patients by the oral administration of ascorbic acid, 500 mg day-1 for 3 weeks. Blood samples were taken from the same antecubital vein before and after the supplementation period, without venous stasis, after an overnight fast. This protocol allowed patients to be used as their own controls. Five healthy subjects underwent an identical protocol to exclude any effect of ascorbate per se. Mean (SEM) plasma oxalate (mumol l-1) rose from 30.3 (3.5) to 48.4 (6.1) in patients and from 1.4 (0.2) to 6.8 (0.9) in healthy subjects. Whole blood ascorbate (mg l-1) rose from 7.0 (0.7) to 26.6 (2.5) in patients and from 9.3 (1.2) to 17.8 (1.8) in healthy subjects (reference range 7.5-20.0 mg l-1). No changes were observed in either group in plasma creatinine, bicarbonate, haemoglobin, or erythrocyte 2,3,diphosphoglycerate (2,3 DPG) after the 3 week supplementation period. Before supplementation lactate generation (area under curve, mmol min l-1) in the 5 min following a 60 s period of standardized ischaemic forearm exercise was significantly (P = 0.026) greater in patients [69.1 (4.7)] than in healthy subjects [46.9 (6.7)]; no significant change in lactate generation occurred in either group after ascorbate-induced hyperoxalaemia. We conclude that changes in plasma oxalate of the order of 20 mumol l-1 have no significant effect on lactate generation or 2,3,DPG levels in uraemic subjects.


Targeting the shikimate pathway in the malaria parasite Plasmodium falciparum.
The shikimate pathway presents an attractive target for malaria chemotherapy. Three shikimic acid analogs exhibited different effects on Plasmodium falciparum growth. (6R)-6-Fluoro-shikimate and (6S)-6-fluoro-shikimate inhibited growth (50% inhibitory concentrations, 1.5 x 10(-5) and 2.7 x 10(-4) M, respectively), whereas 2-fluoro-shikimate had no effect. para-Aminobenzoic acid abrogated the inhibition, demonstrating that the shikimate pathway was specifically targeted.


Oral mucositis in patients receiving low-dose methotrexate therapy for rheumatoid arthritis: report of 2 cases and literature review.
The differential diagnosis of ulcerative oral lesions is diverse. This report discusses the rare causes of oral mucosal ulceration and suggests approaches for diagnosis and treatment. Two cases of methotrexate-induced stomatitis in patients receiving low dose methotrexate for rheumatoid arthritis are presented with a review of the current literature. In case 1, mucositis was caused by an unintended methotrexate overdose. In case 2, oral lesions were the result of chronic methotrexate toxicity. The treatment for methotrexate-induced mucositis required hospitalization in case 1, methotrexate discontinuation in both cases and oral folic acid supplementation in case 2. In both cases, the mucositis healed and no relapse was observed. Mucositis may be an early sign of systemic conditions, and dental providers are often the first doctors involved in the assessment of oral mucosal diseases. Meticulous questioning of the patient's history and the physical examination is important for elucidating the underlying cause.


The impact of electronic medication administration records in a residential aged care home.
This study aimed to compare between electronic medication administration records and paper-based records in the nursing time spent on various activities in a medication round and the medication administration processes followed by nurses in an Australian residential aged care home. It also aimed to identify the benefits and unintended adverse consequences of using the electronic medication administration records. Time-motion observation, taking of field notes, informal conversation and document review were used to collect data in two units of a residential aged care home. Each unit had one nurse administer medication. Seven nurses were observed over 12 morning shifts. Unit 1 used electronic medication administration records and Unit 2 used paper-based records. No significant difference between the two units was found in the nursing time spent on various activities in a medication round, including documentation, verbal communication, medication administration, infection control and transit. Comparison of the medication administration processes between the electronic and paper-based medication administration records identified a procedural problem which violated the organization's documentation requirement. This problem was documenting before providing medication to a resident when using the paper-based records. It was not observed with the electronic medication administration records. Benefits of introducing the electronic medication administration records included improving nurses' compliance with documentation requirements, freedom from the error of signing twice, reducing the possibility of forgetting to medicate a resident, facilitating nurses to record the time of medication administration to a resident and increasing documentation space. Unintended adverse consequences of introducing the electronic medication administration records included inadequate information about residents, late addition of a new resident's medication profile in the records and nurses' forgetting to medicate a resident due to power outage of the portable device. The electronic medication administration records may not change nursing time spent on various activities in a medication round or substantially alter the medication administration processes, but can generate both benefits and unintended adverse consequences. Future research may investigate whether and how the adverse consequences can be prevented.


Histopathologic and genotoxic effects of deltamethrin on marsh frog, Pelophylax ridibundus (Anura: Ranidae).
It is known that amphibians inhabiting agricultural areas are constantly exposed to chemicals such as insecticides. Deltamethrin, a type II pyrethroid insecticide, is widely used in the world. The present study aimed to investigate the toxic effects of different concentrations (0.625, 1.25, and 2.50 mg/kg body wt) of orally applied deltamethrin to marsh frog (Pelophylax ridibundus) after 96 h of treatment. The histopathological abnormalities in liver, gastrointestinal tract, and kidney tissues were evaluated with quantitative analyses. In liver, increase of melanomacrophagic aggregates, non-homogeneous hepatocyte parenchyma, sinusoidal dilatations, infiltration, vascular epithelial degeneration, central vein degeneration, and congestion were determined in exposed frogs. In gastrointestinal tract, vacuolization, hypertrophy, congestion, infiltration, necrosis, and erosion of the epithelial layer, increasing goblet secretion, degeneration in villi, epithelial disorganization, and edema were observed in high-dose groups. In all experimental groups, glomerular shrinkage, hemorrhage, degeneration, infiltration, increase in Bowman distance, and eosinophilic-stained tubular lumens were detected in kidneys. Histopathological changes were more prominent in 1.25 and 2.50 mg/kg groups than the other groups. To determine the genotoxic effects of deltamethrin, the peripheral blood samples of the frogs were used. The erythrocytic nuclear abnormalities such as micro-nucleus, double-nucleus, kidney-shaped nucleus, notched nucleus, and bud nucleus were determined in the frogs, and the genotoxicity did not show a significant increase between control and low-dose groups, statistically. However, the genotoxic effects increased in medium- and especially high-dose groups. The results of this study showed that acute deltamethrin exposure can lead to histopathologic and genotoxic effects in P. ridibundus.


Skeletal-related events and mortality among older men with advanced prostate cancer.
Skeletal-related events (SREs) are defined as a cluster of events including clinical diagnoses and treatment. Using claims data, the burden of SREs as a group has been reported among patients with cancer. We investigate the mortality impact of subcomponents of SREs, a topic that has received limited attention among older men. We analyzed prostate cancer (PCa) and all-cause mortality among men diagnosed with metastatic PCa from 2000 to 2007 using Surveillance, Epidemiology, and End Results data linked with 1999-2009 Medicare data. We created three measures of pathological fracture (PF), spinal cord compression (SCC), and bone surgery (BS) that differed in the use of claims-based bone metastasis information. We reported covariate-adjusted hazard ratios (HRs) using the full sample and a propensity score-matched sample (PSMS). Application of inclusion/exclusion criteria resulted in 7062 men in the full sample (1776 in the PSMS). PCa-specific (all-cause mortality) was 54% (80%) at a median follow-up of 609days. SRE prevalence ranged from 9.7% to 17.1% across the measures. In a PCa mortality model, the HR associated with an SRE ranged from 1.07 (0.98-1.16) to 1.31 (1.18-1.45). The HRs for SCC and PF were statistically significant and positively associated with PCa-specific mortality. The results for BS depended on the measure. Results for SCC and BS, but not for PF, were preserved using a PSMS. The relationship between SREs and mortality among older men with metastatic PCa was driven by SCC and depended on the definition used to measure SREs.


Correction to: Robotic Versus Laparoscopic Right Colectomy with Complete Mesocolic Excision for the Treatment of Colon Cancer: Perioperative Outcomes and 5-Year Survival in a Consecutive Series of 202 Patients.
Dario Ribero's affiliation is corrected as reflected here.


The p53 Protein Family in the Response of Tumor Cells to Ionizing Radiation: Problem Development.
Survival mechanisms are activated in tumor cells in response to therapeutic ionizing radiation. This reduces a treatment's effectiveness. The p53, p63, and p73 proteins belonging to the family of proteins that regulate the numerous pathways of intracellular signal transduction play a key role in the development of radioresistance. This review analyzes the p53-dependent and p53-independent mechanisms involved in overcoming the resistance of tumor cells to radiation exposure.


Boundary-independent polar nonsense-mediated decay.
Nonsense-mediated decay (NMD) is an RNA surveillance mechanism that degrades mRNAs containing premature termination (nonsense) codons. The second signal for this pathway in mammalian cells is an intron that must be at least approximately 55 nucleotides downstream of the nonsense codon. Although the functional significance of this '-55 boundary rule' is not known, it is widely thought to reflect the important role of an exon junction protein complex deposited just upstream of exon-exon junctions after RNA splicing. Here we report that a T-cell receptor (TCR)-beta gene did not conform to this rule. Rather than a definitive boundary position, nonsense codons had a polar effect, such that nonsense codons distant from the terminal downstream intron triggered robust NMD and proximal nonsense codons caused modest NMD. We identified a region of the TCR-beta gene that conferred this boundary-independent polar expression pattern on a heterologous gene. Collectively, our results suggest that TCR-beta transcripts contain one or more sequence elements that elicit an unusual NMD response triggered by a novel second signal that ultimately causes boundary-independent polar regulation. TCR genes may have evolved this unique NMD response because they frequently acquire nonsense codons during normal development.


Case report: the first case of unilateral retinal pigment epithelium dysgenesis in China.
Unilateral retinal pigment epithelium dysgenesis (URPED) is a rare condition and is characterized by a unilateral and solitary lesion in the peripapillary region. The lesion presents with central atrophy, peripheral fibrosis, and hyperplastic changes in the retinal pigment epithelium (RPE). Herein, we report the first case of URPED in a Chinese individual using multimodal imaging techniques such as en-face optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). A 10-year-old girl presented with 20/40 vision in her left eye. Presented as a solitary, unilateral, large and yellowish-white lesion, with fringe-like margins was observed in the posterior pole and lower middle periphery of the left eye continuous with the optic nerve, indicated URPED. Infrared fundal (IR) images showed that the fringe-like contour of the lesion was visible, with diffuse hyperreflective signals specifically in the fovea, while with peripheral dark spots, having a typical leopard-spot like appearance. Fundus autofluorescence (FAF) revealed a markedly scalloped lesion containing a hypoautofluorescence area mixed with an isoautofluorescence area. Spectral-domain optical coherence tomography (SD-OCT) revealed the outer segments of photoreceptors presented with an inhomogeneous signal in the fovea, with a weak local signal. The ellipsoid and interdigitation zones were thinner than normal, while the RPE/Bruch's complex was not flat, with locally visible protrusions. En-face OCT image at the level of the RPE zone showed a mottled hyperreflective signal with peripheral hyporeflective spots, fringe-like margin lesions. OCTA of the avascular area of the fovea in the superficial, deep, and outer retinal layers appeared to be oval in shape, the choroid capillary layer revealed an increase in the density of the choroidal vasculature in the fovea. This is the first report on URPED in China. Both en-face OCT and OCTA were essential in observing and studying the disease. Further investigation is required to better define the en-face OCT and OCTA features of URPED and clarify the disease characteristics and prognosis.


Perillaldehyde: A promising antifungal agent to treat oropharyngeal candidiasis.
Perillaldehyde (PAE), a natural monoterpenoid agent extracted from Perilla frutescence, PAE has been reported to present various physiological capabilities, such as anti-inflammation, anti-oxidative and anti-fungal. In this study, we show that PAE exhibits strong antifungal activity against Candida albicans (C. albicans). C. albicans, a fungal pathogen with high incidence of antifungal resistance in clinical settings, is the major cause of oropharyngeal candidiasis (OPC). OPC is characterized by inflammatory immunological responses to fungal infections. Our in vitro results show PAE inhibited several virulence attributes of C. albicans including biofilm formation, yeast-to-hyphal transition and secreted aspartic proteinases (SAPs) gene expression. Using an experimental murine model of OPC, we found that PAE inhibited NLRP3 inflammasome assembly, reduced the excessive accumulation of ROS and prevented the p65 transfer in nuclear; processes all leading to reduced inflammation burden in the host. Together, this supports use PAE as a promising new agent to improve OPC.


Primary in situ immune response in popliteal lymph nodes and spleen of mice after subcutaneous immunization with thymus-dependent or thymus-independent (type 1 and 2) antigens.
Mice were immunized subcutaneously with thymus-independent (TI)-type 1 antigen trinitrophenylated lipopolysaccharide (TNP-LPS), TI-type 2 antigen TNP-Ficoll or thymus-dependent (TD) antigen TNP-keyhole limpet haemocyanin (TNP-KLH) in order to study the primary in situ immune response in popliteal lymph nodes (PLN) and spleen. The spleen responded more rapidly in developing specific antibody-forming cells (AFC) than the lymph nodes did, in spite of the fact that antigens reach the spleen only after passing several lymph node stations. This difference between lymph nodes and spleen in developing AFC was particularly significant with respect to the responses to TI (both type 1 and type 2) antigens. No differences in the distribution of specific AFC in PLN and spleen were observed after immunization with TI and TD antigens. Results are discussed with respect to the relative contributions of lymph nodes and spleen to immune responses to antigens injected subcutaneously.


Indexing climatic and environmental exposure of refugee camps with a case study in East Africa.
This study presents a novel approach to systematically measure climatic and environmental exposure in refugee camps using remote sensing and geospatial data. Using a case study of seventeen refugee camps across five countries in East Africa, we develop a climatic and environmental exposure index to quantify each camp's exposure relative to a population of simulated camp locations within the hosting country. Our results show that seven of seventeen refugee camps are within the upper two quartiles of exposure relative to a simulated population, suggesting that more than six-hundred thousand refugees living in these camps face elevated exposure compared to other potential camp locations. This method stands to improve the process of gathering and analyzing climatic and environmental data on geographically remote humanitarian spaces in a reliable, low-cost, and standardized manner. Automation and refinement of this index could enable real-time updates on climatic and environmental exposure to support decision-making related to disaster risk reduction in refugee camp management.


Ramsay Hunt Syndrome with Pharyngolaryngeal Involvement Mimicking Acute Stroke: A Case Report.
Ramsay Hunt syndrome is a clinical manifestation of the reactivation of latent varicella zoster virus in the geniculate ganglion after acute infection. It is commonly associated with an acute peripheral facial nerve paralysis, auricular vesicular eruption and acute sensorineural hearing loss. However, in some rare cases the involvement of other cranial nerves, especially the glossopharyngeal and vagal is described. We present a 56-year-old male patient who was diagnosed with acute pharyngitis. Two days later, the patient developed dysarthria, hoarseness, and left side facial weakness. Considering a patient's history of cardiovascular events, the acute stroke was suspected. Magnetic resonance imaging ruled out an acute cerebrovascular accident. The patient's otalgia aggravated and he reported hearing loss. Clinical examination revealed facial paralysis affecting the left side of the face, erythematous rash on the left auricle, multiple vesicles present on patient's left tympanic membrane, ulcerous lesion on the left side of the soft palate and ipsilateral velopharyngeal palsy. Indirect laryngoscopy revealed ulcerous lesions in the left side of the epiglottis and left vocal cord paralysis. The patient was diagnosed with Ramsay Hunt syndrome with cranial polyneuropathy. Oral acyclovir and oral prednisolone were administered. Seven months after discharge, facial paralysis improved to lower grade and flexible laryngoscopy showed that the left vocal cord had resumed normal movement. Ramsay Hunt syndrome can be accompanied by involvement of other cranial nerves. Previous history of hypertensive crises and myocardial infarction may influence a diagnosis of Ramsay Hunt syndrome, especially when it has atypical presentation. However, this diagnosis should be considered in patients with unilateral multiple cranial nerve palsies.


Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis.
Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption. In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV). In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin. Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia. PROSPERO CRD42021232593.


Combination of holographic imaging with robotic partial nephrectomy for renal hilar tumor treatment.
To evaluate the clinical value of the holographic imaging technology in combination with robotic-assisted partial nephrectomy (RAPN) for renal hilar tumor treatment. From Dec. 2018 to Dec. 2021, patients diagnosed with renal hilar tumor were included in this retrospective study. Before the surgery, the engineers established the holographic image models based on the enhanced CT data. The models were used in patient consultation, pre-surgery planning and surgery simulation. During the RAPN, the navigation was achieved by real-time overlapping of the holographic images on the robotic surgery endoscopic views. The navigation technique helped the surgeon to identify the important anatomic structures such as tumor, renal vein, renal artery, and pelvis. There were total of eight patients with renal hilar tumor who underwent RAPN combined with holographic imaging technique. The mean age was 57.3 years, the median ASA score was 2. The mean tumor size was 42.4 mm and the median RENAL Nephrometry score was 9.5. The clinical stages were cT1a (37.5%) and cT1b (62.5%). All the procedures were performed uneventfully by one surgeon. The mean operative time was 144.3 min, and the mean warm ischemia time was 27.9 min. The mean estimated blood loss was 86.3 ml. There was no conversion to open surgery or radical nephrectomy. There were no Clavien-Dindo ≥ 3 perioperative complications. Using the holographic imaging technique, the pre-surgery planning, simulation of renal arterial clamp and excision of the tumor, and intraoperative navigation were feasible and helpful in facilitating RAPN.


Harnessing the immune response to treat cancer.
It is well established that the immune system has the capacity to attack malignant cells. During malignant transformation cells acquire numerous molecular and biochemical changes that render them potentially vulnerable to immune cells. Yet it is self-evident that a growing tumour has managed to evade these host defence mechanisms. The exact ways in which the immune system interacts with tumour cells and how cancers are able to escape immunological eradication have only recently started to be fully elucidated. Understanding the relationship between the tumour and the anti-tumour immune response and how this can be altered with conventional treatments and immune-targeted therapies is crucial to developing new treatments for patients with cancer. In this review, focusing on the anti-tumour T-cell response, we summarize our understanding of how tumours, cancer treatments and the immune system interact, how tumours evade the immune response and how this process could be manipulated for the benefit of patients with cancer.


Extraction of Bioactive Compounds.
A bioactive compound influences the health of living organisms and it has extranutritional constituents that typically occur in low quantities in foods, which helps to enhance or boost the immune system. Plants and their products possess bioactive compounds, i.e., secondary metabolites. Here, extraction is an important process to isolate the bioactive compounds. Biological activities of the extract show a significant variation depending on the extraction methods and this also opens a gateway for selecting suitable extraction methods. Hence, different extraction methods have been discussed in this section, which influences the extraction of phytochemicals.


Concurrent validity of the ages and stages questionnaires with Bayley Scales of Infant Development-III at 2 years - Singapore cohort study.
With increasing acceptance of universal developmental screening in primary care, it is essential to evaluate the local validity and psychometric properties of commonly used questionnaires like the parent-completed Ages and Stages Questionnaires, 3rd Edition (ASQ-3) in identifying developmental delays. The aim of this study is to assess the convergent validity of the ASQ-3 with the Bayley Scales of Infant Development-3rd edition (Bayley-III) in identifying developmental delay in a low-risk term cohort in Singapore. ASQ-3 and Bayley-III data was collected prospectively with generation of ASQ-3 cut-off scores using three different criteria: 1-standard deviation (SD) (Criterion-I) or 2-SD (Criterion-II) below the mean, and using a Receiver Operator Curve (ROC) (Criterion-III). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. Correlations between the ASQ-3 and Bayley-III domains were evaluated using Pearson coefficients. With all three criteria across different domains ASQ-3 showed high specificity (72-99%) and NPV (69-98%), but lower sensitivity (19-74%) and PPV (11-59%). Criterion-I identified 11-21% of children as "at-risk of developmental delay," and was the most promising criterion measure, with high specificity (82-91%), NPV (69-74%) and overall agreement of 64-71%. Moderate-strong correlations were seen between ASQ-3 Communication and Bayley-III Language scales (r = 0.44-0.59, p < 0.01). The lowest sensitivities were seen in the motor domains. ASQ-3 is reliable in low-risk settings in identifying typically developing children not at risk of developmental delay, but it has modest sensitivity. Moderate-strong correlations seen in the communication domain are clinically important for early identification of language delay, which is one of the most prevalent areas of early childhood developmental delay.


Fearful apes, happy apes: Is fearfulness associated with uniquely human cooperation?
In the fearful ape hypothesis, Grossmann argues that heightened fearfulness increases human-unique cooperation. We suggest that this conclusion, however, may be premature. In particular, we question Grossmann's singling out of fear as the affective trait that enhances cooperative care. Additionally, we problematize the extent to which heightened fearfulness in humans, and its association with human-unique cooperation, are supported empirically.


A solar-driven degradation-evaporation strategy for membrane self-cleaning in the efficient separation of viscous crude oil/water emulsions.
Membrane separation techniques are promising methods for effectively treating hazardous emulsified oily wastewater, but membrane fouling remains a serious challenge because the high viscosity and complex composition of crude oil make it easy to adhere to membranes and difficult to be removed by conventional physical or chemical cleaning means. Herein, a two-stage solar-driven (photo-Fenton degradation/evaporation) strategy was proposed to realize the self-cleaning of membranes fouled by viscous crude oil (>60,000 mPa s), wherein the photo-Fenton process helped to degrade the heavy components into light components, and all light components removed during the solar-driven evaporation process. A 1D/2D heterostructure membrane with photo-Fenton activity and anti-crude-oil-fouling performance was prepared via a facile self-assembly vacuum-assist method. The addition of rod-like g-C3N4 (RCN) increased the interlayer distance of α-FeOOH/porous g-C3N4 (FPCN) nanosheets, resulting in a high permeation flux. The FPCN-RCN membrane exhibited both high permeation flux of 779 ± 19 L m-2h-1bar-1 and a separation efficiency of 99.4% for highly viscous crude oil-in-water emulsion. Importantly, the viscous crude oil fouled on the membrane was completely removed by the photo-Fenton degradation/solar-driven evaporation strategy, and the flux recovery rate of the membrane was ∼100%. Therefore, the FPCN-RCN membrane combined with the novel self-cleaning strategy exhibits great potential for practical emulsified oily wastewater treatment.


Does Perceived Safety Modify the Effectiveness of a Walking-Group Intervention Designed to Promote Physical Activity?
To examine whether perceived safety modified the effectiveness of the Walk Your Heart to Health (WYHH) intervention in promoting physical activity and reducing central adiposity in predominantly non-Latino black (henceforth black) and Latino communities. Generalized estimation equations were used to assess modifying effects of perceived safety on the route and perceived neighborhood safety on (1) WYHH participation at 8 weeks and 32 weeks, (2) associations between participation and physical activity, and (3) associations between physical activity and central adiposity. Community-based and faith-based organizations in black and Latino communities. There were 603 adults, aged 18 years and older, who were predominantly black, Latino, and female. Participation and physical activity (piezoelectric pedometer) were measured at each walking session. Perceived safety on the route (questionnaire), perceived neighborhood safety (questionnaire), and waist circumference were measured at baseline, 8 weeks, and 32 weeks. Secondary analysis of repeated measures using generalized estimation equations. Retention was 90% at 8 weeks and 64% at 32 weeks. Perceived safety on the route, but not perceived neighborhood safety, dampened participation at 8 weeks but not 32 weeks. Consistent participation in the intervention increased physical activity and reduced central adiposity irrespective of perceived safety on the walking route or perceived neighborhood safety. Efforts to improve safety in conjunction with interventions focused on increasing physical activity can work toward improving physical activity for blacks and Latinos, leading to a myriad of improved health outcomes including reduced central adiposity.


Serological and molecular survey of tick-borne zoonotic pathogens including severe fever with thrombocytopenia syndrome virus in wild boars in Miyazaki Prefecture, Japan.
Miyazaki Prefecture is one of the hotspots of severe fever with thrombocytopenia syndrome (SFTS) cases and related deaths in Japan since 2013 and other pathogens of tick-borne diseases (TBDs). Japanese spotted fever and scrub typhus are also endemic in this region. A total of 105 wild boars, hunted in 2009, were serologically examined as sentinels for TBDs to indirectly demonstrate the potential hazard of ticks transmitting pathogens to humans in the studied area. The collected blood and spleens of the wild boars underwent serological and molecular tests for SFTSV, Rickettsia japonica (Rj) [antibody to spotted fever group rickettsiae (SFGR) were tested by using species-common antigen], and Orientia tsutsugamushi (Ot). Seroprevalences of SFTSV, SFGR, and Ot were 41.9%, 29.5%, and 33.3%, respectively. SFTS viral RNA was identified in 7.6% of the sera, whereas DNA of Rj or Ot was not detected in any sample. In total, 43.8% of the boars possessed an infection history with SFTSV (viral gene and/or antibody). Of these, 23.8% had multiple-infection history with SFGR and/or Ot. The high prevalence of SFTSV in wild boars might reflect the high risk of exposure to the virus in the studied areas. In addition, SFTSV infection was significantly correlated with Ot infection, and so were SFGR infection and Ot infection, indicating that these pathogens have common factors for infection or transmission. These data caution of the higher risk of SFTSV infection in areas with reported cases of other TBDs.


Plasma triglyceride levels and risk of stroke and carotid atherosclerosis: a systematic review of the epidemiological studies.
The contribution of lipids to stroke risk remains uncertain; little attention has been paid to the effect of triglyceride levels, an emerging risk factor. We performed two independent systematic PubMed literature searches for epidemiological studies that examined the association of triglyceride levels with stroke and carotid intima-media thickness (CIMT). We identified 31 studies on the relationship between triglyceride levels and stroke risk and 38 on triglyceride levels and CIMT. Although study designs varied widely, nine of the 17 prospective cohort studies (n=140,788) and six of the 14 case-control studies (n=3458 cases, 4089 controls) supported a positive association between elevated triglyceride levels and increased risk of stroke. Combining all available data from prospective studies (n=9) produced a pooled relative risk of main stroke outcome per 1 standard-deviation increase of 1.10 (95% confidence interval, 1.07-1.13) without evidence of heterogeneity. One prospective study and one case-control study reported a negative relationship with haemorrhagic stroke. Of the 38 studies on CIMT (n=43,161), 11 reported a significant correlation between CIMT and triglyceride levels, of which three were unadjusted, and one reported an inverse relationship. All of the three studies with longitudinal analysis, two of which were restricted to women, reported a positive association between baseline triglyceride levels and progression of CIMT. The weight of evidence in prospective cohort studies favours a positive association between triglyceride levels and stroke, and supports the evaluation of triglyceride-lowering therapy to prevent stroke. However, this review shows the need for additional large prospective studies, especially in stroke subtypes, to establish firmly the independent detrimental effect of triglyceride levels in stroke risk.


Apamin-Sensitive K+ Current Upregulation in Volume-Overload Heart Failure is Associated with the Decreased Interaction of CK2 with SK2.
Recent studies have shown that the sensitivity of apamin-sensitive K(+) current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) to intracellular Ca(2+) is increased in heart failure (HF), leading to I KAS upregulation, action potential duration shortening, early after depolarization, and recurrent spontaneous ventricular fibrillation. We hypothesized that casein kinase 2 (CK2) interacted with small conductance calcium-activated potassium channels (SK) is decreased in HF, and protein phosphatase 2A (PP2A) is increased on the opposite, upregulating the sensitivity of I KAS to intracellular Ca(2+) in HF. Rat model of volume-overload HF was established by an abdominal arteriovenous fistula procedure. The expression of SK channels, PP2A and CK2 was detected by Western blot analysis. Interaction and colocalization of CK2 with SK channel were detected by co-immunoprecipitation analysis and double immunofluorescence staining. In HF rat left ventricle, SK3 was increased by 100 % (P < 0.05), and SK2 was not significantly changed. PP2A protein was increased by 94.7 % in HF rats (P < 0.05), whereas the level of CK2 was almost unchanged. We found that CK2 colocalized with SK2 and SK3 in rat left ventricle. With anti-CK2α antibody, SK2 and SK3 were immunoprecipitated, the level of precipitated SK2 decreased by half, whereas precipitated SK3 was almost unchanged. In conclusion, the increased expression of total PP2A and decreased interaction of CK2 with SK2 may underlie enhanced sensitivity of I KAS to intracellular Ca(2+) in volume-overload HF rat.


Random-effects meta-analysis of inconsistent effects: a time for change.
A primary goal of meta-analysis is to improve the estimation of treatment effects by pooling results of similar studies. This article explains how the most widely used method for pooling heterogeneous studies--the Der Simonian-Laird (DL) estimator--can produce biased estimates with falsely high precision. A classic example is presented to show that use of the DL estimator can lead to erroneous conclusions. Particular problems with the DL estimator are discussed, and several alternative methods for summarizing heterogeneous evidence are presented. The authors support replacing universal use of the DL estimator with analyses based on a critical synthesis that recognizes the uncertainty in the evidence,focuses on describing and explaining the probable sources of variation in the evidence, and uses random-effects estimates that provide more accurate confidence limits than the DL estimator.


Different hypertension thresholds and cognitive decline: a pooled analysis of three ageing cohorts.
The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for high blood pressure (BP) in adults came up with a new definition of hypertension with a threshold BP level of 130/80 mmHg. But the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines adhered to a conventional hypertension definition as BP ≥ 140/90 mmHg. We aimed to compare the trajectories of cognitive decline between participants with BP < 130/80 mmHg in all BP measurement waves and others with all BP < 140/90 mmHg. This pooled analysis involved middle-aged and older participants from three nationally representative ageing cohorts, including the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health Retirement Longitudinal Study (CHARLS). Participants were divided into the Normal (BP < 130/80 mmHg on all occasions throughout the study), the Borderline (BP < 140/90 mmHg on all occasions throughout the study but not in the Normal group), and the High (the rest of participants) BP groups. Global cognitive Z score was calculated from tests on memory, executive function, and orientation. A total of 17,590 participants (HRS 6964, median follow-ups 12 years; ELSA 5334, median follow-ups 16 years; CHARLS 5292, median follow-ups 7 years) were included. No significant difference in global cognitive decline rate was detected between the Normal and the borderline groups (men, pooled β = - 0.006 standard deviation [SD]/year; 95% confidence interval [CI], - 0.020 to 0.008; P = 0.377; women, pooled β = 0.006 SD/year; 95% CI - 0.005 to 0.018; P = 0.269). Participants in the High group had a significantly faster cognitive decline (men, pooled β = - 0.011 SD/year; 95% CI - 0.020 to - 0.002; P = 0.013; women, pooled β = - 0.017 SD/year; 95% CI - 0.026 to - 0.008; P < 0.001) than that in the Borderline group. Individuals in the Borderline group did not experience significantly faster cognitive decline compared with those in the Normal group. It might not be necessary for individuals with borderline BP (between 130/80 and 140/90 mmHg) to initiate antihypertension therapy in consideration of cognitive decline.


An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP+ mononuclear cells and PDGF-BB secretion.
Osteoporosis (OP) is a common age-related disease characterized by a deterioration of bone mass and structure that predisposes patients to fragility fractures. Pharmaceutical therapies that promote anabolic bone formation in OP patients and OP-induced fracture are needed. We investigated whether a neutralizing antibody against Siglec-15 can simultaneously inhibit bone resorption and stimulate bone formation. We found that the multinucleation of osteoclasts was inhibited in SIGLEC-15 conditional knockout mice and mice undergoing Siglec-15 neutralizing antibody treatment. The secretion of platelet-derived growth factor-BB (PDGF-BB), the number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear cells, and bone formation were significantly increased in the SIGLEC-15 conditional knockout mice and antibody-treated mice. The anabolic effect of the Siglec-15 neutralizing antibody on bone formation was blunted in mice with Pdgfb deleted in TRAP+ cells. These findings showed that the anabolic effect of the Siglec-15 neutralizing antibody was mediated by elevating PDGF-BB production of TRAP+ mononuclear cells. To test the therapeutic potential of the Siglec-15 neutralizing antibody, we injected the antibody in an ovariectomy-induced osteoporotic mouse model, which mimics postmenopausal osteoporosis in women, and in two fracture healing models because fracture is the most serious health consequence of osteoporosis. The Siglec-15 neutralizing antibody effectively reduced bone resorption and stimulated bone formation in estrogen deficiency-induced osteoporosis. Of note, the Siglec-15 neutralizing antibody promoted intramembranous and endochondral ossification at the damaged area of cortical bone in fracture healing mouse models. Thus, the Siglec-15 neutralizing antibody shows significant translational potential as a novel therapy for OP and bone fracture.


Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system.
Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option for meeting the treatment demands of Chinese patients.


Isolation and characterization of a serine protease-producing marine bacterium Marinomonas arctica PT-1.
A serine protease-producing marine bacterial strain named as PT-1 was isolated and identified as a family of Marinomonas arctica, based on molecular characterization of 16S rRNA gene sequence, phylogenetic tree, and fatty acid composition analyses. Optimized culture conditions for growth of the bacterium PT-1 and production of protease (ProA) were determined to be pH 8.0 in the presence of 5 % NaCl, at 37 °C during 24 h of incubation in the presence of 1.0 % skim milk. The molecular weight of the purified ProA was estimated to be 63-kDa as a major band by SDS-PAGE. We were intrigued to find that the activity of ProA was not inhibited by pepstatin A, chymostatin, and leupeptin known as inhibitors for cysteine protease. However, phenylmethylsulfonyl fluoride (PMSF) completely inhibited protease activity, suggesting that the ProA is like a serine protease. To the best of our knowledge, this is the first report on serine protease of Marinomonas species.


Pathogenesis of Paget disease of bone.
Paget disease of bone (PDB) is a common disease characterized by focal areas of increased and disorganized bone turnover. Some patients are asymptomatic, whereas others develop complications such as pain, osteoarthritis, fracture, deformity, deafness, and nerve compression syndromes. PDB is primarily caused by dysregulation of osteoclast differentiation and function, and there is increasing evidence that this is due, in part, to genetic factors. One of the most important predisposing genes is SQSTM1, which harbors mutations that cause osteoclast activation in 5-20 % of PDB patients. Seven additional susceptibility loci for PDB have been identified by genomewide association studies on chromosomes 1p13, 7q33, 8q22, 10p13, 14q32, 15q24, and 18q21. Although the causal variants remain to be discovered, three of these loci contain CSF1, TNFRSF11A, and TM7SF4, genes that are known to play a critical role in osteoclast differentiation and function. Environmental factors are also important in the pathogenesis of PDB, as reflected by the fact that in many countries the disease has become less common and less severe over recent years. The most widely studied environmental trigger is paramyxovirus infection, but attempts to detect viral transcripts in tissues from patients with PDB have yielded mixed results. Although our understanding of the pathophysiology of PDB has advanced tremendously over the past 10 years, many questions remain unanswered, such as the mechanisms responsible for the focal nature of the disease and the recent changes in prevalence and severity.


Recurrence and survival after laparoscopy versus laparotomy without lymphadenectomy in early-stage endometrial cancer: Long-term outcomes of a randomised trial.
Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively. Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined. In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable. Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer.


No differences in patient-reported outcomes between medial pivot insert and symmetrical insert in total knee arthroplasty: A randomized analysis.
Although total knee arthroplasty (TKA) using a medial pivot insert reportedly improves kinematics compared with a symmetrical insert, improvements in patient-reported outcomes have not yet been reported. The aim of this study was to determine whether insert designs influenced patient-reported outcomes. Seventy TKAs for osteoarthritis were randomly allocated to a symmetrical dish insert (SD group: 35 knees) or medial pivot insert (MP group: 35 knees). Thirty-two of the SD group (74.4 ± 6.6 years old) and 33 of the MP group (73.8 ± 6.0 years old) completed the two-year follow-up. The knee range of motion (ROM) and 2011 Knee Society score (2011KSS) were analyzed pre-operatively and postoperatively. There was no difference in pre-operative ROM or 2011KSS (Symptom: 7.3 ± 5.9 in SD group, 8.4 ± 5.4 in MP group, P = 0.432; Satisfaction: 12.6 ± 6.9 in SD group, 11.8 ± 5.9 in MP group, P = 0.581; Activity: 35.8 ± 18.1 in SD group, 35.2 ± 18.6 in MP group, P = 0.883). At two years, although both group showed good improvement, there were no differences in ROM or 2011KSS (Symptom: 19.3 ± 5.0 in SD group, 18.3 ± 4.1 in MP group, P = 0.351; Satisfaction: 24.0 ± 7.6 in SD group, 22.9 ± 7.9 in MP group, P = 0.548; Activity: 60.3 ± 14.8 in SD group, 54.3 ± 17.3 in MP group, P = 0.137). The medial pivot insert was not superior to the symmetrical insert in patient-reported outcomes at two years after TKA.


Mind and consciousness: Towards a final answer?
A review is given of recent developments in our scientific understanding of consciousness to help guide further progress, leading to a possible final answer to the question of how the brain may create consciousness. The review commences with a brief description of the nature of consciousness, and moves to an overview of various approaches presently being pursued to understand it (quantum mechanics, 40-Hz, dynamical systems theory and complexity, narrative centre of gravity, global workspace, relational mind). To help move the discussion forward we use the fact that attention acts as the gateway to consciousness, implying the need to analyze attention most closely. An engineering control approach is introduced to model the movement of attention, based on experimental data indicating separate sites for attention modulation and for the creation of that modulation: and using the analogy with motor control in the brain, to which an engineering approach has already been applied by others. Simulation and brain imaging results support the presence of several of the relevant attention control modules in the brain. The attention control framework is extended to analyze how consciousness could arise during attentive processing, in terms of the COrollary Discharge of Attention Movement (CODAM) model. The relation between the CODAM model of consciousness and modern approaches to consciousness in the philosophy of mind is then briefly described. An overall summary and a program of future explorations of the CODAM model conclude the review.


Effects of copper ions released from metallic copper on CHO-K1 cells.
The aim of this study was to investigate the cytotoxic and genotoxic effect of copper extracts obtained from metallic copper in Chinese hamster ovary (CHO-K1) cell line using neutral red (NR), sister chromatid exchange (SCE), chromosomal aberrations (CA) and cell-cycle kinetics tests. Cells were cultured in Ham-F10 with different copper-containing extracts obtained after the immersion of copper disks for 1, 2, 3, 9, 12, 24, 48 and 72 h in culture medium. Results from cytotoxicity assay showed an inverted U-shape response evidenced in changes in lysosomal activity and mitotic index. The analysis of CA revealed an increase of abnormal metaphases for copper concentration (cCu) in the 5.67-7.42 mg/L dose-range (p<0.001). In addition, SCE frequencies were higher for treated cells when compared with controls in the 1.56-7.42 mg/L concentration range (p<0.001). The absence of metaphases indicated cytotoxicity for cCu≥10.85 mg/L. Results show that cells close to copper-containing materials releasing copper ions are susceptible to cytotoxic and genotoxic effects.


Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway.
Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line. The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses. We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α2, integrin α4, and integrin α5 and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC). The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.


Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients.
We conducted a double-blind pilot study of 8 patients with established cerebral infarction to evaluate the effect of a single dose of amphetamine on recovery of motor function using the Fugl-Meyer scale. Four patients received amphetamine; the rest were given placebo. All underwent a session of physical therapy. Patients treated with amphetamine obtained greater increments in motor scores than the controls. Along with animal studies, these findings may allow the development of a pharmacological approach to stroke rehabilitation.


Central retinal artery occlusion secondary to presumed traumatic carotid artery dissection in a healthy child.
To describe a rare case of a 13 years-old healthy child that presented CRAO secondary to carotid artery dissection, which occurred after a neck rotation movement. Case report with prospective literature review. One patient described in the case report. Not applicable. Internal carotid artery dissection is a rare condition, specially in children, that can lead to serious cerebral-ocular ischemic events. It may occur due to direct vessel trauma or spontaneously. Prompt imaging screening is of paramount importance because early antithrombotic treatment or surgical intervention may significantly reduce the incidence of devastating ischemic events, such as stroke or central retinal artery occlusion.


Preparation of nitrogen self-doped hierarchical porous carbon with rapid-freezing support for cooperative pollutant adsorption and catalytic oxidation of persulfate.
Herein, we report a method to synthesize nitrogen self-doped hierarchical porous carbon materials derived from chitosan. This method uses potassium hydroxide (KOH) activation and rapid-freezing technology. The catalyst (CA-900Q 1-1) obtained after rapid-freezing and KOH activation treatment show excellent persulfate activation ability. It can remove 20 mg bisphenol A (BPA) within 10 min better than traditional metal oxidate and nanomaterials. In the aquatic environment, CA-900Q 1-1 has a high resistance to inorganic anions. CA-900Q 1-1, possessing a high proportion of graphitic nitrogen, provides a sufficient number of active sites for persulfate activation. In addition, the catalyst yielded sizeable specific surface areas (SSAs) (1756.1 m2/g) and a hierarchical pore structure, which helps to improve the mass transfer in the carbon framework. The efficient adsorption of pollutants by the catalyst shortens the time required for target organic molecules to migrate to the catalyst surface and hierarchical pore structure. Furthermore, the catalyst has excellent electrical conductivity (R = 1.73 Ω), which enables pollutants adsorbed on the catalyst surface to transfer electrons to the persulfate through the N-doped sp2-hybrid carbon network faster.


Self-Healing Ti3C2 MXene/PDMS Supramolecular Elastomers Based on Small Biomolecules Modification for Wearable Sensors.
Flexible conductive composites can be used as wearable strain sensors, which are widely used in the fields of new-generation robotics, electronic skin, and human detection. However, how to make conductive composites that simultaneously possess flexibility, stretchability, self-healing, and sensing capability is challenging research. In this work, we innovatively designed and prepared a silicone polymer conductive composite. MXenes and amino poly(dimethylsiloxane) were modified by small biomolecules via an esterification reaction and a Schiff base reaction, respectively. The modified MXenes are uniformly dispersed, which endows the composite with good electrical conductivity. The reversibility of multiple hydrogen bonds and imine bonds in the composite system makes it have ideal tensile properties and high-efficiency self-healing ability without external stimulation. The conductive composite containing 10 wt % A-MXenes showed an elongation of 81%, and its mechanical strength could reach 1.81 MPa. After repair, the tensile properties and the electrical conductivity could be restored to 98.4 and 97.6%, respectively. In addition, the conductive composite is further evaluated for the value of wearable strain sensors. Even after cut-healed processes, the conductive composite can still accurately detect tiny human movements (including speaking, swallowing, and pressing). This kind of self-healing MXene/PDMS elastomers based on the modification of small biomolecules has great potential as wearable strain sensors. This simple preparation method provides guidance for future multifunctional flexible electronic materials.


Ischemia/reperfusion-induced MiD51 upregulation recruits Drp1 to mitochondria and contributes to myocardial injury.
The translocation of Drp1 from the cytosol to mitochondria leads to Drp1 activation and mitochondrial fission in myocardial ischemia/reperfusion (MI/R). However, the molecular mechanism underlying mitochondrial Drp1 translocation remains poorly understood. Mitochondrial Drp1 recruitment relies on 4 binding partners including MiD49, MiD51, Mff and Fis1. This study was to elucidate which one facilitate mitochondrial Drp1 translocation and its role in MI/R injury. MI/R was induced by ligating the left anterior descending coronary artery for 30 min and subsequent reperfusion for 3 h. Primary neonatal cardiomyocytes were subjected to hypoxia for 2 h and reoxygenation for 4 h. SiRNA or Adeno-associated virus (AAV) expressing shRNA was used to knock down the key binding partner in vitro or in vivo respectively. The expression of MiD51 rather than other binding partners (MiD49, Mff or Fis1) was increased after MI/R. MiD51 knockdown inhibited hypoxia/reoxygenation (H/R) or ischemia/reperfusion (I/R)-induced mitochondrial Drp1 translocation. SiRNA-induced knockdown of MiD51 suppressed mitochondrial oxidative stress, improved mitochondrial function and alleviate cellular injury in H/R cardiomyocytes. AAV-mediated knockdown of MiD51 reduced myocardial injury and improved cardiac function in the I/R hearts, while mitochondrial Drp1 translocation and cardiac function were not affected by MiD51 knockdown in the hearts without I/R. MiD51 is identified as the binding partner that promotes mitochondrial Drp1 translocation and contributes to MI/R injury. Inhibition of MiD51 may be a potential therapeutic target to alleviate MI/R injury.