Data set of smallholder farm households in banana-coffee-based farming systems containing data on farm households, agricultural production and use of organic farm waste.
The data was collected in the Karagwe and Kyerwa districts of the Kagera region in north-west Tanzania. It encompasses 150 smallholder farming households, which were interviewed on the composition of their household, agricultural production and use of organic farm waste. The data covers the two previous rainy seasons and the associated vegetation periods between September 2016 and August 2017. The knowledge of experts from the following institutions was included in the discussion on the selection criteria: two local non-profit organisations, i.e., WOMEDA and the MAVUNO Project; the International Institute of Tropical Agriculture (IITA); and the National Land Use Planning Commission (NLUPC). Households were selected for inclusion if all of the following applied to them: 1) less than 10 acres of land (4.7 ha) registered in the village offices, 2) no agricultural training, and 3) decline in the fertility of their land since they started farming (self-reported). We selected 150 smallholder households out of a pool of 5,000 households known to WOMEDA in six divisions of the Kyerwa and Karagwe districts. The questionnaire contained 54 questions. The original language of the survey was Kiswahili. All interviews were audio recorded. The answers were digitalised and translated into English. The data set contains the raw data with 130 quantitative and qualitative variables. For quantitative variables, the only analysis that was made was the conversion of units, e.g., land area was converted from acres to hectares, harvest from buckets to kilograms and then to tons, and heads of livestock to Tropical Livestock Units (TLU). Qualitative variables were summarised into categories. All data has been anonymised. The data set includes geographical variables, household information, agricultural information, gender-specific responsibilities, economic data, farm waste management, and water, energy and food availability (Water-Energy-Food (WEF) Nexus). Variables are written in italics. The following geographical variables are part of the data set: district, division, ward, village, hamlet, longitude, latitude, and altitude. Household information includes start of farming, household size, gender and age of household members. Agricultural information includes land size, size of homegarden, crops, livestock and livestock keeping, trees, and access to forest. Gender-specific responsibilities includes producing and exchanging seeds, weed control, terracing, distributing organic material to the fields, care of annual and perennial crops, harvesting of crops, decisions about the harvest and animal products, selling and buying products, working on their own farm and off-farm, cooking, storing food, collecting and caring for drinking water, washing, and toilet cleaning. Economic data includes distance to the market, journey time to market, transport methods, labourers employed by the household, working off-farm, and assets such as type of house. Variables relevant to the WEF Nexus are drinking water source and treatment, meals per day, months without food, cooking fuel, and type of toilet. Variables on farm waste management are the use of crop residues, food and kitchen waste, livestock manure, cooking ash, animal bones, and human urine and faeces. The data can be potentially reused and further developed for the purpose of agricultural production analysis, socio-economic analysis, comparison to other regions, conceptualisation of waste and nutrient management, establishment of land use concepts, and further analysis on food security and healthy diets.


Design of cost-efficient and photocatalytically active Zn-based MOFs decorated with Cu2O nanoparticles for CO2 methanation.
Here we show for the first time a MOF that is photocatalytically active for light-assisted CO2 methanation under mild conditions (215 °C) without the inclusion of metallic nanoparticles or any sacrificial agent. The presence of Cu2O nanoparticles causes a 50% increase in the photocatalytic activity. This result paves the way for developing efficient and cost-effective materials for CO2 elimination.


p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan.
Recent studies have implicated aflatoxin B1 (AFB1) exposure as an etiological agent in hepatocellular carcinoma (HCC) and suggested an interaction with chronic hepatitis B virus (HBV) infection. Worldwide AFB1 exposure correlates with a specific mutation at codon 249 in the p53 tumor suppressor gene in liver tumors. This study investigated the roles of HBV and AFB1 in the HCC carcinogenic pathway involving p53 mutations. In cases and controls, chronic HBV infection was assessed by serum hepatitis B surface antigen (HBsAg) and AFB1 exposure by immunohistochemical detection of AFB1-DNA adduct in liver tissue. p53 protein mutations in tumor tissues of HCC cases were identified by immunohistochemistry and DNA mutations by single-stranded conformational polymorphism and sequencing analysis. Both chronic HBsAg carrier status and liver AFB1-DNA adducts were significantly higher in cases than in controls with odds ratios (OR) of 8.4 and 3.9, respectively (P < 0.01). Moreover, HCC risk was greatest in individuals with both AFB1-DNA adducts and HBsAg, suggesting a viral-chemical interaction. Mutant p53 protein, mutations in the p53 gene, and specific codon 249 mutations were detected in 37, 29, and 13%, respectively, of the HCC cases. Most of the DNA mutations were transversions, and the only major clustering site for mutations was codon 249. AFB1-DNA adducts were associated with p53 protein (OR = 2.9, P = 0.054) and DNA mutations (OR = 2.9, P = 0.082) but with borderline significance. All of the codon 249 mutations (n = 12) occurred in HBsAg-seropositive carriers, resulting in an OR of 10.0 (P < 0.05), suggesting that HBV may be involved in the selection of these mutations. The ORs between HBsAg and p53 DNA and protein mutations were 2.6 (P = 0.077) and 1.8 (P > 0.05), respectively. Both p53 DNA and protein mutations were related to tumor stage, suggesting that they are late events. These studies provided further support for the role of aflatoxin exposure in HCC in Taiwan and insight into viral-chemical interactions and molecular pathogenesis.


Idobata-Nagaya: a community housing solution for socially isolated older adults following the great East Japan earthquake.
Following the Great East Japan Earthquake, the living environment of socially isolated older adults has become a pressing concern. In response, Nagaya, a collective housing program, was established in Soma City, Fukushima, Japan to address social isolation among older adults and support their long-term health. This study aimed to identify characteristics of individuals in Nagaya and examine the sustainability of this initiative. We conducted a retrospective analysis of residents who were relocated to Nagaya, emphasizing their characteristics, the continuity of their stay in Nagaya, and their care certification levels, using data up to December 31, 2022. We employed Kaplan-Meier curves to analyze the duration for which residents continued to reside in Nagaya and the time leading up to the requiring care-level certification. Of 65 people who moved to Nagaya after the disaster, 30 people (46.2%) continued to live there, 21 (32.3%) died during their stay, and 14 (21.5%) moved out. The overall duration of occupancy averaged 6.39 years (SD 3.83 years). The proportion of requiring care-level certification occurrences per person-year was 0.0577 for those without care certification and 0.3358 for those with requiring support level at the time of moving in. In summary, Nagaya-style communal housing may offer suitable living environments for older adults with diverse needs during disasters and serve as a valuable tool for developing public policies in aging societies.


Accelerated Biodegradation of the Agrochemical Ametoctradin by Soil-Derived Microbial Consortia.
Pesticide-resistant plant pathogens are an increasing threat to the global food supply and have generated a need for novel, efficacious agrochemicals. The current regulatory process for approving new agrochemicals is a tedious but necessary process. One way to accelerate the safety evaluation process is to utilize in vitro systems to demonstrate pesticide degradation by soil microbes prior to ex vivo soil evaluations. This approach may have the capability to generate metabolic profiles free of inhibitory substances, such as humic acids, commonly present in ex vivo soil systems. In this study, we used a packed-bed microbial bioreactor to assess the role of the natural soil microbial community during biodegradation of the triazolopyrimidine fungicide, ametoctradin. Metabolite profiles produced during in vitro ametoctradin degradation were similar to the metabolite profiles obtained during environmental fate studies and demonstrated the degradation of 81% of the parent compound in 72 h compared to a half-life of 2 weeks when ametoctradin was left in the soil. The microbial communities of four different soil locations and the bioreactor microbiome were compared using high throughput sequencing. It was found that biodegradation of ametoctradin in both ex vivo soils and in vitro in the bioreactor correlated with an increase in the relative abundance of Burkholderiales, well characterized microbial degraders of xenobiotic compounds.


Physician prescribing of opioid agonist treatments in provincial correctional facilities in Ontario, Canada: A survey.
Substance use and substance use disorders are common in people who experience detention or incarceration in Canada, and opioid agonist treatment (OAT) may reduce the harms associated with substance use disorders. We aimed to define current physician practice in provincial correctional facilities in Ontario with respect to prescribing OAT and to identify potential barriers and facilitators to prescribing OAT. We invited all physicians practicing in the 26 provincial correctional facilities for adults in Ontario to participate in an online survey. Twenty-seven physicians participated, with representation from most correctional facilities in Ontario. Of participating physicians, 52% reported prescribing methadone and 48% reported prescribing buprenorphine/naloxone to patients in provincial correctional facilities. Nineteen percent of participants reported initiating methadone treatment and 11% reported initiating buprenorphine/naloxone for patients in custody. Participants identified multiple barriers to initiating OAT in provincial correctional facilities including concerns about medication diversion and safety, concerns about initiating treatment in patients who are not currently using opioids, lack of linkage with community-based providers and the Ministry of Community Safety and Correctional Services policy. Identified facilitators to initiating OAT were support from institutional health care staff and administrative staff, adequate resources for program delivery and access to linkage with community-based OAT providers. This study identifies opportunities to improve OAT programs and to improve access to OAT for persons in provincial correctional facilities in Ontario.


Baseline markers of inflammation, lipids, glucose, and Dietary Inflammatory Index scores do not differ between adults willing to participate in an intensive inflammation reduction intervention and those who do not.
Chronic inflammation is associated with numerous chronic diseases and can be managed with diet. The purpose of this study was to examine differences in baseline characteristics and plasma inflammation levels between two groups of participants that participated in an intensive, lifestyle intervention or a remotely delivered intervention. This work also assessed the association between Dietary Inflammatory Index (DII)® scores and participants' inflammatory and metabolic biomarkers at baseline. Ninety-five participants (61 intervention, 34 control) chose to enroll in either a 12-month intervention consisting of a face-to-face nutrition, physical activity, and stress management intervention or a remotely-delivered intervention (control group) focusing on general cancer prevention. The intervention group met at the University of South Carolina for classes and the control group had materials emailed to them. A quantile regression was used to compare participants' high-sensitivity C-reactive protein and interleukin-6 levels. Multiple linear regression was used to determine the association between DII scores and biomarkers. There were significant differences in age, body mass index, body fat percentage, and blood pressure between groups, but there were no differences in levels of inflammatory biomarkers. Values of interleukin-6 at the 90th percentile of its distribution were 8.31 pg/ml higher among those in DII quartile 4 compared with quartile 1 ( p = 0.02). All other outcomes were not significant. Given similar levels of inflammatory biomarkers, participants opting for the control group would also have benefited from a more intensive lifestyle intervention focusing on reducing inflammation.


XBP1 as a novel molecular target to attenuate drug resistance in hepatocellular carcinoma.
Despite improvements in clinical management of hepatocellular carcinoma (HCC), prognosis remains poor with a 5-year survival rate less than 40%. Drug resistance in HCC makes it challenging to treat; therefore, it is imperative to develop new therapeutic strategies. Higher expression of X-box binding protein 1 (XBP1) in tumor cells is highly correlated with poor prognosis. In tumor cells, XBP1 modulates the unfolded protein response (UPR) to restore homeostasis in endoplasmic reticulum. Targeting XBP1 could be a promising therapeutic strategy to overcome HCC resistance and improve the survival rate of patients. This review provides the recent evidence that indicates XBP1 is involved in HCC drug resistance via DNA damage response, drug inactivation, and inhibition of apoptosis. In addition, the potential roles of XBP1 in inducing resistance in HCC cells were highlighted, and we showed how its inhibition could sensitize tumor cells to controlled cell death. Due to the diversity in molecular mechanism of multidrug-resistance, targeting one specific pathway is inadequate. XBP1 inhibition could be a potential therapeutic target to overcome verity of resistance mechanisms. The main function of this transcription factor in HCC treatment response is an attractive area for further studies and should be discussed more.


Growth of quailbush in acidic, metalliferous desert mine tailings: effect of Azospirillum brasilense Sp6 on biomass production and rhizosphere community structure.
Mine tailing deposits in semiarid and arid environments frequently remain devoid of vegetation due to the toxicity of the substrate and the absence of a diverse soil microbial community capable of supporting seed germination and plant growth. The contribution of the plant growth promoting bacterium (PGPB) Azospirillum brasilense Sp6 to the growth of quailbush in compost-amended, moderately acidic, high-metal content mine tailings using an irrigation-based reclamation strategy was examined along with its influence on the rhizosphere bacterial community. Sp6 inoculation resulted in a significant (2.2-fold) increase in plant biomass production. The data suggest that the inoculum successfully colonized the root surface and persisted throughout the 60-day experiment in both the rhizosphere, as demonstrated by excision and sequencing of the appropriate denaturing gradient gel electrophoresis (DGGE) band, and the rhizoplane, as indicated by fluorescent in situ hybridization of root surfaces. Changes in rhizosphere community structure in response to Sp6 inoculation were evaluated after 15, 30, and 60 days using DGGE analysis of 16S rRNA polymerase chain reaction amplicons. A comparison of DGGE profiles using canonical correspondence analysis revealed a significant treatment effect (Sp6-inoculated vs. uninoculated plants vs. unplanted) on bacterial community structure at 15, 30, and 60 days (p < 0.05). These data indicate that in an extremely stressed environment such as acid mine tailings, an inoculated plant growth promoting bacterium not only can persist and stimulate plant growth but also can directly or indirectly influence rhizobacterial community development.


Dual-energy X-ray absorptiometry diagnostic discordance between Z-scores and T-scores in a young Iranian population.
Dual-energy X-ray Absorptiometry (DXA) is considered the gold standard for non-invasive measurement of bone mass. T-scores and Z-scores are used to present the results of bone mass. The present study was designed to evaluate the discordance between T-scores and Z-scores calculated at a same level and its relation with age, gender and body mass index (BMI) in a representative sample of normal population. This cross-sectional study was conducted as a part of a comprehensive survey, Iranian Multicenter Osteoporosis Study (IMOS), designed to assess bone health among healthy adults. Each individual underwent both L1-L4 antero-posterior lumbar spine and hip DXA scan. The difference between the T- and Z-scores measured at each of the four skeletal sites was then calculated. A -1.21 to 1.21 point difference was noted in the Z- and T- scores measured at each site. While the difference between the T-and Z-scores was less than 0.5 SD in most of the cases, the difference was higher than 1 SD in about 5% of the subjects. Standardization of Z-score definition and calculation techniques as well as developing an ethnicity-matched reference population is needed to improve the reliability of DXA-generated Z-scores.


Paracetamol overdose in Victoria remains a significant health-care burden.
Paracetamol is the most frequently used analgesic in Australia and can be purchased without a prescription. We aimed to investigate the epidemiology and outcome of paracetamol overdoses occurring in Victoria, Australia. The Victorian admitted episode dataset was examined for all patients who had a diagnosis of paracetamol poisoning (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification [ICD-10-AM]: T39.1) or paracetamol adverse effect in therapeutic use (Y45.5) from July 1, 2000 to June 30, 2007. Data extracted included all ICD-10 codes related to their admissions, gender, age range, date of admission, and cause of death (if applicable). Over 7 years, there was a total of 14,662 hospital admissions for paracetamol overdose with a mean of 2095 cases per year. Accidental overdoses comprised 15% (n = 2149) of cases. The overdose rate fell from 46 cases per 100,000 in 2001 to 39 cases per 100,000 in 2006 (P < 0.001). Most overdoses occurred in women (71%), and patients between 15 and 50 years old comprised 78% of all cases. Complications and mortality were relatively uncommon, with only 26 deaths directly attributable to paracetamol overdose over the 7 years. No child under 15 years old died from their overdose. Admission to Victorian hospitals with paracetamol overdose presents an enormous and in many cases preventable health-care burden. Fortunately, there has been a gradual fall in admissions, and most cases appear relatively benign. Further reductions in overdose could be achieved with increased awareness by physicians and the general public regarding the potential for accidental overdose, and increasing funding for mental health initiatives.


[Epilepsy-related psychoses].
Epilepsy-related psychoses lie in the border zone between neurology and psychiatry. The aim of this article is to give a brief overview of current knowledge of these psychoses, and to offer recommendations for their treatment. The article is based on a discretionary selection of articles found through a search in PubMed, as well as the authors' own experience with this patient group. Epilepsy-related psychoses may occur during, after or between seizures. In addition, psychoses may occur as a side-effect of antiepileptic drugs, and as so-called alternative psychosis. The latter may arise in patients who, with the aid of treatment (medication or surgery), have become completely seizure-free. Ictal psychoses and the majority of postictal psychoses are often of such short duration that treatment with antipsychotics is not appropriate. In these cases, optimizing antiepileptic treatment is the best prophylaxis. Treatment with antipsychotics may, however, be indicated for interictal psychoses and for some patients with especially long-lasting or recurrent postictal psychoses. Different types of epilepsy-related psychosis require different types of treatment, and some are treated with antipychotics. In those circumstances, we recommend the use of medication that is less likely to lower the seizure threshold, for example risperidone.


Antipyretic, parasitologic, and immunologic effects of combining sulfadoxine/pyrimethamine with chloroquine or paracetamol for treating uncomplicated Plasmodium falciparum malaria.
Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1-4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar parasite reduction (0-48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P < 0.001) and similarly in the four treatment groups between days 0, 2, and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production.


Optical properties of humic substances and CDOM: effects of borohydride reduction.
Treatment of Suwanee River humic (SRHA) and fulvic (SRFA) acids, a commercial lignin (LAC), and a series of solid phase extracts (C18) from the Middle Atlantic Bight (MAB extracts) with sodium borohydride (NaBH(4)), a selective reductant of carbonyl-containing compounds including quinones and aromatic ketones, produces a preferential loss of visible absorption (> or = 50% for SRFA) and substantially enhanced, blue-shifted fluorescence emission (2- to 3-fold increase). Comparison of the results with those obtained from a series of model quinones and hydroquinones demonstrates that these spectral changes cannot be assigned directly to the absorption and emission of visible light by quinones/hydroquinones. Instead, these results are consistent with a charge transfer model in which the visible absorption is due primarily to charge transfer transitions arising among hydroxy- (methoxy-) aromatic donors and carbonyl-containing acceptors. Unlike most of the model hydroquinones, the changes in optical properties of the natural samples following NaBH(4) reduction were largely irreversible in the presence of air and following addition of a Cu(2+) catalyst, providing tentative evidence that aromatic ketones (or other similar carbonyl-containing structures) may play a more important role than quinones in the optical properties of these materials.


Focus information is used to interpret binocular images.
Focus information-blur and accommodation-is highly correlated with depth in natural viewing. We examined the use of focus information in solving the binocular correspondence problem and in interpreting monocular occlusions. We presented transparent scenes consisting of two planes. Observers judged the slant of the farther plane, which was seen through the nearer plane. To do this, they had to solve the correspondence problem. In one condition, the two planes were presented with sharp rendering on one image plane, as is done in conventional stereo displays. In another condition, the planes were presented on two image planes at different focal distances, simulating focus information in natural viewing. Depth discrimination performance improved significantly when focus information was correct, which shows that the visual system utilizes the information contained in depth-of-field blur in solving binocular correspondence. In a second experiment, we presented images in which one eye could see texture behind an occluder that the other eye could not see. When the occluder's texture was sharp along with the occluded texture, binocular rivalry was prominent. When the occluded and occluding textures were presented with different blurs, rivalry was significantly reduced. This shows that blur aids the interpretation of scene layout near monocular occlusions.


Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.
The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with ≥ 70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and ≥ 20% in 84 patients. Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.


Probing quantum correlations in many-body systems: a review of scalable methods.
We review methods that allow one to detect and characterize quantum correlations in many-body systems, with a special focus on approaches which are scalable. Namely, those applicable to systems with many degrees of freedom, without requiring a number of measurements or computational resources to analyze the data that scale exponentially with the system size. We begin with introducing the concepts of quantum entanglement, Einstein-Podolsky-Rosen steering, and Bell nonlocality in the bipartite scenario, to then present their multipartite generalization. We review recent progress on characterizing these quantum correlations from partial information on the system state, such as through data-driven methods or witnesses based on low-order moments of collective observables. We then review state-of-the-art experiments that demonstrate the preparation, manipulation and detection of highly-entangled many-body systems. For each platform (e.g. atoms, ions, photons, superconducting circuits) we illustrate the available toolbox for state preparation and measurement, emphasizing the challenges that each system poses. To conclude, we present a list of timely open problems in the field.


Mosquito and human hepatocyte infections with Plasmodium ovale curtisi and Plasmodium ovale wallikeri.
Human ovale malaria is caused by the two closely related species, Plasmodium ovale curtisi and P. ovale wallikeri. Both species are known to relapse from quiescent hepatic forms months or years after the primary infection occurred. Although some studies have succeeded in establishing mosquito transmission for ovale malaria, none have specifically described transmission and human hepatocyte infection of both sibling species. Here we describe a simplified protocol for successful transmission of both P. ovale curtisi and P. ovale wallikeri to Anopheles coluzzii mosquitoes and streamlined monitoring of infection using sensitive parasite DNA detection, by loop-activated amplification, in blood-fed mosquitoes. In one experimental infection with P. ovale curtisi and one with P. ovale wallikeri, viable sporozoites were isolated from mosquito salivary glands and used to successfully infect cultured human hepatocytes. This protocol provides a method for the utilisation of pretreatment clinical blood samples from ovale malaria patients, collected in EDTA, for mosquito infection studies and generation of the hepatic life cycle stages of P. ovale curtisi and P. ovale wallikeri. We also demonstrate the utility of loop-activated amplification as a rapid and sensitive alternative to dissection for estimating the prevalence of infection in Anopheles mosquitoes fed with Plasmodium-infected blood.


Current review and comparison of the new nonsteroidal anti-inflammatory agents.
New pharmacodynamic chemical agents have been released for the treatment of rheumatoid arthritis and other arthritides. These agents, the aryl-alkanoic acid derivatives, which are classified as nonsteroidal anti-inflammatory agents, exert an anti-inflammatory effect on locally affected tissues. A suggested mechanism of action may be to inhibit the synthesis of prostaglandins, which are involved in the basic inflammatory tissue response. These agents have been found to be not significantly more effective than aspirin, but they may be useful in patients who cannot tolerate aspirin.


Intrathecal lactate predicting hydrocephalus after aneurysmal subarachnoid hemorrhage.
Evidence shows possible benefits from continuous drainage by lumbar drain after aneurysmal subarachnoid hemorrhage (SAH). Under the hypothesis that compartmentalization occurs between the ventricle and subarachnoid space after massive SAH, this study aimed to evaluate the biochemical differences between ventricular and intrathecal cerebrospinal fluid (CSF) and assess the role of CSF lactate in shunt-dependent hydrocephalus (SDHC) after aneurysmal SAH. Patients with modified Fisher grade III/IV aneurysmal SAH who underwent early obliteration were evaluated. Intrathecal and intraventricular CSF were obtained on day 7 post-SAH to measure their biochemical composition in terms of total protein, glucose, ferritin, and lactate. The associations of SDHC with the clinical parameters and CSF data were analyzed. There were 28 patients (mean age, 55.4 y; males, 46.6%), including 18 (64.3%) with SDHC. Intrathecal CSF had significantly higher levels of total protein, ferritin, hemoglobin, and lactate but lower glucose level than intraventricular CSF (all P < 0.0001). By multivariate analysis of clinical and CSF parameters, elevated intrathecal CSF lactate (P = 0.036) and the presence of intraventricular hemorrhage (P = 0.05) were independent factors associated with SDHC. Moreover, intrathecal lactate >5.5 μM effectively predicted the occurrence of SDHC (odds ratio: 32, 95% confidence interval: 3.8-270.8; P = 0.0015). By compartmentalization of the subarachnoid space after SAH, intrathecal lactate level is a useful predictive parameter for long-term SDHC in patients with aneurysmal SAH patients.


Evaluating the Factor Structure of Each Facet of the Five Facet Mindfulness Questionnaire.
Nearly all studies treat the Five Facet Mindfulness Questionnaire as five independent scales (one measuring each of the five facets), yet almost no methodological work has examined the psychometric structure of the facets independently. We address this gap using factor analytic methods. Exploratory and confirmatory factor models were fit to item response data from a sample of 522 adults recruited online. Findings were replicated in a sample of 454 adults receiving aftercare for substance use disorder. Parallel analysis suggested multiple factors for all five facets, in both samples. Exploratory factor models suggested the presence of method factors on the acting with awareness (items using the term "distraction") and describing facets (items that were reverse-scored). Confirmatory factor models fit poorly for all facets, in both samples. In follow-up analyses, model fit improved substantially on the acting with awareness and describing facets when method factors were included in a bifactor model. Model fit was also better for the facets of FFMQ short forms than for the full-length facets. The short-form facets and original facets correlated similarly with external criteria in both samples. None of the FFMQ facets fit a unidimensional factor model; yet, follow-up analyses suggested each can be considered substantively unidimensional. Initial tests suggest the facets' multidimensionality did not materially impact their relation to other psychological constructs, suggesting multidimensionality can be ignored for some purposes. The use of short-form facets or latent variable models (e.g., bifactor specifications) are both viable solutions for addressing multidimensionality when desired.


Iron Consumption Is Not Consistently Associated with Fecundability among North American and Danish Pregnancy Planners.
Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners.


New and emerging therapies for acute myeloid leukaemia.
The treatment of acute myeloid leukemia (AML) has remained relatively unchanged for the past 3-4 decades with generally poor outcomes, especially in elderly populations unfit for intensive therapy. Recent advancements, however, have identified several cytogenetic and molecular markers that have not only improved prognostication but have also led to the development of several new targeted therapies for specific subpopulations. In 2017, the US Food and Drug Administration approved four new treatments with indications for fms like tyrosine kinase 3 (FLT3)-mutated AML (midostaurin), newly diagnosed or relapsed/refractory CD33+AML (gemtuzumab ozogamicin), newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (CPX-351) and relapsed/refractory AML with an isocitrate dehydrogenase (IDH)2 mutation (enasidenib). These newly approved therapies have demonstrated improved response in their target populations in several pivotal clinical trials with some also demonstrating improved overall survival. Additional novel therapies in development for AML include agents that target B cell lymphoma 2, FLT3, IDH1, the ubiquitination pathway, as well as cell therapy using engineered T cells with chimeric antigen receptors. This review provides a summary of the four newly approved therapies for AML, as well as several promising therapies currently in development.


Urothelial tumors of the urinary bladder in young patients: a clinicopathologic study of 59 cases.
Urothelial tumors are rare in young patients. Because of their rarity, the natural history of the disease in young patients remains poorly understood. To understand the pathologic and clinical features of urothelial tumors of the urinary bladder in young patients. We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution and analyzed the tumors' pathologic features and the patients' clinical outcomes. All patients were 30 years or younger, with a mean age of 23.5 years (range, 4-30). Thirty-eight patients (64%) were male, and 21 (36%) were female. Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%), including papillary urothelial neoplasms of low malignant potential (7 of 49; 14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade papillary urothelial carcinomas (4 of 49; 8%). Only a few (n=10) of the urothelial tumors were invasive, invading the lamina propria (n=5; 50%), muscularis propria (n=4; 40%), or perivesical soft tissue (n=1; 10%). Clinical follow-up information was available for 41 patients (69%), with a mean follow-up time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors, only 1 patient (3%) later developed an invasive urothelial carcinoma and died of the disease, and 30 of these patients (97%) were alive at the end of follow-up, although 10 (32%) had local tumor recurrences. In the 10 patients with invasive urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%) were alive with metastases (the other 2 [20%] were alive with no recurrence). Urothelial tumors in young patients are mostly noninvasive, papillary carcinomas and have an excellent prognosis; however, a small subset of patients may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.


The magnesium-chelatase H subunit binds abscisic acid and functions in abscisic acid signaling: new evidence in Arabidopsis.
Using a newly developed abscisic acid (ABA)-affinity chromatography technique, we showed that the magnesium-chelatase H subunit ABAR/CHLH (for putative abscisic acid receptor/chelatase H subunit) specifically binds ABA through the C-terminal half but not the N-terminal half. A set of potential agonists/antagonists to ABA, including 2-trans,4-trans-ABA, gibberellin, cytokinin-like regulator 6-benzylaminopurine, auxin indole-3-acetic acid, auxin-like substance naphthalene acetic acid, and jasmonic acid methyl ester, did not bind ABAR/CHLH. A C-terminal C370 truncated ABAR with 369 amino acid residues (631-999) was shown to bind ABA, which may be a core of the ABA-binding domain in the C-terminal half. Consistently, expression of the ABAR/CHLH C-terminal half truncated proteins fused with green fluorescent protein (GFP) in wild-type plants conferred ABA hypersensitivity in all major ABA responses, including seed germination, postgermination growth, and stomatal movement, and the expression of the same truncated proteins fused with GFP in an ABA-insensitive cch mutant of the ABAR/CHLH gene restored the ABA sensitivity of the mutant in all of the ABA responses. However, the effect of expression of the ABAR N-terminal half fused with GFP in the wild-type plants was limited to seedling growth, and the restoring effect of the ABA sensitivity of the cch mutant was limited to seed germination. In addition, we identified two new mutant alleles of ABAR/CHLH from the mutant pool in the Arabidopsis Biological Resource Center via Arabidopsis (Arabidopsis thaliana) Targeting-Induced Local Lesions in Genomes. The abar-2 mutant has a point mutation resulting in the N-terminal Leu-348-->Phe, and the abar-3 mutant has a point mutation resulting in the N-terminal Ser-183-->Phe. The two mutants show altered ABA-related phenotypes in seed germination and postgermination growth but not in stomatal movement. These findings support the idea that ABAR/CHLH is an ABA receptor and reveal that the C-terminal half of ABAR/CHLH plays a central role in ABA signaling, which is consistent with its ABA-binding ability, but the N-terminal half is also functionally required, likely through a regulatory action on the C-terminal half.


Is the VO2 slow component in heavy arm-cranking exercise associated with recruitment of type II muscle fibers as assessed by an increase in surface EMG?
The recruitment of additional type II muscle fibers is one mechanism often suggested to be responsible for the slow component of oxygen uptake (VO2 (SC)). We hypothesized that surface electromyogram (EMG) of the biceps brachii, triceps brachii, anterior deltoid, and infraspinatus muscles could be related to the VO2 (SC) amplitude during arm-cranking exercises above ventilatory threshold (VT). Eight healthy subjects performed transitions from rest to 6-min heavy exercise at a constant power output of approximately 40% between VT and peak VO2. A 2-component exponential model was used to fit the VO2 response. EMG were recorded the last 15 s of each minute to obtain root mean square (RMS) and mean power frequency (MPF). Mean EMG responses for RMS and MPF were calculated by averaging EMG responses of the 4 muscles. The VO2 (SC) amplitude was of 530 +/- 166 mL/min and occurred after 134 +/- 31 s of exercise onset. Significant correlations were found for most of the subjects between EMG parameters and the VO2 SC amplitude as determined between the 2nd and the 6th minute. For all muscles, RMS values significantly increased over time during the VO2 (SC), whereas MPF decreased significantly. These results suggest a relation between the recruitment of additional type II muscle fibers and the VO2 (SC) in arm-cranking exercises.


ZnO/CuSCN Nano-Heterostructure as a Highly Efficient Field Emitter: a Combined Experimental and Theoretical Investigation.
We report the synthesis of two-dimensional porous ZnO nanosheets, CuSCN nanocoins, and ZnO/CuSCN nano-heterostructure thin films grown on fluorine-doped tin oxide substrates via two simple and low-cost solution chemical routes, i.e., chemical bath deposition and successive ionic layer adsorption and reaction methods. Detail characterizations regarding the structural, optoelectronic, and morphological properties have been carried out, which reveal high-quality and crystalline synthesized materials. Field emission (FE) investigations performed at room temperature with a base pressure of 1 × 10-8 mbar demonstrate superior FE performance of the ZnO/CuSCN nano-heterostructure compared to the isolated porous ZnO nanosheets and CuSCN nanocoins. For instance, the turn-on field required to draw a current density of 10 μA/cm2 is found to be 2.2, 1.1, and 0.7 V/μm for the ZnO, CuSCN, and ZnO/CuSCN nano-heterostructure, respectively. The observed significant improvement in the FE characteristics (ultralow turn-on field of 0.7 V/μm for an emission current density of 10 μA/cm2 and the achieved high current density of 2.2 mA/cm2 at a relatively low applied electric field of 1.8 V/μm) for the ZnO/CuSCN nano-heterostructure is superior to the isolated porous ZnO nanosheets, CuSCN nanocoins, and other reported semiconducting nano-heterostructures. Complementary first-principles density functional theory calculations predict a lower work function for the ZnO/CuSCN nano-heterostructure (4.58 eV), compared to the isolated ZnO (5.24 eV) and CuSCN (4.91 eV), validating the superior FE characteristics of the ZnO/CuSCN nano-heterostructure. The ZnO/CuSCN nanocomposite could provide a promising class of FE cathodes, flat panel displays, microwave tubes, and electron sources.


A role for PAF-acether (platelet-activating factor) in platelet-dependent vascular diseases?
Platelets-isolated or in conjunction with leukocytes-interact with vessel walls in many experimental and human diseases. Several mediators are held responsible for platelet activation and interaction with leukocytes, among which PAF-acether (platelet-activating factor) is a prime candidate. This phospholipid mediator is released by most inflammatory cells, including neutrophils, by isolated organs such as kidney and heart, is a potent platelet and neutrophil agonist, and exerts major vasoactive properties. Its biosynthesis involves a two-step enzymatic process yielding the active molecule from the membrane alkyl-ether choline-containing phospholipids. The first step implicates a phospholipase A2 that hydrolyzes a long-chain fatty acid (which can be arachidonic acid) from membrane phospholipids, leaving the intermediate compound lyso PAF-acether, a PAF-acether precursor that is acetylated by an acetyltransferase in a second step. It can also result from deacetylation of PAF-acether by an acetylhydrolase. PAF-acether release might explain the intervention of platelets in diseases such as glomerulonephritis and allergic vasculitis, in which the involvement of neutrophils and platelets is frequently noted. The end result of these complex sets of cell-to-cell interactions is the release of most known inflammatory mediators, influencing vascular permeability, cell infiltration, and smooth muscle contraction. Nevertheless, direct evidence for the implication of these rather well-defined cellular and molecular interactions in human pathologic states remains to be obtained.


Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer.
Argininosuccinate synthetase 1 (ASS1) is a rate-limiting enzyme in arginine biosynthesis. Although ASS1 expression levels are often reduced in several tumors and low ASS1 expression can be a poor prognostic factor, the underlying mechanism has not been elucidated. In this study, we reveal a novel association between ASS1 and migration/invasion of endometrial tumors via regulation of mechanistic target of rapamycin complex (mTORC) 1 signaling. ASS1-knockout cells showed enhanced migration and invasion in response to arginine following arginine starvation. In ASS1-knockout cells, DEPTOR, an inhibitor of mTORC1 signal, was downregulated and mTORC1 signaling was more activated in response to arginine. ASS1 epigenetically enhanced DEPTOR expression by altering the histone methylation. Consistent with these findings, tumor cells at the invasive front of endometrioid carcinoma cases showed lower ASS1 and DEPTOR expression. Our findings suggest that ASS1 levels in each tumor cell are associated with invasion capability in response to arginine within the tumor microenvironment through mTORC1 signal regulation.


Preoperative factors of apathy in subthalamic stimulated Parkinson disease: a PET study.
The current literature provides discrepant results regarding preoperative sociodemographic and clinical factors, and no information about preoperative cerebral metabolic patterns associated with apathy after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. To resolve this issue, we set out to identify preoperative metabolic patterns and sociodemographic and clinical factors associated with increased apathy after STN-DBS. Forty-four patients with Parkinson disease were enrolled in this study. They all underwent STN-DBS. Metabolic activity was assessed with F-18 fluorodeoxyglucose PET 3 months before surgery. Apathy was assessed on the Apathy Evaluation Scale 3 months before and after STN-DBS. We controlled for preoperative age, levodopa therapy, and overall cognitive functions. Increased apathy after STN-DBS was significantly associated with reduced preoperative metabolism within the right ventral striatum. None of the sociodemographic and clinical variables tested were associated with apathy after STN-DBS. Preoperative PET, but not sociodemographic or clinical factors, is associated with apathy after STN-DBS.


Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study.
Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40-60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aβ and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aβ load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p's ≤ .001), and higher rates of Aβ deposition than males (p < .01). CMRglc decline exceeded Aβ and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.


Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants.
Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. However, it is unclear whether slow feed advancement may delay establishment of full enteral feeding, and if it could be associated with infectious morbidities secondary to prolonged exposure to parenteral nutrition. To determine the effects of slow rates of enteral feed advancement on the risk of NEC, mortality, and other morbidities in very preterm or VLBW infants. We searched CENTRAL (2020, Issue 10), Ovid MEDLINE (1946 to October 2020), Embase via Ovid (1974 to October 2020), Maternity and Infant Care database (MIDIRS) (1971 to October 2020), CINAHL (1982 to October 2020), and clinical trials databases and reference lists of retrieved articles for eligible trials. We included randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes on the risk of NEC in very preterm or VLBW infants. Two review authors separately evaluated trial risk of bias, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence. Outcomes of interest were NEC, all-cause mortality, feed intolerance, and invasive infection. We included 14 trials involving a total of 4033 infants (2804 infants participated in one large trial). None of the trials masked parents, caregivers, or investigators. Risk of bias was otherwise low. Most infants were stable very preterm or VLBW infants of birth weight appropriate for gestation. About one-third of all infants were extremely preterm or extremely low birth weight (ELBW), and about one-fifth were small for gestational age, growth-restricted, or compromised as indicated by absent or reversed end-diastolic flow velocity in the foetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 24 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Meta-analyses showed that slow advancement of enteral feed volumes probably has little or no effect on the risk of NEC (RR 1.06, 95% confidence interval (CI) 0.83 to 1.37; RD 0.00, 95% CI -0.01 to 0.02; 14 trials, 4026 infants; moderate-certainty evidence) or all-cause mortality prior to hospital discharge (RR 1.13, 95% CI 0.91 to 1.39; RD 0.01, 95% CI -0.01 to 0.02; 13 trials, 3860 infants; moderate-certainty evidence). Meta-analyses suggested that slow advancement may slightly increase feed intolerance (RR 1.18, 95% CI 0.95 to 1.46; RD 0.05, 95% CI -0.02 to 0.12; 9 trials, 719 infants; low-certainty evidence) and may slightly increase the risk of invasive infection (RR 1.14, 95% CI 0.99 to 1.31; RD 0.02, 95% CI -0.00 to 0.05; 11 trials, 3583 infants; low-certainty evidence). The available trial data indicate that advancing enteral feed volumes slowly (daily increments up to 24 mL/kg) compared with faster rates probably does not reduce the risk of NEC, death, or feed intolerance in very preterm or VLBW infants. Advancing the volume of enteral feeds at a slow rate may slightly increase the risk of invasive infection.


[Effect of polymyxins B and M on oxygen uptake by rat liver mitochondria].
Polycationic peptide antibiotics, polymixins B and M, are studied for their effect on oxygen uptake by rat liver mitochondria. They both inhibit the process at state 3 and 3p according to Chance. Low concentrations of polymixin M do not affect oxygen uptake by mitochondria at state 4, but its high concentrations inhibit it. Concentration dependence of polymixin B effect on mitochondria at state 4 is of a bell-like character. Competitive interrelations are found between polymixins M and B in their effect on mitochondria at state 4. Chromatography reveals differences in peptide mobility in a thin layer. It is supposed that polymixin inhibition of oxygen uptake by mitochondria is associated with a disordering effect of the polymixins on the membrane structure during peptide binding to the lipid phase of the membranes. Low concentrations of polymixin B are likely to promote an increase in membrane permeability of mitochondria at state 4.


[Polyamines in malignant lymphoma of the skin and in Kaposi's sarcoma].
High-pressure liquid chromatography was used to detect polyamines, the markers of lymphoproliferative diseases of the skin and of Kaposi's sarcoma. The urine polyamine detection may become one of the diagnostic tests in these conditions, but its findings should be confirmed by clinical and histologic data. Measurements of the urine polyamines may be helpful in assessment of the treatment efficacy.


Response of vertebral fractures to treatment with denosumab in a patient with postpartum osteoporosis: a case report and literature review.
Postpartum osteoporosis (PO) is a rare condition characterized by low bone mineral density (BMD) and an increased risk of vertebral fragility fracture. We encountered a 34-year-old woman who developed back pain 1 week after delivery. Magnetic resonance imaging of the lumbar spine revealed three vertebral compression fractures. Pretreatment BMD evaluation by dual-energy X-ray absorptiometry revealed a low T-score and Z-score (-2.0 and -2.0, respectively; BMD, 0.876 g/cm2) in the affected region of the spine. The patient was diagnosed with PO and treated with subcutaneous injection of denosumab 60 mg (Prolia; Amgen, Inc., Thousand Oaks, CA, USA) every 6 months. After two treatments, the BMD had significantly increased and the back pain was improved; the patient therefore decided to terminate the treatment. Two months later, her back pain worsened and BMD decreased as measured by dual-energy X-ray absorptiometry examination of the lumbar spine. Therefore, the patient resumed treatment with denosumab, and the BMD of the lumbar spine increased after another two treatments. Therefore, we consider denosumab to be promising in the management of PO with respect to increased BMD and decreased pain.


Prevalence and Factors Associated With Polypharmacy Use Among Adult Patients in Saudi Arabia.
Polypharmacy is very common in clinical practice, especially among adult patients. The use of multiple medications may increase the risk of adverse drug events, medication cost, and medication errors. In addition, polypharmacy exacerbates treatment complexity, which consequently leads to poor patients' adherence to their medications. Despite being a well-recognized problem, few studies have investigated the prevalence and predictors of polypharmacy in Saudi Arabia. The aims of the study were to investigate the prevalence of polypharmacy among adult patients in a tertiary teaching hospital and to determine patients' characteristics that are associated with polypharmacy. This was a retrospective cross-sectional study using data extracted from the electronic health records database for a period of 6 months between January and June 2016 in outpatient setting. Descriptive statistics were used to analyze the study sample. A multivariate logistic regression model was used to examine the association between different variables and polypharmacy. Statistical analysis software (SAS 9.2) was used to analyze the study data. A total of 17,237 observations (67.2% females) were included in the final analysis. Of these, nearly 54% (n = 9222) of reported observations were found using up to four prescription drugs and the other 46% (n = 8015) were using five or more prescription drugs. Interestingly, the prevalence of polypharmacy use was doubled among adults with hypertension as compared with those without hypertension (odds ratio [OR] = 2.68, 95% confidence interval [CI] = 2.51-2.87). In addition, polypharmacy use was two times more prevalent among adults with diabetes as compared with those without diabetes (OR = 2.31, 95% CI = 1.99-2.28) and five times more prevalent in patient with dementia (OR = 5.57, 95% CI = 1.26-24.7). Moreover, polypharmacy in adult patients was significantly influenced by sex (OR = 1.69, 95% CI = 1.59-1.80) and nationality (OR = 2.15, 95% CI = 2.00-2.31). Polypharmacy is common among adult patients especially those who are older than 60 years. Polypharmacy may affect the overall process of drug therapy. It can be a risk factor to develop undesirable adverse drug events, especially in those with chronic health conditions. A special care should be taken to manage polypharmacy among adults in Saudi Arabia.


Assessment of the paradoxical effect of caspofungin in therapy of candidiasis.
Paradoxical growth of some Candida albicans isolates in the presence of caspofungin (CAS) in vitro has been demonstrated previously. We sought to determine whether a similar phenomenon occurred in vivo. A systemic model of candidiasis was studied in CD-1 mice by intravenous inoculation of different isolates of C. albicans. Infected animals were treated with CAS at various dosages (0.01 to 20 mg/kg) and CFU remaining in the kidneys determined. Four clinical isolates that showed paradoxical growth in vitro and one that did not were tested. Recovery of CFU from the kidneys showed that dosages of CAS at 0.1 mg/kg and above were efficacious in the reduction of C. albicans, but were not curative. Against isolates that show paradoxical growth in vitro, CAS was efficacious, but lacked dose responsiveness above 0.5 mg/kg against three of the four. One isolate, 95-68, showed paradoxical growth in vivo with significantly higher CFU recovered from mice given CAS at 20 mg/kg than those given CAS at 5 mg/kg, but the effect was not reproducible in a subsequent experiment. When CAS was given prophylactically and therapeutically, improved efficacy and cure rate were observed. Overall, these data indicate that CAS is highly efficacious against systemic murine candidiasis and a paradoxical effect was not reproducibly demonstrated in vivo.


Anticoagulation in COVID-19: a single-center retrospective study.
Introduction: COVID-19 induces a pro-thrombotic state as evidenced by microvascular thrombi in the renal and pulmonary vasculature. Therapeutic anticoagulation in COVID-19 has been debated and data remain anecdotal. Hypothesis: We hypothesize that therapeutic anticoagulation is associated with a reduction in in-hospital mortality, upgrade to intensive care unit, invasive mechanical ventilation, and acute renal failure necessitating dialysis by decreasing the over-all clot burden. Methods: A retrospective cohort study was done to determine the impact of therapeutic anticoagulation in hospitalized COVID-19 patients. Independent t-test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aOR) with its 95% confidence interval (CI) respectively. Results: A total of 176 hospitalized COVID-19 patients were divided into two groups, therapeutic anticoagulation and prophylactic anticoagulation. The mean age, baseline comorbidities and other medications used during hospitalization were similar in both groups. The aOR for in-hospital mortality (OR 3.05, 95% CI 1.15-8.10, p = 0.04), upgrade to intensive care (OR 3.08, 95% CI 1.43-6.64, p = 0.006) and invasive mechanical ventilation (OR 4.27, 95% CI 1.95-9.34, p = 0.00) were significantly lower while there was no statistically significant difference in the rate of developing acute renal failure (OR 1.87 95% CI 0.46-7.63, p = 0.64) between two groups. Conclusions: In patients with COVID-19, therapeutic anticoagulation offers a significant reduction in the rate of in-hospital mortality, upgrade to intensive medical care, and invasive mechanical ventilation. It should be preferred over prophylactic anticoagulation in COVID-19 patients unless randomized controlled trials prove otherwise.


Epigenetic and transcriptional determinants of the human breast.
While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial-specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage, whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harbouring more than twice the number of hypomethylated enhancer elements compared with myoepithelial cells.


Three-stage processing of category and variation information by entangled interactive mechanisms of peri-occipital and peri-frontal cortices.
Object recognition has been a central question in human vision research. The general consensus is that the ventral and dorsal visual streams are the major processing pathways undertaking objects' category and variation processing. This overlooks mounting evidence supporting the role of peri-frontal areas in category processing. Yet, many aspects of visual processing in peri-frontal areas have remained unattended including whether these areas play role only during active recognition and whether they interact with lower visual areas or process information independently. To address these questions, subjects were presented with a set of variation-controlled object images while their EEG were recorded. Considerable amounts of category and variation information were decodable from occipital, parietal, temporal and prefrontal electrodes. Using information-selectivity indices, phase and Granger causality analyses, three processing stages were identified showing distinct directions of information transaction between peri-frontal and peri-occipital areas suggesting their parallel yet interactive role in visual processing. A brain-plausible model supported the possibility of interactive mechanisms in peri-occipital and peri-frontal areas. These findings, while promoting the role of prefrontal areas in object recognition, extend their contributions from active recognition, in which peri-frontal to peri-occipital pathways are activated by higher cognitive processes, to the general sensory-driven object and variation processing.


Emotion theory and research: highlights, unanswered questions, and emerging issues.
Emotion feeling is a phase of neurobiological activity, the key component of emotions and emotion-cognition interactions. Emotion schemas, the most frequently occurring emotion experiences, are dynamic emotion-cognition interactions that may consist of momentary/situational responding or enduring traits of personality that emerge over developmental time. Emotions play a critical role in the evolution of consciousness and the operations of all mental processes. Types of emotion relate differentially to types or levels of consciousness. Unbridled imagination and the ability for sympathetic regulation of empathy may represent both potential gains and losses from the evolution and ontogeny of emotion processes and consciousness. Unresolved issues include psychology's neglect of levels of consciousness that are distinct from access or reflective consciousness and use of the term "unconscious mind" as a dumpster for all mental processes that are considered unreportable. The relation of memes and the mirror neuron system to empathy, sympathy, and cultural influences on the development of socioemotional skills are unresolved issues destined to attract future research.


Black-box identification of a class of nonlinear systems by a recurrent neurofuzzy network.
This brief presents a structure for black-box identification based on continuous-time recurrent neurofuzzy networks for a class of dynamic nonlinear systems. The proposed network catches the dynamics of a system by generating its own states, using only input and output measurements of the system. The training algorithm is based on adaptive observer theory, the stability of the network, the convergence of the training algorithm, and the ultimate bound on the identification error as well as the parameter error are established. Experimental results are included to illustrate the effectiveness of the proposed method.


Single-Cell RNA Sequencing Analysis Reveals Greater Epithelial Ridge Cells Degeneration During Postnatal Development of Cochlea in Rats.
Greater epithelial ridge cells, a transient neonatal cell group in the cochlear duct, which plays a crucial role in the functional maturation of hair cell, structural development of tectorial membrane, and refinement of audio localization before hearing. Greater epithelial ridge cells are methodologically homogeneous, while whether different cell subtypes are existence in this intriguing region and the degeneration mechanism during postnatal cochlear development are poorly understood. In the present study, single-cell RNA sequencing was performed on the cochlear duct of postnatal rats at day 1 (P1) and day 7 (P7) to identify subsets of greater epithelial ridge cell and progression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to examine genes enriched biological processes in these clusters. We identified a total of 26 clusters at P1 and P7 rats and found that the cell number of five cell clusters decreased significantly, while four clusters had similar gene expression patterns and biological properties. The genes of these four cell populations were mainly enriched in Ribosome and P13K-Akt signal pathway. Among them, Rps16, Rpsa, Col4a2, Col6a2, Ctsk, and Jun are particularly interesting as their expression might contribute to the greater epithelial ridge cells degeneration. In conclusion, our study provides an important reference resource of greater epithelial ridge cells landscape and mechanism insights for further understanding greater epithelial ridge cells degeneration during postnatal rat cochlear development.


High-resolution maps of the murine Chromosome 2 region containing the cholesterol gallstone locus, Lith1.
The Lith1 region on Chromosome (Chr) 2 contains a gene that markedly affects the prevalence of cholesterol gallstones in inbred mice. We report the high-resolution genetic and radiation hybrid maps of the chromosomal region surrounding Lith1, using three resources: a DNA panel from 188 progeny from two reciprocal backcrosses between C57BL/6 and Mus spretus inbred strains; 423 progeny of an N4 generation from backcrossing the susceptible C57L/J alleles at Lith1 into the resistant AKR/J strain; and the newly developed hamster-mouse T31 radiation hybrid panel. We mapped 17 microsatellite markers in the D2Mit182 to D2Mit14 region and two candidate genes for Lith1, the canalicular bile salt export pump (Bsep) also known as sister of P-glycoprotein (Spgp) and the low-density-lipoprotein-receptor-related gene megalin (Gp330). Both genetic maps were in agreement and ordered the microsatellite markers into a 10.4 +/- 1.5 cM region. The high-resolution physical map revealed ordering of microsatellite markers and relative distances between markers in almost complete agreement with the genetic maps. Mapping of Bsep revealed its location on Chr 2, homologous to the human chromosomal position (Nature Genet 20, 233-238, 1998). The radiation hybrid results also provided the highest resolution of the area containing the two candidate genes, which both mapped in the Lith1 region with close linkage, being separated by a distance of only 15 cR(3000). The total radiation hybrid map length of the region between D2Mit182 and D2Mit14 was 326 cR(3000), suggesting that 31 cR(3000) is equivalent to 1 cM in this region of Chr 2.


Aberrant synaptic integration in adult lamina I projection neurons following neonatal tissue damage.
Mounting evidence suggests that neonatal tissue damage evokes alterations in spinal pain reflexes which persist into adulthood. However, less is known about potential concomitant effects on the transmission of nociceptive information to the brain, as the degree to which early injury modulates synaptic integration and membrane excitability in mature spinal projection neurons remains unclear. Here we demonstrate that neonatal surgical injury leads to a significant shift in the balance between synaptic excitation and inhibition onto identified lamina I projection neurons of the adult mouse spinal cord. The strength of direct primary afferent input to mature spino-parabrachial neurons was enhanced following neonatal tissue damage, whereas the efficacy of both GABAergic and glycinergic inhibition onto the same population was compromised. This was accompanied by reorganization in the pattern of sensory input to adult projection neurons, which included a greater prevalence of monosynaptic input from low-threshold A-fibers when preceded by early tissue damage. In addition, neonatal incision resulted in greater primary afferent-evoked action potential discharge in mature projection neurons. Overall, these results demonstrate that tissue damage during early life causes a long-term increase in the gain of spinal nociceptive circuits, and suggest that the prolonged consequences of neonatal trauma may not be restricted to the spinal cord but rather include excessive ascending signaling to supraspinal pain centers.


Prolonged grief, depression, and posttraumatic stress in disaster-bereaved individuals: latent class analysis.
Background: Hundreds of individuals lost one or more significant others in the MH17 plane crash in 2014 in Ukraine. The current study is the first to explore subgroups of disaster-bereaved individuals based on presence of psychopathology clusters. This may inform the development of diagnostic instruments and tailored interventions. Objective: Aims of the current study were to examine (1) subgroups based on presence of prolonged grief disorder (PGD), major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) symptom clusters and (2) associations between class membership, disaster-related variables (i.e. experiencing multiple losses, conducting multiple burials for the same deceased, and time to confirmation of death), and a sense of unrealness. Method: Self-rated PGD (10 items of the Traumatic Grief Inventory represented in two symptom clusters), MDD (16-item Quick Inventory Of Depressive Symptomatology represented in one symptom cluster), and PTSD (20-item PTSD Checklist for DSM-5 represented in four symptom clusters) from 167 participants were subjected to latent class analysis to identify subgroups (i.e. classes). Correlates of class membership were assessed using the three-step approach. Results: A three-class solution yielded the best model fit. Class 1 (Resilient class; 20.0%) was predominantly characterized by low probability of PGD, MDD, and PTSD symptom clusters, class 2 (PGD class; 41.8%) by moderate to high probability of presence of PGD, and class 3 (Combined class; 38.2%) by moderate to high probability of presence of PGD, MDD, and PTSD symptom clusters. Compared with the Resilient class, a sense of unrealness was more likely to be experienced by individuals in the PGD class and the Combined class. Conclusions: Our results indicate that subgroups of disaster-bereaved individuals can be distinguished based on the presence of PGD, MDD, and PTSD symptom clusters. A sense of unrealness was the strongest distinguishing feature of the subgroups.


Fibromatous periorchitis.
We report a case of diffuse fibrous pseudotumour/fibromatous periorchitis, in a 43 year old male, that completely encased the right testis and was adjacent to a hydrocoele cavity. Although fibrous pseudotumours of this region are uncommon, they are reported to be the second most common benign paratesticular lesion after adenomatoid tumours. These comprise approximately 6 percent of paratesticular lesions, and are accepted as reactive lesions secondary to trauma, hydrocoele, infections or inflammation. Fibrous pseudotumours have a peak incidence in the third decade of life but can occur at any age. Clinically these lesions mimic malignancy resulting in the treatment by radical orchidectomy. Fibrous pseudotumours should be considered in differential diagnosis when one encounters a predominantly fibrocollagenous lesion.


Radionuclide quantitation of right-to-left intracardiac shunts in children.
A simple, noninvasive method for measurement of right-to-left intracardiac shunts would enhance the management of patients with congenital heart disease. This study describes application of data processing techniques used previously in dye-indicator curves to data recorded during the initial transit of radioactive bolus through the central circulation. Radionuclide angiocardiograms were performed in 20 children, mean age 30 months, immediately after cardiac catheterization for congenital heart disease. The radionuclide data recorded over the carotid artery were used to replace arterial sampling required for dye indicators, and forward triangles were fitted to calculate the right-to-left shunt in an approach similar to that of Wood for indicator-dilution curves. Ten of the children had right-to-left shunts by Fick and radionuclide measurement, and 10 of the children with septal defects had no right-to-left shunt by either technique. Both the radionuclide and Fick measurements correlated well (r = 0.95). Therefore, radionuclide angiocardiographic data may be used for accurate calculation of right-to-left shunts in small children, eliminating the need for arterial sampling.


Multitasking simulation: Present application and future directions.
The Accreditation Council for Graduate Medical Education lists multi-tasking as a core competency in several medical specialties due to increasing demands on providers to manage the care of multiple patients simultaneously. Trainees often learn multitasking on the job without any formal curriculum, leading to high error rates. Multitasking simulation training has demonstrated success in reducing error rates among trainees. Studies of multitasking simulation demonstrate that this type of simulation is feasible, does not hinder the acquisition of procedural skill, and leads to better performance during subsequent periods of multitasking. Although some healthcare agencies have discouraged multitasking due to higher error rates among multitasking providers, it cannot be eliminated entirely in settings such as the emergency department in which providers care for more than one patient simultaneously. Simulation can help trainees to identify situations in which multitasking is inappropriate, while preparing them for situations in which multitasking is inevitable.


Osteoporosis, jawbones and periodontal disease.
The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk.


[Radiometric method of determining ATP: D-pantothenate-4'-phosphotransferase activity].
A radiometric procedure is developed for estimation of pantothenate kinase (EC 22.214.171.124) activity in various preparations of rat liver tissue; sodium 14C-D-pantothenate was used as a substrate and the reaction end product 4'-phosphopantothenic acid was measured. Optimal separation of the substrate and the end product was achieved by means of chromatography on DEAE-Sephadex A-25. 4'-phosphopantothenic acid was eluted from the column by 0.4 N HCl thus avoiding the label dilution and possible quenching of scintillation.


Advances in neurology at Turner's Lane Military Hospital.
The work of physicians at Turner's Lane Military Hospital, Philadelphia, stimulated interest in neurology in the United States, leading to the post-Civil War emergence of neurology as a distinct medical specialty. These physicians advanced their profession and benefitted their patients.


Functional and immunological relevance of Anaplasma marginale major surface protein 1a sequence and structural analysis.
Bovine anaplasmosis is caused by cattle infection with the tick-borne bacterium, Anaplasma marginale. The major surface protein 1a (MSP1a) has been used as a genetic marker for identifying A. marginale strains based on N-terminal tandem repeats and a 5'-UTR microsatellite located in the msp1a gene. The MSP1a tandem repeats contain immune relevant elements and functional domains that bind to bovine erythrocytes and tick cells, thus providing information about the evolution of host-pathogen and vector-pathogen interactions. Here we propose one nomenclature for A. marginale strain classification based on MSP1a. All tandem repeats among A. marginale strains were classified and the amino acid variability/frequency in each position was determined. The sequence variation at immunodominant B cell epitopes was determined and the secondary (2D) structure of the tandem repeats was modeled. A total of 224 different strains of A. marginale were classified, showing 11 genotypes based on the 5'-UTR microsatellite and 193 different tandem repeats with high amino acid variability per position. Our results showed phylogenetic correlation between MSP1a sequence, secondary structure, B-cell epitope composition and tick transmissibility of A. marginale strains. The analysis of MSP1a sequences provides relevant information about the biology of A. marginale to design vaccines with a cross-protective capacity based on MSP1a B-cell epitopes.


Increasing prevalence of HIV-2 and dual HIV-1-2 infections among patients attending various outdoor patient departments in Mumbai (Bombay).
Between 1993-96, a serological study was carried out for differentially identifying HIV-1 and HIV-2 infections among the high risk group persons attending the various outdoor patient departments of BYL Nair Municipal Hospital, Mumbai. This study indicates that although HIV-1 is still the predominant virus among the high risk HIV infected persons in Mumbai, dual HIV-1-2 infections are increasing especially among promiscuous heterosexuals and female commercial sex workers. Increases in HIV-2 infections were observed later than dual HIV-1-2 infections, indicating that it is the HIV-1 infected individuals who through continued high risk behavior got infected by HIV-2.


Genetic Testing Enhances the Precision Diagnosis and Treatment of Breast Cancer.
The contemporary comprehension of breast cancer has progressed to the molecular level. As a heterogeneous malignancy, conventional pathological diagnosis and histological classification could no longer meet the needs of precisely managing breast cancer. Genetic testing based on gene expression profiles and gene mutations has emerged and substantially contributed to the precise diagnosis and treatment of breast cancer. Multigene assays (MGAs) are explored for early-stage breast cancer patients, aiding the selection of adjuvant therapy and predicting prognosis. For metastatic breast cancer patients, testing specific genes indicates potentially effective antitumor agents. In this review, genetic testing in early-stage and metastatic breast cancer is summarized, as well as the advantages and challenges of genetic testing in breast cancer.


Factors affecting response to hepatitis B vaccine among hemodialysis patients in a large Saudi Hemodialysis Center.
The aim of this study is to determine the response to hepatitis B virus (HBV) vaccination in patients on hemodialysis (HD) and to identify the factors that could affect this response. This retrospective study was carried out during the period from January 2009 to December 2009 in the Prince Salman Center for Kidney Diseases (PSCKD), Riyadh, and included 144 patients (78 males and 66 females) on regular HD, all of whom received hepatitis B vacci-nation. Patients were divided into two groups according to the level of hepatitis B surface antibodies (HBsAb): Responders group (>10 IU/L) and non-responders group (<10 IU/L). The study looked at the factors that may affect the responsiveness to hepatitis B vaccination, like gender, age, co-existence of hepatitis C virus (HCV) infection, dialysis adequacy that was evaluated by urea reduction ratio (URR) and Kt/V, hemoglobin level, albumin level, protein catabolic rate (PCR), body mass index (BMI), subjective global nutritional status (SGA) and HbA1c. There were 129 patients (89.6%) in the responders group including 69 males and 60 females and 15 patients (10.4%) in the non-responders group including nine males and six females. The mean age in the responders group and the non-responders group was 50.56 ± 15.35 and 56.87 ± 12.52 years, respectively (P = 0.128). The mean value of the PCR was 1.03 ± 0.17 and 0.88 ± 0.17 g/kg/day in the responders group and non-responders group, respectively (P = 0.002). There was no statically significant difference between the two groups regarding the presence or absence of HCV infection, age, gender, diabetes mellitus, URR, Kt/V, hemoglobin level and albumin level. We report a high response rate (89%) for HBV vaccination in our HD patients. The PCR was the only factor that affected the response to HBV vaccination in these patients.


Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity.
Aging-associated muscle wasting and impaired regeneration are caused by deficiencies in muscle stem cell (MuSC) number and function. We postulated that aged MuSCs are intrinsically impaired in their responsiveness to omnipresent mechanical cues through alterations in MuSC morphology, mechanical properties, and number of integrins, culminating in impaired proliferative capacity. Here we show that aged MuSCs exhibited significantly lower growth rate and reduced integrin-α7 expression as well as lower number of phospho-paxillin clusters than young MuSCs. Moreover, aged MuSCs were less firmly attached to matrigel-coated glass substrates compared to young MuSCs, as 43% of the cells detached in response to pulsating fluid shear stress (1 Pa). YAP nuclear localization was 59% higher than in young MuSCs, yet YAP target genes Cyr61 and Ctgf were substantially downregulated. When subjected to pulsating fluid shear stress, aged MuSCs exhibited reduced upregulation of proliferation-related genes. Together these results indicate that aged MuSCs exhibit impaired mechanosensitivity and growth potential, accompanied by altered morphology and mechanical properties as well as reduced integrin-α7 expression. Aging-associated impaired muscle regenerative capacity and muscle wasting is likely due to aging-induced intrinsic MuSC alterations and dysfunctional mechanosensitivity.


Electronic structures of the MoS2/TiO2 (anatase) heterojunction: influence of physical and chemical modifications at the 2D- or 1D-interfaces.
To tackle the challenge of CO2 photoreduction, semiconducting layered transition metal dichalcogenides like MoS2 have attracted much attention due to their tunable 2D nano-structures. By using advanced periodic density functional theory calculations (HSE06 functional), we provide a systematic quantification of the optoelectronic properties of various interfacial heterostructures composed of 2H-MoS2 and anatase TiO2. We systematically determine the band gaps, and conduction band (CB) and valence band (VB) positions to figure out the nature of the heterojunction. Two main surface orientations of anatase TiO2 particles, (101) and (001), are considered with 2D-MoS2 nanosheets or nanoribbons forming either a 2D physical (van der Waals) or through a 1D chemical interface. The possibility to chemically modify the MoS2/TiO2 interface, either by sulfidation or hydration, and its effect on the electronic structure are deeply investigated. These modifications in the heterostructure lead to important changes in the electronic properties and charge transfer between the two materials which impact both photon absorption properties and charge carrier dynamics suspected to influence in turn the photocatalytic activity. While a type I hetrojunction is found for the 1D chemical interface, a type II heterojunction with appropriate CB/VB positions for CO2 reduction and H2O oxidation is identified for the 2D physical interface which could lead to the targeted Z-scheme mechanism with strong potential interest in photocatalysis applications.


Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.
Historically, early detection of small asymptomatic kidney tumors presages better patient outcome. Screening for asymptomatic renal tumors by abdominal imaging is not cost-effective and cannot reliably distinguish benign from malignant tumors. This investigation evaluated the clinical utility, sensitivity, and specificity of urine aquaporin-1 (AQP1) and perilipin-2 (PLIN2) concentrations as unique, noninvasive biomarkers to diagnose malignant clear cell or papillary renal cell carcinoma (RCC) in a screening paradigm. From February through December 2012, urine samples were obtained from 720 patients undergoing routine abdominal computed tomography (CT) (screening population), 80 healthy controls, and 19 patients with pathologically confirmed RCC. Urine AQP1 and PLIN2 concentrations were measured by sensitive and specific enzyme-linked immunosorbent assay and Western blot procedures, respectively, in all groups. In the otherwise asymptomatic screening population, the absence or presence of a renal mass and RCC were verified by abdominal CT and by postnephrectomy pathologic diagnosis, respectively. Urine AQP1 and PLIN2 concentrations were significantly higher (all P < .001) in the 19 patients with known RCC (AQP1 median [95% CI], 225.0 [121.0-450.0] ng/mg urine creatinine; and PLIN2 median [95% CI], 37.8 [22.8-83.7] absorbance units/mg creatinine) than in the 80 healthy controls (AQP1 median [95% CI], 1.1 [0.9-1.3] ng/mg urine creatinine; and PLIN2 median [95% CI], 3.1 [2.4-3.7] absorbance units/mg creatinine) and the 720 patient screening population (AQP1 median [95% CI], 0.5 [0.0-1.0] ng/mg urine creatinine; and PLIN2 median [95% CI], 0 [0-0] absorbance units/mg creatinine). The area under the receiver operating characteristic curve for urine AQP1 and PLIN2 concentrations individually or in combination was 0.990 or greater, with 95% or greater sensitivity and 91% or greater specificity compared with controls or the screening population. Of the 720 screened patients, 3 had biomarker concentrations suggestive of RCC and were found to have an imaged renal mass by CT. Two of the patients had pathologically confirmed RCC in further evaluation. These results demonstrate the clinical utility, specificity, and sensitivity of urine AQP1 and PLIN2 to diagnose RCC. These tumor-specific proteins have high clinical validity and substantial potential as specific diagnostic and screening biomarkers for clear cell or papillary RCC and in the differential diagnosis of imaged renal masses.


GingerRoot: A Novel DNA Transposon Encoding Integrase-Related Transposase in Plants and Animals.
Transposable elements represent the largest components of many eukaryotic genomes and different genomes harbor different combinations of elements. Here, we discovered a novel DNA transposon in the genome of the clubmoss Selaginella lepidophylla. Further searching for related sequences to the conserved DDE region uncovered the presence of this superfamily of elements in fish, coral, sea anemone, and other animal species. However, this element appears restricted to Bryophytes and Lycophytes in plants. This transposon, named GingerRoot, is associated with a 6 bp (base pair) target site duplication, and 100-150 bp terminal inverted repeats. Analysis of transposase sequences identified the DDE motif, a catalytic domain, which shows similarity to the integrase of Gypsy-like long terminal repeat retrotransposons, the most abundant component in plant genomes. A total of 77 intact and several hundred truncated copies of GingerRoot elements were identified in S. lepidophylla. Like Gypsy retrotransposons, GingerRoots show a lack of insertion preference near genes, which contrasts to the compact genome size of about 100 Mb. Nevertheless, a considerable portion of GingerRoot elements was found to carry gene fragments, suggesting the capacity of duplicating gene sequences is unlikely attributed to the proximity to genes. Elements carrying gene fragments appear to be less methylated, more diverged, and more distal to genes than those without gene fragments, indicating they are preferentially retained in gene-poor regions. This study has identified a broadly dispersed, novel DNA transposon, and the first plant DNA transposon with an integrase-related transposase, suggesting the possibility of de novo formation of Gypsy-like elements in plants.


Role-shifting PKCζ fosters its own proapoptotic destruction by complexing with Bcl10 at the nuclear envelope of human cervical carcinoma cells: a proteomic and biochemical study.
Many features of deadly human cervical cancers (HCCs) still require elucidation. Among HCC-derived cell lines, here we used the C4-I one since its quantitative gene expression pattern most closely mimics invasive HCCs, including protein kinase-Cζ (PKCζ) overexpression. Via proteomic, bioinformatic, and biochemical approaches we identified 31 and 33 proteins co-immunoprecipitating with PKCζ from nuclear membranes (NMs) of, respectively, untreated or VP-16-exposed C4-I cells. Such proteins belonged to eight functional groups, whose compositions and relative sizes changed with either context. Of the 56 proteins identified, only eight were shared between the two subproteomes, including Bcl10. Surprisingly, proteins known to associate with Bcl10, like Carma1/3 and Malt1, in so-called CBM signalosomes were absent. Notably, in VP-16-treated C4-I cells, PKCζ•Bcl10 complexes increasingly accrued at NMs, where PKCζ phosphorylated Bcl10, as PKCζ also did in vitro and in cell-free systems, both processes being thwarted by interfering RNA (iRNA) PKCζ depletion. Caspase-3 was associated with PKCζ•Bcl10 complexes and proteolyzed PKCζ leading to its inactivation/destruction; both events were prevented by Bcl10 iRNA suppression. Thus, PKCζ's molecular interactions and functional roles changed strikingly according to the untreated or apoptogen-treated cells context, and by complexing with Bcl10, PKCζ surprisingly favored its own demise, which suggests both proteins as HCCs therapeutic targets.


Laparoscopic simulation training with proficiency targets improves practice and performance of novice surgeons.
This study compares a laparoscopic skill training protocol without proficiency targets to the same protocol with explicit targets and notification of progress. Fourteen surgery interns were randomized into 2 groups. The intervention group received task-specific proficiency criteria to guide practice. The control group did not. After training, participants were evaluated by blinded faculty during laparoscopic cholecystectomy. The control group met significantly fewer of the 7 LapSim (Surgical Science Sweden AB, Gotëborg) targets (mean = 1.14) than the intervention group (mean = 7.00; P = .001) and significantly fewer of the 5 video trainer targets (mean = .86) than the intervention group (mean = 5.00; P = .001). Ratings of depth perception, bimanual dexterity, efficiency, tissue handling, autonomy, and overall competence were higher for the intervention group. Effect sizes ranged from medium to large (.394-.981), indicating an impact of the proficiency-based training protocol. Delineation of proficiency targets with reporting of progress improves interns' practice results, and appears to have a positive effect on their early operating room (OR) performance of laparoscopic cholecystectomy.