Chinese medicine Xiaoshui decoction inhibits malignant pleural effusion in mice and mediates tumor-associated macrophage polarization by activating autophagy.
Xiaoshui decoction (XSD) is a traditional Chinese medicine compound prescription that has been shown to reinforce the spleen and remove the fluid retention, while being widely used in the treatment of malignant pleural effusion (MPE). We previously reported that XSD alleviates symptoms and improves the quality of life in patients with MPE; however, the mechanism employed by XSD on MPE has not yet been elucidated. To investigate the role and mechanism of XSD in inhibiting the development of MPE, and in regulating macrophage polarization in vitro and in vivo. A murine MPE model was used to study the effect of XSD on MPE. Mice with MPE were randomly allocated to a control group and XSD-low-dose (1.144 g/mL), XSD-middle-dose (2.288 g/mL), XSD-high-dose (4.576 g/mL), or cisplatin groups. RAW264.7 cells were induced to form tumor-associated macrophages (TAMs) as well as M1 and M2 macrophages using different conditioned media in vitro. XSD effectively inhibited MPE formation, reduced pleural permeability and angiogenesis, and prolonged mice survival. Particularly, XSD treatment induced the polarization of TAMs to the M1 phenotype in MPE. Moreover, in-vitro XSD remarkably promoted the expansion of M1 macrophages and reduced M2 macrophages by enhancing autophagy. XSD inhibits MPE development and regulates macrophage polarization by activating autophagy, indicating that XSD may serve as a novel option for integrative MPE therapies.


Certification in infection control matters: Impact of infection control department characteristics and policies on rates of multidrug-resistant infections.
The study objective is to describe infection control policies aimed at multidrug-resistant organisms (MDRO) in California hospitals and assess the relationship among these policies, structural characteristics, and rates of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) bloodstream infections and Clostridium difficile infections. Data on infection control policies, structural characteristics, and MDRO rates were collected through a 2010 survey of California infection control departments. Bivariate and multivariable Poisson and negative binomial regressions were conducted. One hundred eighty hospitals provided data (response rate, 54%). Targeted MRSA screening upon admission was reported by the majority of hospitals (87%). The majority of hospitals implemented contact precautions for confirmed MDRO and C difficile patients; presumptive isolation/contact precautions for patients with pending screens were less frequently implemented. Few infection control policies were associated with lower MDRO rates. Hospitals with a certified infection control director had significantly lower rates of MRSA bloodstream infections (P < .05). Although most California hospitals are involved in activities to decrease MDRO, there is variation in specific activities utilized with the most focus placed on MRSA. This study highlights the importance of certification and its significant impact on infection rates. Additional research is needed to confirm these findings.


A multicenter study of the prevalence and risk factors of malaria and anemia among pregnant women at first antenatal care visit in Ghana.
Malaria in pregnancy remains a major public health problem in Africa and Ghana and has been associated with a variety of pregnancy-related adverse complications. The development of effective and timely health policies for the prevention and control of malaria and anemia in pregnancy; requires current and consistent data on the prevalence and risk factors. We report the prevalence and risk factors of malaria and anemia from three major hospitals across three regions in Ghana. This multicenter cross-sectional study comprising a total of 628 pregnant women was conducted at the antenatal care units of the Achimota Hospital in the Greater Accra Region (n = 199), St. Michael's Hospital in the Ashanti Region (n = 221), and Effia Nkwanta Regional Hospital in the Western Region (n = 211). Questionnaires were administered to obtain socio-demographic, obstetrics and clinical data. Venous blood, stool and urine samples were collected for hematological profile and parasite identification using microscopy. Risk factors were evaluated using logistic regression models. The overall prevalence of P. falciparum malaria was 8.9%. Factors independently associated with malaria were self-reported mosquito exposure (moderate exposure: aOR = 3.11, 95% CI (1.12-8.61) and severe exposure: aOR = 10.46, 95% CI (3.86-28.34)) and non-use mosquito repellents (aOR = 3.29, 95% CI (1.70-6.39)). Multiparty (parity of 2: aOR = 0.19, 95% CI (0.05-0.70) and parity ≥3: aOR = 0.11, 95% CI (0.03-0.45)) and age (20-30 years old: aOR = 0.22, 95% CI (0.09-0.56)) reduced the odds of infection. The overall prevalence of anemia was 42.4%. The prevalence of mild, moderate and severe anemia were 35.7%, 6.1% and 0.6%, respectively. The use of water other than purified water (tap water: aOR = 3.05, 95% CI (2.06-4.51) and well water: aOR = 2.45, 95% CI (1.35-4.44)), increasing gestational age (second trimester: aOR = 2.05, 95% CI (1.41-2.97) and third trimester: aOR = 7.20, 95% CI (3.06-16.92)) and malaria (aOR = 2.40, 95% CI (1.27-4.53)) were independent risk factors for anemia. Although the prevalence of malaria is relatively low, that of anemia remains high. We recommend increasing efforts to make ITNs more available to strengthen malaria prevention. Public health education programs could help improve uptake and proper use of ITNs. To help reduce anemia in pregnancy, women should be empowered economically and interventions that reduce malnutrition should be encouraged. Women should be educated on early initiation of antenatal care to enhance surveillance, identification and treatment of anemia.


The potential of multilayer green roofs for stormwater management in urban area under semi-arid Mediterranean climate conditions.
Different low impact development measures have been proposed to make cities more flood-resilient, and recent literature is paying great attention to the evaluation of their direct benefits in terms of flood risk mitigation and the numerous co-benefits that they may offer. This study describes an experimental prototype of a technologically advanced multilayer green roof installed in a Mediterranean urban area (i.e., Palermo, Italy) and explores the results of an analysis of data collected over a one-year monitoring period by a complex sensors network. Multilayer green roofs, or "blue-green" roofs (BGRs), are characterized by a high water retention capacity compared to traditional green roofs due to the presence of an additional storage layer (blue layer), usually equipped with a valve that allows for regulating discharge outflow and water storage. Due to their recent development, BGRs are still scarcely explored in literature and have never been tested before in semi-arid environments, where they could represent valid measures to counter possible climate change and growing urbanization effects. In this study, the hydrological effectiveness of the experimental BGR is quantitatively evaluated by using appropriate indicators, based on the comparison between the hydrological response of the system and an equal size benchmark "grey" roof. The analyses are prevalently focused on the system's stormwater retention function, also investigating the relative contributions of the green layer and the storage layer to the overall retention capacity through the introduction of new BGRs specific indicators. Results emphasize the high impact of storms characteristics, antecedent soil moisture of the green layer, and initial water storage in the blue layer on the system's retention capacity. The overall mean retention rate for the experimental BGR, on average equal to 77% at the daily scale and 61% at the event scale, is comparable to the typical values of traditional extensive green roofs and could be further improved through a "retention-oriented" management of the outflow valve. The system was able to entirely retain almost half of the rainfall events occurred during the monitoring period and, for all the others, it was however extremely effective in reducing runoff peaks and delaying the hydrograph produced.


Knockout of beta-2 microglobulin reduces stem cell-induced immune rejection and enhances ischaemic hindlimb repair via exosome/miR-24/Bim pathway.
Generating universal human umbilical mesenchymal stem cells (UMSCs) without immune rejection is desirable for clinical application. Here we developed an innovative strategy using CRISPR/Cas9 to generate B2M- UMSCs in which human leucocyte antigen (HLA) light chain β2-microglobulin (B2M) was deleted. The therapeutic potential of B2M- UMSCs was examined in a mouse ischaemic hindlimb model. We show that B2M- UMSCs facilitated perfusion recovery and enhanced running capability, without inducing immune rejection. The beneficial effect was mediated by exosomes. Mechanistically, microRNA (miR) sequencing identified miR-24 as a major component of the exosomes originating from B2M- UMSCs. We identified Bim as a potential target of miR-24 through bioinformatics analysis, which was further confirmed by loss-of-function and gain-of-function approaches. Taken together, our data revealed that knockout of B2M is a convenient and efficient strategy to prevent UMSCs-induced immune rejection, and it provides a universal clinical-scale cell source for tissue repair and regeneration without the need for HLA matching in the future.


Minimally invasive small incision surgical technique for unicompartmental knee arthroplasty.
It is always a challenge for orthopaedic surgeons to minimise surgical incisions while ensuring excellent surgical results. We propose the minimally invasive small incision (MISI) technique and an extramedullary positioning technique in the unicompartmental knee arthroplasty (UKA) surgery. This study aimed to clarify the early postoperative clinical outcomes and component alignment between MISI and conventional minimally invasive surgical (MIS) techniques. We prospectively enrolled 60 patients who underwent MISI-UKA and 60 patients who underwent MIS-UKA as controls. Clinical parameters include the time of straight leg raising, postoperative walking time with walker assistance, hospital stay, Numerical Rating Scale (NRS) pain score and Knee Society Score (KSS). The postoperative components and lower extremity alignment were compared between the two groups with radiographic image measurement. The MISI group obtained a smaller incision during knee extension (P < 0.001) but a longer tourniquet usage time than the MIS group. The MISI group lost less blood (P < 0.001). The MISI group achieved straight leg raising and walking with aid earlier after surgery, with a shorter hospital stay than the MIS group (P < 0.001). Range of motion (ROM), NRS and KSS scores revealed no significant difference between the two groups in six months postoperative follow-up (P > 0.05). Radiographic measurement results between the two groups revealed no statistical difference (P > 0.05) CONCLUSION: The MISI-UKA could achieve faster earlier recovery after surgery and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the conventional MIS-UKA.


[Characterization of pesticide exposures reported between 2006 and 2013 to a poison information center in Chile].
Pesticides are widely used to increase crop yields and vector control. However, both acute and chronic exposure have health consequences. There is paucity of information about the global occurrence of pesticide poisonings. To characterize the reports of pesticide exposures received by a University Poison Information Center. All pesticide exposures reported in Chile between 2006 and 2013 were analyzed. A data-collection sheet provided by the International Programme on Chemical Safety of the World Health Organization, was used to collect information. In the study period, 13,181 reports were analyzed. The main age groups exposed were preschoolers and adults. Sixty one percent of exposures occurred accidentally and 24.8% were suicide attempts. Exposures to acetylcholinesterase inhibitors was reported in 29.3% of cases, to superwarfarin rodenticides in 28.5% and to pyrethroids in 24.0%. An increased risk of suicide attempts with pesticides was observed among women, when compared with men (odds ratio: 1.5; 95% confidence intervals: 1.4-1.6; p < 0.001). The risk was higher among teenage girls. The amount of cases under acetyl cholinesterase inhibitor exposure, the most toxic pesticides currently in use should be highlighted. Workers should be educated and all cases should be reported to take actions aiming at reducing these events.


Cytotoxicity of diesel exhaust particle extract--a comparison among five diesel passenger cars of different manufactures.
The cytotoxicity of the dichloromethane extracts of diesel exhaust particles from passenger cars of different manufactures was studied in cultured chinese hamster ovary cells. While exhaust particles from diesel cars of the same make and model yielded extracts of similar cytotoxicity, those from cars of different manufactures yielded extracts with a 3-fold difference in cytotoxicity. Using data on the percentages of extractable organic chemicals and total exhaust particulate emission rates, the emission rate of cytotoxin into the environment from the different cars were calculated. Of the 3 factors that could affect the emission rate of cytotoxins (cytotoxicity of the extractable chemicals, amount of cytotoxins per particle, and particulate emission rate), the differences in particulate emission rates were found to be the predominant factors leading to the differences in the emission rate of cytotoxins. Our findings indicate the need to consider other chemical and physical data, not just the activities of the extracts, when the potential health risk due to the exhaust emissions of different automobiles are compared.


State-level educational disparities in mortality in the United States, 2010-2014.
The present study examined educational disparities in mortality for 49 states and the District of Columbia in the United States based on the 2010-2014 national mortality data. A total of 3,165,762 deaths at ages 25-74years were included in analysis. Absolute and relative disparities were estimated as Relative Index of Inequality (RII) and Slope Index of Inequality (SII), respectively, based on age-standardized death rates by education, race/ethnicity sex, and state. We found that educational disparities in mortality existed in every US state with varying magnitude across states and by sex. The disparities were generally larger in men than in women on both absolute and relative scales. Across states, for all races combined, the RII varied in the range of 4.2 to 14.9 in men and 3.2 to 10.1 in women; the SII (1/100,000 persons) ranged from 934.0 to 1633.4 in men and from 333.7 to 672.5 in women. Hispanic origin seems to alter the pattern of educational disparities by state. In non-Hispanic whites, some Midwest states had the smallest disparities on both relative and absolute scales. Maryland, Virginia, and Massachusetts had a large relative disparity but a moderate absolute disparity. In general, southern states had a large absolute disparity but a moderate relative disparity. There was a strong correlation (0.66; 95% CI, 0.46-0.79) between educational disparities in mortality and disparities in combined major risk factors (smoking, obesity, and hypertension) by state. These findings call for tailored interventions among socially disadvantaged populations, especially in high disparity states and among young adults.


Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation.
Multiple follicular stimulation for IVF may be associated with greatly elevated serum E2 concentrations that are presumed to be antinidatory. This factor was analyzed in 825 consecutive embryo transfer cycles. The pregnancy rate decreased significantly after the transfer of one and two embryos in association with preovulatory E2 levels greater than the 90th percentile for the group (2320 pg/ml). The pregnancy rate did not vary with preovulatory E2 concentration following the transfer of three embryos. Highly significant correlations were noted between preovulatory E2 and early luteal phase concentrations of E2 and P. In a subgroup of 245 cycles, there were no significant relationships between implantation and early luteal phase levels of P or the ratio of E2/P. There was a small but nonsignificant tendency for the pregnancy rate to decrease in association with raised luteal E2. It is concluded that excessive E2 levels at the time of ovulation induction with hCG had an adverse effect on implantation when one or two embryos are transferred, but this may be overcome by the transfer of three embryos. The consequences for embryo transfer are discussed.


A needle-type optical enzyme sensor system for determining glucose levels in fish blood.
A needle-type biosensor system was developed for rapid and simple determination of glucose levels in fish blood. The sensor comprises a needle-type hollow container (18-gauge needle), immobilized enzyme membrane and optic fiber probe with ruthenium complex. The enzyme membrane was prepared from glucose oxidase, azide-unit pendant water-soluble photopolymer and an ultra-thin dialysis membrane. The optic fiber probe was inserted into the rolled enzyme membrane placed in the needle-type hollow container. The calibration curve was linear for glucose levels in fish plasma. One assay was completed within 3 min. A good reproducibility was observed for 60 times without exchange of the enzyme membrane. The sensor was inserted into the caudal vein of fish to measure blood glucose levels. The sensor responded immediately after insertion and glucose levels could be monitored. Good correlations were observed between values determined using the sensor and conventional methods in the range of 48-157 mg dl(-l) (correlation coefficient, 0.9474).


Improving the stability of chitosan-gelatin-based hydrogels for cell delivery using transglutaminase and controlled release of doxycycline.
Although local cell delivery is an option to repair tissues, particularly using chitosan-based hydrogels, significant attrition of injected cells prior to engraftment has been a problem. To address this problem, we explored the possibility of stabilizing the chitosan-gelatin (CG) injectable hydrogels using (1) controlled release of doxycycline (DOX) to prevent premature degradation due to increased gelatinase activity (MMP-2 and MMP-9), and (2) transglutaminase (TG) to in situ cross-link gelatin to improve the mechanical stability. We prepared DOX-loaded PLGA nanoparticles, loaded into the CG hydrogels, measured DOX release for 5 days, and modeled using a single-compartmental assumption. Next, we assessed the influence of TG and DOX on hydrogel compression properties by incubating hydrogels for 7 days in PBS. We evaluated the effect of these changes on retention of fibroblasts and alterations in MMP-2/MMP-9 activity by seeding 500,000 fibroblasts for 5 days. These results showed that 90 % of DOX released from cross-linked CG hydrogels after 4 days, unlike CG hydrogels where 90 % of DOX was released within the first day. Addition of TG enhanced the CG hydrogel stability significantly. More than 60 % of seeded fibroblasts were recovered from the CG-TG hydrogels at day 5, unlike 40 % recovered from CG-hydrogels. Inhibition of MMP-2/MMP-9 were observed. In summary, controlled release of DOX from CG hydrogels cross-linked with TG shows a significant potential as a carrier for cell delivery.


BRAF V600E mutation-specific immunohistochemical analysis in ameloblastomas: a 44-patient cohort study from a single institution.
The aim of this study is to investigate the presence and prevalence of BRAF V600E mutation in ameloblastomas using anti-BRAF V600E monoclonal antibody (VE1 clone) and to identify any clinicopathologic correlation with BRAF V600E mutation in ameloblastoma. The pathology files of the Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, Lagos State University College of Medicine, Lagos, Nigeria, were searched for the diagnosis of ameloblastoma from 2016 to 2020. Archived non-decalcified formalin-fixed paraffin-embedded tissue underwent immunohistochemistry using anti-BRAF V600E antibody at the University of Pittsburgh, Pennsylvania. Clinicopathologic data such as age at diagnosis, gender, jaw bone involved (mandible or maxilla), tumor location (anterior or posterior) and histologic subtype were collected. The clinicopathologic parameters were analyzed using Chi-square test and Fisher's exact test according to the BRAF status. Forty-four cases of ameloblastoma were retrieved. The male to female ratio was 1.32:1. The average age of patients at diagnosis was 33.3 years. Thirty-nine cases were located in the mandible and 5 cases in the maxilla. Only cases in the mandible were positive for anti-BRAF V600E antibody (n = 15/39; 38.5%). There was a significant correlation between BRAF V600E expression in mandibular tumors and histologic subtype (p = 0.02); however, no significance was observed for gender, age and tumor location. BRAF V600E mutation preferentially occurs in mandibular ameloblastomas, especially in non-plexiform ameloblastomas. These patients may benefit therapeutically from the use of BRAF inhibitors.


Dependence of the reflectance of a multilayer reflector on the thickness of the outer layer.
At nonnormal incidence, the radiant reflectance of a highly reflecting multilayer coating strongly depends on the thickness of the outer layer.


Patient autonomy problems in palliative care: systematic development and evaluation of a questionnaire.
No instrument to assess autonomy problems in palliative care is currently available. The purpose of this study was to develop a comprehensive and concise questionnaire to measure autonomy problems in palliative cancer patients and to study its validity and reliability. We systematically developed a questionnaire through: a) a literature review of the concepts and elements of autonomy; b) qualitative analysis of interviews with patients and professional carers; c) the construction of questionnaires; and d) testing validity and reliability. The basic conceptual elements were: dependency, losing control, and limitation of activities. Patients with disseminated cancer in the palliative stage of the disease (n = 64) participated in the study. A 9-item Patient Autonomy Questionnaire (PAQ) was developed (Cronbach's alpha 0.86), followed by a concise 4-item version (PAQs) (Cronbach's alpha 0.71). Autonomy problems were more prevalent than pain problems. The development of the PAQ may help draw attention to autonomy problems.


An in-depth characterization of a large cohort of adult patients with eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a chronic, allergic, immune-mediated disease associated with increased risk of comorbid atopic conditions. To perform an in-depth characterization of a large cohort of manually verified adult patients with EoE, including evaluation of less studied associations, such as pollen food allergy syndrome, anaphylaxis, autoimmunity, and psychiatric comorbidities. We performed a manual retrospective electronic medical record review of 1,218 patients with EoE identified by International Classification of Diseases, Ninth Revision and International Classification of Disease, 10th Revision codes from the University of Pennsylvania Health Systems. Through manual medical record review, we evaluated patient demographics, family and smoking history, laboratory and endoscopic findings, treatment, and comorbid atopic, autoimmune, and psychiatric conditions. A total of 950 of the 1,218 patients had biopsy-proven EoE. This cohort was predominantly male, white, and never-smokers who presented most commonly with dysphagia, with an initial biopsy results showing 49 eosinophils per high-powered field, a serum absolute eosinophilic count of 446,000/µL, and mean total IgE level of 243 IU/mL. Of the patients, 55% had impaction (of which 38% required endoscopic removal), and 56% had strictures or fibrosis (of which 56% underwent dilatation). Therapy used was predominantly (77%) medical only. Comorbid atopy, pollen food allergy syndrome, drug allergy, anaphylaxis, autoimmunity, and psychiatric illnesses were higher in the EoE cohort compared with the general University of Pennsylvania Health Systems population. Our adult cohort of manually verified, biopsy-proven EoE had an increased risk of pollen food allergy syndrome, anaphylaxis, and comorbid autoimmune and psychiatric conditions compared with the University of Pennsylvania Health Systems population. There was also an increased prevalence of impaction and stricture or fibrosis requiring endoscopic intervention compared with the pediatric population.


Costly coagulation profile tests prior to performing breast biopsies. Do we really need it?
To reassess the need for routine coagulation profile testing in patients undergoing image-guided breast biopsies. This is a retrospective cross-sectional study. Data was collected from the logbook of patients that underwent image-guided biopsies in the breast unit at the Department of Radiology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Patients' electronic records between November 2013 and October 2014 were included in the study. Exclusion criteria were those on anticoagulants, or platelet aggregation inhibitors, and patients with known primary, or secondary bleeding diathesis. The study was analyzed using the IBM Statistical Packages for Social Sciences Version 22 (IBMCorp, Armonk, NY, USA). A total of 136 patients were included in our study. Neither partial thromboplastin time (PTT), or thrombocytopenia was related to bleeding with p-values of 0.536 PTT and 0.997 thrombocytopenia. Needle gauge was found to be significantly related to bleeding episodes with a p=0.020. We advise against the routine use of coagulation profiles to predict bleeding risk. A thorough bleeding assessment is more advantageous. Laboratory tests should be tailored according to the patient's history and examination findings.


Medicinal plant diversity and uses in the Sango bay area, Southern Uganda.
An inventory is presented for the medicinal plants of the Sango bay area in Southern Uganda. Fieldwork was conducted between March and August 2004, using semi-structured interviews, questionnaires and participant observation as well as transect walks in wild herbal plant collection areas. One hundred and eighty-six plant species belonging to 163 genera and 58 families with medicinal values were recorded. Remedies from these plants are prepared mainly as decoctions and infusions and administered in a variety of ways. The majority (51.3%) of these plants are herbaceous, growing mainly in the wild. Grasslands provided the highest number of species for medicinal use (54.6%) followed by home gardens (25.4%) and fallow land (19.5%). A review of Ugandan and other literature indicated that 72 (38.5%) medicinal plants reported in this study have not been reported previously as having medicinal value. According to respondents, plant species including Hallea rubrostipulata (K. Schum) J-F Leroy (Rubiaceae) and Warburgia ugandensis Sprague (Canellaceae) are threatened because of poor harvesting techniques and unsustainable harvesting intensities. Suggestions for future conservation programs, sustainable utilization and ethnopharmacological studies are given.


Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study.
Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23% (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be performed, taking into account the specific contrast agent used, in order to obtain accurate intravascular OFDI measurements.


Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms.
Because of the limitations of current staging systems and evolving definitions, there are limited data on oligometastatic non-small cell lung cancer (NSCLC) epidemiology. The purpose of this study was to evaluate metastatic disease burden and the incidence of oligometastatic disease using recent clinical trial eligibility criteria. A cohort of patients with metastatic NSCLC, diagnosed from 2016 to 2019, were randomly sampled from a curated tumor registry. Definitions for oligometastatic disease were obtained from relevant clinical trials. The Stanford Cancer Institute Research Database was used to identify baseline patient factors, systemic and local therapy, extent and location of metastatic lesions, and survival outcomes. Among 120 patients presenting with metastatic NSCLC, the majority had de novo metastatic disease (75%) with a median of 4 metastatic lesions involving 3 organ systems. Of these, 37.5% would have been eligible for at least 1 oligometastatic trial, with 28.3% meeting criteria for the MD Anderson Cancer Center trial, 20.0% for NRG-LU002, 6.7% for SINDAS, and 16.7% for SABR-COMET. By adding malignant pleural effusions and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs 42.4 months; P < .001), whereas presence of malignant pleural effusions was not. Of those tumors identified as oligometastatic, 44.4% received local therapy and 28.9% underwent ablative therapy to all sites. There was a trend toward greater overall survival (44.4 vs 24.9 months; P = .055) and progression-free survival (8.0 vs 5.4 months; P = .06) in patients meeting eligibility for at least 1 oligometastatic trial. Around 48% of patients with metastatic NSCLC had ≤3 metastases at presentation and 28% met clinical trial criteria for oligometastatic disease. Future research is needed to better define the oligometastatic state and identify patients most likely to benefit from local therapy.


Longer operative time is associated with increased post-operative complications in patients undergoing minimally-invasive surgery for endometrial cancer.
To examine the impact of operative time on the development of post-operative medical and surgical complications in patients undergoing minimally-invasive surgery for endometrial cancer. Patients who underwent laparoscopic surgery for endometrial cancer from 2005 to 2014 were identified from the ACS-NSQIP database. Operative times were initially divided into hour-long intervals and complication rates were determined. Outcomes included development of any complication, medical complication, or surgical complication. Subsequent analysis were based on dividing patients into 2 groups based on operative times <240min and operative times ≥240min. Associations between categorical variables were determined using Chi-Squared and Fisher's exact tests. Differences between means of continuous variables were determined using Student's t-tests. Univariate and multivariate analysis using logistic regression were used to identify predictors of post-operative complications. 9145 patients were included, of which 639 (7%) experienced a complication. As operative time increased, rates of complications also increased. Operative time ≥240min was associated with increased overall complication rate (11.7% vs. 6%, p<0.001), medical complication rate (9.3% vs. 4.2%, p<0.001), and surgical complication rate (3.9% vs. 2.4%, p=0.001). When performing multi-variate logistic regression of factors associated with increased complication rates, increased operative time, COPD, hypertension, diabetes, ASA class ≥3, dependent functional status, and chronic steroid use were found to be independently associated with increased complications. Lymphadenectomy was not associated with increased operative time or increase in complications. Increased operative time is independently associated with increased risk of developing complications after laparoscopic surgery for endometrial cancer.


Depletion of a nucleolar protein activates xenobiotic detoxification genes in Caenorhabditis elegans via Nrf /SKN-1 and p53/CEP-1.
The nucleolus has recently emerged as a major coordinator of cellular stress responses by regulating the tumor suppressor p53. However, it is not known if the nucleolus regulates the cap 'n' collar (CnC) transcription factors SKN-1 and Nrf2, which activate conserved antioxidant and detoxification responses in C. elegans and mammals, respectively. A screen for negative regulators of detoxification genes in C. elegans identified the conserved WD40 repeat containing protein WDR-46. This protein is highly conserved with yeast UTP7, which functions in 18S rRNA processing and assembly of the 40S small ribosomal subunit. WDR-46 is expressed in the nucleoli of multiple tissues in C. elegans and is required for rRNA processing. Mutation or silencing of WDR-46 activates the single C. elegans CnC homologue SKN-1 and increases expression of its target genes. Depletion of wdr-46 reduces lifespan and stress resistance and SKN-1 partially compensates. Lastly, the C. elegans p53 homologue CEP-1 is partially required for activation of gst-4 when wdr-46 or other ribosome processing genes are silenced but not when translation initiation genes are silenced suggesting that disruptions to nucleolar function can activate SKN-1 by a mechanism that involves p53/cep-1 and is independent of protein translation.


Computer-assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma.
Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high-risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans. We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG-avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG-positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys. There was good reliability between methods and observers. The user-interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency. We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG-positive lesions over time is a strength of these methods.


Diagnostic yield and complications of transthoracic computed tomography-guided biopsies.
The widespread use of computed tomography (CT) improves detection of pulmonary lesions, which are not only detected at an increased rate but also at a smaller size. CT-guided lung biopsies are now more frequently used than fluoroscopy-guided lung biopsies. The main aim of the present paper was to investigate the outcome and complications of the biopsies. We retrospectively collected the results and information from 520 CT-guided thorax biopsies. All biopsies were performed with CT-guided "beam-through" technique, using a 64-slice CT scanner. In 86% of the biopsies, the tissue material was found to be sufficient. In 32% of the biopsies, a complication arose, mostly pneumothorax (30%), but chest drainage was needed in only 15% of the 520 cases. Patients with more than ten cigarette pack-years had a complication risk that was twice as high at that of patients with fewer pack-years. We found that the risk of pneumothorax increased the further the lesion was from the skin surface, the smaller the lesions were and when the patient was biopsied in a lateral position. We also found a higher risk of complications in females than in males. CT-guided biopsy is an excellent tool for analysing pulmonary lesions. The present study clearly shows that the risk of developing a pneumothorax is significantly increased among smokers and former smokers with more than ten pack-years. none. not relevant.


Structural characterization of a rice actin gene.
We have isolated and sequenced a full-length cDNA clone containing information for the rice actin gene RAc1. Transcript terminus mapping and sequence alignment between the RAc1 cDNA clone and a previously isolated RAc1 genomic clone were used to determine the structure of the RAc1 gene. This allowed us to make the first complete structural characterization of a plant actin gene. The analysis revealed the presence of a 5'-noncoding exon, separated by an intron, from the first translated exon of the RAc1 gene. This is one of the few reported cases of a plant gene containing such a 5'-noncoding exon. Sequence comparison between the previously isolated plant actin genes suggests that such an exon may be a common feature of plant actin gene structure. The present study also confirms that the rice actin gene family is composed of at least eight unique members.


Simian retrovirus-D serotype 1 (SRV-1) envelope glycoproteins gp70 and gp20: expression in yeast cells and identification of specific antibodies in sera from monkeys that recovered from SRV-1 infection.
The gp70 and transmembrane gp20 envelope proteins of simian retrovirus-D serotype 1 (SRV-1) were expressed in Saccharomyces cerevisiae as fusion proteins with human superoxide dismutase (SOD). Expression of the SOD-gp70 and SOD-gp20 sequences yielded fusion proteins of 52 and 29 kilodaltons, respectively. The yeast-expressed SRV-1 envelope proteins were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies in the sera of rhesus macaques that recovered from SRV-1. Sera from 47 of 49 such monkeys tested positive for antibodies to the SOD-gp70 fusion protein, while 45 of 49 reacted positively to SOD-gp20. None of 26 SRV-1-nonexposed monkeys tested positive in either ELISA. Monkeys immunized with the recombinant SRV-1 gp20 and gp70 proteins made good ELISA and Western blot (immunoblot) antibodies to whole SRV-1. This antibody was not neutralizing in vitro, however.


An update on explaining the rural-urban gap in under-five mortality in India.
Rural Indians have higher mortality rates than urban Indians. However, the rural-urban gap in under-five mortality has changed is less researched. This paper aims to assess 1) whether the rural-urban gap in under-five mortality has reduced over time 2) Whether rural children are still experiencing a higher likelihood of death after eliminating the role of other socioeconomic factors 3) What factors are responsible for India's rural-urban gap in under-five mortality. We used all rounds for National Family Health Survey data for understanding the trend of rural-urban gap in under-five mortality. Using NFHS-2019-21 data, we carried out a binary logistic regression analysis to examine the factors associated with under-five mortality. Fairlie's decomposition technique was applied to understand the relative contribution of different covariates to the rural-urban gap in under-five mortality. India has witnessed a more than 50% reduction in under-five mortality rate between 1992 and 93 and 2019-21. From 1992 to 93 to 2019-21, the annual decrease in rural and urban under-five mortality is 1.6% and 2.7%, respectively. Yet, rural population still contributes a higher proportion of the under-five deaths. The rural-urban gap in under-five mortality has reduced from 44 per thousand live births in 1992-1993 to 30 per thousand in 2004-2005 which further decreased to 14 per thousand in 2019-2021. There is no disadvantage for the rural children due to their place of residence if they belong to economically well-off household or their mothers are educated. It is wealth index rather than place of residence which determines the under-five mortality. Economic (50.82% contribution) and educational differential (28.57% contribution) are the main reasons for rural-urban under-five mortality gaps. The existing rural-urban gap in under-five mortality suggests that the social and health policies need to be need to reach rural children from poor families and uneducated mothers. This call for attention to ensure that the future programme must emphasize mothers from economically and educationally disadvantaged sections. While there should be more emphasis on equal access to health care facilities by the rural population, there should also be an effort to strengthen the rural economy and quality of education.


MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway.
Mucin (MUC) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated. MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20. MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin β1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin β1 signaling by MUC20 was significantly suppressed by integrin β1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells. Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin β1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.


The seizure-related phenotype of brain-derived neurotrophic factor knockdown mice.
The present investigation focused on the seizure-related phenotype of mice lacking one allele of brain-derived neurotrophic factor. Thresholds for producing seizures in brain-derived neurotrophic factor wild-type and brain-derived neurotrophic factor heterozygous mice were compared in several seizure models, including thresholds for electrically-induced clonic, tonic-clonic and 6 Hz limbic seizures, as well as seizures induced chemically by kainate, pilocarpine and pentylenetetrazol. In addition, the rate of amygdala kindling, as well as pre- and post-kindling seizure thresholds was determined. Seizure thresholds for clonic and tonic-clonic electrically induced seizures did not differ between brain-derived neurotrophic factor wild-type and heterozygous mice. However, heterozygous mice had higher thresholds for 6 Hz limbic seizures compared with wild-type mice. Heterozygous mice also required larger doses of kainate to produce limbic seizures. Somewhat surprisingly, heterozygous mice required significantly lower doses of pilocarpine to produce limbic seizures. However, heterozygous mice required a higher dose of pentylenetetrazol to induce twitches, but not clonic seizures, compared with wild-type mice. In addition, heterozygous mice required more current to elicit focal afterdischarges in the amygdala both pre- and post-kindling than did wild-type mice, and, heterozygous mice kindled more slowly than wild-type mice. The present findings provide additional support for the hypothesis that brain-derived neurotrophic factor is involved not only in normal excitability, but may also be involved in abnormal excitability such as occurs in seizure disorders and epileptogenesis.


Deep Learning-based structure modelling illuminates structure and function in uncharted regions of β-solenoid fold space.
Repeat proteins are common in all domains of life and exhibit a wide range of functions. One class of repeat protein contains solenoid folds where the repeating unit consists of β-strands separated by tight turns. β-solenoids have distinguishing structural features such as handedness, twist, oligomerisation state, coil shape and size which give rise to their diversity. Characterised β-solenoid repeat proteins are known to form regions in bacterial and viral virulence factors, antifreeze proteins and functional amyloids. For many of these proteins, the experimental structure has not been solved, as they are difficult to crystallise or model. Here we use various deep learning-based structure-modelling methods to discover novel predicted β-solenoids, perform structural database searches to mine further structural neighbours and relate their predicted structure to possible functions. We find both eukaryotic and prokaryotic adhesins, confirming a known functional linkage between adhesin function and the β-solenoid fold. We further identify exceptionally long, flat β-solenoid folds as possible structures of mucin tandem repeat regions and unprecedentedly small β-solenoid structures. Additionally, we characterise a novel β-solenoid coil shape, the FapC Greek key β-solenoid as well as plausible complexes between it and other proteins involved in Pseudomonas functional amyloid fibres.


Studies on tissue characterization by texture analysis with co-occurrence matrix method using ultrasonography and CT imaging.
We used texture analysis with the co-occurrence matrix method to analyze ultrasonograms from normal and diseased livers, and X-ray CT images obtained from normal cases and cases of idiopathic interstitial pneumonia. Ten cases of normal, fatty, and cirrhotic livers; 10 cases of normal lungs; and 10 cases of idiopathic interstitial pneumonia, all confirmed by clinical findings, laboratory data, surgery, or biopsy, were the subjects of this study. We compared the results of texture analysis in normal and diseased livers under the same conditions of gain, focus, magnification rate, probe frequency, and depth of the region of interest. Here we discuss the relationship between Fisher ratio of texture analysis and pathological character. Although the normal and diseased liver groups did not differ significantly, the different pathological grades of fibrosis and the different size of nodules in the cirrhotic and normal liver groups did have different Fisher ratios. We compared the results of texture analysis with images obtained from normal cases and cases of idiopathic interstitial pneumonia. Significant differences between normal lungs and those with idiopathic interstitial pneumonia were also found. We thus think that texture analysis can be used to analyze ultrasonograms obtained from lesions of different pathological grades and to classify CT images as well.


Comparison of Kinect and Leap Motion for Intraoperative Image Interaction.
Background. Touchless interaction devices have increasingly garnered attention for intraoperative imaging interaction, but there are limited recommendations on which touchless interaction mechanisms should be implemented in the operating room. The objective of this study was to evaluate the efficiency, accuracy, and satisfaction of 2 current touchless interaction mechanisms-hand motion and body motion for intraoperative image interaction. Methods. We used the TedCas plugin for ClearCanvas DICOM viewer to display and manipulate CT images. Ten surgeons performed 5 image interaction tasks-step-through, pan, zoom, circle measure, and line measure-on the 3 input interaction devices-the Microsoft Kinect, the Leap Motion, and a mouse. Results. The Kinect shared similar accuracy with the Leap Motion for most of the tasks. But it had an increased error rate in the step-through task. The Leap Motion led to shorter task completion time than the Kinect and was preferred by the surgeons, especially for the measure tasks. Discussion. Our study suggests that hand tracking devices, such as the Leap Motion, should be used for intraoperative imagining manipulation tasks that require high precision.


Glycan modification of the tumor antigen gp100 targets DC-SIGN to enhance dendritic cell induced antigen presentation to T cells.
Dendritic cells (DC) have gained much interest in the field of anticancer vaccine development because of their central function in immune regulation. However, the clinical application of ex vivo cultured DC has significant disadvantages. A vaccine that targets dendritic cells in vivo and enhances antigen presentation would be of great benefit. Because of its DC-restricted expression pattern, and its function as an antigen uptake receptor, DC-SIGN is an interesting candidate target structure for human immature DC. Here, we studied whether modification of the melanoma differentiation antigen gp100 with DC-SIGN-interacting glycans enhances targeting to human DC. A high-mannose form of gp100, as protein or as tumor lysate, not only interacted specifically with DC through DC-SIGN but also resulted in an enhanced antigen presentation to gp100-specific CD4(+) T cells. Our results indicate that glycan modification of tumor antigens to target C-type lectin receptors, such as DC-SIGN, is a new way to develop in vivo targeting DC strategies that simultaneously enhance the induction of tumor-specific T cells.


Massive enlargement of gastric pouch as a complication of gastrojejunal anastomotic stenosis following one anastomosis laparoscopic gastric bypass: A case report.
By 2030 it is predicted that 1 in 5 women and 1 in 7 men will be living with obesity. The only long-term effective strategy for achieving significant weight loss over time is surgical treatment. One Anastomosis Gastric Bypass (OAGB) has been proposed as an effective therapeutic option. Stenosis of Gastro-Jejunal Anastomosis (GJA) is one of the most common long-term complications and its cause recognized as multifactorial. We present the case of a patient with a history of progressive postoperative oral intolerance after OAGB with 60 kg weight loss (BMI 20.7 kg/m2). Severe stenosis of the GJA and massive dilation of the gastric remnant was documented, treated multiple times with endoscopic balloon dilation. He was referred to our unit due to persistent symptoms. Revision surgery to a Gastric Bypass was programmed, ultimately performed via an open approach with resection of 80 % of the gastric remnant. Endoscopic dilatation and surgical revision are the two primary treatment options for GJA stricture. In refractory cases to pneumatic dilation, laparoscopic revision surgery is indicated, however an open approach is frequently required, as surgeries are technically demanding due to distorted anatomy in this population. Operations to correct chronic complications are tailored to the patient's anatomy as well as the symptoms or pathologies they are intended to correct. Whilst revision surgeries are associated with an increased risk of conversion, complications and longer hospital stay, they can be performed safely in experienced centers.


Updated clinical evidence of Chinese herbal medicine for insomnia: a systematic review and meta-analysis of randomized controlled trials.
This systematic review is to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for people with insomnia. Randomized controlled trials (RCTs) investigating oral CHM alone or in combination with conventional therapies for primary insomnia were identified by searching English and Chinese publications and databases of clinical trial registration. Risk of bias was assessed according to the Cochrane Handbook 5.1. Meta-analysis was conducted using RevMan 5.2.4. Seventy-nine trials (7886 participants) were finally included in the review, and 76 were included in the meta-analysis. Twenty-seven trials reported the methods of random sequence generation, and five of them used the allocation concealment. Blinding of participants and personnel were used in 10 studies. The main meta-analysis showed that CHM alone was more effective than placebo by reducing scores of Pittsburgh Sleep Quality Index (mean difference, MD: -3.06, 95% confidence interval, CI: -5.14 to -0.98, I(2) = 97%) and benzodiazepine drugs (BZDs) (MD: -1.94, 95% CI: -2.45 to -1.43, I(2) = 96%). The effect was also seen when CHM was combined with BZDs compared with placebo plus BZDs (MD: -1.88, 95% CI: -2.78 to -0.97, I(2) = 0%) or cognitive and behavioral therapy (MD: -3.80, 95% CI: -4.91 to -2.68, I(2) = 68%) alone. There was no significant difference between CHM and placebo regarding the frequency of adverse events (relative risk, RR: 1.65, 95% CI: 0.67-4.10, I(2) = 0). Overall, oral CHM used as a monotherapy or as an adjunct to conventional therapies appears safe, and it may improve subjective sleep in people with insomnia. However, the typical effect of CHM for insomnia cannot be determined due to heterogeneity. Further study focusing on individual CHM formula for insomnia is needed. The development of a comparable placebo is also needed to improve the successful blinding in RCTs.


Cardiovascular, neurological, and pulmonary events following vaccination with the BNT162b2, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines: An analysis of European data.
The ChAdOx1 nCoV-19 (ChA) (AstraZeneca) and Ad26.COV2.S (AD26) (Janssen) vaccines are virus-based coronavirus disease 2019 (COVID-19) vaccines used worldwide. In spring 2021, venous blood clots and thrombocytopenia were described in some vaccine recipients. We evaluated the frequency of severe adverse events (SAEs) documented in the EudraVigilance European database in young adult (18-64 years old) and older (≥65 years old) vaccine recipients up to 23 June 2021 and related them to coagulation disorders and arterial, cardiac, and nervous system events. Comparison between the frequency of SAEs and SAE-related deaths in ChA and AD26 vs. BNT162b2 COVID-19 (BNT) (Pfizer/BioNTech) vaccine recipients demonstrated: 1) ChA and AD26 recipients than BNT recipients had higher frequencies of not only SAEs caused by venous blood clots and hemorrhage, but also thromboembolic disease and arterial events, including myocardial infarction and stroke; 2) a corresponding higher frequency of SAE-related deaths. The frequency was higher in both young adults and older adults. Comparison between the frequency of SAEs and SAE-related deaths in AD26 vs. ChA recipients demonstrated in AD26 recipients: 1) lower frequency of thrombocytopenia; 2) lower frequency of SAEs in young adult recipients; 3) higher frequency of SAEs in older recipients. Interestingly, most of the venous thrombotic SAEs associated with ChA and AD26 vaccines were not associated with thrombocytopenia, suggesting that TTS (thrombosis with thrombocytopenia syndrome) is not the only type of thrombosis observed following virus-based vaccines. In conclusion, both virus-based COVID-19 vaccines show more SAEs than BNT, but the frequency of the SAE type in the different age groups differs, suggesting that the mechanisms responsible of SAEs overlap only partly.


Haemoparasite infection kinetics and the population structure of Theileria parva on a single farm in Uganda.
The development of sensitive PCR-based species-specific diagnostics and parasite genotyping methods offer the opportunity to provide important and detailed information on the infection dynamics of tick-borne disease. In this study we have exploited such tools to investigate the infection kinetics and parasite diversity within Theileria parva in a single farm in Uganda. Initial analysis of a sample of cattle showed high levels of infection with three Theileria species and Ehrlichia bovis, with most animals being infected with more than one pathogen. To study the infection dynamics, newborn calves were sampled longitudinally and it was shown that all animals became infected with T. parva, T. mutans, T. velifera and E. bovis with the average time to first infection being 53, 74, 116 and 109 days, respectively. However, the majority of these calves cleared the infections with T. parva and E. bovis but remained infected with the other two species of Theileria. In order to investigate the diversity of infecting genotypes of T. parva, samples from six calves were genotyped with a single mini-satellite marker at time points over a nine-month period. Each animal was infected with multiple different sets of genotypes and these were lost over different periods of time, implying that immunity is induced against particular infecting strains. To undertake a higher resolution analysis of parasite genotypes, samples from 30 calves were genotyped with a full panel of 12 micro- and mini-satellite markers but, due to the presence of mixed infections, only 16 samples could be used to generate parasite multi-locus genotypes (MLGs). A high degree of diversity of T. parva was seen on the farm, although some MLGs occurred more than once. Similarity analysis demonstrated a level of sub-structuring and the T. parva population was found to be in linkage disequilibrium. The basis for this high diversity coupled with apparent sub-structuring is discussed in relation to the possible causes.


The International Union of Toxicology (IUTOX): history and its role in information on toxicology.
The International Union of Toxicology (IUTOX) was founded in 1980 in Brussels. The initiative was started by the Society of Toxicology (SOT), USA, and the European Society of Toxicology in 1975 (EST), and the foundation prepared by an Inter Society Liason Committee. Eight National Societies of Toxicology were founding members of IUTOX besides SOT and EST. It now comprises 43 national/regional Societies from all over the world, representing over 20,000 toxicologists. Information has always been a key element in toxicology. Information exchange in IUTOX has evolved from letters and phone calls to fax, e-mail and the use of the Internet. Initially, newsletters were created which were mailed and later displayed on the Web. The website has been developed as a major information tool with many useful links, thereby providing information for the scientific community, the media and the lay public.


The effects of positive end-expiratory pressure (PEEP) application on optic nerve sheath diameter in patients undergoing laparoscopic cholecystectomy: a randomized trial.
Positive end-expiratory pressure (PEEP) can overcome respiratory changes that occur during pneumoperitoneum application in laparoscopic procedures, but it can also increase intracranial pressure. We investigated PEEP vs. no PEEP application on ultrasound measurement of optic nerve sheath diameter (indirect measure of increased intracranial pressure) in laparoscopic cholecystectomy. Eighty ASA I-II patients aged between 18 and 60 years scheduled for elective laparoscopic cholecystectomy were included. The study was registered in the Australian New Zealand Clinical Trials (ACTRN12618000771257). Patients were randomly divided into either Group C (control, PEEP not applied), or Group P (PEEP applied at 10 cmH20). Optic nerve sheath diameter, hemodynamic, and respiratory parameters were recorded at six different time points. Ocular ultrasonography was used to measure optic nerve sheath diameter. Peak pressure (PPeak) values were significantly higher in Group P after application of PEEP (p = 0.012). Mean respiratory rate was higher in Group C at all time points after application of pneumoperitoneum (p < 0.05). The mean values of optic nerve sheath diameters measured at all time points were similar between the groups (p > 0.05). The pulmonary dynamic compliance value was significantly higher in group P as long as PEEP was applied (p = 0.001). During laparoscopic cholecystectomy, application of 10 cmH2O PEEP did not induce a significant change in optic nerve sheath diameter (indirect indicator of intracranial pressure) compared to no PEEP application. It would appear that PEEP can be used safely to correct respiratory mechanics in cases of laparoscopic cholecystectomy, with no significant effect on optic nerve sheath diameter.


Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans.
To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD.


Evaluation of a bilinear model for attenuation correction using CT numbers generated from a parametric method.
A parametric model is used for the calculation of the CT number of some selected human tissues of known compositions (Hi) in two hybrid systems, one SPECT-CT and one PET-CT. Only one well characterized substance, not necessarily tissue-like, needs to be scanned with the protocol of interest. The linear attenuation coefficients of these tissues for some energies of interest (μ(i)) have been calculated from their tabulated compositions and the NIST databases. These coefficients have been compared with those calculated with the bilinear model from the CT number (μ(B)i). No relevant differences have been found for bones and lung. In the soft tissue region, the differences can be up to 5%. These discrepancies are attributed to the different chemical composition for the tissues assumed by both methods.


Steroid sulfatase and sulfuryl transferase activity in monkey brain tissue.
Dehydroepiandrosterone and its sulfated form are commonly known as modulators of gamma-aminobutyrate A and N-methyl-D-aspartate receptors. In spite of poor permeability of the blood-brain barrier for sulfated steroids, high concentrations of dehydroepiandrosterone and also its sulfate have been found in brain tissue. Physiological concentrations of these neuromodulators are maintained by two enzymes present in the blood and many peripheral tissues, including the brain, namely, steroid sulfatase and neurosteroid sulfuryl transferase (NSST). This prompted us to investigate activities of these enzymes in primate brain tissue. Rather low neurosteroid sulfuryl transferase activity was detectable in in vitro incubations of cytosol fractions from male and female Macaca mulatta brains, dissected to cerebral cortex, subcortex, and cerebellum. In male monkeys, the highest activity was found in the cerebellum followed by cortex and subcortex. On the other hand, in female monkeys, the highest activity was determined in the cortex followed by subcortex and cerebellum. Steroid sulfatase activity was determined in in vitro microsomal samples from each of the above-mentioned brain regions. Specific activities in female cerebral regions declined in the order: cerebellum, cortex, and subcortex. In male monkeys, no significant difference among the studied regions was observed. Using dehydroepiandrosterone sulfate as a substrate, the apparent kinetic characteristics of steroid sulfatase were determined as follows: K(M) 36.10 +/- 8.33 microM, V(max) 8.38 +/- 1.68 nmol/h/mg protein. These results will serve as a basis for further studies concerning the pathophysiology of human brain tumors.


Absolute time-of-arrival measurements of optical pulses from the Crab pulsar.
An attempt is made to understand the characteristics of pulsar slowdown in terms of various possible emission mechanisms. Though magnetic-dipole radiation seems to be dominant, the deviations from a pure dipolar decay are large compared with errors in measurement and indicate the presence of more complicated braking mechanisms, small fluctuations, and major "jumps", or period discontinuities. Some rapid-relaxation effect is evident following the discontinuous jump in period in September 1969, but there is no evidence of the quasi-sinusoidal behaviour reported before the jump by Arecibo. An alternative interpretation of the Arecibo data is given.


Comparison of blood lipid profile/thyroid function markers between unipolar and bipolar depressed patients and in depressed patients with anhedonia or suicidal thoughts.
This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups.


Evidence that during very low density lipoprotein assembly in rat hepatocytes most of the triacylglycerol and phospholipid are packaged with apolipoprotein B in the Golgi complex.
Rat liver lipids were labelled by an intraportal injection of [3H]palmitic acid followed by isolation of rough and smooth endoplasmic reticulum or 'cis' or 'trans'-enriched Golgi fractions. The preparations were separated into membrane and contents and the apolipoprotein B of the content fractions was immunoprecipitated. More than 90% of the labelled triacylglycerol and phospholipid secreted into the blood immunoprecipitated with apolipoprotein B. Under the same experimental conditions 8, 12, 27 and 59% of the lipids of the rough, smooth, 'cis-Golgi' and 'trans-Golgi' contents, respectively, were immunoprecipitated. Thus, the 'trans-Golgi' region appears to be the major intracellular site of assembly of apolipoprotein B with triacylglycerol and phospholipid.


Pineal 5-methoxytryptophol rhythms in the box turtle: effect of photoperiod and environmental temperature.
The effect of different photoperiods and temperatures on pineal 5-methoxytryptophol (ML) content was investigated in male box turtles, Terrapene carolina triunguis. A rhythm in pineal ML was evident in the long photoperiod (18 h light (L)-6 h dark (D] with high daytime levels of 178 +/- 48 pg/gland (means +/- S.E.M.) which dropped to 38 +/- 6 pg/gland during lights off. In the short photoperiod (8L:16D) no clearcut ML rhythm was observed. Diurnal (10.00-12.00 h) ML concentrations rose linearly (P less than 0.05) with increasing ambient temperatures (5, 15, 20 and 27 degrees C). Day/night differences in ML levels, however, were not significant. Pineal ML in the box turtle thus seems to be modified by the photoperiod and, to a lesser extent, by temperature.


The application of flow cytometric DNA analysis in detecting the presence of malignant cells in ovarian carcinoma peritoneal fluids.
To compare flow cytometric detection of malignant cells with standard cytological evaluation in patients with ovarian carcinoma. The City Hospital Trust, The Women's Hospital and CRC Trials Unit, Birmingham. Forty-three patients with histologically proven ovarian carcinoma and positive cytology, and a control population of 20 patients undergoing surgery for benign gynaecological conditions. Prospective, blinded study examining ascitic fluid or peritoneal washings obtained at primary surgery by flow cytometric DNA analysis and cytological examination. Flow cytometry detected aneuploid cells in 27/43 (63%) of malignant and 7/20 (35%) of benign fluid specimens. In malignant samples the mean aneuploid count was 38.5% (range 1-98%) with a mean S-phase fraction of 5.2% (range 0-33.9%). In benign specimens the mean aneuploid count was 30.4% (range 14.5-66.4%). Based on these results, the overall sensitivity of cytometric detection of malignant cells was 71.4%, specificity 65%, with a positive predictive value of 85.1%. False positivity was found mainly in patients with benign ovarian cysts. Further examination revealed four false negative and four false positive results, where the peritoneal fluid and ovarian tissue DNA ploidy status concurred. Assuming such results to be correct increased the sensitivity of the test to 88.5% and specificity to 85%. Although flow cytometry can glean information beyond the capabilities of cytological assessment, using the premise that aneuploid cells alone indicate malignancy, it remains secondary to cytology in the detection of malignant cells in peritoneal fluids.


Escherichia coli pollution in a Baltic Sea lagoon: a model-based source and spatial risk assessment.
Tourism around the Oder (Szczecin) Lagoon, at the southern Baltic coast, has a long tradition, is an important source of income and shall be further developed. Insufficient bathing water quality and frequent beach closings, especially in the Oder river mouth, hamper tourism development. Monitoring data gives only an incomplete picture of Escherichia coli (E. coli) bacteria sources, spatial transport patterns, risks and does neither support an efficient bathing water quality management nor decision making. We apply a 3D ocean model and a Lagrangian particle tracking model to analyse pollution events and to obtain spatial E. coli pollution maps based on scenario simulations. Model results suggests that insufficient sewage treatment in the city of Szczecin is the major source of faecal pollution, even for beaches 20km downstream. E. coli mortality rate and emission intensity are key parameters for concentration levels downstream. Wind and river discharge play a modifying role. Prevailing southwestern wind conditions cause E. coli transport along the eastern coast and favour high concentration levels at the beaches. Our simulations indicate that beach closings in 2006 would not have been necessary according to the new EU-Bathing Water Quality Directive (2006/7/EC). The implementation of the new directive will, very likely, reduce the number of beach closings, but not the risk for summer tourists. Model results suggest, that a full sewage treatment in Szczecin would allow the establishment of new beaches closer to the city (north of Dabie lake).


Correlation between HPV-negative cervical lesions and cervical microenvironment.
To investigate the correlation between high-risk human papillomavirus (HR HPV)-negative cervical lesions and cervical microenvironment in Inner Mongolia, China, and to find the pathogenic factors of HR HPV-negative cervical lesions. 74 cases of HR HPV-negative healthy women and 80 cases of patients with cervical lesions (28 cases of LSIL, 49 cases of HSIL and 3 cases of CSCC) were selected as the study group; 26 cases of HPV-positive women and 352 cases of patients with cervical lesions (108 cases of LSIL, 214 cases of HSIL and 30 cases of CSCC) were control group. Questionnaires were collected from the study group and the control group and specimens were collected. Gram staining, hematoxylin and eosin staining microscopy, and substrate colorimetry method were used to detect vaginal micro-ecological indicators; ELISA was used to detect the concentration of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid. Genetic testing was used to detect HPV, mycoplasma, and chlamydia infection. The changes of vaginal micro-ecology evaluation index and local immune factor concentration in healthy women and cervical lesions of all grades in the study group and the control group were compared. Patients with cervical lesions, compared with healthy women, had a decrease in dominant lactobacilli and dysbacteriosis (P < 0.05), and this trend became more apparent as the disease progressed. The diversity and concentration of the flora in the HPV-negative group increased, the abnormal composition ratio decreased, and the HPV-positive group showed the opposite trend. As the lesion progressed, H2O2 decreased first and then increased, and the overall trend of SNa, LE, GUS, and GADP increased. The infection rate of trichomoniasis, BV and chlamydia increased and infection rate of Candida decreased. Also, compared with healthy women, patients with cervical lesions showed changes in immune factor concentration (P < 0.05). As the lesion progressed, IL-2 decreased, IL-10 increased, and IL-2/IL-10 decreased. However, IL-2 expression in HPV-negative group was higher than HSIL. SIgA was significantly lower in patients with cervical lesions than in healthy women. IgG had an upward trend in the HPV positive group. This study showed that vaginal micro-ecological imbalance and weakening of local cervical immune function are important reasons for the development of cervical lesions. It is expected to inhibit the development of cervical lesions by regulating the balance of vaginal micro-ecology and enhancing local immune function. By detecting Lactobacillus vaginalis, pre-enzyme, IL-2, IL-10, SIgA, it can guide the further diversion of HPV-positive women and predict the development direction of cervical lesions after HPV infection.


Toward explainable heat load patterns prediction for district heating.
Heat networks play a vital role in the energy sector by offering thermal energy to residents in certain countries. Effective management and optimization of heat networks require a deep understanding of users' heat usage patterns. Irregular patterns, such as peak usage periods, can exceed the design capacities of the system. However, previous work has mostly neglected the analysis of heat usage profiles or performed on a small scale. To close the gap, this study proposes a data-driven approach to analyze and predict heat load in a district heating network. The study uses data from over eight heating seasons of a cogeneration DH plant in Cheongju, Korea, to build analysis and forecast models using supervised machine learning (ML) algorithms, including support vector regression (SVR), boosting algorithms, and multilayer perceptron (MLP). The models take weather data, holiday information, and historical hourly heat load as input variables. The performance of these algorithms is compared using different training sample sizes of the dataset. The results show that boosting algorithms, particularly XGBoost, are more suitable ML algorithms with lower prediction errors than SVR and MLP. Finally, different explainable artificial intelligence approaches are applied to provide an in-depth interpretation of the trained model and the importance of input variables.


Fungal strain and crop cultivar affect growth of sweet pepper plants after root inoculation with entomopathogenic fungi.
As endophytes, entomopathogenic fungi can protect plants against biotic and abiotic stresses and at the same time promote plant growth and plant health. To date, most studies have investigated whether Beauveria bassiana can enhance plant growth and plant health, while only little is known about other entomopathogenic fungi. In this study, we evaluated whether root inoculation of the entomopathogenic fungi Akanthomyces muscarius ARSEF 5128, B. bassiana ARSEF 3097 and Cordyceps fumosorosea ARSEF 3682 can promote plant growth of sweet pepper (Capsicum annuum L.), and whether effects are cultivar-dependent. Plant height, stem diameter, number of leaves, canopy area, and plant weight were assessed four weeks following inoculation in two independent experiments using two cultivars of sweet pepper (cv. 'IDS RZ F1' and cv. 'Maduro'). Results showed that the three entomopathogenic fungi were able to enhance plant growth, particularly canopy area and plant weight. Further, results showed that effects significantly depended on cultivar and fungal strain, with the strongest fungal effects obtained for cv. 'IDS RZ F1', especially when inoculated with C. fumosorosea. We conclude that inoculation of sweet pepper roots with entomopathogenic fungi can stimulate plant growth, but effects depend on fungal strain and crop cultivar.


Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration.
Although cardinal cortical interneuron identity is established upon cell-cycle exit, it remains unclear whether specific interneuron subtypes are pre-established, and if so, how their identity is maintained prior to circuit integration. We conditionally removed Sox6 (Sox6-cKO) in migrating somatostatin (Sst+) interneurons and assessed the effects on their mature identity. In adolescent mice, five of eight molecular Sst+ subtypes were nearly absent in the Sox6-cKO cortex without a reduction in cell number. Sox6-cKO cells displayed electrophysiological maturity and expressed genes enriched within the broad class of Sst+ interneurons. Furthermore, we could infer subtype identity prior to cortical integration (embryonic day 18.5), suggesting that the loss in subtype was due to disrupted subtype maintenance. Conversely, Sox6 removal at postnatal day 7 did not disrupt marker expression in the mature cortex. Therefore, Sox6 is necessary during migration for maintenance of Sst+ subtype identity, indicating that subtype maintenance requires active transcriptional programs.


The calcaneus in ankylosing spondylitis. A radiographic study of 43 patients.
A prospective study analysing the radiological findings of calcaneus bone in ankylosing spondylitis is presented. It includes 43 patients with a relatively low mean age (33.5 years). The morphology of their lesions correlated with disease duration. Abnormal radiological findings were observed in 63% of the patients and in 58% of the radiographs, but in only 3 of 20 normal subjects. Erosive lesions were more frequently found in early stages, whereas sclerotic and proliferative lesions were typical of advanced stages of the disease. Only one patient suffered relevant local pain. No clinico-radiological correlation could be established.


Multiple intracranial meningiomas: diagnosis, biological behavior and treatment.
Multiple intracranial meningiomas (MIM) are a rare pathology when not associated with neurofibromatosis. The prevalence rate of those tumors varied from 2.3 to 8.9% of all intracranial meningiomas. To present, analyze and discuss the cases of seven patients diagnosed with multiple intracranial meningiomas, describing their clinical and histological characteristics, as well as their biological behavior. The patients records, surgical descriptions, imaging studies and the histopathological exams were retrospectively reviewed. This is the largest series of MIM publisted in Brazil. This sample consists of five women and two men. The age varied from 42 to 84 (average 53.8). Twenty-two meningiomas were identified and varied from 1.5 to 192 cm(3), with an 62.8 cm(3) average volume. The number of procedures varied from 1 to 5 per patient. No surgical death occurred in this series. Despite the multiplicity of tumors, number of recurrences, the new tumors, repeated operations and re-operations, radiotherapy and a number of postoperative complications, the patients experienced a long survival in conjunction with a fairly good quality of life.


A Method of Transposon Insertion Sequencing in Comprehensively Identifying Vibrio vulnificus Genes Required for Growth in Human Serum.
One of the most powerful approaches to detect the loci that enable a pathogen to cause disease is the creation of a high-density transposon mutant library by transposon insertion sequencing (TIS) and the screening of the library using an adequate in vivo and/or ex vivo model of the disease. Here we describe the procedure for detection of the putative loci required for a septicemic pathogen to cause sepsis in humans by using TIS plus an ex vivo model of septicaemia: to grow the pathogen in fresh and inactivated human serum. We selected V. vulnificus because it is a highly invasive pathogen capable of spreading from an infection site to the bloodstream, causing sepsis and death in less than 24 h. To survive and proliferate in blood (or host serum), the pathogen requires mechanisms to overcome the innate immune defenses and metabolic limitations of this host niche. Initially, genes under-represented for insertions can be used to estimate the V. vulnificus essential gene set. Analysis of the relative abundance of insertion mutants in the library after exposure to serum would detect which genes are essential for the pathogen to overcome the diverse limitations imposed by serum.


A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages.
Critical events in the life cycle of malaria-causing parasites depend on cyclic guanosine monophosphate homeostasis by guanylyl cyclases (GCs) and phosphodiesterases, including merozoite egress or invasion of erythrocytes and gametocyte activation. These processes rely on a single GCα, but in the absence of known signaling receptors, how this pathway integrates distinct triggers is unknown. We show that temperature-dependent epistatic interactions between phosphodiesterases counterbalance GCα basal activity preventing gametocyte activation before mosquito blood feed. GCα interacts with two multipass membrane cofactors in schizonts and gametocytes: UGO (unique GC organizer) and SLF (signaling linking factor). While SLF regulates GCα basal activity, UGO is essential for GCα up-regulation in response to natural signals inducing merozoite egress and gametocyte activation. This work identifies a GC membrane receptor platform that senses signals triggering processes specific to an intracellular parasitic lifestyle, including host cell egress and invasion to ensure intraerythrocytic amplification and transmission to mosquitoes.


Interleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic.
No field method exists for identifying asymptomatic individuals in areas where Leishmania infantum is endemic. This work reports that, 24 h after stimulating whole blood with soluble Leishmania antigen (SLA), plasma interferon-γ (IFN-γ) and interleukin-2 (IL-2) become significantly elevated in samples from asymptomatic individuals (n=47) compared with those from negative controls (n=50), all of them recruited from a blood bank. When compared with the reference test SLA-lymphoproliferative assay, IL-2 appears as a new, 100% sensitive and specific marker for asymptomatic individuals with a positive cellular response (compared with 100% and 84.78%, respectively, for IFN-γ). Further studies in other transmission areas and in other cohorts of exposed people need to be performed to confirm these results. Once validated, IFN-γ and IL-2 levels in SLA-stimulated whole blood could be reliably used in the field to estimate the prevalence of those asymptomatic individuals with Leishmania-specific cellular immune responses.


The Bactrocera dorsalis caspase-1 gene is expressed throughout development and required for female fertility.
The oriental fruit fly Bactrocera dorsalis is one of the most destructive pests of fruits and vegetables. The sterile insect technique (SIT) is an effective and environmentally friendly approach to the control of tephritid fruit flies. The pro-apoptotic gene head involution defective (hid) has been used as an effective lethal effector in SIT. It initiates an interaction cascade including activation of caspase-like proteases. However, the biological role of caspase activity in tephritid fruit flies has yet to be explored. In this study, the B. dorsalis caspase-1 gene (Bdcp-1) was cloned and characterized. Sequence comparison showed that Bdcp-1 protein shared highly homology with Drosophila effector caspases Drice and Dcp-1. It is predicted to contain a short pro-domain because two proteolytic cleavage sites (Asp16 and Asp223 ) are present. Expression patterns indicated that Bdcp-1 is highly transcribed in embryos and expression was upregulated during metamorphosis and upon ultraviolet irradiation. RNA interference showed that Bdcp-1 is essential for ovarian development and female fertility. For example, knockdown of Bdcp-1 caused transcriptional downregulation of expression of the yolk protein-1 gene (Bdyp-1) and delayed ovarian development. The percentage of spawning females and female fecundity were significantly reduced. This study illustrates the function of the Bdcp-1 gene and provides an attractive method to develop a biological way to control the oriental fruit fly through the control of caspases. © 2020 Society of Chemical Industry.


Functional NifD-K fusion protein in Azotobacter vinelandii is a homodimeric complex equivalent to the native heterotetrameric MoFe protein.
The MoFe protein of the complex metalloenzyme nitrogenase folds as a heterotetramer containing two copies each of the homologous alpha and beta subunits, encoded by the nifD and the nifK genes respectively. Recently, the functional expression of a fusion NifD-K protein of nitrogenase was demonstrated in Azotobacter vinelandii, strongly implying that the MoFe protein is flexible as it could accommodate major structural changes, yet remain functional [M.H. Suh, L. Pulakat, N. Gavini, J. Biol. Chem. 278 (2003) 5353-5360]. This finding led us to further explore the type of interaction between the fused MoFe protein units. We aimed to determine whether an interaction exists between the two fusion MoFe proteins to form a homodimer that is equivalent to native heterotetrameric MoFe protein. Using the Bacteriomatch Two-Hybrid System, translationally fused constructs of NifD-K (fusion) with the full-length lambdaCI of the pBT bait vector and also NifD-K (fusion) with the N-terminal alpha-RNAP of the pTRG target vector were made. To compare the extent of interaction between the fused NifD-K proteins to that of the beta-beta interactions in the native MoFe protein, we proceeded to generate translationally fused constructs of NifK with the alpha-RNAP of the pTRG vector and lambdaCI protein of the pBT vector. The strength of the interaction between the proteins in study was determined by measuring the beta-galactosidase activity and extent of ampicillin resistance of the colonies expressing these proteins. This analysis demonstrated that direct protein-protein interaction exists between NifD-K fusion proteins, suggesting that they exist as homodimers. As the interaction takes place at the beta-interfaces of the NifD-K fusion proteins, we propose that these homodimers of NifD-K fusion protein may function in a similar manner as that of the heterotetrameric native MoFe protein. The observation that the extent of protein-protein interaction between the beta-subunits of the native MoFe protein in BacterioMatch Two-Hybrid System is comparable to the extent of protein-protein interaction observed between the NifD-K fusion proteins in the same system further supports this idea.


Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes.
To evaluate the relationship between common genetic variation in genes involved in the biosynthesis and signaling of estrogen and progesterone and endometriosis risk. Genetic polymorphism analysis. Population-based case-control study conducted in Group Health Cooperative enrollees in western Washington. Women with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001 (n = 256) and age- and reference year-matched female control subjects without a history of endometriosis (n = 567). None. We evaluated the relationship between common genetic variation and endometriosis risk, using gene-based tests and single-variant analysis of genetic polymorphisms in ESR1, ESR2, PGR, CYP17A1, CYP19A1, HSD17B1, HSD17B2, CYP1A1, CYP1A2, COMT, and GSTM1. The most consistent gene-based association with endometriosis risk was for CYP19A1. We did not find evidence for consistent significant associations between previously reported candidate SNPs in sex hormone-related genes and endometriosis risk. In summary, we report increased endometriosis risk with CYP19A1 gene-based tests; replication of the association between endometriosis and this gene or gene region is necessary in a larger study population.


Retinotopic mapping in the human visual cortex using vascular space occupancy-dependent functional magnetic resonance imaging.
Recently, we introduced a new methodology, vascular space occupancy functional magnetic resonance imaging, which detects brain activation on the basis of blood volume changes in parenchymal microvasculature and may provide higher spatial specificity than the blood oxygenation level-dependent method. To study whether this technique can be used for advanced brain mapping applications, we performed retinotopic mapping using alternating horizontal and vertical wedges that stimulate different portions of the visual field. The results using vascular space occupancy functional magnetic resonance imaging showed clear boundaries for V1/V2/VP/V4v in the ventral areas and V1/V2/V3/V3A in the dorsal areas, similar to the maps obtained using blood oxygenation level-dependent functional magnetic resonance imaging. Vascular space occupancy functional magnetic resonance imaging is a useful addition to the other neuroimaging techniques. Disadvantages of vascular space occupancy functional magnetic resonance imaging include lower contrast-to-noise ratio (about 1/3 of that of blood oxygenation level-dependent method) and limited volume coverage (nine slices for TR=3 s).


EFFICACY OF ESTRADIOL IN PERIMENOPAUSAL DEPRESSION: SO MUCH PROMISE AND SO FEW ANSWERS.
Controversy regarding the antidepressant efficacy of hormone replacement therapy (HRT) stems almost from its inception and reflects the same methodological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression. Methodologic differences of note (other than study design) include menopausal state (perimenopause vs. postmenopause), determination of state (earlier studies used age as a proxy measure), baseline symptomatology (asymptomatic vs. depressive symptoms vs. syndromic depression), route of hormone administration (transdermal vs. oral), and symptom or syndrome measure. Zweifel and O'Brien's 1997 meta-analysis included 26 studies of the effects of menopausal HRT on depressed mood and revealed an overall effect size of 0.68. This moderate to large effect size, showing lower ratings of depressed mood in treated patients compared with controls, implicated HRT as a potential treatment of or prophylactic for depression in menopausal women. Since this publication, multiple studies have aimed to discern the relationship between HRT and menopausal mood. The purpose of this systematic review is to examine the findings and quality of the evidence amassed since Zweifel and O'Brien's meta-analysis. Of the 24 studies meeting criteria for review, only five RCTs examined depressed subjects, and only two of the study samples were solely perimenopausal. One can generalize from the studies reviewed here only with great caution, but there is little evidence to support the use of estradiol to improve mood in nondepressed patients (not surprisingly) and some evidence to support the antidepressant efficacy of estradiol in perimenopausal but not postmenopausal women.


A systematic review and meta-analysis of thoracoscopic versus thoracotomy sleeve lobectomy.
Operative safety and oncologic adequacy of thoracoscopic sleeve lobectomy remain controversial. As such, the purpose of this meta-analysis was to evaluate evidence comparing thoracoscopy and thoracotomy in sleeve lobectomy for centrally located non-small cell lung cancer (NSCLC). Electronic searches of PubMed and Web of Science databases were undertaken from inception to March 2020. Comparative studies about thoracoscopic and thoracotomy sleeve lobectomy, with evaluation for perioperative outcomes and oncological results were identified. The following outcomes were measured in this meta-analysis: operating time, blood loss, numbers of lymph node, postoperative hospital stay, chest drainage time, postoperative complication rate, mortality, overall survival (OS). The standardized difference (SMD), relative risk (RR) and hazard ratio (HR) with 95% confidence intervals (CI) were pooled using Stata software. Six studies generating 281 thoracoscopy and 369 thoracotomy cases were finally included. There was no significant difference in intraoperative blood loss, number of resected lymph nodes, chest drainage time, postoperative complication rate and mortality between two groups. However, thoracoscopic sleeve lobectomy was associated with longer operation time (SMD 0.59, 95% CI: 0.14 to 1.03, P=0.010). And shorter postoperative hospital stays (SMD -0.24, 95% CI: -0.51 to 0.03, P=0.078) were observed in the thoracoscopy group with marginal significance. Furthermore, sleeve lobectomy via thoracoscopy could achieve comparable OS compared to that via thoracotomy (HR 0.69, 95% CI: 0.38 to 1.00; P<0.001). In addition, there were no evident publication bias in all observational outcomes. Current evidence suggests that thoracoscopic sleeve lobectomy is a safe and efficient surgical procedure for centrally located NSCLC, with comparable perioperative outcomes and equivalent oncological results compared to thoracotomy sleeve lobectomy.


Chenopodium quinoa Willd. (quinoa) grains: A good source of phenolic compounds.
The ingestion of bioactive compounds has revealed health benefits, namely in the prevention and/or treatment of several diseases. This work aims to characterize the phenolic profile of three colour varieties of Chenopodium quinoa Willd. grains (black, red and white), and also evaluate their cytotoxic and antimicrobial activity. All varieties revealed the presence of phenolic compounds, namely, quercetin and kaempferol derivatives. In this study, quinoa grains did not reveal any anti-proliferative capacity in tumour cell lines, and, as expected, they were devoid of any toxicity. All of the analysed extracts possessed antibacterial and antifungal activities (inhibitory and bactericidal/fungicidal) against the microbial strains considered, exhibiting promising values of minimum bactericidal concentrations (mean MBC 0.153-0.916 mg/mL) and minimum fungicidal concentrations (mean MFC 0.211-0.884 mg/mL). Quinoa varieties represent a good source of bioactive compounds, interfering beneficially in the organism, specifically as antimicrobial agents. Thus, these extracts could be used in the development of bioactive ingredients.