Does certification status of oncology nurses make a difference in patient outcomes?
To test hypotheses that patients cared for by Oncology Certified Nurses (OCNs(r)) have superior outcomes compared to those cared for by noncertified nurses. Descriptive ex post facto. A homecare agency in the midwestern United States. 20 nurses (7 certified and 13 noncertified) and charts for 181 of their patients. Retrospective chart review. Symptom management (i.e., pain and fatigue), adverse events (e.g., infection and decubitus ulcers), and episodic care utilization (e.g., visits to care facilities, admissions to care facilities, unscheduled home visits). Contrary to hypotheses, the two groups did not differ with respect to assessment of pain at admission, number of pain assessments subsequent to admission, assessment of fatigue at admission, number of unplanned visits to care facilities, admissions to care facilities, and number of unscheduled home visits. As hypothesized, the OCNs(r) documented a higher number of postadmission fatigue assessments (p less than 0.05). Contrary to hypotheses, patients of OCNs(r) had a greater number of infections and fewer documented instances of patient teaching regarding infection. Little support was found for the hypothesis that nursing care by OCNs(r) results in superior patient outcomes in comparison to care by noncertified nurses. Further research is needed to examine the dimensions of clinical practice that may demonstrate the benefits of care by OCNs(r).


Synthesis, structure, and cytostatic properties of new olivacine derivatives.
Starting from 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine and 6-methylpicolinic acid, 9-methoxy-5-methyl-1-(6-methylpyridin-2-yl)-6H-pyrido[4,3-b]carbazole 10 and its 6-alkylderivatives 12-17 were obtained. The newly obtained compounds showed significant cytostatic activity against cultured L1210 cells and high cytotoxicity towards various human tumor cell lines.


Kinematic alignment fails to achieve balancing in 50% of varus knees and resects more bone compared to functional alignment.
Evidence is emerging that tibio-femoral compartmental balancing is related to clinical outcomes after total knee arthroplasty (TKA). The purpose of this study was to assess if kinematic alignment (KA) delivered a balanced knee in flexion and extension after TKA on varus deformity, compared to functional alignment (FA). This single-centre retrospective cohort study assessed 110 consecutive TKAs performed with an image-based robotic system for pre-operative varus deformity. The ligament balancing in the medial and lateral femorotibial compartments was assessed intra-operatively with a robotic system to evaluate if a KA plan would deliver a balanced knee. Balance was considered achieved if tibio-femoral compartments (medial/lateral) were equal to or less than 1.5 mm, or if the estimated final gap position more than 2 mm from the global implant thickness (17 mm). Implant positioning was modified within limits previously defined for a FA philosophy to achieve balancing. Resection thickness and implant positioning were compared with the KA plan and after the FA adjustments; and also, between the patients with a final balanced knee in extension and at 90° of flexion. A total of 102 patients were eligible for final analysis. Mean age was 67.3 ± 8.2 years, average BMI was 29.1 ± 5.2 kg/m2, mean pre-operative coronal alignment was 174.0° ± 3.3° and sagittal alignment 3.4° ± 5.9°. Mean post-operative coronal alignment was 177.7° ± 1.0° and sagittal alignment 0.8° ± 1.9°. A KA plan delivered medial-lateral tibio-femoral compartment balancing in 67 cases (65.7%) for the extension gap and in 50 cases (49.1%) for the flexion gap. All measured bone resection depths were significantly less for FA compared to KA. To achieve balancing targets, final femoral component position was more externally rotated relative to the posterior condylar axis, (0.5° with KA compared to 1.7° with FA (p < 0.0001), and the tibia in more varus (3.0° KA vs. 3.5° FA p = 0.0024). Only one soft tissue release was required. KA failed to deliver a balanced TKA in more than 50% of cases, especially regarding the flexion gap. Consideration of soft tissue laxity led to significantly less bone resection, with more externally rotated femoral component and more varus tibial component.


Induction of P-glycoprotein, glutathione-S-transferase and cytochrome P450 in rat liver by atrazine.
We studied the effects of intraperitoneally administered atrazine on two hepatic neoplastic markers, P-glycoprotein (P-gp), and glutathione-S-transferase (GST), and several phase I drug-metabolizing enzyme cytochrome P450 (CYP) subfamilies in hepatic microsomes and cytosol of Fischer rats. The P-gp content was increased after 24 h of atrazine administration at 50 mg/kg, and maximum P-gp induction was observed at 300 mg/kg for 3 days. GST-P was induced at a lower dose than P-gp, from 10 mg/kg, but no other form of GST, such as GST1A1, was induced by the same dose. Among the CYP families, CYP1A2 was highly and CYP2B was slightly induced by atrazine while the CYP3A content remained unchanged. The liver plasma membrane marker alkaline phosphatase (AP) was not induced by the same doses. The inductions of P-gp, GST-P and CYP1A2 observed may explain some of the reported tumor-promoting properties and toxicity of atrazine in vivo.


Missing colorectal liver metastases: the surgical challenge.
New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon's point of view. A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.


Soil chemical properties rather than the abundance of active and potentially active microorganisms control soil enzyme kinetics.
Soil enzymes secreted by microorganisms play a critical role in nutrient cycling, soil structure maintenance, and crop production. However, understanding of the linkage between soil enzyme kinetics and microbial metabolism and active microbial communities is remarkably limited. In this study, we measured the kinetics of three hydrolase enzymes, active microbial abundance and substrate-induced respiration (SIR) from 21 farmlands differing in their fertilities collected from the Loess Plateau, China. Results showed the high fertility soils had higher total organic carbon (TOC) and nutrient contents, potential microbial activity, the colony-forming units (CFU) of actinomycetes, and values of enzyme Vmax and Km than those of low fertility soils. We also observed that the CFU of fungi and other bacterial groups did not change with soil fertility status. Soil chemical properties explained 74.0% of the variance in Vmax and 28.3% of the variance in Km, respectively. Whereas, the abundance of main microbial groups and fungi/bacteria ratio only explained 10.2% and 7% of the variance of Vmax and Km, respectively. The interactive effect of soil properties and microbial community could explain 20.2% of the variance in Km. Our results suggest that the substrate availability would mainly drive enzyme kinetics compared to the abundance of active/potentially active microbes in the farmland soils.


Allene oxide cyclase: a new enzyme in plant lipid metabolism.
The mechanism of the biosynthesis of 12-oxo-10,15(Z)-phytodienoic acid (12-oxo-PDA) from 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid in preparations of corn (Zea mays L.) was studied. In the initial reaction the hydroperoxide was converted into an unstable allene oxide, 12,13(S)-epoxy-9(Z),11,15(Z)-octadecatrienoic acid, by action of a particle-bound hydroperoxide dehydrase. A new enzyme, allene oxide cyclase, catalyzed subsequent cyclization of allene oxide into 9(S),13(S)-12-oxo-PDA. In addition, because of its chemical instability, the allene oxide underwent competing nonenzymatic reactions such as hydrolysis into alpha- and gamma-ketol derivatives as well as spontaneous cyclization into racemic 12-oxo-PDA. (+/-)-cis-12,13-Epoxy-9(Z)-octadecenoic acid and (+/-)-cis-12,13-epoxy-9(Z),15(Z)-octadecadienoic acid, in which the epoxy group was located in the same position as in the allene oxide substrate, served as potent inhibitors of corn allene oxide cyclase. On the other hand, the isomeric (+/-)-cis-9,10-epoxy-12(Z)-octadecenoic acid had little inhibitory effect. Allene oxide cyclase was present in the soluble fraction of corn homogenate and had a molecular weight of about 45,000 as judged by gel filtration. The enzyme activity was detected in several plant tissues, the highest levels being observed in potato tubers and in leaves of spinach and white cabbage.


Salinity tolerance of the chlorophyll b-synthesizing cyanobacterium Prochlorothrix hollandica strain SAG 10.89.
Ecophysiological investigations on the salinity acclimation of the cyanobacterium Prochlorothrix hollandica SAG 10.89 led to significantly revised salinity tolerance limits. Besides potential effects of cultivation techniques, clear ion composition effects mainly explain formerly described hypersensitivity to NaCl-mediated salinity and lack of osmolyte detection. An extraordinarily broad plasticity of cellular chlorophyll a/b ratios occurred with variations of NaCl-induced salinity. Photosynthesis characteristics, pigment regulation, respiration, and biomass yield in growth medium with field-like ion composition indicated generally reduced acclimation pressure. A simultaneously significant increase in osmolyte (sucrose) accumulation indicated more efficient osmotic acclimation. Minor growth inhibition up to salinities of 10 practical salinity units enlarged the potential habitat of P. hollandica but at the most to about 300,000 km2 in the Baltic Sea. This supports probable observations of Prochlorothrix sp. in phytoplankton assemblages of open waters in Baltic Sea-monitoring studies. Brackish habitats differ from so far known habitats of Prochlorothrix spp. in turbidity, productivity, and plankton composition. Adjusted physiological features dispel fundamental doubts on the establishment of filamentous prochlorophytes in brackish waters.


Angiography of atrioventricular canal defects.
The axial angiograms of 20 patients with an atrioventricular (A-V) canal defect were carefully examined and compared with anatomic observations made at operation. A common A-V valve was present in 15 patients and two separate valves in 5. The atrial septal defect, the anatomy of the ventricular septum and the morphology and functional status of the A-V valves were well demonstrated. There ws consistent angiographic deformation of the normally straight contour extending from the noncoronary aortic cusp to the crux cordis observed in the four chamber and elongated right anterior oblique projections of the left ventricular angiogram of each patient. This deformity is caused by the deficiency or absence of the A-V septum and is the best angiographic sign of the malformation. The differentiation of two separate valves from a common A-V valve was uniformly made. When a common A-V valve was present, three of the five leaflets were usually identified but distinction of the free floating from the tethered anterior leaflet was not always possible. It is concluded that axial techniques provide more complete angiographic definition of the anatomic abnormalities of A-V canal defects than are demonstrated from frontal and lateral views.


The development of aboriginal brain injury coordinator positions: a culturally secure rehabilitation service initiative as part of a clinical trial.
Brain injury, resulting from stroke and traumatic brain injury, is a common occurrence in Australia, with Aboriginal people affected at a significant rate and impact felt by individuals, families and communities. Access to brain injury rehabilitation services for Aboriginal people is reported to be often limited, with very little support outside the hospital environment. Our research involving Aboriginal brain injury survivors and their families to date has revealed that people often manage 'on their own' following such events. Following recommendations from survivors and their families, the Healing Right Way clinical trial, currently underway in Western Australia, has created the role of Aboriginal Brain Injury Coordinator (ABIC) to assist in navigating information and services, particularly after discharge from hospital. Eight positions for this role have been instigated across metropolitan and rural regions in the state. Healing Right Way's aim is to enhance rehabilitation services and improve quality of life for Aboriginal Australians after brain injury. The ABIC's role is to provide education, support, liaison and advocacy services to participants and their families over a six-month period, commencing soon after the participant's stroke or injury has occurred. This paper outlines the development of this role, the partnerships involved, experiences to date and identifies some facilitators and barriers encountered that may impact the role's ongoing sustainability. Details of components of the planned full Process Evaluation of Healing Right Way related to the ABIC role and the partnerships surrounding it are also provided. In combination with the trial's ultimate results, this detail will assist in future service planning and provide a model of culturally secure care for stroke and brain injury services that can also inform other sub-acute and primary care models.


Cost and use of conservative management of lumbar disc herniation before surgical discectomy.
Lumbar discectomy is one of the most common spine surgical procedures. With the exception of true emergencies (eg, cauda equina syndrome), lumbar discectomy is usually performed as an elective procedure after a prudent trial of nonoperative treatment. Although several studies have compared costs of definitive operative or nonoperative management of lumbar disc herniation, no information has been published regarding the cost of conservative care in patients who ultimately underwent surgical discectomy. The purpose of this study was to determine the financial costs (and relative distribution of those costs) associated with the nonoperative management of lumbar disc herniation in patients who ultimately failed conservative care and elected to undergo surgical discectomy. This is a retrospective database review. The sample comprises patients within the database who underwent lumbar discectomy. The outcome measures were frequency of associated procedures and the costs of those procedures. A search was conducted using a commercially available online database of insurance records of orthopedic patients to identify all patients within the database undergoing lumbar discectomy between 2004 and 2006. Patients were identified by American Medical Association Current Procedural Terminology code. The associated charge codes for the 90-day period before the surgery were reviewed and categorized as outpatient physician visits, imaging studies, physical therapy, injection, chiropractic manipulation, medication charges, preoperative studies, or miscellaneous charges. The frequency of each code and the percentage of patients for whom that code was submitted to the insurance companies were noted, as were the associated charges. In total, 30,709 patients in the database met eligibility criteria. A total of $105,799,925 was charged during the 90 days preoperatively, an average of $3,445 per patient. Average charge for discectomy procedure was $7,841. Charges for injection procedures totaled $16,211,246 or 32% of total charges, diagnostic imaging $15,648,769 (31%), outpatient visits $6,552,135 (13%), physical therapy visits $5,723,644 (11%), chiropractic manipulation $1,177,406 (2%), preoperative studies $426,976 (0.8%), medications $263,039 (0.5%), and miscellaneous charges $1,177,371 (2%). Charges for preoperative care of patients with lumbar disc herniation are substantial and are split almost evenly between diagnostic charges (outpatient visits, imaging, laboratory studies, and miscellaneous) and therapeutic charges (injections, physical therapy, chiropractic manipulation, and medications). Although a large number of patients will ultimately require surgical intervention, given that many patients will improve with nonoperative therapy, a trial of conservative management is appropriate. Additional studies to identify patients who may ultimately fail nonoperative treatment and would benefit from early discectomy would be beneficial.


Expression profile of circular RNAs in oral lichen planus.
This study sought to identify the circular RNAs (circRNAs) differentially expressed in oral lichen planus (OLP) to investigate the possible role of circRNAs in this disease's pathogenesis. Six OLP and six normal oral mucosal tissues were used for circRNA detection and sequencing. 10 selected circRNAs were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted micro (mi)RNAs and messenger (m)RNAs of circRNAs, and competing endogenous (ce)RNA networks were mapped. One hundred and thirty-five circRNAs were identified differentially expressed in OLP tissues compared to normal control tissues, including 83 upregulated circRNAs, and 52 down-regulated circRNAs. RT-qPCR confirmed that 10 circRNAs were all abnormally expressed in OLP. The GO functional analysis and KEGG pathway analysis showed that differentially expressed circRNAs were involved in 535 GO functional items and 78 signal pathways. A ceRNA network analysis showed that circRNAs might interact with a variety of miRNAs. This study mapped the expression profile of abnormally expressed circRNAs in OLP tissues for the first time and showed that circRNAs appear to play an important role in the pathogenesis of OLP.


The possible relationship between Laurence-Moon-Biedl-Bardet syndrome and a schizophrenic-like psychosis.
The Laurence-Moon-Biedl-Bardet syndrome is probably transmitted hereditarily and recognizable mainly by: a) retinitis pigmentosa; b) hypogonadism and obesity; and c) orthopedic anomalities such as polidactylia, syndactylia, and acroecephalosyndactylia with oligophrenia. Sometimes, other disturbance, mainly dermatological (alopecia), neurological, urological, endocrinological, and, rarely, congenital heart defects, may coexist.


The early response of articular cartilage to ACL transection in a canine model.
Ten outbred dogs underwent unilateral transection of the anterior cruciate ligament of the knee (stifle) joint with sacrifice from 6 to 27 weeks post-operatively. On the operated side were found mild degenerative changes histologically and evidence of increased proteoglycan synthesis with no net loss of uronic acid. Water content was increased in the medial femoral condyle. Contralateral knees showed evidence of increased proteoglycan synthesis and uronic acid content without histologic cartilage lesions.


A simple method for the cultivation of the "unculturable" asterinaceous fungi (Asterinales/Dothideomycetes).
Although asterinaceous fungi have been studied for many years, all previous attempts to isolate, cultivate, and propagate these fungi in vitro have failed. This paper provides the first reports of in vitro isolation of representative strains of species belonging to five fungi from different genera belonging to Asterinales. To confirm if the sequences of DNA obtained from the mycelia are the same obtained in the direct extraction, a phylogenetic analysis of nuc LSU rDNA was performed. This paper reports for the first time the success of in vitro culturing of asterinaceous fungi using the ascospores ejection technique, opening perspectives of studies of genetics, physiology, among other aspects of the biology for this very understudied group of fungi.


Coating liposomes with yttrium basic carbonate: making hybrid nanocapsules.
Novel yttrium basic carbonate hybrid nanocapsules have been prepared using liposome templates. The method resorts to urea hydrolysis to increase the precipitation driving force of Y(OH)CO(3)xH(2)O homogeneously. The head groups at the outer vesicle layer act as adsorption sites for hydrolyzing Y(III) ions, thus assisting heterogeneous nucleation. The criteria behind the synthesis, as well as the potentialities of the advanced procedure, are stressed.


Increase water solubility of Centella asiatica extract by indigenous bioenhancers could improve oral bioavailability and disposition kinetics of triterpenoid glycosides in beagle dogs.
A newly standardised extract of Centella asiatica (Centell-S) with better water solubility than the previous standardised extract of C. asiatica (ECa 233) was developed, and pharmacokinetic profiles of bioactive triterpenoids were investigated in beagle dogs. The test substances were administered via intravenous or oral administration with single and multiple doses for 7 days. The concentrations of major bioactive triterpenoids, including madecassoside, asiaticoside, madecassic acid, and asiatic acid, in biological samples were measured by liquid chromatography-tandem mass spectrometry. The dogs in this study showed good tolerability to all test substances, based on the physical appearance and blood chemistry 24 h after dosing. The major bioactive triterpenoids found in systemic blood circulation were madecassoside, asiaticoside, and asiatic acid; the concentration of these components ranged from 1 to 10,000 µg/L after intravenous administration of 1.0 mg/kg Centell-S. Oral administration of 10 and 20 mg/kg Centell-S generated approximately twofold higher plasma levels of both madecassoside and asiaticoside compared with equivalent doses of ECa 233. In addition, there was an accumulation of triterpenoid glycosides after multiple oral administrations of Centell-S for 7 days, while triterpenic acids showed little tendency for accumulation. Beagles had good tolerability to both standardised extracts of C. asiatica, and showed a similar pattern of bioactive triterpenoids to humans. Centell-S increased oral bioavailability of major triterpenoid glycosides and can be further developed into a phytopharmaceutical product.


Circadian gene expression is suppressed during sevoflurane anesthesia and the suppression persists after awakening.
General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. We previously showed that inhalation anesthesia affects the expression of 1.5% of 10,000 genes, which included so-called circadian genes. In the current study, we confirmed that inhalation of sevoflurane alters circadian gene expression, and investigated whether this alteration persists after awakening from anesthesia. Rats were anesthetized with 4.0% sevoflurane for 0 h, 2 h and 6 h (n=9 each group), before being sacrificed. Rats were also anesthetized for 6 h and allowed to recover after anesthesia, then sacrificed 2 h, 6 h and 24 h after awakening (n=9 each group). Anesthesia was started for each group so that all rats would be sacrificed at 13:00, and gene expression in the whole brain was examined using real-time RT-PCR. Expression of the genes encoding Per2, Dbp, Arc, Egr1, Krox20 and NGFI-B was suppressed during inhalation of sevoflurane for 2 h and 6 h. Although the suppression tended to be alleviated after awakening from anesthesia, the expression levels after a recovery period of 24 h remained significantly lower than the control levels of these genes, except for Krox20. We demonstrated that circadian gene expression is suppressed in whole brain during sevoflurane anesthesia, and the suppression continues for at least 24 h after termination of sevoflurane treatment. This suggests that sevoflurane anesthesia may have effects at the molecular level and that these effects are long lasting.


Accumulation and distribution of metal(loid)s in the halophytic saltmarsh shrub, Austral seablite, Suaeda australis in New South Wales, Australia.
We examined the patterns of uptake and partitioning of metal(loid)s in Suaeda australis from three highly urbanised estuaries (Sydney Olympic Park, Hunter Wetlands and Lake Macquarie) in NSW, Australia. Of these, Sydney Olympic Park was found to be the most contaminated estuary in terms of combined sediment metal(loid) load, followed by Hunter Wetlands and lowest in Lake Macquarie (via PERMANOVA). Uptake in roots was greater for the essential metals Cu and Zn along with the non-essential metal Cd and the metalloid Se (root BCFs >1) and lower for Pb and As (root BCFs <1). Substantial barriers for translocation from roots to stems were identified for all metal(loid)s (stem TFs; 0.07-0.68). Conversely, unrestricted flow from stems to leaves was observed for all metal(loid)s at unity or higher (leaf TFs ≥ 1). Strong linear relationships between sediment and root for Zn and Pb were observed, indicating roots as a useful bioindicator.


Heterogeneous phenotype of human melanoma cells with in vitro and in vivo features of tumor-initiating cells.
Melanospheres, the melanoma cells that grow as nonadherent colonies and that show in vitro self-renewing capacity and multipotency, were selected from melanoma specimens or from melanoma cell lines. Melanospheres were highly tumorigenic, and intradermal injections in severe combined immunodeficient (SCID) mice of as few as 100 cells generated tumors that maintained tumorigenic potential into subsequent recipients. Primary and serially transplanted xenografts recapitulated the phenotypic features of the original melanoma of the patient. Melanoma cells cultured in the presence of fetal calf serum (FCS) were also tumorigenic in SCID mice, although with lower efficiency; these xenografts showed a homogeneous phenotype for the expression of melanoma-associated markers, Melan-A/Mart-1, HMB45, and MITF, and contained cells with features of fully differentiated cells. Melanospheres were heterogeneous for the expression of stem cell markers and showed a significantly enhanced expression of the Nanog and Oct3/4 transcription factors when compared with adherent melanoma cells. No direct and unique correlation between any of the examined stem cell markers and in vivo tumorigenicity was found. Taken together, our data provide further evidence on the heterogeneous nature of human melanomas and show that melanospheres and their corresponding tumors, which are generated in vivo in immunocompromised mice, represent a model to investigate melanoma biology.


Light-dependent photoreceptor orientation in mouse retina.
Almost a century ago, Stiles and Crawford reported that the human eye is more sensitive to light entering through the pupil center than through its periphery (Stiles-Crawford effect). This psychophysical phenomenon, later found to correlate with photoreceptor orientation toward the pupil, was dynamically phototropic, adjustable within days to an eccentrically displaced pupil. For decades, this phototropism has been speculated to involve coordinated movements of the rectilinear photoreceptor outer and inner segments. We report here that, unexpectedly, the murine photoreceptor outer segment has a seemingly light-independent orientation, but the inner segment's orientation undergoes light-dependent movement, giving rise to nonrectilinear outer and inner segments in adult mice born and reared in darkness. Light during an early critical period (~P0 to P8), however, largely sets the correct photoreceptor orientation permanently afterward. Unexpectedly, abolishing rod and cone phototransductions did not mimic darkness in early life, suggesting photosignaling extrinsic to rods and cones is involved.


Trends and Factors Associated with Place of Death for Individuals with Dementia in the United States.
To assess trends and factors associated with place of death among individuals with Alzheimer's disease-related dementias (ADRD). Cross-sectional analysis. Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research, 2003-2017. Natural deaths occurring between 2003 and 2017 for which ADRD was determined to be the underlying cause. Place of death was categorized as hospital, home, nursing facility, hospice facility, and other. Aggregate data included age, race, Hispanic ethnicity, sex, urbanization, and census division. Individual-level predictors included age, race, Hispanic ethnicity, sex, marital status, and education. From 2003 to 2017, nursing facility and hospital deaths declined from 65.7% and 12.7% to 55.0% and 8.0% while home and hospice facility deaths increased from 13.6% and .2% to 21.9% and 6.2%, respectively. Odds of hospital and hospice facility deaths declined with age while odds of nursing facility deaths increased with age. Male sex was associated with higher odds of hospital or hospice facility death and lower odds of home or nursing facility death. Nonwhite race, Hispanic ethnicity, and being married were associated with increased odds of hospital or home death and reduced odds of nursing facility death. More education was associated with higher odds of home or in a hospice facility death and reduced odds of death in a nursing facility or hospital. Significant disparities in place of death by urban-rural status were also noted. As ADRD deaths at home increase, the need for caregiver support and home-based palliative care may become more critical. Further research should examine the care preferences and experiences of ADRD patients and caregivers, the financial impact of home death on families and insurers, and explore factors that may contribute to differences in actual and preferred place of death. J Am Geriatr Soc 68:250-255, 2020.


A case control study on immunity to two Epstein-Barr virus-associated antigens, and to herpes simplex virus and adenovirus in a population-based group of patients with Hodgkin's disease in Denmark, 1971-73.
One hundred and eighty-five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2-year period, were individually matched with healthy controls of the same age, sex, and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein-Barr viral capsid antierences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL-A antigens, stage of disease and histology did not alter this pattern, except that significant case-control differences in EB-VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB-VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB-VCA and EBV-EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients.


Chloroplast-to-chromoplast transition envisions provitamin A biofortification in green vegetables.
The carotenoids available in food are vital dietary micronutrients for human health. Plants synthesize and accumulate different carotenoids in plastids in a tissue-specific manner. The level of β-carotene (provitamin A) and other nutritionally important carotenoids is substantially low in the green tissues such as leaves compared to the fruits and roots. In photosynthetic tissues, chloroplasts can accumulate a moderate level of carotenoids, mainly to facilitate photosynthesis and environmental stress tolerance. However, chromoplasts from the storage tissues such as tomato fruit and carrot root can synthesize and accumulate carotenoids to a substantially higher level. A synthetic biology approach that utilizes a transient expression of bacterial phytoene synthase (crtB) gene in the photosynthetic leaves can induce the transition of chloroplasts into chromoplasts. The plastid-localized heterologous expression of crtB in leaves can induce the overaccumulation of phytoene, triggering the chloroplast-to-chromoplast transition; therefore, enhancing the biosynthesis and accumulation of carotenoids, including provitamin A. The transition of chloroplasts into chromoplasts, however, altered the photosynthetic thylakoids, consequently reducing the photosynthetic efficiency and plant growth. An efficient metabolic engineering strategy is desirable to enhance the production of targeted carotenoids in leaves without perturbing the photosynthetic efficiency and plant growth. Collectively, a synthetic biology strategy that triggers the transformation of chloroplasts into chromoplasts in photosynthetic tissues unfolds new avenues for carotenoid biofortification in the leafy food and vegetable crops, which can increase the dietary intake of carotenoids, therefore, combating the crisis of vitamin A deficiency.


Physicochemical characterization of cross-linked human serum albumin dimer and its synthetic heme hybrid as an oxygen carrier.
The recombinant human serum albumin (rHSA) dimer, which was cross-linked by a thiol group of Cys-34 with 1,6-bis(maleimido)hexane, has been physicochemically characterized. Reduction of the inert mixed-disulfide of Cys-34 beforehand improved the efficiency of the cross-linking reaction. The purified dimer showed a double mass and absorption coefficient, but unaltered molar ellipticity, isoelectric point (pI: 4.8) and denaturing temperature (65 degrees C). The concentration dependence of the colloid osmotic pressure (COP) demonstrated that the 8.5 g dL(-1) dimer solution has the same COP with the physiological 5 g dL(-1) rHSA. The antigenic epitopes of the albumin units are preserved after bridging the Cys-34, and the circulation lifetime of the 125I-labeled variant in rat was 18 h. A total of 16 molecules of the tetrakis[(1-methylcyclohexanamido)phenyl]porphinatoiron(II) derivative (FecycP) is incorporated into the hydrophobic cavities of the HSA dimer, giving an albumin-heme hybrid in dimeric form. It can reversibly bind and release O2 under physiological conditions (37 degrees C, pH 7.3) like hemoglobin or myoglobin. Magnetic circular dichroism (CD) revealed the formation of an O2-adduct complex and laser flash photolysis experiments showed the three-component kinetics of the O2-recombination reaction. The O2-binding affinity and the O2-association and -dissociation rate constants of this synthetic hemoprotein have also been evaluated.


Malignancy in uremia: dialysis versus transplantation.
The incidence of cancer was compared in 499 dialysis patients and 121 renal transplant recipients. De novo malignancy developed in 15 patients on chronic dialysis (3 per cent) and in 6 transplant recipients (4.9 per cent), a significant increase over the expected number in the age-matched general population. There was no difference in the incidence of cancer in uremic patients on dialysis or after transplantation. A total of 10 dialysis patients (67 per cent) and 1 transplant patient (16 per cent) died of cancer. Neoplasms in the dialysis patients were the common types of mesenchymal tumors, while superficial skin cancers were seen more frequently in the transplant recipients. The differences in tumor types accounted for the higher mortality rate from cancer in the dialysis patients and may reflect different patterns of immunosuppression in these 2 patient populations.


Rare Diseases of the Oral Cavity, Neck, and Pharynx.
Diseases occurring with an incidence of less than 1-10 cases per 10 000 individuals are considered as rare. Currently, between 5 000 and 8 000 rare or orphan diseases are known, every year about 250 rare diseases are newly described. Many of those pathologies concern the head and neck area. In many cases, a long time is required to diagnose an orphan disease. The lives of patients who are affected by those diseases are often determined by medical consultations and inpatient stays. Most orphan diseases are of genetic origin and cannot be cured despite medical progress. However, during the last years, the perception of and the knowledge about rare diseases has increased also due to the fact that publicly available databases have been created and self-help groups have been established which foster the autonomy of affected people. Only recently, innovative technical progress in the field of biogenetics allows individually characterizing the genetic origin of rare diseases in single patients. Based on this, it should be possible in the near future to elaborate tailored treatment concepts for patients suffering from rare diseases in the sense of translational and personalized medicine. This article deals with orphan diseases of the lip, oral cavity, pharynx, and cervical soft tissues depicting these developments. The readers will be provided with a compact overview about selected diseases of these anatomical regions. References to further information for medical staff and affected patients support deeper knowledge and lead to the current state of knowledge in this highly dynamic field.


Transplant center experience influences spontaneous survival and waitlist mortality in acute liver failure: An analysis of the UNOS database.
Transplant centers coordinate complex care in acute liver failure (ALF), for which liver transplant (LT) can be lifesaving. We studied associations between waitlist outcomes and center (1) ALF waitlist volume (low: <20; medium: 20-39; high: 40+ listings) and (2) total LT volume (<600, 600-1199, 1200+ LTs) in a retrospective cohort of 3248 adults with ALF listed for LT at 92 centers nationally from 2002 to 2019. Predicted outcome probabilities (LT, died/too sick, spontaneous survival [SS]) were obtained with multinomial regression, and observed-to-expected ratios were calculated. Median center outcome rates were 72.6% LT, 18.2% died/too sick, and 6.1% SS. SS was significantly higher with greater center ALF volume (median 0% for low-, 5.9% for medium-, and 8.6% for high-volume centers; P = .039), while waitlist mortality was highest at low-volume centers (median 21.4%, IQR: 16.1%-26.7%; P = .042). Significant heterogeneity in center performance was observed for waitlist mortality (observed-to-expected ratio range: 0-4.1) and particularly for SS (0-6.4), which persisted despite accounting for recipient case mix. This novel study demonstrates that increased center experience is associated with greater SS and reduced waitlist mortality for ALF. More-focused management pathways are needed to improve ALF outcomes at less-experienced centers and to identify opportunities for improvement at large.


Placentation in Marsupials.
It is sometimes implied that marsupials are "aplacental," on the presumption that the only mammals that have a placenta are the eponymous "placental" mammals. This misconception has persisted despite the interest in and descriptions of the marsupial placenta, even in Amoroso's definitive chapter. It was also said that marsupials had no maternal recognition of pregnancy and no placental hormone production. In addition, it was thought that genomic imprinting could not exist in marsupials because pregnancy was so short. We now know that none of these ideas have held true with extensive studies over the last four decades definitively showing that they are indeed mammals with a fully functional placenta, and with their own specializations.


Oxidative stress, spermatogenesis and fertility.
Reactive oxygen species production and glutathione depletion in mammalian male germ cells are physiological events that are requisite to the functional maturation and capacitation of spermatozoa. In relation to this oxidative stress, an oxidation of the bulk of protein sulfydryl groups takes place during the final phases of male germ cell maturation. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase catalyzes this reaction, and accounts for both the assembly of the mid-piece of spermatozoa and chromatin condensation. This process highlights the role of H2O2 and selenium in spermatogenesis and provides a mechanism for coupling a 'physiologically controlled' oxidative stress to a specialized phenotypic function.


[Prenatal diagnosis of exencephaly at 10 weeks gestation, confirmed at 13 weeks gestation].
First trimester diagnosis of the exencephaly anencephaly sequence has been reported since the introduction of transvaginal sonography, the earliest being described at 10 weeks 5 days gestation. We report the discovery of exencephaly at 10 weeks gestation. The diagnosis was confirmed by repeat ultrasonography at 13 weeks.


Resistance training alone or combined with leucine supplementation improves the serum lipid profile of diabetic rats, whereas leucine alone does not.
Diabetes mellitus is associated with dyslipidemia, which contributes to a higher risk of thrombosis, atherosclerosis and cardiovascular disease. This study evaluated the effects of leucine and resistance training on the serum lipid profile in rats with streptozotocin-induced diabetes for 8 weeks. Wistar rats with neonatal streptozotocin-induced diabetes were treated with leucine supplementation (5%) and/or resistance training (3 days per week) for 8 weeks, and divided in DL (diabetic and leucine), DT (diabetic and resistance training group) and DLT (diabetic, leucine and resistance training) groups. Others 2 groups of animals received isonitrogen AIN-93M diet that was defined as a control diet: group D (diabetic untreated) and group C (non-diabetic). The decrease in serum total cholesterol and increase in high-density lipoprotein cholesterol (HDL-C) was observed in the resistance training-induced diabetic rats when compared with diabetic rats. There was no change in serum lipid profile in leucine-supplemented diabetic rats and no synergistic effect of leucine and resistance training. The fasting glucose levels were reduced in all animals treated compared to D group. The diabetic trained rats demonstrate a protective effect of resistance training on the serum lipid profile.


Immunocytochemical demonstration of GABAergic synapses on identified rubrospinal neurons.
GABAergic synapses on rubrospinal neurons were demonstrated with immunocytochemistry combined with intracellular injection of horseradish peroxidase. Sections containing red nucleus neurons were processed for glutamic acid decarboxylase (GAD) immunohistochemistry. GAD-immunoreactive synaptic endings formed synaptic contacts with somata and dendrites of red nucleus neurons and identified rubrospinal neurons. Our observation provides further evidence that GABA acts as an inhibitory transmitter mediating cortically evoked inhibitory postsynaptic potentials in red nucleus neurons.


Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy.
While statins are used as first-line treatments for high-risk patients with hypercholesterolemia, statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment options include up-titration of statin dose, switching to a more potent statin, or combination therapy, e.g., with ezetimibe. The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease (CVD) and who had been previously treated with a statin. A systematic literature search was performed and evidence bases were established for populations of atorvastatin-, simvastatin-, and rosuvastatin-experienced patients using eligible randomized controlled trials (RCTs). Based on the available data, we constructed networks of evidence and conducted a Bayesian network meta-analysis (NMA) within each statin population. The primary outcome of interest was percent change from baseline in LDL-C. Changes in total cholesterol were explored as a secondary outcome. Across all patient populations, 35 RCTs were identified and included in the evidence base. Among patients on simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD) in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to doubling the starting dose of simvastatin. In the population of patients on atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of - 14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL-C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting rosuvastatin dose. Similar trends were observed for changes in total cholesterol. Given the available data, the addition of ezetimibe to ongoing simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose.


Anticoagulant therapy by continuous heparin-antithrombin III infusion in newborns with disseminated intravascular coagulation.
In ten newborns with severe alteration of the coagulation system due to DIC, AT III concentrate was infused continuously after prior activation with heparin. The rise in AT III activity showed a great variability among the infants and for one child during the course of the therapy. The mean rise of AT III activity by 40 U/kg per day heparin was 8.7%. If AT III concentrate (40 U/kg per day) was activated with 200 U/kg per day heparin, excessive anticoagulation effect was only observed in one child. In four children who had failed to respond to prior heparin therapy, improvement of the coagulation status was achieved within 2 days.


Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position.
In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different prion-infected murine cell models. They also exhibited greater binding affinities for a human prion protein fragment (hPrP(121-231)) than quinacrine, and had permeabilities on the PAMPA-BBB assay that fall within the range of CNS permeant candidates. When evaluated on bidirectional assays on a Pgp overexpressing cell line, one analog was less susceptible to Pgp efflux activity compared to quinacrine. Taken together, the results point to an important role for the substituted 9-amino side chain attached to the acridine, tetrahydroacridine and quinoline scaffolds. The nature of this side chain influenced cell-based potency, PAMPA permeability and binding affinity to hPrP(121-231).


Human galectin-9 on the porcine cells affects the cytotoxic activity of M1-differentiated THP-1 cells through inducing a shift in M2-differentiated THP-1 cells.
In xenotransplantation, immune rejection by macrophages occurs rapidly and remains a major obstacle. Studies to control immune rejection in macrophages have been continuing to date. Recent studies have reported that human galectin-9 (hGal-9) can regulate the function of regulatory T cells (Treg), as well as cytotoxicity T cells (CTL) and natural killer cells (NK). Although the effect of hGal-9 on lymphocytes has been well studied, the relationship between hGal-9 and myeloid cells has been scarcely studied. To confirm the decreased cytotoxic activity effect by hGal-9 in M1-differentiated THP-1 cells, we established the hGal-9 expressing transgenic porcine cell line. hGal-9 siRNA was transfected to transgenic cells and recombinant hGal-9 (rhGal-9) was treated to co-culturing condition, and then, flow cytometry assay was conducted for analyzing the cytotoxic activity of M1-differentiated THP-1 cells. Related inflammatory cytokines (IL-1β, IL-10, TNF-α, IL-6, IL-12, IL-23, and TGF-β) and related enzymes (iNOS and Arginase 1) were analyzed by qPCR and Western blot assay. To identify the shift in M1/M2-differentiated THP-1 cells, expression levels of CCR7, CD163, iNOS, and Arginase 1 and population of M2 marker positive cells were analyzed. The expression levels of pro-inflammatory cytokines in M1-differentiated THP-1 cells co-cultured with hGal-9-expressing porcine kidney epithelial cells were decreased, but not in co-cultured THP-1 cells. However, the expression levels of anti-inflammatory cytokines were also increased in co-cultured M1-differentiated THP-1 cells. The cytotoxicity effect of M1-differentiated THP-1 cells on transgenic cells was decreased while the expression levels of anti-inflammatory cytokines and M2 macrophages-related molecules were increased. M2 differentiation program was turned on while M1 program was turned down by enhancing the phosphorylation levels of Akt and PI3K and the expression level of PPAR-γ. Due to these changes, differentiation of M2 program was enhanced in cells co-cultured with hGal-9. These data suggested that hGal-9 has a reduction in M1-differentiated THP-1 cell cytotoxic activity-related acute immune rejection in pig-to-human xenotransplantation in addition to its role in lymphoid lineage immune cell regulation.


Measuring the Impact of the COVID-19 Pandemic on Sexually Transmitted Diseases Public Health Surveillance and Program Operations in the State of California.
As public health personnel and resources are redirected to COVID-19, sexually transmitted diseases (STD) programs have been unable to sustain pre-COVID-19 activities. We used California (CA) surveillance data to describe trends in case reporting for gonorrhea, chlamydia, and syphilis of any stage in the pre- versus post-COVID-19 eras (January-June 2019 and January-June 2020). We also analyzed data from an electronic survey administered by the CA STD Control Branch to local health jurisdictions in April, June, and September of 2020, assessing the impact of COVID-19 on STD programs. There were sharp declines in cases of all reportable bacterial STDs occurring in conjunction with the March 19, 2020 CA stay-at-home order, most of which did not return to baseline by July. Comparing January-June 2020 to January-June of 2019, there were decreases in reported cases of chlamydia (31%), late syphilis (19%), primary/secondary syphilis (15%), early nonprimary nonsecondary syphilis (14%), and gonorrhea (13%). The largest percentage declines in STD case reporting were among Hispanic, Asian/Pacific Islander, and Black persons. Seventy-eight percent of local health jurisdiction respondents indicated that half or more of their workforce had been redeployed to COVID-19 by September 2020. During the COVID-19 era, STD case reporting and programmatic functions have diminished throughout CA. Because this may contribute to decreases or delays in STD diagnosis and treatment-with resultant increases in STD transmission-providers and public health officials should prepare for potential increases in STD-related morbidity in the months and years to come.


Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats.
Chronic liver injury and cirrhosis leads to liver failure. Hyperammonemia is a deleterious consequence of liver failure. On the other hand, oxidative stress seems to play a pivotal role in the pathogenesis of liver fibrosis as well as in the cytotoxic mechanism of ammonia. There is no promising therapeutic agent against ammonia-induced complications. The present study was conducted to evaluate the role of carnosine (CA) administration on liver pathological changes, elevated plasma ammonia, and its consequent events in cirrhotic rats. Bile duct ligated (BDL) rats were used as a model of cirrhosis. CA (250, 500, and 1000mg/kg, daily, i.p) was administered for 28 consecutive days to BDL animals. At the end of treatments, markers of oxidative stress and liver fibrosis was determined in liver and serum biomarkers of liver injury and plasma ammonia was assessed. Moreover, changes in animals' locomotor activity were monitored. Severe bridging fibrosis, inflammation, and necrosis in liver, along with elevated serum biomarkers of liver injury were evident in BDL animals. Furthermore, plasma ammonia was drastically elevated in cirrhotic rats and animals' locomotor activity was suppressed. It was found that CA (250, 500, and 1000mg/kg, daily, i.p) significantly alleviated liver injury and its consequent events in cirrhotic rats. The data suggested that CA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia and brain damage as a deleterious consequence of cirrhosis and liver failure.


Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery.
To Study the Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery. The ABS General Surgery CE is normally an in-person oral examination. Due to the COVID-19 outbreak, the ABS was required to reschedule these. After 2 small pilots, the CE's October administration represented the first large-scale remote virtual exam. The purpose of this report is to compare the outcomes of this virtual and the previous in-person CEs. CE candidates were asked to provide feedback on their experience via a survey. The passing rate was compared to the 1025 candidates who took the 2019-2020 in-person CEs. Of the 308 candidates who registered for the virtual CE, 306 completed the exam (99.4%) and 188 completed the survey (61.4%). The majority had a very positive experience. They rated the virtual CE as very good/excellent in security (90%), ease of exam platform (77%), audio quality (71%), video quality (69%), and overall satisfaction (86%). Notably, when asked their preference, 78% preferred the virtual exam. There were no differences in the passing rates between the virtual or in-person exams. The first virtual CE by the ABS was completed using available internet technology. There was high satisfaction, with the majority preferring the virtual platform. Compared to past in-person CEs, there was no difference in outcomes as measured by passing rates. These data suggest that expansion of the virtual CE may be desirable.


Low serum vitamin D concentration is correlated with anemia, microinflammation, and oxidative stress in patients with peritoneal dialysis.
Peritoneal dialysis (PD) is a form of dialysis to replace the function of kidney, that uses the peritoneum as a dialysis membrane to remove metabolites and water retained in the body. Vitamin D deficiency is prevalent in patients treated with PD. This research investigated the correlation between serum 25-hydroxyvitamin D [25(OH)D] concentration and anemia, microinflammation, and oxidative stress in PD patients. 62 PD patients and 56 healthy volunteers were recruited in this research. Serum concentrations of 25(OH)D and basic parameters of anemia were detected. The correlation between serum 25(OH)D concentration with anemia, oxidative stress, and microinflammatory state were analyzed. In the PD group, the concentration of 25(OH)D was lower than the healthy control (HC) group (p < 0.001). Hemoglobin, red blood cell count (RBC), and total iron binding capacity (TIBC) in the PD group was significantly lower (all p < 0.001), while high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) concentrations were significantly higher, than the HC group (all p < 0.001). In the PD group, malondialdehyde (MDA) concentration was higher than in the HC group (p < 0.001), while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were lower (both p < 0.001). Serum 25(OH)D exhibited positive correlation with hemoglobin (r = 0.4509, p = 0.0002), RBC (r = 0.3712, p = 0.0030), TIBC (r = 0.4700, p = 0.0001), SOD (r = 0.4992, p < 0.0001) and GSH-Px (r = 0.4312, p = 0.0005), and negative correlation with hs-CRP (r = - 0.4040, p = 0.0011), TNF-α (r = - 0.4721, p = 0.0001), IL-6 (r = - 0.5378, p < 0.0001) and MDA (r = - 0.3056, p = 0.0157). In conclusion, reduced serum 25(OH)D concentrations in PD patients contribute to anemia, oxidative stress and microinflammatory state.


Effect of climatic elements on the frequency of secretory otitis media.
A relationship between the number of children hospitalized for secretory otitis media and climatic elements was observed during a 10-year period (1981-1990). The highest correlation was obtained between the number of secretory otitis media cases and the number of sunny hours in a month, followed by that between the number of secretory otitis media cases and the mean monthly temperature and relative air humidity. The largest number of children were hospitalized for secretory otitis media toward the end of winter, and the lowest toward the end of summer (in August and September).


Quantitative Analysis of Circulating Tumor Cells Using RNA-Based Digital Scoring.
Circulating tumor cells (CTCs) provide valuable information about the molecular evolution of cancers, as they may initially respond and ultimately progress on therapy. As intact tumor cells isolated from the bloodstream, CTCs also enable assessment of heterogeneous subpopulations, and their analysis may include DNA, RNA, and protein biomarkers. New microfluidic cell isolation strategies greatly facilitate the challenge of enriching viable tumor cells from the billions of hematopoietic cells within a standard blood specimen. While counting and characterization of enriched CTCs have primarily relied on immunostaining for tumor cell-specific antigens, new RNA-based analytic platforms are providing new insight into the identity of CTCs and providing new tools for clinical applications. Single-cell RNA sequencing of CTCs reveals a high degree of heterogeneity among cancer cells from a single individual, while new digital RNA-based amplification platforms may now allow high-sensitivity and high-throughput quantitative scoring of CTCs for clinical applications. Here, we focus on transcriptomic analysis of CTCs and its relevance in understanding metastatic cancer progression and in developing diagnostic assays to monitor cancer.


Neuroanatomical Correlates of Social Intelligence Measured by the Guilford Test.
Social interactions are a crucial aspect of human behaviour. Numerous neurophysiological studies have focused on socio-cognitive processes associated with the so-called theory of mind-the ability to attribute mental states to oneself and others. Theory of mind is closely related to social intelligence defined as a set of abilities that facilitate effective social interactions. Social intelligence encompasses multiple theory of mind components and can be measured by the Four Factor Test of Social Intelligence (the Guilford-Sullivan test). However, it is unclear whether the differences in social intelligence are reflected in structural brain differences. During the experiment, 48 healthy right-handed individuals completed the Guilford-Sullivan test. T1-weighted structural MRI images were obtained for all participants. Voxel-based morphometry analysis was performed to reveal grey matter volume differences between the two groups (24 subjects in each)-with high social intelligence scores and with low social intelligence scores, respectively. Participants with high social intelligence scores had larger grey matter volumes of the bilateral caudate. The obtained results suggest the caudate nucleus involvement in the neural system of socio-cognitive processes, reflected by its structural characteristics.


A different approach to the quantification of human seminal plasma metabolites using high-resolution NMR spectroscopy.
In this study, a reliable method was established for the absolute quantification of metabolite concentrations in human seminal plasma using ERETIC2, a quantification tool developed by Bruker based on the PULCON principle. The performance of the ERETIC2 was examined using an AVANCE III HD NMR spectrometer (600 MHz) equipped with a triple inverse 1.7 mm TXI probe in terms of some experimental parameters that may affect the accuracy and precision of the quantitative results. Then, the accuracy, precision, and repeatibility of ERETIC2 were determined using L-asparagine solutions at different concentrations. And it was evaluated by comparing it with the classical internal standard (IS) quantification method. The relative standard deviation (RSD) values for ERETIC2 were calculated in the range of 0.55-1.90% and the minimum recovery value was 99.9%, while the RSD values for the IS method were calculated in the range of 0.88-5.83% and recovery value was minimum 91.0%. Besides, the RSD values of the inter-day precisions for the ERETIC2 and IS methods were obtained to be in the range of 1.25 - 3.03% and 0.97 - 3.46%, respectively. Finally, the concentration values of seminal plasma metabolites were determined using different pulse programs with both methods for samples obtained from normozoospermic control and azoospermic patient groups. The results proved that this quantification method developed using NMR spectroscopy is easy to use in complex sample systems such as biological fluids and is a good alternative to the classical internal standard method in terms of accuracy and sensitivity. In addition, the improvement of the spectral resolution and sensitivity with the microcoil probe technology and the possibility of analyzing with minimum sample quantities has contributed positively to the results of this method.


Sentinel node biopsy alone for node-positive breast cancer: 12-year experience at a single institution.
Complete node dissection for a tumor-positive sentinel node (SN) is becoming more controversial. We report our institution's 12-year experience with sentinel node biopsy (SNB) alone for a tumor-positive SN. This was a retrospective review from 1998 to 2009. Of 3,806 patients who underwent SNB, 2,139 underwent SNB alone, of which 1,997 were tumor-negative and 123 were tumor-positive. SNs were staged node-positive (N1mic or N1) according to American Joint Committee on Cancer criteria. One hundred and twenty-three node-positive patients underwent SNB alone with no completion axillary dissection for invasive breast cancer. Mean age was 57 years (range 32 to 92 years) and stage distribution was as follows: stage IIA: 76 (62%) patients; stage IIB: 40 (33%) patients; and stage III: 4 patients (3%). Mean size of the tumors was 1.9 cm (range 0.1 to 9 cm). Eighty-nine (72%) underwent lumpectomy and 34 (28%) underwent mastectomy. Ninety-three percent of patients underwent some form of adjuvant therapy. Forty-two patients (34%) did not undergo radiation and there were no axillary recurrences in this group. At median follow-up of 95 months, there has been 1 axillary recurrence (0.8%) and 13 deaths, 4 of which were attributed to metastatic breast cancer and the rest to non-breast-related causes. Axillary recurrence is rare after SN biopsy alone. This might be related to favorable tumor and patient characteristics and frequent use of adjuvant therapy.


Precursor-oriented design of nano-alumina for efficient removal of antibiotics.
Rapid and efficient removal of environmental antibiotics is vital to curb bacterial resistance. Through rational precursors-oriented design, we attain the best Al2O3 absorbent by 500 °C calcination of ammonium aluminium carbonate hydroxide (AACH) precursor from NH4HCO3 route (AACH-NH4HCO3-500) for fast and efficient removal of tetracycline (TC) and other antibiotics from environmental waters including high-salinity wastewater. AACH-NH4HCO3-500 (0.25 g·L-1) can remove (69.92 ± 1.78)% of aqueous TC (0.025 g·L-1) within 5 min and (97.62 ± 2.75)% within 2 h, and the adsorption capacity is 444.4 mg·g-1, which is the highest qmax of TC for the 2 h-adsorptions among numerous adsorbents. AACH-NH4HCO3-500 has fine tolerance to the coexisting substances, and can be easily regenerated and reused, and has no harm even discarded. The relations among the synthetic methods, the structural features, and the adsorption functions of Al2O3 are disclosed through a systematic comparison of the commercial Al2O3 and different Al2O3 nanomaterials attained from three precursors produced by five different routes. The reasons behind the exceptional adsorption performance are discussed throughout. Our findings would facilitate the development of excellent adsorbents for removal of other pollutants.


[CT of a rare benign liver lymphangioma].
Lymphangiomas of the liver are very rare hamartomas and can occur singly or in multiple form. CT findings of this disease have not been reported so far. Based on a case where diagnosis had been confirmed by biopsy, the CT image is described and the findings discussed.


Organic hydrogen peroxide-driven low charge potentials for high-performance lithium-oxygen batteries with carbon cathodes.
Reducing the high charge potential is a crucial concern in advancing the performance of lithium-oxygen batteries. Here, for water-containing lithium-oxygen batteries with lithium hydroxide products, we find that a hydrogen peroxide aqueous solution added in the electrolyte can effectively promote the decomposition of lithium hydroxide compounds at the ultralow charge potential on a catalyst-free Ketjen Black-based cathode. Furthermore, for non-aqueous lithium-oxygen batteries with lithium peroxide products, we introduce a urea hydrogen peroxide, chelating hydrogen peroxide without any water in the organic, as an electrolyte additive in lithium-oxygen batteries with a lithium metal anode and succeed in the realization of the low charge potential of ∼3.26 V, which is among the best levels reported. In addition, the undesired water generally accompanying hydrogen peroxide solutions is circumvented to protect the lithium metal anode and ensure good battery cycling stability. Our results should provide illuminating insights into approaches to enhancing lithium-oxygen batteries.


GRK2 participation in cardiac hypertrophy induced by isoproterenol through the regulation of Nrf2 signaling and the promotion of NLRP3 inflammasome and oxidative stress.
In cases of heart failure, cardiac hypertrophy may be caused by the upregulation of G-protein-coupled receptor kinase 2 (GRK2). Both NLRP3 inflammasome and oxidative stress contribute to cardiovascular disease. In this study, we clarified the effect of GRK2 on cardiac hypertrophy in H9c2 cells induced by isoproterenol (ISO) and examined the underlying mechanisms. We randomly categorized H9c2 cells into five groups: an ISO group, a paroxetine plus ISO group, a GRK2 small-interfering RNA (siRNA) plus ISO group, a GRK2 siRNA combined with ML385 plus ISO group, and a control group. To determine the effect of GRK2 on cardiac hypertrophy induced by ISO, we carried out CCK8 assays, RT-PCR, TUNEL staining, ELISA assay, DCFH-DA staining, immunofluorescence staining, and western blotting. By using paroxetine or siRNA to inhibit GRK2, we significantly decreased cell viability; reduced the mRNA levels of ANP, BNP, and β-MHC; and limited the apoptosis rate and protein levels of cleaved caspase-3 and cytochrome c in H9c2 cells treated with ISO. We also found that oxidative stress induced by ISO could be mitigated with paroxetine or GRK2 siRNA. This result was validated by decreased activities of the antioxidant enzymes CAT, GPX, and SOD and increased MDA levels and ROS production. We observed that the protein expression of NLRP3, ASC, and caspase-1 and the intensity of NLRP3 could be inhibited by paroxetine or GRK2 siRNA. Both paroxetine and GRK2 siRNA were able to abolish the increase in GRK2 expression induced by ISO. They also could increase protein levels of HO-1, nuclear Nrf2, and Nrf2 immunofluorescence intensity; however, they could not change the protein level of cytoplasmic Nrf2. By combining treatment with ML385, we were able to reverse GRK2 inhibition on H9c2 cells treated with ISO. According to the results of this study, GRK2 participated in cardiac hypertrophy induced by ISO by mitigating NLRP3 inflammasome and oxidative stress through the signaling of Nrf2 in H9c2 cells.


Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to low doses of heavy-ion radiation.
Adaptive response (AR) and bystander effect are two important phenomena involved in biological responses to low doses of ionizing radiation (IR). Furthermore, there is a strong interest in better understanding the biological effects of high-LET radiation. We previously demonstrated the ability of low doses of X-rays to induce an AR to challenging heavy-ion radiation [8]. In this study, we assessed in vitro the ability of priming low doses (0.01Gy) of heavy-ion radiation to induce a similar AR to a subsequent challenging dose (1-4Gy) of high-LET IR (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm) in TK6, AHH-1 and NH32 cells. Our results showed that low doses of high-LET radiation can induce an AR characterized by lower mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and faster DNA repair kinetics, in cells expressing p53.


A ribonuclease-resistant region of 5S RNA and its relation to the RNA binding sites of proteins L18 and L25.
An RNA fragment, constituting three subfragments of nucleotide sequences 1-11, 69-87 and 89-120, is the most ribonuclease-resistant part of the native 5S RNA of Escherichia coli, at 0 degrees C. A smaller fragment of nucleotide sequence 69-87 and 90-110 is ribonuclease-resistant at 25 degrees. Degradation of the L25-5S RNA complex with ribonuclease A or T2 yielded RNA fragments similar to those of the free 5S RNA at 0 degrees C and 25 degrees C; moreover L25 remained strongly bound to both RNA fragments and also produced some opening of the RNA structure in at least two positions. Protein L18 initially protected most of the 5S RNA against ribonuclease digestion, at 0 degrees C, but was then gradually released prior to the formation of the larger RNA fragment. It cannot be concluded, therefore, as it was earlier (Gray et al., 1973), that this RNA fragment contains the primary binding site of L18.


Dose- and age-dependent effects of clomiphene citrate administered to prepubertal female rats on development of anovulatory sterility and pyosalpinx.
The influences of dose of clomiphene and age at clomiphene treatment in prepubertal female rats on development of anovulatory sterility and pyosalpinx were investigated. By varying the amount of clomiphene administered, it was found that 50 micrograms is the minimal dose of clomiphene which will produce anovulatory sterility and pyosalpinx in a majority of female rats treated at 5 days of age. By varying the age of rats at clomiphene treatment, it was observed that the period of clomiphene sensitivity in female rats is within the first 10 days of life, in which administration of 500 micrograms clomiphene will result in subsequent anovulatory sterility and pyosalpinx. These results demonstrate that the induction of anovulatory sterility and pyosalpinx is dependent upon the dose of clomiphene and the age of rats at clomiphene injection.


Laparoscopic and renal sparing approaches to tumours of the ureter and kidney.
Until recently, malignancies of the kidney and ureter were managed with open radical surgery. Over the last decade the urologic community has adopted the skill of laparoscopic surgery for the treatment of these tumours. Parenchymal sparing procedures have become the standard of care in the treatment of selected patients with renal and ureteral tumours and many of these surgical procedures can be performed laparoscopically or ureteroscopically. Due partly to necessity and partly to the advancement of technology, renal and ureteral sparing procedures have become commonplace for definitive treatment and palliation of these tumours. The morbidity of such procedures is significantly less than for open surgery and the future of urologic minimally invasive surgery appears secure. This review article is aimed at updating the reader in the most recent advances in these techniques.


Homeostasis and the functional roles of CD4+ Treg cells in aging.
An upward trend in life expectancy has been observed in a majority of developed countries and leading to increasing in aging-related diseases. Aging is a risk factor for the development of widespread clinical conditions such as cardiovascular and autoimmune diseases, cancer, infections. Although studies have been very active, the problem of aging still remains one of the most obscure aspects of human biology. Regulatory T (Treg) cells with immunosuppressive properties have a pivotal role in the maintenance of immune homeostasis. Alterations in Treg cell functionality appear to be of great importance in the development of immune senescence and contribute to increased susceptibility to immune-mediated diseases with age. This review highlights recent findings regarding the age-related changes in the numbers and functional activity of human Tregs. Some of the mechanisms that maintain the balance of Tregs during human aging are discussed. The possible roles of Tregs in the pathogenesis of diseases associated with advanced age are also considered. Age-related systemic changes, such as thymic involution, hormonal status, and epigenetic modifications, may affect the state of the Treg population and trigger various diseases. These changes involve decline or amplification in the functional activity of Tregs, an increase in the memory Treg subset and shifting of a Th17/Treg balance. Taken together, the reviewed data suggest equal or even increased Treg functionality with age. Thus, age-mediated Treg expansion and higher Treg activity may contribute to elevated immune suppression and increased risk of infections and cancer.


MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue.
MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.


[Energy demands and supply in polytraumatized patients in the postoperative phase].
Normal enteral feeding cannot be maintained after trauma. Post-aggression metabolism or socalled "flow phase" usually results from hormonal changes, including rise in catecholamine and cortisole, drop in testosterone as well as T3 and T4, and relative hGH deficit. Glucose intolerance, increased demand for energy, and catabolism are the consequences along with reduced protein uptake and increased protein breakdown with all associated complications. Indirect calorimetry is an important method to determine energy requirements and, above all, is used to monitor nutrition and other therapeutic interventions. Substrate requirement and distribution of substrate supplies are discussed in some detail. All-in-one solutions and tube feeding have quite often proved helpful in providing patients with sufficient and properly adapted nutrition. On top of adequate nutrition, catabolism is therapeutically controlled by medication, using beta-blockers and hGH. The need for supervision of nutrition is also discussed.


A widely unappreciated cause of failure of an automatic noninvasive blood pressure monitor.
Many anesthesiologists have come to depend on automatic noninvasive blood pressure monitoring to obtain blood pressure (BP) readings. A case is presented in which, during a critical phase of the anesthetic, an automatic noninvasive blood pressure (ANIBP) device not only failed to provide meaningful clinical data but, in fact, gave an error message that was misleading. At the time of the message, the patient was noted to be in ventricular trigeminy at a rate of 92 beats/min. It appears that the repetitive beat-to-beat fall in blood pressure due to the dysrhythmia "fooled" the automatic noninvasive blood pressure device's software algorithm into believing that there was an air leak in the system. Thus, in addition to pointing out an unappreciated and potentially troubling device-related critical event, the present case demonstrates the importance of good human factors design for medical devices used in the critical care setting. In particular, the issue is raised of how medical devices should deal with uncertain or potentially misleading data.


Rotary-jet spun polycaprolactone/nano-hydroxyapatite scaffolds modified by simulated body fluid influenced the flexural mode of the neoformed bone.
Polycaprolactone (PCL) is a biocompatible, biodegradable synthetic polymer which in combination with nanohydroxyapatite (nHAp) can give rise to a low cost, nontoxic bioactive product with excellent mechanical properties and slow degradation. Here we produced, characterized and evaluated in vivo the bone formation of PCL/nHAp scaffolds produced by the rotary jet spinning technique. The scaffolds produced were firstly soaked into simulated body fluid for 21 days to also obtain nHAp onto PCL/nHAp scaffolds. Afterwards, the scaffolds were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy and Raman spectroscopy. For in vivo experiments, 20 male Wistar rats were used and randomly divided in 4 experimental groups (n = 5). A critical defect of 3 mm in diameter was made in the tibia of the animals, which were filled with G1 control (clot); G2-PCL scaffold; G3-PCL/nHAp (5%) scaffold; G4-PCL/nHAp (20%) scaffold. All animals were euthanized 60 days after surgery, and the bone repair in the right tibiae were evaluated by radiographic analysis, histological analysis and histomorphometric analysis. While in the left tibias, the areas of bone repair were submitted to the flexural strength test. Radiographic and histomorphometric analyses no showed statistical difference in new bone formation between the groups, but in the three-point flexural tests, the PCL/nHAp (20%) scaffold positively influenced the flexural mode of the neoformed bone. These findings indicate that PCL/nHAp (20%) scaffold improve biomechanical properties of neoformed bone and could be used for bone medicine regenerative.


Perioperative diagnosis of mesenteric ischemia in acute aortic dissection by transesophageal echocardiography.
Although computed tomography, angiography, or magnetic resonance imaging is most commonly used for diagnosing mesenteric ischemia caused by acute aortic dissection, use of these modalities is often limited in the perioperative period. Thus, we have introduced transesophageal echocardiography to cover this deficit. Purpose of this study is to report the feasibility and accuracy of transesophageal echocardiographic diagnosis on mesenteric ischemia. The consecutive 24 cases with acute aortic dissection which involved abdominal aorta and underwent surgery were examined. The celiac artery and superior mesenteric artery was visualized with 5 MHz biplane transesophageal echocardiography and was assessed for presence of dissection and blood flow in each of true and false lumen. The transesophageal echocardiographic findings were then correlated to the clinical course, computed tomographic findings, and laboratory data. The celiac artery and superior mesenteric artery was successfully visualized in 24 cases (100%) and 23 cases (95.8%), respectively. Perfusion patterns in superior mesenteric artery were categorized into four patterns: (1) intact artery with adequate perfusion (type A: 14 cases); (2) dissection in the artery but with adequate perfusion in true lumen (type B: 5 cases); (3) dissection in the artery with narrowed true lumen compressed by false lumen without detectable blood flow (type C: 1 case); and (4) obstruction of arterial orifice by the intimal flap with narrowed true lumen in the proximal aorta (type D: 2 cases). One case with immediate postoperative death and another case with unsuccessful visualization of superior mesenteric artery were excluded from the analysis. Clinically apparent intestinal ischemia was present in three cases: one case with type C and two cases with type D, but in none of the remaining 19 cases with type A or type B (both sensitivity and specificity were 100%). The superior mesenteric artery was opacified in all of these three cases with ischemia. The transesophageal echocardiographic assessment is feasible in nearly all patients and potentially provides correct diagnosis on intestinal ischemia in the perioperative period of acute aortic dissection. Types C and D indicate significant mesenteric malperfusion.


The effect of cardiopulmonary bypass on cerebral blood flow.
The experiments dealth with the effect of total cardiopulmonary bypass on global and regional cerebral blood flow. Global cerebral blood flow was determined with radioactive microspheres, regional cerebral flow by direct observation through transillumination and high-speed cinematography. The latter permitted observations of changes in caliber of cerebral arterioles and of red cell velocity. Arterial blood gas tension and pH were continuously monitored. Measurements were carried out prior to and immediately following cardiopulmonary bypass. Studies on global cerebral flows showed that during cardiopulmonary bypass cerebral blood flow rose and cerebral vascular resistance declined while blood pressure did not change significantly. During bypass, cerebral blood flow and blood pressure in animals treated as a group became interdependent and showed direct proportionally. Direct observations of the cortical microvasculature by means of high-speed cinematography revealed dilatation of cerebral cortical arterioles. Even though blood pressure remained unchanged, the diameter of cortical arterioles increased. Volume flow calculated from red cells velocity and arteriolar diameter showed a tendency of arteriolar flow to increase. The condition is reminiscent of the 'luxury perfusion syndrome' (overabundant cerebral flow relative to metabolic needs of cerebral tissue).


Thorotrast induced adhesive arachnoiditis associated with meningioma and schwannoma.
Adhesive arachnoiditis, a meningioma and a schwannoma were found at autopsy in a 56 year old man who had undergone Thorotrast myelography 33 years previously. Thorotrast was demonstrated in tissue sections by transmission and scanning electron microscopy, radioautography, and x-ray spectrometry.


The Zavanelli manoeuvre revisited: A review of the literature and a guide to performing cephalic replacement for severe shoulder dystocia.
The Zavanelli manoeuvre is often the final resort of the clinician facing undeliverable shoulder dystocia and we present retrospective pooled data comprising 110 shoulder dystocia cases, 11 impacted breech and 11 locked twin deliveries assessed from ten case series and 38 individual case reports. Although recommended when other external and internal manipulations have failed, we suspect that many clinicians have not had formal training on how to conduct the manoeuvre and may be unfamiliar with the steps involved, leading to a reluctance and delay in initiating this. We describe original descriptions of the manoeuvre, examine its use in intractable shoulder dystocia and illustrate stepwise the cephalic replacement technique. For this review, we have concentrated mainly on the outcomes of the Zavanelli manoeuvre in shoulder dystocia but have also touched on its role in impacted breech and locked twin deliveries. Lastly, we discuss the cognitive load an obstetrician faces when having to make time critical decisions in severe shoulder dystocia and share how other disciplines train and prepare their personnel to manage similar rare and unexpected scenarios.


[A change of the medium salinity as a functional load for evaluation of physiological state of the crayfish Astacus leptodactylus].
The necessity of developing criteria for evaluation of the functional state of benthic invertebrates for toxicological studies or for their use as biosensors in systems of the water quality biomonitoring is emphasized. It is proposed to evaluate the organism state with aid of standard test actions dosed by strength and duration. For freshwater crayfish, such action--the functional load--can be the medium salinity change by 1%o, which can be achieved by addition of sodium chloride. Peculiarities of the response reaction of the crayfish cardiac system to such action have been shown by non-invasive method of recording of cardiac activity.


[Analysis of a pedigree with inherited factor V deficiency caused by compound heterozygous mutation].
Objective: To explore the molecular pathogenesis of a family with hereditary factor Ⅴ (FⅤ) deficiency. Methods: All the exons, flanking sequences, 5' and 3' untranslated regions of the F5 of the proband, and the corresponding mutation sites of the family members were analyzed via direct DNA sequencing. The CAT measurement was used to detect the amount of thrombin produced. The ClustalX software was used to analyze the conservation of mutation sites. The online bioinformatics software, Mutation Taster, PolyPhen-2, PROVEAN, LRT, and SIFT were applied to predict the effects of mutation sites on protein function. The Swiss-PdbViewer software was used to analyze the changes in the protein model and intermolecular force before and after amino acid variation. Results: The proband had a heterozygous missense mutation c.1258G>T (p.Gly392Cys) in exon 8 of the F5, and a heterozygous deletion mutation c.4797delG (p.Glu1572Lys fsX19) in exon 14, which results in a frameshift and produces a truncated protein. Her grandfather and father had p.Gly392Cys heterozygous variation, whereas her maternal grandmother, mother, little aunt, and cousin all had p.Glu1572LysfsX19 heterozygous variation. The ratio of proband's thrombin generation delay to peak time was significantly increased. Conservation analysis results showed that p.Gly392 was located in a conserved region among the 10 homologous species. Five online bioinformatics software predicted that p.Gly392Cys was pathogenic, and Mutation Taster also predicted p.Glu1572Lys fsX19 as a pathogenic variant. Protein model analysis showed that the replacement of Gly392 by Cys392 can lead to the extension of the original hydrogen bond and the formation of a new steric hindrance, which affected the stability of the protein structure. Conclusion: The c.1258G>T heterozygous missense mutation in exon 8 and the c.4797delG heterozygous deletion mutation in exon 14 of the F5 may be responsible for the decrease of FⅤ levels in this family.


Effect of endosulfan (thiodan) on vitellogenesis and its modulation by different hormones in the vitellogenic catfish Clarias batrachus.
This programme was planned in order to study the reproductive dysfunction caused by endosulfan in the fish Clarias batrachus with special reference to vitellogenesis. Vitellogenin was measured by radioimmunoassay. Endosulfan caused a drastic reduction in the plasma vitellogenin which was partially reversed by estradiol-17 beta (E2) in intact and ovariectomized fish. Hormones in combination were more effective than any single hormone in overcoming the impact of endosulfan. Triiodothyronine (T3), ovine luteinizing hormone releasing hormone (oLHRH) were effective in minimizing the effect of endosulfan whereas cortisol (F) and ovine somatotropic hormone (oStH) did not reduce the effect of endosulfan. Amongst the combined hormone treatments, E2 + oLHRH and E2 + T3 were the most potent in overcoming the effect of endosulfan on vitellogenesis.


An interactive metabolic map of bio-based chemicals.
Metabolic engineering for the bio-based production of chemicals requires thorough understanding of metabolic reactions including enzymes, cofactors, reactants, and products. Here we present an interactive bio-based chemicals map that visualizes compounds, enzymes, and reaction pathways together with strategies for the production of chemicals by biological, chemical, and combined methods.


Template design based on molecular and crystal structure similarity to regulate conformational polymorphism nucleation: the case of α,ω-alkanedi-carb-oxy-lic acids.
Template design on polymorph control, especially conformational polymorphs, is still in its infancy and the result of polymorph control is often accidental. A method of regulating the crystallization of conformational polymorphs based on the crystal structure similarity of templates and the target crystal form has been developed. Crystal structure similarity was considered to be able to introduce lattice matching (geometric term) with chemical interactions to regulate conformational polymorph nucleation. The method was successfully applied to induce the crystallization of DA7-II [HOOC-(CH2) n -2-COOH (diacids), named DAn, where n = 7, 9, 15, 17 and II represents the metastable polymorph] on the surface of DA15-II. An analogous two-dimensional plane - the (002) face of both DA15-II and DA7-II - was firstly predicted as the epitaxially attached face with similar lattice parameters and the strongest adsorption energy. The powder DA15-II template with the preferred orientation face in (002) presented much stronger inducing DA7-II ability than the template with other preferred orientation faces. The epitaxial growth of DA7-II on DA15-II through an identical (002) face was clearly observed and verified by the single-crystal inducing experiments. The molecular dynamics simulation results demonstrated that the strong interactions occurred between DA7 molecules and the (002) face of DA15-II. This method has been verified and further applied to the crystallization of DA7-II on the surface of DA17-II and DA9-II on the surface of DA15-II. This study developed a strategy based on structure similarity to regulate the conformational polymorph and verified the significant role of lattice matching and chemical effects on the design and preparation of templates.


Hairpin DNA-enabled ratiometric electrochemical aptasensor for detection of malathion.
A hairpin DNA-enabled ratiometric electrochemical aptasensor is reported for sensitive and reliable detection of malathion (MAL). The approach employs hairpin DNA (ferrocene-labeled, Fc-hDNA) as a carrier to hybridize MAL aptamers (methylene blue-labeled, MB-Apt) to form double-stranded DNA structures on an electrode. The presence of MAL induces the removal of aptamers, and hDNA re-forms hairpin structures, causing a decrease in the oxidation current of MB (IMB) and an increase in the oxidation current of Fc (IFc). The ratiometric signal of IFc/IMB responds quantitatively to MAL concentrations. To compare analytical performances, a linear single-stranded DNA (ssDNA) is also used to construct the ssDNA-based aptasensor. We demonstrate that hairpin DNA possessing a rigid two-dimensional structure can improve the assembly efficiency of aptamers and the stability of redox probes. The approach combines the advantages of the ratiometric electrochemical method with hairpin DNA-based conformational switching probes, enabling hDNA-based aptasensor with enhanced sensitivity and reliability, offering a linear range of 0.001 to 1.0 ng mL-1. The platform was applied to detect MAL in lettuce, and the statistical analysis indicated that no significant differences were found between the developed platform and HPLC-MS.


Influence of aspirin on SR-BI expression in human carotid plaques.
We recently showed that aspirin promotes scavenger receptor class-B type I (SR-BI) protein expression in vitro in primary human macrophages and in vivo in resident peritoneal macrophages of mice. We compared SR-BI and CD68 expression in carotid atherosclerotic specimens from endarterectomized patients with (n=38) or without (n=19) low-dose aspirin medication (100 mg/day) prior to endarterectomy. We found no differences concerning expression of CD68, indicating that aspirin did not influence macrophage content within atherosclerotic plaques. However, aspirin increased the expression of SR-BI protein in the analyzed specimens. In human THP-1-derived macrophages, induction of SR-BI protein by aspirin was abrogated by concomitant pharmacological inhibition of nuclear factor-kappa B (NF-kappaB). In in vitro experiments employing cultured primary macrophages from NF-kappaB/p50 KO mice, aspirin was not able to influence SR-BI expression. Additionally, no considerable effects on SR-BI expression were observed in vivo in resident macrophages of NF-kappaB/p50 KO mice orally treated with low or high doses of aspirin, respectively. We suggest that aspirin treatment might lead to enhanced expression of SR-BI in human plaque macrophages and that this effect is dependent on the presence of NF-kappaB.


Various indices of brain metabolism and activity in a model of chronic neurological dysfunction: triethyl tin intoxication in the rat.
A number of pathological agents of interest in the therapy of cerebrovascular disease can retard the development of the neurologic deficit induced by triethyl tin. Locomotor activity was decreased at a time when no evidence of neurologic deficit could be detected. Conduction velocity in the peripheral as well as assessed from measurement of cerebral blood flow, local cerebral glucose utilization, brain water and electrolyte content as well as neuropathology were measured before and frank deficit could be clinically detected.


E74-like factor 3 suppresses microRNA-485-5p transcription to trigger growth and metastasis of ovarian cancer cells with the involvement of CLDN4/Wnt/β-catenin axis.
Ovarian cancer (OC) is one of the most prevailing gynecological malignancies with high mortality rate, while E74 like ETS transcription factor 3 (ELF3) is reported to be associated with tumorigenesis. This work aims to analyze the role of ELF3 on the suppression of miR-485-5p transcription in OC. Expression of ELF3 in OC and its correlation with overall survival were predicted on a bioinformation system GEPIA. Then, the level of ELF3 in OC tissues and cells and in normal ones was evaluated. Binding relationships between ELF3 and microRNA (miR)-485-5p, and between miR-485-5p and claudin-4 (CLND4) were predicted through Bioinformatics tools. Altered expression of ELF3, miR-485-5p and CLND4 was introduced alone or jointly to probe their influences on OC cell growth. ELF3 was suggested to be highly expressed in OC, which was linked to poor prognosis in patients. Abundant expression of ELF3 was identified in OC tissues and cell lines as relative to the normal ones. ELF3 inhibition suppressed growth and metastasis of OC cells. ELF3 transcriptionally suppressed miR-485-5p expression to further enhance CLDN4 expression. Overexpression of miR-485-5p led to similar trends as ELF3 inhibition did. Importantly, upregulation of CLDN4 was found to block the roles of ELF3 inhibition in OC cells. In addition, the Wnt/signaling pathway suppressed by miR-485-5p mimic was reactivated following CLDN4 overexpression. This study evidenced that ELF3 suppresses miR-485-5p transcription to enhance CLDN4 expression, leading to Wnt/β-catenin activation and promoting OC cell growth and metastasis. This work may provide new ideas for gene-based therapies for OC.


Neuropsychological development in children with Dravet syndrome.
Aim of this study is to report a detailed profile of neuropsychological development in children with Dravet syndrome. Twelve children with Dravet syndrome were longitudinally assessed using a detailed clinical and neuropsychological evaluation. Six had typical features of severe myoclonic epilepsy in infancy (SMEI) whereas the other six resulted borderline. All twelve underwent serial neuropsychological assessments with neurodevelopmental scales and further assessment of specific cognitive abilities. Our results reported an apparent normal development before disease onset, a general evolution in two main stages, more active the first one and with a general trend towards a clinical stabilization afterwards. The onset of cognitive decline was generally later than what is reported in other series; furthermore, the impairment of cognitive development is less severe, especially in borderline cases. As to specific cognitive competence, attention, visual motor integration, visual perception as well as executive functions are the most impaired abilities; language appears less involved, with a predominance of phonological defects. In our cohort the global development of patients appear less affected than in previous studies. Furthermore, our study points out an impairment of several specific cognitive skills even in patients with a developmental quotient apparently in the normal range. Language and other cognitive skill impairment such as attention, visuo-spatial organization, working memory and executive function appear consistent with what is usually found in cerebellar disorders.