Emergency medicine physician burnout and wellness in Canada before COVID19: A national survey.
Emergency medicine (EM) is a high-risk specialty for burnout. COVID-19 has had and will continue to have important consequences on wellness and burnout for EM physicians in Canada. Baseline data are crucial to monitor the health of EM physicians in Canada, and evaluate any interventions designed to help during and after COVID-19. To describe the rates of burnout, depression, and suicidality in practicing EM physicians in Canada, just before the COVID-19 pandemic. A modified snowball method was used for survey distribution. Participants completed the Maslach Burnout Inventory - Health Services Tool (MBI-HSS), a screening measure for depression (PHQ-9), and a question regarding if the physician had ever or in the past 12 months contemplated suicide. A total of 384 respondent surveys were included in the final analysis: 86.1% (329/382) met at least one of the criteria for burnout, 58% (217/374) scored minimal to none on the PHQ-9 screening tool for depression, 14.3% (53/371) had contemplated suicide during their staff career in EM, and of those, 5.9% (22/371) had actively considered suicide in the past year. Canadian EM physicians just before the COVID-19 pandemic had an alarming number of respondents meet the threshold for burnout, confirming EM as a high-risk specialty. This important baseline information can be used to monitor the physical and mental risks to EM physicians during and after COVID-19, and evaluate support for mental health and wellness, which is urgently needed now and post pandemic.


[Studies and computer analyses on the kinetics of nephrotropic contrast media in patients with different kidney function].
The local quantity of the contrast excretion depends on the filtration rate and the plasma level. Since the latter is influenced by dosage and kind of application from this result immediate practical consequences for the excretion urography, for which at present a large dose and the bolus injection are preferred.


A feasibility study of a manualized resilience-based telehealth program for persons with multiple sclerosis and their support partners.
Resilience is a protective factor that emerges when individuals are faced with challenges and stressors. Multiple sclerosis (MS) is a chronic neurological disease that introduces a great deal of stress for the individual and his/her support partner. We designed a telehealth resilience-building dyadic program for persons with MS (PwMS) and their support partners. To evaluate the feasibility of the resilience intervention. The secondary objective was to assess the benefits of the intervention. Sixty-two participants (M = 49.5 years, 31 dyads of PwMS) and support partners) were recruited to participate. Out of the 31 dyads, 26 were spouses, 2 were cohabiting partners, and 3 were parent-child dyads. The feasibility goals of the intervention were met, as determined by high participant satisfaction and acceptable completion rates. Preliminary outcomes relating to resilience were positive, suggesting that this intervention had a positive impact on participants. To the best of our knowledge, this is the first resilience-building intervention delivered via telehealth for both PwMS and their support partners. The study showed an increase in resilience-building skills for addressing the challenges faced by PwMS and their support partners. These skills can be promoted and taught, clinically supported by telehealth, an affordable, accessible healthcare solution. Trial Registration at ClinicalTrials.gov (NCT03555253).


Structural and biochemical characterization establishes a detailed understanding of KEAP1-CUL3 complex assembly.
KEAP1 promotes the ubiquitin-dependent degradation of NRF2 by assembling into a CUL3-dependent ubiquitin ligase complex. Oxidative and electrophilic stress inhibit KEAP1 allowing NRF2 to accumulate for the transactivation of stress response genes. To date there are no structures of the KEAP1-CUL3 interaction nor binding data to show the contributions of different domains to their binding affinity. We determined a crystal structure of the BTB and 3-box domains of human KEAP1 in complex with the CUL3 N-terminal domain that showed a heterotetrameric assembly with 2:2 stoichiometry. To support the structural data, we developed a versatile TR-FRET-based assay system to profile the binding of BTB-domain-containing proteins to CUL3 and determine the contribution of distinct protein features, revealing the importance of the CUL3 N-terminal extension for high affinity binding. We further provide direct evidence that the investigational drug CDDO does not disrupt the KEAP1-CUL3 interaction, even at high concentrations, but reduces the affinity of KEAP1-CUL3 binding. The TR-FRET-based assay system offers a generalizable platform for profiling this protein class and may form a suitable screening platform for ligands that disrupt these interactions by targeting the BTB or 3-box domains to block E3 ligase function.


Seizure-induced memory impairment is reduced by choline supplementation before or after status epilepticus.
Prenatal choline supplementation can protect rats against cognitive deficits induced by status epilepticus induced by the cholinergic agent pilocarpine [J. Neurosci. 20 (2000) 1]. In the present day, we have extended this novel finding by investigating the effects of pre- and postnatal choline supplementation in memory deficits associated with status epilepticus induced with kainic acid (KA). In the first experiment pregnant rats received a normal, choline-supplemented, or choline deficient diet starting on the 11th day of gestation and continuing until postnatal (P) 7. At P42, rats were given a convulsant dosage of KA. Two weeks following the KA-induced status epilepticus rats underwent testing of visual-spatial memory using the Morris water maze test. Rats receiving supplemental choline performed better in the water maze than the deficient and control groups. Moreover, the activity of hippocampal choline acetyltransferase was 18% lower in the choline deficient animals as compared with the other two groups. In the second experiment we administered KA to P35 rats that had been given a normal diet. Following the status epilepticus the rats were given a choline-supplemented or control diet for 4 weeks and then tested in the water maze. Rats receiving choline supplementation performed far better than rats receiving a regular diet. This study demonstrates that choline supplementation prior to or following KA-induced status epilepticus can protect rats from memory deficits induced by status epilepticus.


Class-Aware Attention Network for infectious keratitis diagnosis using corneal photographs.
Infectious keratitis is one of the common ophthalmic diseases and also one of the main blinding eye diseases in China, hence rapid and accurate diagnosis and treatment for infectious keratitis are urgent to prevent the progression of the disease and limit the degree of corneal injury. Unfortunately, the traditional manual diagnosis accuracy is usually unsatisfactory due to the indistinguishable visual features. In this paper, we propose a novel end-to-end fully convolutional network, named Class-Aware Attention Network (CAA-Net), for automatically diagnosing infectious keratitis (normal, viral keratitis, fungal keratitis, and bacterial keratitis) using corneal photographs. In CAA-Net, a class-aware classification module is first trained to learn class-related discriminative features using separate branches for each class. Then, the learned class-aware discriminative features are fed into the main branch and fused with other feature maps using two attention strategies to assist the final multi-class classification performance. For the experiments, we have built a new corneal photograph dataset with 1886 images from 519 patients and conducted comprehensive experiments to verify the effectiveness of our proposed method. The code is available at https://github.com/SWF-hao/CAA-Net_Pytorch.


Vascular/perivascular inflammation in IgG4-related disease.
Immunoglobulin G4-related disease (IgG4-RD) is characterized by the infiltration of IgG4-positive plasma cells and fibrosclerotic inflammation in multiple organs. Although vascular complications are present in some patients with IgG4-RD, vascular and/or perivascular inflammatory activity compared to control subjects remains unknown. This study sought to investigate vascular/perivascular inflammation in IgG4-RD patients compared to control subjects using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography (FDG-PET/CT). We examined 37 consecutive patients diagnosed as IgG4-RD (29 males, mean age of 64.3 ± 8.3 years old), who underwent FDG-PET/CT. Thirty-seven age- and gender-matched subjects without IgG4-RD were employed as controls. Vascular/perivascular inflammation was quantified by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). All IgG4-RD patients presented with multiple region involvements. Twelve (32.4%) of the IgG4-RD patients had vascular complications, all of which appeared in the abdominal aorta. IgG4-RD patients had significantly higher TBR values in the descending aorta, abdominal aorta, and common iliac artery than control subjects. Also, IgG4-RD patients with vascular complication exhibited higher TBR values in the infra-renal aorta and common iliac artery than those without vascular complication. We found that vascular FDG activity is significantly elevated in IgG4-RD patients regardless of vascular complication than control subjects. FDG-PET/CT is a useful modality for assessing vascular/perivascular inflammation, which may contribute vascular complication in IgG4-RD patients.


Antioxidant capacity and interaction of endogenous phenolic compounds from tea seed oil.
Endogenous phenols play a significant role in delaying oil rancidity. In this study, the profile of 22 endogenous phenols was determined from tea seed oil by UPLC-MS/MS, of which 15 phenols were identified for the first time. Then seven phenols with high content and strong antioxidant capacity were selected to investigate interaction using the DPPH· and Rancimat. It was found that the interaction of combinations was inconsistent in different media. Combined quercetin + esculetin, caffeoyl tartaric acid + esculetin, caffeoyl tartaric acid + gentisic acid and esculetin + gentisic acid showed synergistic antioxidant effects in oil and ethanol systems. Moreover, through the evaluation of the lipid oxidation process, combined esculetin + gentisic acid exhibited the greatest synergistic antioxidant effect. Notably, combined quercetin + esculetin had an inhibitory effect on the formation of volatile compounds. These findings may provide a basis for explaining the oxidation stability of tea seed oil.


High pressure stent-assisted balloon coronary angioplasty: a case report.
We reported the first high pressure stent assisted balloon angioplasty successfully implanted in this country. The use of intracoronary stent and its future direction were also reviewed. Regimen for post stent can be adjusted for each individual patient.


Peripersonal space is diversely sensitive to a temporary vs permanent state of anxiety.
Peripersonal Space (PPS) is the multisensory space immediately surrounding our body. Visual and tactile stimuli here are promptly processed, since their interaction gradually strengthens as the distance between visual stimulus and the body decreases. Recently, a modified version of the Temporal Order Judgment (TOJ) task was proposed to assess PPS based on the spatial congruence between somatosensory and visual stimuli. Here, we used this paradigm to explore how a temporary vs a permanent state of anxiety can alter PPS. Indeed, previous research showed that PPS boundaries are not fixed, but they can be enlarged by contingent factors (i.e. emotional features). Participants performed the TOJ paradigm twice, just before and after completing an anxiety-inducing task (experimental breathing condition) or a neutral one (control breathing condition), while their trait and state anxiety levels were repeatedly measured. We found that the pattern of visuo-tactile integration in PPS changes in the very opposite way following the two breathing tasks for participants with high levels of temporary anxiety, by strengthening and weakening its power after the experimental and control conditions, respectively. On the contrary, both the breathing tasks are capable of reducing the cross-modal interplay as compared to baseline for high trait-anxious participants, who show an overall stronger visuo-tactile integration inside the PPS than low trait anxious individuals. These results are discussed in the light of the double dissociation between orienting and alerting attentional network over-functioning, reported in state anxiety participants, and impoverished prefrontal attentional control shown by trait anxiety individuals.


Different bacterial host-based lux reporter array for fast identification and toxicity indication of multiple metal ions.
Although luminescent bacteria-based bioluminescence inhibition assay has been widely used in the toxicity assessment of environmental pollutants, the response of a luminescent bacterium usually lacks specificity to a target analyte. Recently, some specific analyte inductive promoters were fused to the lux genes for the purpose of selective bioluminescent sensing, and suits of specific promoters were fused to lux genes to compose a bioluminescent array sensor for simultaneous identification of multiple analytes. However, specific promoter-based methods still suffer from drawbacks including limited selectivity, slow responding time, expensive to construct different promoters involved plasmids, and laborious to find new promoters. Herein, we proposed a novel strategy to construct a lux reporter array sensor by directly transforming the natural lux genes in different bacterial hosts without the involvement of any specific promoters. Due to the distinct pathways of signal production, the responding time of the current different bacterial host (DBH)-based lux reporter array has nearly an order of magnitude faster than with specific promoter-based methods. The DBH-based lux reporter array was successfully used for simultaneous identification, quantification, and toxicity/bioactivity assessment of multiple metal ions. Obviously, all the chemical synthetic material-based metal ion sensing methods cannot simultaneously achieve analysis and toxicity evaluation. This approach possessed additional advantages of facile construction, easy operation, high selectivity, fast response, and strong adaptability to other analytes. A different bacterial host-based lux reporter array was established for simultaneous analysis and toxicity assessment of multiple metal ions.


Metabolomics on serum levels and liver of male Tupaia belangeri from 12 locations in China by GC-MS.
To investigate adaptive strategies of Tupaia belangeri to environmental factors in different populations, 12 locations were selected, including higher and lower altitude areas. Total of 96 and 90 metabolites were annotated in serum and liver respectively, which were mainly concentrated in primary metabolites. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed that the locations were divided into two groups in serum metabolites, but each group had a few samples overlap. The samples of each group overlap to some degree in the liver metabolites. The tricarboxylic acid (TCA) cycle occupies a central position in metabolism. The concentrations of TCA intermediates, lipid metabolites and amino acid metabolites were higher in higher altitude areas, and the concentrations of carbohydrate and glycolysis intermediates were higher in lower altitude areas. Different areas adapted to the changes of environmental and altitude by regulating the concentration of metabolites in serum and liver, and revealed the adaptive mechanism of T. belangeri in different living environments.


Design of amino acid- and carbohydrate-based anticancer drugs to inhibit polymerase η.
DNA polymerase η (polη) is of significant value for designing new families of anticancer drugs. This protein takes a role in many stages of the cell cycle, including DNA replication, translesion DNA synthesis, and the repairing process of DNA. According to many studies, a high level of expression of polη in most cases has been associated with low rates of patients' survival, regardless of considering the stage of tumor cells. Thus, the design of new drugs with fewer side effects to inhibit polη in cancerous cells has attracted attention in recent years. This project aims to design and explore the alternative inhibitors for polη, which are based on carbohydrates and amino acids. In terms of physicochemical properties, they are similar to the traditional anticancer drugs such as Cytarabine (cytosine arabinose). These alternative inhibitors are supposed to disrupt the DNA replication process in cancerous cells and prevent the tumor cells from mitosis. These newly designed structures, which are based on natural products, are expected to be non-toxic and to have the same chemotherapeutic impact as the traditional agents. The combinatorial use of quantum mechanics studies and molecular dynamic simulation has enabled us to precisely predict the inhibition mechanism of the newly designed structure, which is based on carbohydrates and amino acids, and compare it with that of the traditional chemotherapeutic drugs such as Cytarabine. Our results suggest that the inhibitors containing the natural building blocks of amino acid and carbohydrate could be considered alternative drugs for Cytarabine to block polη.


Examining the influence of Mother-in-law on family planning use in South Asia: insights from Bangladesh, India, Nepal, and Pakistan.
Contraceptive use contributes to improved maternal and child health, education, empowerment of women, slow population growth, and economic development. The role of the family in influencing women's health and health-seeking behavior is undergoing significant changes, owing to higher education, media exposure, and numerous government initiatives, in addition to women's enhanced agency across South Asia. Against this backdrop, this study assesses the relationship between women's living arrangements and contraceptive methods used in selected south Asian countries (India, Pakistan, Nepal, and Bangladesh). Data of currently married women aged 15-49 from the recent round of Demographic and Health Survey (DHS) of four South Asian countries, i.e., Nepal (2016), Pakistan (2017-18), Bangladesh (2017-18), and India (2019-21) had been used. Bivariate and multinomial logistic regression was performed using Stata with a 5% significance level. Living arrangement of women had a significant association with contraceptive use in South Asia. The Mother-in-law (MIL) influenced the contraceptive method used by the Daughter-in-law (DIL), albeit a country-specific method choice. Modern limiting methods were significantly higher among women living with MIL in India. The use of the modern spacing method was considerably high among women co-residing with husband and/or unmarried child(ren) and MIL in Nepal and India. In Bangladesh, women living with husband and other family member including MIL were more likely to use modern spacing methods.. Women co-residing with the MIL had a higher likelihood of using any traditional contraceptive method in India. The study suggests family planning program to cover MIL for enhancing their understanding on the benefits of contraceptive use and modifying norms around fertility. Strengthening the interaction between the grassroots level health workers and the MIL, enhancing social network of DIL may help informed choice and enhance the use of modern spacing methods. Women's family planning demands met with modern contraception, and informed contraceptive choices, must also be achieved to reach the 2030 Agenda for Sustainable Development.


Classical versus custom orbital wall reconstruction: Selected factors regarding surgery and hospitalization.
Nowadays, in orbital wall reconstruction, maxillofacial surgeons have the possibility to treat patients in modern ways such as with individual implants. Nevertheless, conventional treatment including standard titanium mesh shaped during the surgical procedure is also widely used. The aim of this study was to compare the above methods of orbital wall reconstructions. In the first group (39 cases), patients were treated by means of computer-aided design/computer-aided manufacturing (CAD/CAM) milled individual implants made of ultra-high-molecular-weight polyethylene, dioxide zirconium and rapid prototyping titanium mesh pre-bent on an ABS model made by a three-dimensional (3D) printer. In the second group (54 cases), intraoperative bending of titanium mesh was implemented. Ophthalmologic outcomes were the same in both groups. In patients who had greater destruction of the orbit, surgical procedures were longer regardless of the material used for individual implants (p < 0.05). Time of surgery was shorter in patients in whom individual implants were used. Intraoperative bleeding was higher in patients who were treated using intraoperative bending titanium mesh (p < 0.01). Application of CAD/CAM techniques do not give better ophthalmologic results in reference center but improve patient condition postoperatively. For this reason, CAD/CAM is a safer treatment method for patients.


Switchable cascade C-H annulation to polycyclic pyryliums and pyridiniums: discovering mitochondria-targeting fluorescent probes.
Disclosed herein is a counterion additive-switched rhodium-catalyzed cascade triple C-H annulation of 4-hydroxy-1-naphthaldehydes with alkynes, in which six chemical bonds are formed in one-pot. This reaction enables the rapid assembly of diverse polycyclic pyrylium and pyridinium fluorophores, which leads to two specific mitochondria-labeling reagents with low cytotoxicity and superior photostability.


Changes in phytochemical content, bioaccesibility and antioxidant capacity of corn tortillas during simulated in vitro gastrointestinal digestion.
There is a little information about the effect of corn process conditions on the bioactive compounds of tortillas during gastrointestinal digestion. Tortillas elaborated with traditional and extrusion nixtamalization process were subjected to in vitro digestion. Extracts recovered from digestion were employed to determine the changes in phytochemicals, bioaccesibility and antioxidant capacity (DPPH, ABTS and FRAP). Digestion contributed to a greater solubilization of phenolic compounds in raw corn and tortillas, especially in the intestinal phase (311.4-583.2 mg GAE/100 g). With bioaccessibility indexes of 162.83 to 960.7 %. Intestinal phase affected the content of anthocyanins, reaching a lower bioaccessibility value than the found in undigested samples (17.90-29.91 %). Even though the traditional white tortilla showed the highest bioaccessibility values, blue tortilla showed a higher antioxidant activity in different phases of digestion. Both tortillas could function as prebiotic agents in the large intestine. Corn-based products are valuable as part of a healthy diet.


Extended treatment with peginterferon α-2a in combination with lamivudine or adefovir for 96 weeks yields high rates of HBeAg and HBsAg seroconversion.
The study aimed to investigate the efficacy and safety of peginterferon α-2a (PEG IFNα-2a) in combination with lamivudine or adefovir in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). In total, 47 patients with HBeAg-positive CHB received either PEG IFNα-2a (135 μg once weekly) plus lamivudine (100 mg daily) or adefovir (10 mg daily). All patients completed 96 weeks of therapy and were followed up for a further 24 weeks. Baseline characteristics and treatment efficacy of the two groups were similar. All patients achieved hepatitis B virus (HBV) DNA <500 copies/mL at 96 weeks, and none had a virological rebound after stopping the therapy. The rate of HBeAg seroconversion was 46.8% at 48 weeks, increased to 74.5% at 96 weeks, and kept at 72.3% at 120 weeks. Hepatitis B surface antigen (HBsAg) seroconversion rate was 6.4% at 48 weeks, increased to 21.3% at 96 weeks, and kept at 27.7% at 120 weeks. Extended treatment with PEG IFNα-2a with lamivudine or adefovir for 96 weeks is a promising strategy to achieve high rates of sustainable HBeAg and HBsAg seroconversion and HBV DNA suppression in patients with HBeAg-positive CHB.


[Arthroplasty of the hip joint with correction of acetabular defects using osteocartilaginous autotransplants].
The author describes a method of autoplastic substitution of defects in the most loaded portions of the cotyloid cavity in patients with tuberculous coxitis. In 5 patients operated on by the method described favourable results were obtained.


Repeat Hepatectomy for Recurrent Colorectal Liver Metastases: Is it Worth the Challenge?
Repeat hepatectomy (RH) is considered a valuable option for management of recurrent colorectal liver metastases (R-CLM). Here, the outcome of RH for R-CLM was compared to that of patients who underwent single hepatectomy (SH) after subdividing the later according to re-recurrence status. Between 2001 and 2013, patients who received hepatectomy for CLM and R-CLM were included in study. Patients with non-resectable R-CLM were excluded. One hundred sixteen patients were included: 86 patients in SH group and 30 patients in RH group. Repeat hepatectomy group had more synchronous CLM (76.7 versus 50 %, p = 0.011). From the 86 patients who underwent SH, 69 patients did not have R-CLM. Survival analysis was done from the time of first hepatectomy for the no R-CLM group and the time of RH for the RH group. The 3- and 5-year survival rates for the no R-CLM group were 66.4 and 48.8%, respectively, and for the RH group were 56 and 44.8% respectively (p = 0.841). Multivariate analysis showed that larger size of R-CLM is an independent risk factor for survival after RH. Repeat hepatectomy for R-CLM shows a comparable OS to non-recurrent CLM after single hepatectomy, despite the RH group had higher incidence of synchronous CLM.


Culture of retinoblastoma cells from clinical specimens: growth-promoting effect of 2-mercaptoethanol.
Establishment of new tumor cell lines is an important first step for biological studies of tumor cells. High success rates in establishing retinoblastoma cell lines have been reported when feeder-layer culture but not liquid-culture techniques were used. Liquid culture is, however, essential for studies in which feeder-layer cells are undesirable. In a previous study, we formulated a medium (RB-- medium), the components of which were almost identical to those of a soft-agar medium developed for colony formation of established retinoblastoma cell lines, in which one cell line from 12 primary retinoblastoma specimens was established. In this study, another medium (RB++ medium), RB-- medium to which 20 microM 2-mercaptoethanol and 375 microM asparagine were added, was tested for its ability to grow retinoblastoma cells from clinical specimens. In the RB++ medium, 6 cell lines from 16 primary sites, 2 from 2 intraocular-recurrent and 3 from 3 metastatic retinoblastomas grew for over a year. The major reason for the apparent improvement of the RB++ medium on the RB-- medium was demonstrated to be the addition of 2-mercaptoethanol.


[Experiment study of c-fos expression on myocardial acute ischemia/reperfusion injury in rats].
To investigate the changes of c-fos mRNA induced by myocardial ischemia/reperfusion(I/R) during acute period. The model of I/R was established, and the rats was divided normal control, ischmia and I/R groups. Insitu hybridization (ISH) and computerized image analysis method was used to observe alteration of c-fos mRNA in cardiac myocytes. After 10 min ischemia and 30 min reperfusion, the area of reperfusion showed a part of cardiac myocytes weak staining, and get to peak at I-60 min/R-30 min. The myocardium in normal control and ischemia groups less than 60 min showed negative staining. No changes were found in all groups by HE staining. c-fos mRNA detection may become an important method for diagnosis of I/R.


Risk of atrial fibrillation as a function of the electrocardiographic PR interval: results from the Copenhagen ECG Study.
Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF). To determine if there was a nonlinear relation between PR interval duration and the risk of AF. We included 288,181 individuals, corresponding to one third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram (ECG) recorded in a general practitioner's core facility from 2001 to 2010. Data on drug use, comorbidity, and outcomes were collected from Danish registries. During a median follow-up period of 5.7 years, 11,087 developed AF. Having a PR interval ≥95th percentile (≥196 ms for women, ≥204 ms for men) was associated with an increased risk of AF as evidenced by a multivariable-adjusted hazard ratio (HR) of 1.18 (95% confidence interval [CI] 1.06-1.30, P = .001) for women and 1.30 (1.17-1.44, P < .001) for men compared with the respective reference groups (PR interval between 40th and 60th percentile). Having a short PR interval <5th percentile (≤121 ms for women, ≤129 ms for men) was also associated with an increased risk of AF for women (HR 1.32, 95% CI 1.12-1.56, P = .001), but this was not significant for men (HR 1.09, 95% CI 0.92-1.29, P = .33). In this large ECG study, we found an increased risk of AF for longer PR intervals for both women and men. With respect to short PR intervals, we also observed an increased risk of AF for women.


Retraction: Down-regulation of HOXB5 inhibits TGF-β-induced migration and invasion in hepatocellular carcinoma cells via inactivation of the PI3K/Akt pathway.
[This retracts the article DOI: 10.1039/C8RA06860G.].


Osteoblastic cells from rat long bone. I. Characterization of their differentiation in culture.
We here report the characterization for osteogenic markers alkaline phosphate (AP), osteocalcin, and mineral deposition of osteoblast cultures derived from cells migrating out from seven-day-old rat tibia fragments. The cells outgrown from bone fragments responded to stimulation with PTH with cAMP increase. We show in these cultures a high level of biosynthesis of type III collagen and osteonectin, and report the stimulatory effect that conditioned serum-free media (CM) from these cultures exert on the migration of endothelial cells (EA hy 926). The cultures were kept for the initial seven days in a Coon's modified F12 medium, then were switched to a medium containing ascorbic acid and beta-glycerophosphate (BGP), and cultured for another 41 days. They showed constitutive and timely restricted osteoblast markers and mineralization. Maximal AP activity occurred in concomitance with cell doubling, then fell to low levels by the time cultures were stationary. 45Ca incorporation in the monolayer increased after four weeks of culture, in concomitance with the appearance of unmineralized nodules, and remained high throughout the phase of mineral deposition. Biosynthesis of collagens type I, type III, and type V was detected at all times; secreted newly synthesized collagens decreased overall, relative to total secreted newly synthesized proteins, and on a per cell basis, with progression of the culture, while the ratio of collagen type III/collagen type I increased. Osteonectin was detected by immunohistochemistry and high amounts of osteonectin were synthesized constitutively. Osteocalcin was detected on virtually all cells tested at 21 and 28 days. A preliminary step in neoangiogenesis is the migration of endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Photo-chemical aspects of iron complexes exhibiting photo-activated chemotherapy (PACT).
Iron is the trace element of natural selection by the biological systems due to its versatile coordination chemistry, and is recently explored for medicinal and diagnostic applications. Photo-activated states of iron complexes exhibiting substitution, dissociation, isomerization reactions, intramolecular redox reactions or energy transfer to other molecules have attracted the attention across the globe for the potent applications in photo-chemotherapy. There is a significant advancement on the development of iron-based complexes for photochemotherapeutic applications. Here in we reviewed the photo-activated states and photochemistry of iron complexes, and recent advances made in the area of photochemotherapy of iron complexes relevant to the photochemistry of iron complexes.


The current status of orthodontic education in U.S. pediatric dental residencies.
The purpose of this study was to survey the current status of orthodontic education at pediatric dental residencies in the United States. A similar survey was conducted >10 years ago. With changing healthcare politics, social demands, and technology, it is important to have current information about dental education. A 23-item anonymous survey was sent to individual pediatric dental residency program directors via Qualtrics email software. The survey was sent a total of 4 times over an 8-week period. If the surveys were not completed in a predetermined amount of time, they were resent to those who had not yet completed them. There were 34 responders for a 24% response rate. Of the respondents, 73% reported teaching biomechanics of tooth movement, and 45% reported teaching 2 × 4 mechanics to "marginally acceptable" level. Early (91%) to late mixed dentition (77%) is the most commonly treated orthodontic case. While most programs do not require a minimum number of orthodontic cases for graduation (85%), residents' understanding of growth and development is mostly (71%) evaluated through the results of the American Board of Pediatric Dentistry Qualifying Examination. This study summarizes the current climate of the orthodontic education component in U.S. pediatric dental residencies.


Association of insulin resistance with intra- and extra-cranial atherosclerotic burden in the nondiabetic community population.
Few population-based studies have investigated the association between insulin resistance and atherosclerotic burden in intra- and extra-cranial arteries. The purpose of this study is to explore the relationship between insulin resistance and intra- and extra-cranial atherosclerotic burden in community-based nondiabetic participants. This is a cross-sectional analysis from a population-based prospective cohort-PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI0-120) were stratified by the quartiles, respectively. The atherosclerotic presence of plaques and burden was evaluated by high-resolution MRI. Binary or ordinal logistic regression was performed to assess the association between HOMA-IR or ISI0-120 and the presence and burden of atherosclerosis. Among the 2754 participants, the mean age was 60.9 ± 6.6 years, and 1296 (47.1%) were males. Compared with the lowest quartile of HOMR-IR, the highest quartile of HOMA-IR (indicating a higher level of insulin resistance) was associated with an increased presence of plaques (OR:1.54, 95% CI:1.14-2.08), and atherosclerotic burden (OR:1.53, 95%CI:1.14-2.07) in intracranial arteries. Meanwhile, we observed a similar relationship between HOMA-IR and the presence or burden in extracranial atherosclerosis. The first (indicating a higher level of insulin resistance) quartiles of ISI0-120 were associated with the intracranial plaques (Q1, OR:1.56, 95%CI:1.16-2.11) and atherosclerotic burden (Q1, OR:1.57, 95%CI:1.17-2.12), but not extracranial plaques or atherosclerotic burden, compared with the fourth quartile of ISI0-120. Insulin resistance was associated with an increased intra-and extra-cranial atherosclerotic burden in the nondiabetic elderly Chinese population.


Comparison of intracytoplasmic sperm injection outcomes in azoospermic men who underwent testicular sperm extraction vs. microdissection testicular sperm extraction: A cross-sectional study.
Outcomes of intracytoplasmic sperm injection (ICSI) may be different in azoospermic men who undergo testicular sperm extraction (TESE) vs. microdissection-TESE (micro-TESE). This study was conducted to compare the ICSI outcomes in men who underwent TESE vs. micro-TESE due to obstructive azoospermia and nonobstructive azoospermia, respectively. A total of310azoospermic men who underwent ICSI from September 2016 to September 2020 were enrolled in this cross-sectional study and divided into two groups (172 cases in the TESE and 138 cases in the micro-TESE group). The paternal and maternal age, and the fertilization, biochemical pregnancy, abortion and live birth rates were compared between the two groups. Maternal mean age was significantly higher in the TESE group (34.9 ± 4.2 yr vs. 32.3 ± 5.7 yr). The fertilization and biochemical pregnancy rates were significantly higher in the TESE group, but the abortion rate was similar in the two groups. The live birth rate was higher in the TESE group, but this difference was not significant (p = 0.06). Also, the maternal and paternal age did not affect ICSI outcomes. Individuals who underwent TESE had higher fertilization and biochemical pregnancy rates than those who underwent micro-TESE, but the live birth rate was not significantly different.


Congenital esophagobronchial fistula in an adult.
Congenital esophagobronchial fistula occurring in infancy and childhood is a well-recognized entity necessitating urgent surgical treatment. Persistence of such a communication into adulthood is rare and would seem possible only if the tract were small so that aspiration into the lung could be tolerated. The case of a 38-year-old woman is presented in this report who was cured of lifelong symptoms of aspiration by surgical division of a presumed congenital esophagobronchial fistula.


Calcium and phosphorus balance in very low birth weight babies on total parenteral nutrition.
A balance study of Ca and P has been performed in 12 Very Low Birth Wt babies receiving prolonged Total Parenteral Nutrition. The mean intake of both minerals was 54.4 mg/kg/day (range 40-70). In order to avoid the formation and precipitation of CaP crystals in the solution, fructose-1,6-diphosphate was used as a source of P. 30 balance studies were performed between the seven and 63 day of life: they were always positive with a mean retention of 47.4 mg/kg/day of Ca and 48.1 mg/kg/day of P. For both minerals, 88% of the amount infused was retained: the correlation between intake and retention was linear and statistically significative (Ca:r = 0.9, p < 0.0001; P:r = 0.68, p < 0.0001). The post-natal and post-conceptional ages of the babies had no influence on Ca and P balance. The blood levels of Ca and P were poorly correlated to both intake and excretion, and were not as indicative of the mineral balance as the retention rates calculated on the basis of the 24 h urinary excretion of the minerals. A very useful test for clinical monitoring of Ca and P balance proved to be the Ca/creatinine and P/creatinine ratios measured on simple urine samples, which were strongly correlated to 24 h excretion. All infants developed radiological signs of mild osteopenia, but there was no case of acute metabolic derangement or rickets. Our data demonstrated that even in sick VLBW infants on TPN it is possible to achieve good retention rates of Ca and P, which are not different from those observed in well VLBW babies fed a 'standard' premature formula.


Exploration of a methodology aimed at exploring the characteristics of teenage dating violence and preliminary findings.
The aim of this study was to explore a novel approach toward investigating violence in adolescent dating relationships by administering a reflective survey to female college students. RESEARCH HYPOTHESIS: Results from the Danger Assessment (DA) tool and the Abuse Assessment Screen (AAS) will be highly correlated with concepts from the Theory of Female Adolescents' Safety as Determined by the Dynamics of the Circle (TFASDC). A descriptive cross-sectional survey of 188 female college students was conducted. This study was carried out in a Northeastern academic university and health center. MAIN RESEARCH VARIABLES AND MEASUREMENT: Main research variables and measurement included the AAS, the DA, and concepts from the TFASDC. One in three participants reported dating violence on the DA; and one in five, on the AAS. Nine percent of the sample reported forced sex on the DA. Concepts from the TFASDC correlated to dating violence include the following: low scores on group belonging, increased number of sex and/or dating partners, dating an older boy, and time in relationship. The TFASDC holds promise for use as both a risk- and a strength-based assessment in teenagers, with the ultimate goal of fostering the development of healthy relationships.


A possible role of the plasmalemmal cytoskeleton, nitric oxide synthase, and innervation in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study.
In reference to a possible neuropathy in the pathogenesis of infantile hypertrophic pyloric stenosis (IHPS), previous studies have described alterations in peptidergic transmission while others have recently attributed an important role to nitrinergic activity. Little attention has been given to the organization of the extracellular matrix (ECM) and the constituent cytoskeleton and subsarcolemma of the pyloric smooth-muscle cell. To study a possible relationship between neuronal and muscular elements in IHPS, 9 biopsies from patients with IHPS and 5 biopsies of normal pylorus were examined using immunohistochemical techniques with regard to the distribution of nerve cells and fibers (bNOS and PGP 9.5) and the ECM (laminin) and cytoskeleton (talin, vinculin, dystrophin, alpha-smooth iso-actin, desmin) components of the pyloric muscle. Our results showed anti-protein gene product 9.5 and b-nitric oxide synthase immunoreaction respectively reduced or absent in nerve fibers with a positive reaction inside the ganglion cells. An uneven distribution of the ECM component laminin was evident, together with a negative immunoreaction to talin and dystrophin. The imunolocalization of vinculin, alpha-smooth iso-actin, and desmin was similar to the controls. Our findings suggest that there is a close relationship between the nerve and muscle elements in the pathophysiology of IHPS and that non-alteration of some elements of cytoskeleton organization can play an important role in regaining pyloric function after pyloromyotomy.


Molecular signaling in the regulation of mucins.
Mucins are large, highly glycosylated proteins involved in the protection of epithelia. The 20 different mucins show a diverse and highly regulated distribution among different epithelia. Most of the studies on mucin regulation done to date have been on the membrane mucins MUC1 and MUC4 and the gel-forming mucins. Multiple mechanisms have been implicated in that regulation, including examples at the transcriptional, transcript stabilization and post-translational levels. Several signaling pathways have been demonstrated to be involved, most frequently the canonical Erk MAP kinase pathway, but also the cytokine-JAK-STAT pathway and TGFbeta-SMAD pathways. Diversity in Erk signaling is achieved through multiple activation mechanisms and multiple downstream transcriptional factors that are affected. Given the still limited amount of information available on regulation of most of the mucins, other mechanisms and pathways are likely to be uncovered in the future.


Adaptive mechanisms to oxidative stress during aging.
Whether or not oxidative stress is the cause of the aging process, as proposed by the oxidative stress theory of aging remains unknown; but accumulated evidence overwhelmingly identifies increased oxidative stress with age as a source of damage to cellular structure and function. From an evolutionary perspective, the utilization of oxygen as a life supporting means makes oxidative stress an inescapable part of an organism's biological system. The inseparability of oxidative stress from the biological system can be viewed as an adaptive response that all aerobic organisms undergo to ward-off the potentially harmful effects of oxygen and its derivatives, including free radicals. The organism's adaptive mechanisms include an intricate network of defenses that regulate and guard against any over-acting oxidative reactions to ensure its survival. This review discusses and illustrates several adaptive responses at various levels (from gene regulation to physical exercise) that organisms use as part of their survival strategy.


Identification of myokines susceptible to improve glucose homeostasis after bariatric surgery.
The identification of myokines susceptible to improve glucose homeostasis following bariatric surgery could lead to new therapeutic approaches for type 2 diabetes. Changes in the homeostasis model assessment (HOMA) test were assessed in patients before and 3 months after bariatric surgery. Changes in myokines expression and circulating levels were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Myokines known to regulate glucose homeostasis were identified using literature (targeted study) and putative myokines using RNA-sequencing (untargeted study). A linear regression analysis adjusted for age and sex was used to search for associations between changes in the HOMA test and changes in myokines. In the targeted study, brain-derived neurotrophic factor (BDNF) expression was upregulated (+30%, P = .006) while BDNF circulating levels were decreased (-12%, P = .001). Upregulated BDNF expression was associated with decreased HOMA of insulin resistance (HOMA-IR) (adjusted estimate [95% confidence interval {CI}]: -0.51 [-0.88 to -0.13], P = .010). Decreased BDNF serum levels were associated with decreased HOMA of beta-cell function (HOMA-B) (adjusted estimate [95% CI] = 0.002 [0.00002-0.0031], P = .046). In the untargeted study, upregulated putative myokines included XYLT1 (+64%, P < .001), LGR5 (+57, P< .001), and SPINK5 (+46%, P < .001). Upregulated LGR5 was associated with decreased HOMA-IR (adjusted estimate [95% CI] = -0.50 [-0.86 to -0.13], P = .009). Upregulated XYLT1 and SPINK5 were associated with increased HOMA of insulin sensitivity (HOMA-S) (respectively, adjusted estimate [95% CI] = 109.1 [28.5-189.8], P = .009 and 16.5 [0.87-32.19], P = .039). Improved glucose homeostasis following bariatric surgery is associated with changes in myokines expression and circulating levels. In particular, upregulation of BDNF, XYLT1, SPINK5, and LGR5 is associated with improved insulin sensitivity. These results suggest that these myokines could contribute to improved glucose homeostasis following bariatric surgery. NCT03341793 on ClinicalTrials.gov (https://clinicaltrials.gov/).


Individual levels of activity of O6-alkylguanine-DNA alkyltransferase in monkey gastric mucosa during chronic exposure to a gastrocarcinogen N-ethyl-N'-nitro-N-nitrosoguanidine.
The activity of a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), was studied in gastric mucosa of 15 Macaca fascicularis monkeys before and during chronic oral exposure to the ethylating carcinogen N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in order to investigate possible causes of inter-individual differences in susceptibility to its gastrocarcinogenic effect. A wide range of AGT activity (307-1903 fmol/mg protein, mean 695) was found before treatment and it decreased during the first year of exposure (means 627, 479 and 452 fmol/mg protein respectively at 6, 12 and 18 months after the beginning of the experiment). The carcinogenesis study is under way and to date four monkeys with low initial AGT level in gastric mucosa died of gastric cancer. The relevance of AGT level measurement for prediction of individual susceptibility to ENNG is discussed.


Role of Metformin, Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Orlistat based Multidrug Therapy in Glycemic Control, Weight Loss, and Euglycemia in Diabesity: A Real-World Experience.
This study evaluated the real-world weight loss and glycemic outcomes of multidrug therapy (MDT) according to various combinations of metformin, sodium-glucose cotransporter -2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor analogs (GLP1a), and orlistat in diabesity. Data retrospectively captured from medical records of 2 different centers in New Delhi for patients >35 years-age having prediabetes/diabetes and on at least any one of the 4 above medications with >6-months follow-up was analyzed. In total, 5,336 patient records were screened; 2,442 with prediabetes/diabetes were considered; 1,509 patients who fulfilled all criteria were analyzed. Use of metformin, SGLT2i, sulfonylureas, DPP4i, pioglitazone, orlistat, and GLP1a was 85.35%, 74.95%, 68.32%, 60%, 39.16%, 9.08%, and 4.17%, respectively. However, 365, 970, and 104 patients were on one of 4 concerned medications (Group-1; 24.18%), dual MDT (Group-2; 64.28%), and triple/quadruple MDT (Group-3; 6.89%). Metformin with SGLT2i was most commonly used dual MDT (94.12%). Analysis according to weight-loss quartiles from 558 patients showed 6.9 kg weight-loss in the highest quartile. People losing maximum weight were significantly younger; had higher use of metformin, SGLT2i, GLP1, orlistat, and lower pioglitazone use; greatest HbA1c reduction (-1.3 vs. -0.3; quartile-1 vs. quartile -4; P < 0.001); and significantly higher occurrence of HbA1c<5.7% (16.8% vs. 6.29%; quartile-1 vs. 4; P < 0.001). Patients in Group-3 had the highest baseline BMI and maximum weight loss with highest number of patients with HbA1c<5.7% (19.44% vs. 10.34%; Group-3 vs. Group-1; P < 0.001). Greater weight loss with HbA1c reduction along with a greater number of patients attaining HbA1c <5.7% highlights that MDT is the way forward to tackle diabesity in India.


An experimental study on using a diagnostic computed radiography system as a quality assurance tool in radiotherapy.
The advent of improved digital imaging modalities in diagnostic and therapy is fast making conventional films a nonexistent entity. However, several radiotherapy centers still persist with film for performing quality assurance (QA) tests. This paper investigates the feasibility of using a diagnostic computed radiography (CR) system as a QA tool in radiotherapy. QA tests such as light field congruence, field size verification, determination of radiation isocentre size, multileaf collimator (MLC) check and determination of isocentric shift for stereotactic radiosurgery (SRS) were performed and compared with film. The maximum variation observed between CR and film was 0.4 mm for field size verification, -0.13 mm for the radiation isocentre size check, 0.77 for MLC check and -0.1 mm for isocentric shift using the Winston Lutz test tool for SRS QA. From these results obtained with the CR it is concluded that a diagnostic CR system can be an excellent cost-effective digital alternative to therapy film as a tool for QA in radiotherapy.


Family Medicine Resident Perspectives on Curricula in Herbal Medicine.
Despite widespread patient use, herbal and dietary supplement education is not required in US-accredited medical schools. Thus, physicians are unprepared to address supplement use with patients. Our objectives were to assess perceived adequacy of medical education on supplements, determine resident perspectives on appropriate placement of curricula in their longitudinal medical education, and evaluate the effects of an innovative workshop on family medicine resident knowledge about supplements and intentions to address this topic with patients. Family medicine residents (N=65) participated in an hour-long workshop covering basic concepts about herbal and dietary supplements, including regulations, literature review techniques, and risk/benefit analysis. The participants completed pre/postworkshop surveys to assess need for increased education and evaluate efficacy of the workshop. Most participants (91.9%) thought they should have received more education than provided on supplements and perceived greater need for curricula in undergraduate medical education than in graduate medical education. Only 47.6% received required education on supplements, significantly less than the 72.6% who thought this education should be required (P<0.05). The workshop increased the proportion of residents planning to address patients' supplement use, increased the frequency residents intend to ask about supplements, and improved resident perceptions of the efficacy of some supplements when used with physician guidance. Residents perceived a lack of adequate medical education on the use of herbal and dietary supplements. Results showed a brief workshop increased resident intentions to discuss supplement use with patients. Further education on supplement use may be warranted.


Interactions between the Fusarium toxin deoxynivalenol and lipopolysaccharides on the in vivo protein synthesis of acute phase proteins, cytokines and metabolic activity of peripheral blood mononuclear cells in pigs.
The in vivo effects of the Fusarium toxin deoxynivalenol (DON) on albumin and fibrinogen synthesis in pigs and metabolic activity of porcine peripheral blood mononuclear cells (PBMCs) were studied alone or in combination with lipopolysaccharides (LPSs) in order to examine proposed synergistic effects of both substances. A total of 36 male castrated pigs (initial weight of 26 kg) were used. Uncontaminated (Control) and naturally DON-contaminated (chronic oral DON, 3.1mg/kg diet) wheat was fed for 37 days. On the day of protein synthesis measurement, pigs recruited from the Control group were treated once intravenously with (iv) DON (100 μg/kg live weight (LW)/h), iv LPS (7.5 μg/kgLW/h) or a combination of both substances, and six pigs from the chronic oral group were treated once with iv LPS. A treatment with DON alone exhibited no alterations of acute phase protein synthesis and metabolic activity of PBMC. There was no evidence that the chosen dosing regimen of DON had influences on the induced sub-acute stage of sepsis, as the LPS challenge, irrespective of DON co-exposure, mediated an acute phase reaction with a typical decrease of albumin synthesis, as well as changes in cytokine concentration and a loss of metabolic activity in PBMC.


Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3β sequence associated with remission in one patient is detectable in other vaccinated patients.
Clinically effective T-cell responses can be elicited by single peptide vaccination with Wilms' tumor 1 (WT1) epitope 126-134 in patients with acute myeloid leukemia (AML). We recently showed that a predominant T-cell receptor (TCR) β chain was associated with vaccine-induced complete remission in an AML patient (patient 1). In this study, we address the question of whether this predominant clone or the accompanying Vβ11 restriction could be found in other AML patients vaccinated with the same WT1 peptide. For assessment of Vβ usage, cytotoxic T lymphocytes (CTLs) from four vaccinated patients were divided into specific and non-specific by epitope-specific enrichment. Vβ families were quantified in both fractions using reverse transcribed quantitative PCR. Vβ11-positive 'complementary determining region 3' (CDR3) sequences were amplified from these samples, from bone marrow samples of 17 other vaccination patients, and from peripheral blood of six healthy controls, cloned and sequenced. We observed a clear bias towards Vβ11 usage of the WT1-specific CTL populations in all four patients. The predominant CDR3β amino acid (AA) sequence of patient 1 was detected in two other patients. CDR3β loops with closely related AA sequences were only found in patient 1. There were no CDR3β AA sequences with side chains of identical chemical properties detected in any patient. We provide the first data addressing TCR Vβ chain usage in WT1-specific T-cell populations after HLA A*0201-restricted single peptide vaccination. We demonstrate both shared Vβ restriction and the sharing of a TCR β transcript with proven clinical impact in one patient.


Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline.
Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two β-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis.


Incidental pathologic extracardiac uptake of (99m)Tc-tetrofosmin in myocardial perfusion imaging: Importance of patient background evaluation.
(99m)Tc-tetrofosmin single photon emission computed tomography ((99m)Tc-tetrofosmin SPECT) has an important role in the assessment of coronary artery disease. Despite being its main indication, this study does not only evaluate myocardial perfusion, but much more. Moreover, during the SPECT acquisition, the field area covered includes many important organs of the thorax and abdomen, so extracardiac abnormalities can be observed. The correct etiologic diagnosis of them is only possible if we understand how (99m)Tc-tetrofosmin works and make a comprehensive investigation of the clinical history of the patient.


Pyrolysis behavior and economics analysis of the biomass pyrolytic polygeneration of forest farming waste.
The pyrolysis behavior of Chinese chestnut and Jatropha curcas shells (CNS and JCS, respectively) were investigated to determine the optimum operating temperature for biomass pyrolytic polygeneration systems. At low temperatures (250-450 °C), CO2 was the main component of the pyrolytic gas, and high acidity oil was obtained. When the temperature increased to 550-650 °C, phenol-enriched oil and high LHV biochar (∼26 MJ/kg) were obtained; H2 and CO yields increased. At high temperatures (750-950 °C), heavy-oil and high LHV pyrolytic gas (∼15 MJ/m3) were obtained. Meanwhile, the biochar showed a highly condensed aromatic ring system and low H/C (∼0.1) and O/C (∼0.05) ratios. CNS and JCS biochars showed different tendencies with regard to their structure evolution. An economic analysis was performed, which suggested that the optimum operating temperatures were 450 °C for CNS and 350 °C for JCS.


Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma.
Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germline variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.


Personality and demographic correlates of New Zealanders' confidence in the safety of childhood vaccinations.
Despite extensive scientific evidence on the safety of standard vaccinations, some parents express skeptical attitudes towards the safety of childhood immunisations. This paper uses data from the 2013/14 New Zealand Attitudes and Values Study (NZAVS) survey (N=16,642) to explore the distribution, and demographic and personality correlates of New Zealanders' attitudes towards the safety of childhood vaccinations. Around two thirds (68.5%) of New Zealanders strongly agreed/were confident that "it is safe to vaccinate children following the standard New Zealand immunisation schedule," 26% were skeptical and 5.5% were strongly opposed. Multiple regression analysis indicated that people lower on Conscientiousness and Agreeableness but higher on Openness to Experience expressed lower confidence about vaccine safety. Having higher subjective health satisfaction, living rurally, being Māori, single, employed and not a parent were all associated with lower confidence, while a higher income and educational attainment were associated with greater confidence. Our findings suggest that the majority of New Zealand adults trust in the safety of scheduled childhood vaccinations, but about one third do express some degree of concern. This finding highlights the importance of improving public education about the safety and necessity of vaccinations.


Voyager 1 explores the termination shock region and the heliosheath beyond.
Voyager 1 crossed the termination shock of the supersonic flow of the solar wind on 16 December 2004 at a distance of 94.01 astronomical units from the Sun, becoming the first spacecraft to begin exploring the heliosheath, the outermost layer of the heliosphere. The shock is a steady source of low-energy protons with an energy spectrum approximately E(-1.41 +/- 0.15) from 0.5 to approximately 3.5 megaelectron volts, consistent with a weak termination shock having a solar wind velocity jump ratio r=2.6(-0.2)(+0.4). However, in contradiction to many predictions, the intensity of anomalous cosmic ray (ACR) helium did not peak at the shock, indicating that the ACR source is not in the shock region local to Voyager 1. The intensities of approximately 10-megaelectron volt electrons, ACRs, and galactic cosmic rays have steadily increased since late 2004 as the effects of solar modulation have decreased.


What is an autotroph?
The concept of autotrophy depends on the growth media for pure cultures supplying a single one carbon source for anabolism. Secondary carbon compounds added to the medium as chelators and/or vitamins confuse the meaning. This note suggests a clarification of definition suitable for contemporary biochemical studies of true autotrophs.


End-of-life passenger vehicles recycling decision system in China based on dynamic material flow analysis and life cycle assessment.
China's automobile industry is developing rapidly, but the recycling rate of end-of-life vehicles has been low. In 2018, the recovery rate of end-of-life passenger vehicles was less than 18% of the scrapped amount. Dynamic material flow analysis can predict the amount of end-of-life passenger cars in China in the future, and analyze the flow of materials in recycling system. Life cycle assessment can be used to quantify greenhouse gas emissions. Therefore, this paper integrates these two methods into the model construction of recycling decision system. Meanwhile, sensitivity analysis of the important factors affecting the efficiency of the recovery system is carried out. Finally, the main recovery indexes of the system are predicted under three scenarios: low-speed, medium speed and high-speed development, which are set based on scrap volume, standard recovery rate, proportion of assembly into remanufacturing and carbon tax price. The research results show that in 2018, 656.9 kg/vehicle of iron, 150.2 kg/vehicle of aluminum and 7.9 kg/vehicle of copper are recovered from end-of-life passenger car in China, and the carbon emission during the recovery process is 651.1 kg of CO2eq/vehicle, with a total emission reduction of 3816.1 kgCO2eq/vehicle compared with the original production, and the economic benefit is about 5055.5 yuan/vehicle. The scenario prediction results show that by 2050, from the low-speed development scenario to the high-speed development scenario, the total amount of iron, aluminum and copper recovered rise from 3.96 million tons, 915 thousand tons and 46 thousand tons to 697 thousand tons, 1.61 million tons and 80 thousand tons respectively throughout the year. The carbon emission in the recovery process rise from 4.98 thousand tons to 9.32 million tons. Compared with the original production, the carbon emission reduction increases from 2.21 million tons to 38.3 million tons, the economic benefit increases from 58.9 billion yuan to 118.8 billion yuan, and the comprehensive benefit increases from 57 billion yuan to 111.6 billion yuan.


Use of statistical process control to support improved care for patients with acute myocardial infarction eligible for thrombolytic treatment: experience from 2 hospitals in England during 2002-2003.
Efforts to reduce mortality from acute myocardial infarction (MI) through expediting thrombolytic and other reperfusion treatments have included the publication of clinical guidelines and standards of care for "door-to-needle" time in many countries. Across England, the National Service Framework, a national program of reform of cardiac care in the National Health Service, has resulted in, inter alia, significant reductions in treatment delay for thrombolysis-eligible patients. One component of the improvement program has been the use of service improvement methodologies, including statistical process control. We describe the early experience of 2 general hospitals in improving care of thrombolysis-eligible MI patients.


Geographic inequalities in health intervention coverage - mapping the composite coverage index in Peru using geospatial modelling.
The composite coverage index (CCI) provides an integrated perspective towards universal health coverage in the context of reproductive, maternal, newborn and child health. Given the sample design of most household surveys does not provide coverage estimates below the first administrative level, approaches for achieving more granular estimates are needed. We used a model-based geostatistical approach to estimate the CCI at multiple resolutions in Peru. We generated estimates for the eight indicators on which the CCI is based for the departments, provinces, and areas of 5 × 5 km of Peru using data from two national household surveys carried out in 2018 and 2019 plus geospatial covariates. Bayesian geostatistical models were fit using the INLA-SPDE approach. We assessed model fit using cross-validation at the survey cluster level and by comparing modelled and direct survey estimates at the department-level. CCI coverage in the provinces along the coast was consistently higher than in the remainder of the country. Jungle areas in the north and east presented the lowest coverage levels and the largest gaps between and within provinces. The greatest inequalities were found, unsurprisingly, in the largest provinces where populations are scattered in jungle territory and are difficult to reach. Our study highlighted provinces with high levels of inequality in CCI coverage indicating areas, mostly low-populated jungle areas, where more attention is needed. We also uncovered other areas, such as the border with Bolivia, where coverage is lower than the coastal provinces and should receive increased efforts. More generally, our results make the case for high-resolution estimates to unveil geographic inequities otherwise hidden by the usual levels of survey representativeness.


Metabolic effects of various antihypertensive agents.
Mortality resulting from coronary artery disease and sudden death has not been significantly reduced by the use of antihypertensive medications in patients with hypertension, despite evidence that hypertension is a major risk factor for myocardial infarction. One possible reason is that the drugs used may have adverse metabolic effects that negate the beneficial effect of lowering blood pressure. Diuretics and beta-blocking agents produce a wide range of biochemical or metabolic alterations-e.g., changes in plasma potassium and in lipoprotein profiles. In general, fewer or less marked alterations are associated with the use of angiotensin-converting enzyme inhibitors, alpha-adrenergic blockers, and slow calcium channel blocking drugs. The effects of these agents alone and in combination and their potential relationship with coronary adverse events are reviewed. Although the clinical relevance of these alterations has yet to be fully determined, it is rational to suggest that given or current knowledge, the antihypertensive agent selected for use should be an effective, well-tolerated drug with a minimum of adverse biochemical or metabolic effects.


[Aims of the guidelines for diagnostic and treatment of fibromyalgia syndrome].
The guidelines aim to provide all professions involved in the treatment of fibromyalgia syndrome (FMS) a systematically developed basis for the diagnosis and therapy of FMS. Diagnostic criteria and empirically founded therapies are presented to reduce the currently insufficient medical care for FMS patients. Recommendations for a stepwise therapeutic approach are designed to improve the quality of medical care, the implementation of effective treatment options as well as reduction of the utilization of non-effective therapies and improvement of the patient-physician relationship. Recommendations on the coordination of medical care (inpatient and outpatient treatment by family physicians, medical specialists and other medical professions, care in emergency and rehabilitation hospitals) aim to reduce rivalry between medical societies and to promote an optimal use of resources. A patient version of the guidelines is aimed at improving patients' knowledge on the etiology and effective treatment options available thus promoting an effective self-management of patients.


Cytotoxic versus anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood cells caused by guaianolide-type sesquiterpene lactones.
Four guaianolide type sesquiterpene lactones (SL), namely the new 1,2-dihydro-3-oxo-costic acid guaianyl ester 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6beta,12-olide (1) and 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6alpha,12-olide (2), as well as the known moroccolide A [5alphaH-2beta,4-epoxy-3beta-hydroxy-guaia-1(10),11(13)-dien-6beta,12-olide, 3] and 3beta-O-(2-methylbutyryl)-moroccolide A [5alphaH-2beta,4-epoxy-3beta-(2-methylbutyryloxy)-guaia-1(10),11(13)-dien-6beta,12-olide, 4] were examined for their cytotoxic and anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood mononuclear cells. Compounds 1, 2 and 4 were found to exert a strong cytotoxicity similar in potency in all investigated cell types, whereas 3 was significantly less active. Along with the cytotoxic effect compounds 1 and 4 showed a potent and comparable down-regulation of the mRNAs of the house-keeping genes beta-actin and GAP-DH in PBMCs after 20 h. In contrast, the down-regulation of the PMA-induced mRNA levels of the NF-kappaB-driven pro-inflammatory genes IL-2, IL-6, GM-CSF, TNF-alpha, and IL-1beta in PBMCs is significantly stronger with compound 4. Compound 3 did not significantly modulate cytokine mRNAs levels at biochemically relevant concentrations. The electromobility shift assay (EMSA), revealed a stronger inhibition of NF-kappaB for 1 (IC(50) 2.5 microM) than for 4 (IC(50) 5 microM). Both compounds were also subjected to an IL-6 luciferase reporter gene assay and showed IC(50) values of 1.0 (1) and 1.2 microM (4). Thus, the NF-kappaB inhibition measured by EMSA, as well as the IL-6 luciferase assay did not reflect the differential modulation of pro-inflammatory genes measured with RT-rt-PCR.


Gd-DTPA-enhanced MR imaging of leptomeningeal spread of primary intracranial CNS tumor in children.
Three children with known primary brain neoplasms and leptomeningeal disease were evaluated with MR imaging. Two of the patients had medulloblastoma and one had pineoblastoma. The presence of leptomeningeal tumor spread was established by positive CSF cytopathology in conjunction with compatible contrast-enhanced CT findings. Contrast-enhanced CT, nonenhanced MR, and Gd-DTPA-enhanced MR studies were then compared. In two cases, leptomeningeal lesions were seen better with Gd-DTPA-enhanced MR than with contrast-enhanced CT. In all three cases, Gd-DTPA MR imaging revealed lesions that were not identified on noncontrast MR. Gd-DTPA-enhanced MR imaging is useful when searching for intracranial leptomeningeal tumor deposits in pediatric patients at risk for this condition.


Psychosocial correlates of the impact of road traffic accidents among South African drivers and passengers.
The aim of the study was to investigate the psychosocial consequences and coping strategies among accident victims in South Africa. Participants (138 drivers and 141 passengers) who had been involved in a road traffic accident were approached and interviewed in public places. In both groups the median age group was between 25 years and 34 years. In 34 accidents (12.2%) a family member was killed, in 68 accidents (24.4%) a non-family member was killed in the accident. In 272 accidents 197 (72.4%) persons (both drivers and passengers) were injured and 168 (61.7%) were hospitalized. Eighty-seven drivers (63%) did not perceive themselves at fault and 51 (37%) did. Following the road traffic accident both drivers and passengers showed a significant decline of their well-being. Drivers who perceived themselves to be at fault did not cope better than those not perceiving themselves at fault. Passengers related to the drivers showed more decline in their well-being than those not related. Path analysis for drivers found that holding oneself responsible had a direct, and mediated by self-blame, guilt and family distress, negative effect on personal well-being. In the passengers group, holding the driver or others responsible led, mediated by increased self-blame, feelings of guilt, and family distress, to lower psychological well-being (PWB). Findings have relevant implications for the development of coping strategies to aid victims of road traffic accidents in dealing with their trauma in this African context, which may differ to those in Western societies.


A federated graph neural network framework for privacy-preserving personalization.
Graph neural network (GNN) is effective in modeling high-order interactions and has been widely used in various personalized applications such as recommendation. However, mainstream personalization methods rely on centralized GNN learning on global graphs, which have considerable privacy risks due to the privacy-sensitive nature of user data. Here, we present a federated GNN framework named FedPerGNN for both effective and privacy-preserving personalization. Through a privacy-preserving model update method, we can collaboratively train GNN models based on decentralized graphs inferred from local data. To further exploit graph information beyond local interactions, we introduce a privacy-preserving graph expansion protocol to incorporate high-order information under privacy protection. Experimental results on six datasets for personalization in different scenarios show that FedPerGNN achieves 4.0% ~ 9.6% lower errors than the state-of-the-art federated personalization methods under good privacy protection. FedPerGNN provides a promising direction to mining decentralized graph data in a privacy-preserving manner for responsible and intelligent personalization.


Alterations in eliminative and sexual reflexes after spinal cord injury: defecatory function and development of spasticity in pelvic floor musculature.
Spinal cord injury often results in loss of normal eliminative and sexual functions. This chapter is focused on defecatory function, although aspects of micturition and erectile function will be covered as well due to the overlap in anatomical organization and response to injury. These systems have both autonomic and somatic components, and are organized in the thoracolumbar (sympathetic), lumbosacral (somatic), and sacral (parasympathetic) spinal cord. Loss of supraspinal descending control and plasticity-mediated alterations at the level of the spinal cord, result in loss of voluntary control and in abnormal functioning of these systems including the development of dyssynergies and spasticity. There are several useful models of spinal cord injury in rodents that exhibit many of the autonomic dysfunctions observed after spinal cord injury in humans. Numerous studies involving these animal models have demonstrated development of abnormalities in bladder, external anal sphincter, and erectile function, such as detrusor-sphincter-dyssynergia and external anal sphincter hyperreflexia. Here we review many of these studies and show some of the anatomical alterations that develop within the spinal cord during the development of these hyperreflexias. Furthermore, we show that spasticity develops in other pelvic floor musculature as well, such as the bulbospongiosus muscle, which results in increased duration and magnitude of pressures developed during erectile events and increased duration of micturition. Advances and continued improvement in the use of current animal models of spinal cord injury should encourage and increase the laboratory work devoted to this relatively neglected area of experimental spinal cord injury.


Unraveling the intracellular and extracellular self-defense of Chlorella sorokiniana toward highly toxic pyridine stress.
A bottleneck of microalgae-based techniques for wastewater bioremediation is activity inhibition of microalgae by toxic pollutants. The defense strategies of Chlorella sorokinana against toxic pyridine were studied. Results indicated that pyridine caused photoinhibition and reactive oxygen species overproduction in a concentration-dependent manner. The 50% inhibitory concentration of pyridine (147 mg L-1) destroyed C/N balance, disrupted multiple metabolic pathways of C. sorokinana. In response to pyridine stress, ascorbate peroxidase and catalase activities increased to scavenge reactive oxygen species under pyridine concentrations lower than 23 mg L-1. At higher pyridine concentrations, the activation of calcium signaling pathways and phytohormones represented the predominant defense response. Extracellular polymeric substances increased 3.6-fold in 147 mg L-1 group than control, which interacted with pyridine through hydrophobic and aromatic stacking to resist pyridine entering algal cells. Unraveling the intracellular and extracellular self-defense mechanisms of microalgae against pyridine stress facilitates the development of microalgal-based technology in wastewater bioremediation.


Evaluation of practical sessions in clinical anatomy: a strategy for educational improvement.
We have evaluated the students' response to the practical teaching sessions in Clinical Anatomy in our Medical School using an action-research method. The aim was to identify problems and to introduce changes that might improve both the program and the performance of the teaching staff. At the end of each section of the program, each student completed a "target type" questionnaire with eight different components. As each one quarter of the whole class had its own teacher, we used an analysis of variance to evaluate the target questions in the various sections of the program, and the performance of the four teachers. This research method gave us feedback on the students' responses while the program was in progress. The results emphasize the importance of action-research in assessing and improving a developing program in a basic discipline of the medical curriculum.


Community pharmacists' naloxone counseling: A theory-informed qualitative study.
Opioid-related overdose (ORO) deaths have reached a record high in the United States. Naloxone is an opioid antagonist that can rapidly reverse an opioid overdose. Pharmacists are in an ideal position to provide naloxone and related counseling, given their accessibility and expertise. However, minimal research is available on community pharmacists' naloxone counseling. The aim of this study was to investigate Georgia community pharmacists' naloxone counseling as well as explore their attitudes, subjective norms, and perceived behavioral control toward counseling. Semi-structured telephone interviews were conducted to elicit pharmacists' beliefs and practices regarding naloxone counseling. The interviews were guided by open-ended questions based on the theory of planned behavior (TPB). Thematic analysis was performed to identify the modal salient beliefs expressed by the pharmacists. The Consolidated Criteria for Reporting Qualitative Research was used to report the study findings. A total of 12 community pharmacists participated. Pharmacists held mixed attitudes toward naloxone counseling. While they recognized it as a vital part of their profession to prevent ORO deaths, they also expressed concerns about offending patients. Regarding normative beliefs, pharmacists identified several groups, including regulatory agencies (e.g., Board of Pharmacy, CDC), managers, news/media, patients, and doctors, influencing their provision of naloxone counseling. Facilitators to counseling included receiving naloxone training and having access to counseling guidelines and resources. Reimbursement issues, high costs of naloxone, and lack of patient awareness were the most commonly cited barriers. Pharmacists reported participating in counseling and providing information on identifying signs of opioid overdose and administering naloxone. The TPB is a useful framework for understanding community pharmacists' beliefs and practices regarding naloxone counseling. Capitalizing on facilitators and targeting barriers related to pharmacists' reimbursement issues, high costs of naloxone, and increasing patients' awareness of naloxone use and benefits may enhance pharmacists' naloxone counseling.


The Money Buffer Effect in China: A Higher Income Cannot Make You Much Happier but Might Allow You to Worry Less.
This study examined the possibility that there is a curvilinear relationship between income and subjective well-being in China. This study also investigated whether this curvilinear relationship is moderated by social class and mediated by respondents' material affluence. The study was conducted in China, and the sample consisted of 900 blue-collar workers and 546 white-collar workers. The results for emotional well-being showed that income significantly predicted negative affect but not positive affect. This finding indicates that in China, high incomes may not make people happier but might allow them to worry less, which we call the "money buffer effect." The results also showed that material affluence mediates the interaction effect between income and social class on subjective well-being. The implications of these results for future research and practice are discussed.


Evaluation of the relevance of the growth modulation index (GMI) from the FFCD 0307 randomized phase III trial comparing the sequence of two chemotherapeutic regimens.
Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI. In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death. Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS). GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.


The AOC promoter of tomato is regulated by developmental and environmental stimuli.
The allene oxide cyclase (AOC) catalyzes the formation of cis-(+)-12-oxophytodienoic acid, an intermediate in jasmonate biosynthesis and is encoded by a single copy gene in tomato. The full length AOC promoter isolated by genome walk contains 3600 bp. Transgenic tomato lines carrying a 1000 bp promoter fragment and the full length promoter, respectively, in front of the beta-glucuronidase (GUS)-encoding uidA gene and several tobacco lines carrying the full length tomato AOC promoter before GUS were used to record organ- and tissue-specific promoter activities during development and in response to various stimuli. High promoter activities corresponding to immunocytochemically detected occurrence of the AOC protein were found in seeds and young seedlings and were confined to the root tip, hypocotyl and cotyledons of 3-d-old seedlings. In 10-d-old seedlings promoter activity appeared preferentially in the elongation zone. Fully developed tomato leaves were free of AOC promoter activity, but showed high activity upon wounding locally and systemically or upon treatment with JA, systemin or glucose. Tomato flowers showed high AOC promoter activities in ovules, sepals, anthers and pollen. Most of the promoter activity patterns found in tomato with the 1000 bp promoter fragment were also detected with the full length tomato AOC promoter in tobacco during development or in response to various stimuli. The data support a spatial and temporal regulation of JA biosynthesis during development and in response to environmental stimuli.


The effects of bee (Apis mellifera) venom phospholipase A2 on Trypanosoma brucei brucei and enterobacteria.
The potential role of phospholipases in trypanosomiasis was investigated using bee venom phospholipase A2 (bvPLA2) as a model. The effects of bvPLA2 on the survival of Trypanosoma brucei brucei, 2h and 12h cultures of Enterobacter cloacae, Escherichia coli, Citrobacter freundii were studied. About 1 mg ml(-1) bvPLA2 was trypanocidal after 30 min. Some growth occurred at lower concentrations up to 2h after treatment but viability decreased up to 8h. Even very low concentrations of bvPLA2 (10(-12) mg ml(-1)) had some trypanocidal activity. Bee venom PLA2 was bactericidal to 2h bacterial cultures but bacteriostatic to 12h ones. Minimum bactericidal concentrations were 10(-5)-10(-6) mg ml(-1). The results showed that bvPLA2 had significant trypanocidal and antibacterial effects on Gram-negative bacteria. The relationship to events occurring during infection is discussed. Phospholipases may play a role in increased endotoxin levels in trypanosomiasis.


In vitro antifungal activity of curcumin mediated by photodynamic therapy on Sporothrix brasiliensis.
Sporothrix brasiliensis is a pathogenic dimorphic fungus that affects humans and animals causing sporotrichosis. The treatment of this disease with conventional antifungals commonly results in therapeutic failures and resistance. Therefore, this study aimed to evaluate the in vitro effect of curcumin (CUR) mediated by photodynamic therapy (PDT) in its pure state and incorporated into pharmaceutical formulation in gel form, on the filamentous and yeast forms of S. brasiliensis. Cells from both forms of the fungus were treated with pure curcumin (PDT-CUR). For this, CUR concentrations ranging from 0.09 to 50 μM were incubated for 15 min and then irradiated with blue LED at 15 J/cm². Similarly, it was performed with PDT-CUR-gel, at lower concentration with fungistatic action. After, a qualitative and quantitative (colony forming units (CFU)) analysis of the results was performed. Additionally, reactive oxygen species (ROS) were detected by flow cytometry. Results PDT with 0.78 μM of CUR caused a significant reduction (p < 0.05) in cells of the filamentous and yeast form, 1.38 log10 and 1.18 log10, respectively, in comparison with the control. From the concentration of 1.56 μM of CUR, there was a total reduction in the number of CFU (≥ 3 log10). The PDT-CUR-gel, in relation to its base without CUR, presented a significant reduction (p < 0.05) of 0.83 log10 for the filamentous form and for the yeast form, 0.72 log10. ROS release was detected after the PDT-CUR assay, showing that this may be an important pathway of death caused by photoinactivation. Conclusion PDT-CUR has an important in vitro antifungal action against S. brasiliensis strains in both morphologies.


Lipid based formulations as supersaturating oral delivery systems: From current to future industrial applications.
Lipid-based formulations, in particular supersaturated lipid-based formulations, are important delivery approaches when formulating challenging compounds, as especially low water-soluble compounds profit from delivery in a pre-dissolved state. In this article, the classification of lipid-based formulation is described, followed by a detailed discussion of different supersaturated lipid-based formulations and the recent advances reported in the literature. The supersaturated lipid-based formulations discussed include both the in situ forming supersaturated systems as well as the thermally induced supersaturated lipid-based formulations. The in situ forming drug supersaturation by lipid-based formulations has been widely employed and numerous clinically available products are on the market. There are some scientific gaps in the field, but in general there is a good understanding of the mechanisms driving the success of these systems. For thermally induced supersaturation, the technology is not yet fully understood and developed, hence more research is required in this field to explore the formulations beyond preclinical studies and initial clinical trials.


Identifying sex-specific risk architectures for predicting amyloid deposition using neural networks.
In older adults without dementia, White Matter Hyperintensities (WMH) in MRI have been shown to be highly associated with cerebral amyloid deposition, measured by the Pittsburgh compound B (PiB) PET. However, the relation to age, sex, and education in explaining this association is not well understood. We use the voxel counts of regional WMH, age, one-hot encoded sex, and education to predict the regional PiB using a multilayer perceptron with only rectilinear activations using mean squared error. We then develop a novel, robust metric to understand the relevance of each input variable for prediction. Our observations indicate that sex is the most relevant predictor of PiB and that WMH is not relevant for prediction. These results indicate that there is a sex-specific risk architecture for Aβ deposition.


2,2'-[Methyl-enebis(sulfanedi-yl)]bis-(pyridine 1-oxide).
The title compound, C11H10N2O2S2, crystallizes with one complete mol-ecule in the asymmetric unit. In the crystal, weak hydrogen bonding is observed between the N-oxide moieties and several C-H units.


Effect of lumen narrowing within coronary stents on proximal and distal vessel segments following bare metal stent implantation.
Adjacent reference vessel response to smaller lumens at stented segments was examined with 3-dimensional intravascular ultrasound analysis. In 128 patients after bare metal stent implantation, minimal lumen area (MLA) within the stent and average lumen area at distal/proximal adjacent reference segments (5 mm) were obtained at baseline and follow-up. In the smaller in-stent MLA group (MLA <3 mm2), lumen area decreased significantly at the distal edge compared with the larger in-stent MLA group (MLA > or =3 mm2), although no significant difference was seen at the proximal edge. In-stent lumen patency may influence vascular responses at adjacent reference segments after bare metal stent implantation.


Sirolimus-eluting stents reduce long-term mortality compared with bare metal stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized controlled trials.
Sirolimus-eluting stents (SES) have demonstrated more favorable outcomes compared with bare metal stents (BMS) for ST-segment elevation myocardial infarction (STEMI) within medium term follow up in randomized controlled trials (RCT). However, long-term outcomes remain unknown. We conducted a meta-analysis of RCT comparing SES with BMS in STEMI patients at long-term follow up, defined as 2 years or more after primary percutaneous coronary intervention (PCI). The clinical end points of our interest were death, recurrent myocardial infarction (MI), definite stent thrombosis (ST), and target lesion revascularization (TLR). We calculated the pooled estimate based on a fixed-effects model using Peto odds ratio (OR) for rare events. If heterogeneity was observed across an individual RCT, an analysis based on a random-effects model was performed. Four RCT were included in this study, involving 1304 patients (656 patients randomized to SES and 648 patients to BMS). Up to 4 years, SES showed a significant reduction in not only TLR (OR: 0.44, 95% confidence interval (CI): 0.31 to 0.62, p<0.001) but also mortality (OR: 0.62, 95% CI: 0.39 to 1.00, p=0.049) compared with BMS. In contrast, the proportions of recurrent MI (OR: 0.82, 95% CI: 0.52 to 1.28, p=0.378) and definite ST (OR: 1.13, 95% CI: 0.56 to 2.27, p=0.740) were comparable between the 2 groups. In this meta-analysis of long-term RCT, primary PCI for STEMI patients with SES was associated with a decrease in mortality as well as TLR without an increase in recurrent MI or definite ST compared with BMS.


A clinicopathologic study of 56 cases of intraocular medulloepitheliomas.
A clinicopathologic and follow-up study of 56 intraocular medulloepitheliomas in the Registry of Ophthalmic Pathology revealed a mean age of five years at the time of definitive diagnosis, most patients having had a delay in surgical therapy of more than one year after onset of signs or symptoms. Histologic evidence of malignancy was observed in 37 tumors, and follow-up studies revealed four patients to have died of metastatic disease. Heteroplastic elements (brain tissue, cartilage, or rhabdomyoblasts) were observed in four benign and 17 malignant tumors; these 21 were designated teratoid medulloepitheliomas. The most important prognostic feature was extraocular extension, observed in ten cases. All four of the known tumor deaths were preceded by clinically obvious orbital spread. In four additional cases with orbital involvement the patients were lost to follow-up. We concluded, therefore, that the prognosis is worse than the results of this study would indicate, especially among those cases observed to habe extraocular extension.


Synthesis and structural characterization of the sodium salt of a new sulfonate-containing water soluble N-donor ligand--self-assembly in the solid state by pi-pi stacking interactions.
The synthesis, spectroscopic characterization, and X-ray crystal structure of the sodium salt of a new sulfonated water-soluble ligand, sodium 2-(2-pyridin-2-yl-ethylamino)-benzenesulfonate (L) are described. Compound L crystallizes in the centrosymmetric space group Pbcn, orthorhombic, a=31.930(13) A, b=7.153(3) A,c=14.193(6) A, alpha=90.00, beta=90.00, gamma=90.00, V=3220(2) A(3), Z=9. pi-pi stacking contacts involving interactions between the pi-donor benzene and the pi-acceptor pyridine systems reinforce and direct the self-assembly of the structural motifs in the solid state.