Apolipoprotein A1, B levels, and their ratio and the risk of a first stroke: a meta-analysis and case-control study.
The associations of levels of apolipoprotein A1 (ApoA1) and apolipoprotein B and ApoB/A1 ratio and risk of a first stroke have not been reliably documented. We performed a meta-analysis to summarize the relationships and confirmed them in a case-control study. We identified relevant publications in PubMed and Embase databases up to June 1, 2015. A Dersimonian-Laird random effects model was used to compute summary relative risks (RRs) and 95 % confidence intervals (CIs). A case-control study was conducted in a southern Chinese population. We included 8 cohort and 4 case-control studies (222,774 subjects; 10,032 first stroke events) in the meta-analysis. Reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio was associated with a first stroke in cohort studies (RR 0.86 [95 % CI 0.79-0.94], 1.66 [1.62-1.69], and 1.66 [1.63-1.70], respectively) and reduced ApoA1 level and increased ApoB/A1 ratio in case-control studies (0.68 [0.47-0.99] and 1.76 [1.50-2.06], respectively). When stratified by stroke type in cohort studies, the RR for ischemic stroke was 0.83 (0.76-0.90), 1.36 (1.32-1.40), and 1.38 (1.35-1.42) for the 3 factors, respectively. In our case-control study (1013 cases; 1029 controls), the OR for a first ischemic stroke was 0.83 (0.74-0.92), 1.33 (1.18-1.48) and 2.10 (1.76-2.51), respectively, with increased ApoA1 level associated with hemorrhagic stroke (1.37 [1.06-1.78]). Meta-analysis suggests that reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio are risk factors for a first ischemic but not hemorrhagic stroke. Elevated ApoA1 level may be a risk factor for a first hemorrhagic stroke.


Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma in patients with von Hippel-Lindau syndrome after at least 5 years of followup.
Although the safety and feasibility of partial adrenalectomy in patients with von Hippel-Lindau syndrome have been established, long-term outcomes have not been examined. In this study we evaluate the recurrence and functional outcomes in a von Hippel-Lindau syndrome cohort treated for pheochromocytoma with partial adrenalectomy with a followup of at least 5 years. We reviewed the records of patients with von Hippel-Lindau syndrome treated with partial adrenalectomy for pheochromocytoma at the National Cancer Institute. Demographic, germline mutation status, surgical indication, oncologic and functional outcome data were collected. Local recurrence was defined as radiographic evidence of recurrent tumor on the ipsilateral side of partial adrenalectomy. Patients were considered steroid dependent if they required steroids at most recent followup. A total of 36 partial adrenalectomies for pheochromocytoma were performed in 26 patients with von Hippel-Lindau syndrome between September 1995 and December 2003. Of these cases 23 were performed open and 13 were performed laparoscopically. Prior surgical history was obtained for all patients. At a median followup of 9.25 years (range 5 to 46) metastatic pheochromocytoma had not developed in any patients. In 3 patients (11%) there were 5 local recurrences treated with surgical extirpation or active surveillance. All recurrences were asymptomatic and detected by radiographic imaging on followup. In addition, 3 of 26 patients (11%) subsequently required partial adrenalectomy for pheochromocytoma on the contralateral adrenal gland. In the entire cohort only 3 patients became steroid dependent (11%). Outcomes of partial adrenalectomy in patients with von Hippel-Lindau syndrome with pheochromocytoma are encouraging at long-term followup and should be recommended as a primary surgical approach whenever possible. Adrenal sparing surgery can obviate the need for steroid replacement in the majority of patients. Local recurrence rates appear to be infrequent and can be managed successfully with subsequent observation or intervention.


Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents.
7-Chloroquinoline-based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine-sensitive (CQS) NF54 (IC50 : 4.2 nm) and chloroquine-resistant (CQR) Dd2 (IC50 : 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β-hematin formation in an NP-40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm.


Acute pancreatitis associated with H1N1 influenza during 2009 pandemic: a case report.
The relationship between viral infections and acute pancreatitis (AP) is not well-defined and universally accepted. Although an association is debated due to lack of solid evidence, a vast number of case reports suggest a possible interrelation. Influenza A virus is one of the most common infectious pathogens in humans but the incidence of subclinical or overt AP during the course of flu is unknown. We report a case of AP, which occurs shortly after a H1N1 infection during the pandemic in 2009.


Effects of needlescopic surgery on postoperative pain in intersphincteric or abdominoperineal resection.
Laparoscopic surgery allows minimally invasive treatment of rectal cancer, and needlescopic surgery (NS) offers even more minimally invasive operations beyond the scope of conventional laparoscopic surgery (CS). The aim of this study was to compare short-term outcomes of NS for intersphincteric resection (ISR) or abdominoperineal resection (APR) to treat anal or rectal cancer without an abdominal incision for specimen extraction and to measure abdominal wound pain compared to CS. Between September 2014 and December 2016, a total of 134 patients underwent laparoscopic ISR or APR. Of these, 26 patients underwent NS, and 108 patients underwent CS. Postoperative abdominal wound pain was estimated using the numerical rating scale. Short-term outcomes were compared between NS and CS. No conversion to CS or open surgery was required. Median operation time was significantly shorter with NS (295 min) than with CS (331.5 min; p = 0.020). Median estimated blood loss was significantly lower with NS (30 ml) than with CS (50 ml; p = 0.011). Postoperative pain score on postoperative day (POD)5 was significantly lower with NS than with CS (p = 0.025), and frequencies of analgesic use were significantly lower with NS than with CS on POD0, POD2, and POD3 (p = 0.032, p = 0.017, p = 0.045, respectively). The postoperative complications occurred at similar frequencies between groups (p = 0.655). NS for ISR or APR offers comparable short-term outcomes to CS, with better pain outcomes.


[Reserve production of renin by glomerular mesangial cells following experimental decrease in renal circulation].
The aorta was partially constricted between the origins of the two renal arteries in rats. The renin activity was studied separately in the capillary parts of the isolated glomeruli and in their arterioles. The renin activity was found in the capillary parts of the glomeruli 3 to 4 weeks after the constriction. The rough and smooth endoplasmic reticulum and the Golgi complex of the mesangial cells were activated at this period. The authors consider these results as a confirmation of the hypothesis on the reserve renin production by mesangial cells under prolonged decrease of renal circulation.


Synthesis, Characterization and Antimicrobial Activity of d Metal Complexes of some 2-Substituted-1H-Benzimidazoles.
The metal complexes of nine 2-substituted-1H-benzimidazoles (I-IX) with Ni(II), Pd(II), Cu(II), Ag(I), Zn(II) salts were synthesized. The compounds were characterized by melting point, analytical data, IR spectroscopy and magnetic susceptibility. The antimicrobial activity of the compounds was determined by the disk diffusion method in Mueller-Hinton Agar on Staphylococcus aureusATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis, Candida albicans ATCC 10231. Cu(II)and Ag(I)complexes of II, III and IV showed considerable activity against S. aureus, S. epidermidis, Ps. aeruginosa, S. typhi, Sh. flexneri and C. albicans microorganisms, the ligands themselves having no effect.


Genetic variability of human adenovirus type 8 causing epidemic and sporadic cases of keratoconjunctivitis.
Human adenovirus type 8 (HAdV-8) is a main aetiological agent of keratoconjunctivitis. It has been reported from both epidemic and sporadic cases. The aim of our study was to investigate the genetic characteristics and chronological pattern of HAdV-8 strains that have been circulating in Tunisia over a 14-year period. Fourteen HAdV-8 isolates from a keratoconjunctivitis outbreak that occurred in 2000 and from sporadic cases between 2001 and 2013 were studied. Nucleotide sequences from the hexon, fiber and penton base genes were determined, including hypervariable regions of the hexon (loops 1 and 2), the fiber (knob) and the penton base (HVR 1 and RGD loops). The sequences were compared to each other and to those of HAdV-8 strains. The Tunisian sequences were unique when compared to the previously published sequences. Also, despite a relatively low degree of genetic variation in the three genomic regions, phylogenetic analysis and alignment of amino acid sequences showed that the sequence from the year 2000 and two other sequences from the year 2013 were similar to each other and differed from the isolates that circulated in the intervening year by two main amino acid changes in the loop 1 hexon gene and the knob-fiber gene. Our results confirm the genetic variability of HAdV-8 and document the chronological changes of circulating genetic variants.


Isolation and characterization of two novel serpins from the tick Rhipicephalus haemaphysaloides.
Two novel serpins with anti-chymotrypsin activity, RHS-1 and RHS-2, were identified in the tick Rhipicephalus haemaphysaloides. The complementary cDNA sequence of RHS-1 was 1286 base pairs (bp) and encoded a deduced 403-amino acid protein with a signal peptide, whereas that of RHS-2 was 1682bp and encoded a deduced 380-amino acid protein with no signal peptide. Although both RHS-1 and RHS-2 exhibited high sequence similarities to known serpins from other ticks, the level of similarity at the amino acid level between the 2 serpins characterized here was only 32.5%. Salivary gland-specific expression of RHS-1 and midgut-specific expression of RHS-2 were found by Western blot using the relevant antiserum. We tested the ability of purified recombinant rRHS-1 and rRHS-2 to inhibit various serine proteases and found that both significantly inhibited chymotrypsin (95.6% and 94.2%, respectively). We further demonstrated that RHS-1, but not RHS-2 exhibited anticoagulation activity, based on activated partial thromboplastin time (APTT). Disruption of the genes encoding the 2 serpins with RNA interference (RNAi) led to a significant decrease in tick attachment and engorgement rates. These results indicate that RHS-1 and RHS-2 are 2 novel serpins with anti-chymotrypsin activity that are involved in blood feeding of R. haemaphysaloides.


Intimate partner violence and postpartum contraceptive use: the role of race/ethnicity and prenatal birth control counseling.
Intimate partner violence (IPV) is a major problem that could affect reproductive decision making. The aim of this study is to examine the association between IPV and contraceptive use and assess whether the association varies by receipt of prenatal birth control counseling and race/ethnicity. This study analyzed the 2004-2008 national Pregnancy Risk Assessment Monitoring System (PRAMS) that included 193,310 women with live births in the United States. IPV was determined by questions that asked about physical abuse by a current or former partner in the 12 months before or during pregnancy. The outcome was postpartum contraceptive use (yes vs. no). Multiple logistic regression analyses were conducted to assess the influence of experiencing IPV at different periods (preconception IPV, prenatal IPV, both preconception and prenatal IPV, preconception and/or prenatal IPV). Data were stratified to assess differential effects by race/ethnicity and receipt of birth control counseling. Approximately 6.2% of women reported IPV, and 15.5% reported no postpartum contraceptive use. Regardless of the timing of abuse, IPV-exposed women were significantly less likely to report contraceptive use after delivery. This was particularly true for Hispanic women who reported no prenatal birth control counseling and women of all other racial/ethnic groups who received prenatal birth control counseling. IPV victimization adversely affects the use of contraceptive methods following delivery in women with live births. Birth control counseling by health providers may mitigate these effects; however, the quality of counseling needs further investigation. Better integration of violence prevention services and family planning programs is greatly needed. Consistent with national recommendations by the U.S. Preventive Service Task Force, clinicians and public health workers are strongly encouraged to screen for IPV. Health providers should educate women on effective contraceptive options and discuss long-acting reversible contraceptives that are not partner dependent within the context of abusive relationships.


[Media coverage of suicide: From the epidemiological observations to prevention avenues].
Media coverage of suicide can result in increased morbi-mortality suicidal rates, due to an imitation process in those who are particularly vulnerable. This phenomenon is known as "Werther effect". Werther effect's magnitude depends on several qualitative and quantitative characteristics of the media coverage, in a dose-effect relationship. An extensive (in terms of audience and history repetition) and salient coverage (glorification of suicide, description of the suicidal method, etc.) increases the risk of contagion. Celebrities' suicide is particularly at risk of Werther effect. Media may also have a preventive role with respect to suicide. Indeed, according to "Papageno effect", journalists could, under certain conditions, help preventing suicide when reporting suicide stories. Two main theories in the field of social psychology have been proposed to account for Werther and Papageno effects: social learning theory and differential identification. Identification of Werther and Papageno effects uncovers new responsibilities and potentialities for the journalists in terms of public health. Their description provides a basis for promising targeted prevention actions.


Giant fibrovascular polyp of the oesophagus: a case report and review of the literature.
We present a case of fibrovascular polyp, a rare submucosal tumour of the oesophagus that has been reported only sporadically in the literature. The biapproach for surgical removal of fibrovascular polyp has only been mentioned once in the literature. A 65-year-old Greek man presented with a 9-month history of gradually progressive intermittent dysphagia. Radiologic work-up with oesophagogram and computed tomography revealed a large, sausage-shaped intraluminal polyp extending from the level of the cervical oesophagus to the level of the upper body of the stomach. The diagnosis of giant fibrovascular polyp was made radiographically and confirmed by endoscopic biopsy. The polyp was removed using a biapproach surgical technique: pharyngotomy and subsequent gastrostomy. Fibrovascular polyp is a rare submucosal tumour. Proper treatment depends on accurate assessment of the origin, size, and vascularity of the pedicle and the size of the tumour. Choice of the appropriate surgical approach depends on the correct diagnosis, which can usually be indicated radiographically by the presence of a smooth, sausage-shaped defect with a discrete bulbous tip.


External fixation design evolution enhances biomechanical frame performance.
External fixation has become a quick and easy application for fracture stabilisation of the extremities and/or pelvis to maintain the reduction and provide stability while sparing the soft tissues. Over the last years, enhanced construct stiffness has become an essential requirement to preserve fracture reduction, particularly in active and overweight patients. This study was performed to determine whether the advancement of design features enhances the external fixation construct stiffness. The stiffness of the recently developed Hoffmann 3 external fixation system was determined and its characteristics compared with the widely clinically accepted Hoffmann II MRI fixation system. A synthetic fracture model was used. Two carbon tubes with a fracture gap of 20 mm were appropriate to determine the stiffness of three different configurations: the basic frame configuration (group H 3, representing Hoffmann 3 with a rod diameter of 11 mm) using a double rod construction with 6 mm Apex pins, was compared with the Hoffmann II MRI fixation system using two 8.0 mm diameter rods with 6 mm (group H II-6 mm) and 5 mm (group H II-5 mm) Apex pins. Each group was tested five times under anterior-posterior bending (N/mm), medio-lateral bending (N/mm) and axial torsion loading directions (Nm/deg). The stiffness results of each construct were compared statistically. The basic frame construct (group H 3) showed consistently higher stiffness properties compared with the other configurations. The anterior-posterior-bending loads resulted in a mean value of 31 N/mm, which was significantly higher compared with the other groups (p=0.008) at 16 N/mm. The medio-lateral-bending test revealed a mean stiffness of 59 N/mm in the H3 group, compared with 43 N/mm in the H II-6 group and 31 N/mm in the H II-5 group. The axial torsion measurements of the Hoffmann 3 group yielded significantly higher results (1.03 Nm/°) compared with group H II-6 (0.61 Nm/°) and group H II-5 (0.56 Nm/°). The Hoffmann 3 construct showed the highest stiffness properties under bending and torsion loads. The enhanced stiffness of the Hoffmann 3 device may be helpful in maintaining fracture reduction and soft tissue compromise. This investigation showed the advancement of Hoffmann design features may be effective in enhancing frame stiffness.


First record of a rare case of accidental urinary myiasis by Telmatoscopus albipunctata (Diptera: Psychodidae), with morphological description, in a human in Brazil.
Telmatoscopus albipunctata is an insect of the Psychodidae family, with a worldwide distribution, particularly in tropical and subtropical countries. Although it does not have hematophagous habits, it has veterinary medical importance due to the mechanical transmission of protozoa and bacteria, many of which cause nosocomial infections. This dipteran has been reported as one of the causative agents of accidental myiasis in humans in several countries, and since it has not been registered in South America, the objective of the present report was to describe a rare case of accidental urinary myiasis caused by T. albipunctata (Diptera: Psychodidae) in humans in Brazil. In the present report, a 25-year-old female patient, resident of the central region of the state of Rio Grande do Sul, Brazil, sought medical attention after finding larvae in her urine. She complained of vaginal itching and skin dermatitis. The larvae were sent to the Veterinary Parasitology Laboratory of the Federal University of Santa Maria, where they were mounted on permanent slides for further taxonomic identification. Morphological characteristics allowed the identification of fourth-stage larvae and pupae of T. albipunctata. Therefore, the present work reports the first record of accidental urinary myiasis caused by T. albipunctata infection in Brazil and South America.


Characteristic pollutants risk assessment of modified manganese residue utilization in sintered product.
The resource disposal of electrolytic manganese residue can effectively solve the problem of environmental pollution caused by it, among which the problem of heavy metal pollution is the most prominent. In this study, a new type of eco-friendly brick mixed with electrolytic manganese residue was designed. The influence of the content of electrolytic manganese residue on its macroscopic properties, microscopic properties, and leaching characteristics was analyzed by test methods such as compressive strength test, radioactivity test, XRF, XRD, FTIR, and ICP test of bricks. The results showed that the manganese content in the EMR leachate was 8120 mg/L, which exceeded the Chinese standard. The leaching experiment of ordinary aqueous solution of sintered bricks mixed with 20% EMR showed that the content of heavy metals was far lower than the Chinese national standard. There was no non-carcinogenic risk of heavy metals in the strong acid leaching solution of sintered bricks mixed with 20% EMR. Only the carcinogenic risk values of Cr for adults and children were 4.21 × 10-4 and 9.82 × 10-4 respectively, both exceeding the USEPA limit, but the application scene of sintered bricks was difficult to achieve strong acidity, so it was judged that it had no carcinogenic risk to the human body. Characteristic heavy metals such as Mn, Cr, and As existed stably in sintered bricks through substitution and encapsulation. In addition, the compressive strength and radioactivity of EMR sintered bricks met the requirements of the Chinese national standard "Fired Ordinary Bricks." This product can be used as national standard MU20 grade brick. This study provided an efficient method for the safe and environmentally friendly disposal of EMR in a sustainable control system.


Site-selective DNA hydrolysis by Ce(IV)-EDTA with the use of one oligonucleotide additive bearing two monophosphates.
Two deoxyuridine derivatives each bearing a monophosphate group at the 5-position with a C3 linker, were incorporated into an oligonucleotide. By using this modified oligonucleotide, a bulge was formed at a predetermined position in a DNA substrate, and two monophosphate groups were placed at both junctions of the bulge. Upon treatment of the mixture with Ce(IV)-EDTA at pH 7.0, the phosphodiester linkages at the bulge site were selectively and efficiently hydrolyzed. The monophosphate groups introduced into the bulge site greatly accelerated site-selective DNA scission. Compared with the previously reported two-additive system, which combines two oligonucleotide additives each with a monophosphate at their termini, the present one-additive system is simpler and more convenient. Furthermore, site-selective DNA hydrolysis by using this one-additive system is successful even at high reaction temperatures (e.g., 55 degrees C). This reflects the thermodynamic stability of the duplexes formed between the substrate and the additive DNA.


Clinical value and influencing factors of establishing stomach cancer organoids by endoscopic biopsy.
To establish an in vitro study model of gastric cancer, gastric cancer organoid culture system, by biopsy under gastroscope, and to explore and analyze the related factors affecting the success rate of culture, to provide a better in vitro model for the study of gastric cancer. Twenty-six patients with advanced gastric cancer were collected. Organoids were cultured by biopsy under gastroscope. Paraffin sections were made and HE staining was used to compare the consistency of gastroscopic pathological morphology and organoids. To explore the influencing factors of cultivating gastric cancer organoids in combination with clinical data. A total of 26 cases were collected by gastroscopy, and 12 cases of gastric cancer organoids were successfully cultured after identification, with a success rate of about 48%. Its histopathological morphology was highly consistent with that of gastric cancer. According to the pathological type, 21 cases were poorly differentiated adenocarcinoma and 12 cases were successful. Four cases of signet ring cell carcinoma failed. According to the location of the lesion, the success rate of sampling and culture of gastric antrum was significantly lower, which may be related to antral edema and anatomical characteristics of gastric antrum. Some of the failed cases are related to the quality of sampling, technique and contamination of tissue cells. We have successfully established gastric cancer organoids through endoscopic biopsy, and analyzed the factors affecting the success rate of culture from various angles, to improve and enhance the organoid culture technology and provide a better platform for tumor research.


Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish.
The process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 in C. elegans and Sneaky in D. melanogaster. Mouse Dcst1 and Dcst2 single knockout (KO) sperm are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO sperm can bind to the oolemma, they show the fusion defect, resulting that Dcst1 KO males become almost sterile and Dcst2 KO males become sterile. Similar to mice, zebrafish dcst1 KO males are subfertile and dcst2 and dcst1/2 double KO males are sterile. Zebrafish dcst1/2 KO sperm are motile and can approach the egg, but are defective in binding to the oolemma. Furthermore, we find that DCST1 and DCST2 interact with each other and are interdependent. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species, highlighting their crucial role as conserved factors in fertilization.


Large-Eddy Simulation of pollutant dispersion around a cubical building: analysis of the turbulent mass transport mechanism by unsteady concentration and velocity statistics.
Pollutant transport due to the turbulent wind flow around buildings is a complex phenomenon which is challenging to reproduce with Computational Fluid Dynamics (CFD). In the present study we use Large-Eddy Simulation (LES) to investigate the turbulent mass transport mechanism in the case of gas dispersion around an isolated cubical building. Close agreement is found between wind-tunnel measurements and the computed average and standard deviation of concentration in the wake of the building. Since the turbulent mass flux is equal to the covariance of velocity and concentration, we perform a detailed statistical analysis of these variables to gain insight into the dispersion process. In particular, the fact that turbulent mass flux in the streamwise direction is directed from the low to high levels of mean concentration (counter-gradient mechanism) is explained. The large vortical structures developing around the building are shown to play an essential role in turbulent mass transport.


Long-term changes (1800-2019) in marine vegetational habitats: Insights from a historic industrialised coastal area.
Macrophytes play an important structural and functional role in marine ecosystems but are experiencing a considerable decline in many areas of the Mediterranean Sea. Despite the long tradition of studies on vegetated marine habitats in the Gulf of Naples (Italy), a gap of knowledge on their long-term dynamics has recently been highlighted, mainly in the most anthropised areas. This work aimed to provide insights from the historic industrialised coastal area of the Site of National Interest (SIN) Bagnoli-Coroglio (Gulf of Pozzuoli, Italy), after decades of chemical contaminations and coastal transformation, to build a baseline for the next remediation and restoration programs. Historical occurrence of macroalgae and seagrasses before, during and after the industrial period was assessed; in particular, we focused the attention mainly on habitat-forming species, due to the vital function played in the trophic net. We observed no differences in the macroalgal diversity between the SIN district and the other parts of the Gulf of Pozzuoli, except for the Gulf of Pozzuoli during the industrial period, where the biodiversity showed a decreasing trend. However, a substantial regression of the largest macrophytes (Fucales) on rocky coasts and of marine monocots on sandy bottoms, all over the area, has been recorded. A loss of about 70% has concerned seagrass cover, mainly Posidonia oceanica, in the contaminated area of the SIN: at present, this engineering species is missing on the bottom, facing the industrialised area. The human-made coastline transformation, the lack of natural substrates and the spatial remoteness among donor populations seem to be the leading causes of the significant decrease, over time, of marine forests in this study area. These factors should be taken into account to establish conservation priorities and for plant restoration.


Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study.
Several lines of research suggest that prefrontal cortex dysfunctions observed in obsessive compulsive disorder (OCD) and schizophrenia (SKZ) are linked to two partially independent neuroanatomic systems: the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex, with different neuroanatomic connections, including the striatum. The primary aim of this study was to test this hypothesis using a double dissociation study of neuropsychological tasks performance of the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. We administered the Wisconsin Card Sorting Test, the Gambling Task, and the four-disk version of the Tower of Hanoi to 110 SKZ and 67 OCD patients and 56 control subjects. A clear double dissociation of Wisconsin Card Sorting Test and Gambling Task performances was found, with SKZ patients performing the Wisconsin Card Sorting test significantly worse than OCD patients and control subjects and OCD patients performing the Gambling Task significantly worse than SKZ and control subjects. Both SKZ and OCD patients performed the Tower of Hanoi significantly worse than control subjects. Results from our double dissociation study confirm the hypothesis of involvement of different frontal lobe subsystems within basal-corticofrontal circuits function in SKZ and OCD.


The CYP1A2 -163C>A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures in Brazilian schizophrenia patients.
We evaluated two polymorphisms at CYP1A2 (*1C and *1F) in a sample of 108 European-derived patients with schizophrenia and their influence on the pro-convulsive effect of clozapine. We found the *1F/*1F genotype to be significantly associated with seizures, and no relationship was observed with combinations of *1F and *1C alleles.


New and little-known species of Tipula Linnaeus (Diptera, Tipulidae) from Laos, with a new synonym.
Only seven species of the genus Tipula Linnaeus were previously known to occur in Laos. Here one new species is added to the fauna of Laos, Tipula (Nippotipula) champasakensissp. nov. Tipula (unplaced) cladomera Alexander, 1936 is designated as a synonym of T. (unplaced) reposita Walker, 1848, syn. nov. A key to species of the genus Tipula from Laos is presented.


Bioengineered skin humanized model of psoriasis.
This protocol describes the generation of a skin humanized mouse model for psoriasis using bioengineering approaches. This method is relatively simple, highly reproducible and ensures the obtention of a large and homogenous number of engrafted animals bearing a portion of human skin with psoriatic phenotype. The technique can employ cells from skin biopsies and blood samples from non-related healthy human donors (allogeneic version), as well as skin and blood cells from psoriatic patients (autologous version). In both cases, the psoriatic phenotype was developed after intradermal administration of in vitro derived T1 lymphocytes along with Th17 recombinant cytokines, in conjunction with mild barrier disruption by tape-stripping. This skin-humanized model for psoriasis emerges as a powerful tool to study the mechanisms underlying the pathogenesis of the disease. More importantly, the feasibility of the system may allow the evaluation of different therapeutic compounds in an in vivo system, employing local and/or systemic administration.


Induction of apoptosis or necrosis by ionizing radiation is dose-dependent in MG-63 osteosarcoma multicellular spheroids.
This study investigates cell growth and death (apoptosis and necrosis) in actively proliferating MG-63 osteosarcoma spheroids in response to two doses of ionizing radiation (5 and 30 Gy). Cell growth was examined by growth curves and by cell cycle analyses utilizing flow cytometry. Death was examined in both disaggregated and whole spheroids by the chromatin dye Hoechst and by Western blot analysis of the bcl-2 family of proteins known to be involved in the apoptotic process. The results indicate that after exposure to 5 Gy MG-63 spheroids die by apoptosis, while after exposure to 30 Gy they die by necrosis. The analysis of the bcl-2 family of proteins demonstrates that bcl-2, bax and bcl-XL are involved in triggering apoptosis in spheroids exposed to 5 Gy. The possibility of studying the mechanisms responsible for radiation-induced cell death in three-dimensional spheroids (which represent much more closely in vivo tumors) is extremely important if the foundations for more selective and controllable clinical radiotherapeutic protocols are to be laid.


Pteroylpoly(gamma-glutamate) synthesis by Corynebacterium species. Purification and properties of folypoly(gamma-glutamate) synthetase.
Folylpolyglutamate synthetase was purified 7000-fold from extracts of Corynebacterium sp. The final preparation, which was greater than 95% pure, had a monomer molecular weight of 53,000. The purified enzyme catalyzed a MgATP-dependent addition of glutamate to a variety of reduced pteroate and reduced pteroylmono-, di-, and triglutamate substrates with the concomitant production of ADP and Pi. Although the specificity for the folate substrate was wide, the pteroate and pteroylmonoglutamate substrates were utilized much more effectively than the polyglutamate derivatives. The most effective substrates were tetrahydropteroate, tetrahydrofolate, and 5,10-methylene-tretrahydrofolate. The most effective diglutamate substrate was 5,10-methylene-tetrahydropteroyldiglutamate. Addition of more than one glutamate moiety was only observed with tetrahydropteroate and 5,10-methylene-tetrahydropteroylmono- and diglutamates as substrates. The enzyme exhibited a preference for ATP as the nucleotide substrate. dATP was almost as effective while UTP and CTP were less effective substitutes. The specificity for L-glutamate appeared to be absolute. Enzyme activity was maximal at about pH 10 and exhibited an absolute requirement for a monovalent cation, of which K+ was the most effective. Preliminary studies suggest that the active form of the enzyme may be a dimer and that K+ may be required to effect dimerization.


Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support.
After left ventricular-assist device (LVAD) support, a proportion of patients recover sufficient ventricular function to enable explantation of the device. The exact molecular mechanisms involved in myocardial recovery remain unknown. Cytoskeletal proteins are essential for the structure and function of the cardiac myocyte and might play a major role. A total of 15 patients with nonischemic cardiomyopathy who required LVAD implantation were studied; 6 recovered sufficiently to allow explantation of the device compared with 9 who did not recover and required transplantation. LV myocardial samples were collected at implantation and explantation/transplantation. Affymetrix microarray analysis was performed on the paired samples and analyzed with reference to sarcomeric and nonsarcomeric cytoskeletal proteins. In the recovery group, of the nonsarcomeric proteins, lamin A/C increased 1.5-fold (P<0.05) and spectrin 1.6-fold (P<0.05) between the times of implantation and explantation. Integrins beta1, beta6, and alpha7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins alpha5 and beta5 increased 2.3-fold (P<0.01) and 1.2-fold (P<0.01) at explantation. The following sarcomeric proteins changed in the recovered group only: beta-actin increased 1.4-fold (P<0.05); alpha-tropomyosin, 1.3-fold (P<0.05); alpha1-actinin, 1.8-fold (P<0.01); and alpha-filamin A, 1.6-fold (P<0.05). Both troponin T3 and alpha2-actinin decreased by 1.6-fold at the time of explantation (P<0.05). Vinculin decreased 1.7-fold (P=0.001) in the recovered group but increased by 1.7-fold (P<0.05) in the nonrecovered group. Vinculin protein levels decreased 4.1-fold in the recovered group. Myocardial recovery was associated with a specific pattern of changes in sarcomeric, nonsarcomeric, and membrane-associated proteins, which could have important implications in understanding the mechanisms involved.


Staphylococcus aureus bacteremia in patients with rheumatoid arthritis - Data from the prospective INSTINCT cohort.
Patients with rheumatoid arthritis (RA) are considered to be at increased risk of severe infections. We here describe the clinical characteristics, course and outcome of RA patients with Staphylococcus aureus bacteremia (SAB). We conducted a post hoc analysis of data from a German bi-center prospective SAB cohort study (period 2006-2014). Patients were followed-up for one year. Primary and secondary outcomes were survival time and osteoarticular infection (OAI). A total of 1069 patients with SAB were analyzed, with 31 patients suffering from RA. RA patients showed significantly more often OAI (15/31 patients, 48% vs. 152/1038, 15%), disseminated infection (12/31, 39% vs. 164/1038, 16%) and severe sepsis/septic shock (12/31, 39% vs. 235/1038, 23%). Day-30 mortality in RA patients was 36% (vs. 19% in non-RA patients, p = 0.034), and day 90 mortality was 58% (vs. 32%, p = 0.003). Multivariate analyses confirmed RA to be an independent risk factor for death (HR 2.3, 95% CI 1.4-3.7) and OAI (OR 4.2, 95% CI 1.8-9.8). Patients with RA exhibit a complicated SAB course and a high mortality, their management is challenging. Adequate antibiotic treatment, prompt invasive diagnostic and therapeutic procedures like joint lavage or surgery are of pivotal importance. Joint damage due to RA may confer a higher risk of acquiring OAI than immunosuppression.


Sex-specific associations between traumatic experiences and resting-state functional connectivity in the Philadelphia Neurodevelopmental Cohort.
Traumatic experiences during childhood or adolescence are a significant risk factor for multiple psychiatric disorders and adversely affect multiple cognitive functions. Resting-state functional magnetic resonance imaging has been used to investigate the effects of traumatic experiences on functional connectivity, but the impact of sex differences has not been well documented. This study investigated sex-specific associations between resting-state functional connectivity (rsFC) and traumatic experiences in typically developing youth. The sample comprised 1395 participants, aged 8-21 years, from the Philadelphia Neurodevelopmental Cohort. Traumatic experiences were assessed based on the structured psychiatric evaluation. Sex, the number of traumatic events, and their interaction were regressed onto voxel-wise intrinsic connectivity distribution parameter values derived from resting-state functional magnetic resonance imaging. Brain regions that passed cluster correction were used as seeds to define resting-state networks. After quality control, the final sample had 914 participants with mean (SD) age 14.6 (3.3) years; 529 (57.8%) females; 437 (47.8%) experienced at least one kind of traumatic event. Four discrete anatomical clusters showed decreased functional connectivity as the number of traumatic events increased. The resting-state networks defined by using these four clusters as seeds corresponded with the somatomotor network. Sex-specific associations were identified in another three clusters for which males showed increased connectivity, and females showed decreased connectivity as the number of traumatic events increased. The resting-state networks defined by the three sex-specific clusters corresponded with the default mode network (DMN). In youth without psychiatric diagnoses, traumatic experiences are associated with an alteration of rsFC in brain regions corresponding with the somatomotor network. Associations differ in direction between males and females in brain regions corresponding with the DMN, suggesting sex-specific responses to early exposure to trauma.


Immunological aspects on IDDM in children.
Diabetes mellitus in childhood is connected to several immunological phenomena which per se do not prove that immunological mechanisms do cause the beta cell destruction, as such mechanisms could be just secondary. However, there is now evidence which strongly supports the autoimmune hypothesis, like the beta-cell destruction in the transplant given from a healthy twin to the diabetic monozygotic co-twin, the effect in newly-diagnosed diabetes of immunosuppression, the passive transfer in experimental animals of an immune process creating diabetes etc. Several facts such as presence of activated T-cells in the insulitis indicate that the cell-mediated immunity is important, while it is still debatable whether humoral factors, and if so which, alone could be responsible for the beta cell destruction. Recently interleukins and other lymphokines have shown to be of great interest as well as the release of free radicals. This knowledge opens new views on the possibility to put an end to or even prevent the beta cell destruction. Rough immunosuppression with cytostatics or cyclosporin has such severe side-effects that such therapy is contra-indicated at least in children. Until more specific therapies are discovered e.g. vaccination with lymphoblasts or blocking the autoantigens with monoclonal antibodies, supportive measures to protect the beta cells may be one practical way.


Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.
Visceral fat accumulation has an important role in the development of several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of type 2 diabetes have been identified by genome-wide association studies. To examine the association of type 2 diabetes susceptibility loci and visceral fat accumulation, we genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography for measurements of visceral fat area (VFA) and subcutaneous fat area (SFA) for the following single-nucleotide polymorphisms (SNPs): NOTCH2 rs10923931, THADA rs7578597, PPARG rs1801282, ADAMTS9 rs4607103, IGF2BP2 rs1470579, VEGFA rs9472138, JAZF1 rs864745, CDKN2A/CDKN2B rs564398 and rs10811661, HHEX rs1111875 and rs5015480, TCF7L2 rs7901695, KCNQ1 rs2237892, KCNJ11 rs5215 and rs5219, EXT2 rs1113132, rs11037909, and rs3740878, MTNR1B rs10830963, DCD rs1153188, TSPAN8/LGR5 rs7961581, and FTO rs8050136 and rs9939609. None of the above SNPs were significantly associated with VFA. The FTO rs8050136 and rs9939609 risk alleles exhibited significant associations with body mass index (BMI; P=0.00088 and P=0.0010, respectively) and SFA (P=0.00013 and P=0.00017, respectively). No other SNPs were significantly associated with BMI or SFA. Our results suggest that two SNPs in the FTO gene are associated with subcutaneous fat accumulation. The contributions of other SNPs are inconclusive because of a limitation of the sample power.


The efficient numerical solution of biological simulation problems.
A subroutine called DESOL for the numerical solution of ordinary differential equations of the type arising in biological simulation problems is described. DESOL is about as efficient as current high quality integrators, but because of its compactness it can be easily used on small computers. The subroutine has excellent stability properties and functions with very little required input from the user. In addition, it has features which aid in debugging associated programs. Several test and example problems are given, as is the derivation of the major formulae used in the package.


The strategy for improving the stability of nitroform derivatives-high-energetic oxidant based on hexanitroethane.
To develop high-energetic stability nitroform compounds, three types of nitroform derivatives based on hexanitroethane structure are designed. The guidelines for selecting these compounds are based on (1) constructing a flexible molecule and weakening the external force by elastic deformation and (2) forming negative ion or introducing electron-rich group to eliminate the electron-deficient situation. The conformations and some important properties of them are calculated at B3LYP/6-311 + G(d) level. Based on the bond order and bond dissociation enthalpy analysis, C-NO2 bond is considered to be the most unstable position, and both of the methods can improve the stability of designed compounds. Based on molecular energy gap (HOMO-LUMO) and density of state (DOS) analysis, it is found that introducing of bridge atoms is helpful to lower the sensitivity, while the construction of anions changes both HOMO-LUMO and DOS which shows obvious ionic properties. A further study on the electrical potential surface shows that the probability for extreme values of designed compounds decreases which is beneficial for high stability. Finally, the explosive properties and impact sensitivity of them are calculated. Results show that their explosive performances are obviously better than current energetic oxidants and some of them maintain low sensitivity.


Increased plasma activity of metalloproteinase 2 in women with metabolic syndrome.
Metalloproteinases (MMPs) play a significant role in vascular remodeling, and they have been suspected to be partly responsible for the pathogenesis of cardiovascular disease. Metalloproteinases have been reported to be increased in atherosclerosis and type 2 diabetes mellitus; however, so far they have not been evaluated in metabolic syndrome (MetS). Plasma activity of MMP-2 and MMP-9, high-sensitivity C-reactive protein concentration, dense low-density lipoprotein, and insulin-resistance markers were measured in 38 nondiabetic women with (n = 19) and without (n = 19) MetS. Women with MetS had significantly higher plasma activity of MMP-2 than controls (median [range], 1.3 [0.4-3.1] vs 0.7 [0.1-1.9]; P = .001). MMP-2 activity positively correlated with waist, homeostasis model assessment, and high-sensitivity C-reactive protein (P < .02) as well as with apolipoprotein B, dense low-density lipoprotein, triglycerides/high-density lipoprotein cholesterol index (P < .001) and negatively with high-density lipoprotein cholesterol (P < .002). Our finding of increased plasma activity of MMP-2 in women with MetS is important because they fit in with an early stage of cardiovascular disease; and measurement of soluble molecules may improve the risk assessment, early diagnosis, and prognosis of cardiovascular disease.


Bone metastases are associated with worse prognosis in patients affected by metastatic colorectal cancer treated with doublet or triplet chemotherapy plus bevacizumab: a subanalysis of the TRIBE and TRIBE2 trials.
Colorectal cancer (CRC) is one of the most common cancers; ∼20% of patients have metastases at diagnosis, and 50%-60% subsequently develop metachronous metastases. Bone involvement, despite being rare, is usually associated with higher disease burden, worse prognosis, impaired quality of life, and significant health-related cost. In the last few years, following the positive results of the TRIBE and TRIBE2 trials, the association of FOLFOXIRI plus bevacizumab has become the new standard of care for metastatic CRC. Despite being highly efficacious in all subgroups, little is known about the activity of this regimen in patients with bone metastases. We carried out a pooled analysis of TRIBE and TRIBE2 studies focusing on patients with skeletal deposits. Our analyses on the whole population showed that patients with baseline bone involvement reported shorter overall survival [OS; 14.0 versus 26.2 months; hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.46-2.87; P < 0.001] and progression-free survival (PFS; 6.2 versus 11.1 months; HR 1.96, 95% CI 1.42-2.69; P < 0.001) compared with those without bone metastases; no significant interaction with the treatment was reported for PFS (P = 0.094) and OS (P = 0.38). Bone metastases had a negative prognostic implication in the multivariate analysis (HR 2.24, 95% CI 1.54-3.26; P < 0.001). Furthermore, patients with bone lesions at first radiological progression (including those with baseline bone metastases) had a shorter OS compared with those who progressed in other sites (10.4 versus 13.2 months; HR 1.48, 95% CI 1.15-1.91; P = 0.002). A trend toward inferior OS (7.5 versus 11 months, HR 1.50, 95% CI 0.92-2.45; P = 0.10) appeared in patients with basal skeletal deposits compared with those with bone involvement at first radiological progression. Our study confirmed the negative prognostic impact of bone metastases in CRC. Furthermore, we demonstrated for the first time that the survival advantage of triplet chemotherapy plus bevacizumab is maintained even in this prognostically unfavorable subgroup.


Sequential combination of 5-fluorouracil, cis-platinum and irradiation. 1. Advanced head and neck cancers.
Based on the synergistic action of 5-fluorouracil (5-FUra), cis-dichlorodiamminoplatinum(II) (cis-DDP) and gamma-rays, which was suggested in experiments on murine tumours, a sequential treatment combining irradiation and chemotherapy for human solid tumours known to be resistant to conventional treatments has been developed. A pilot study was carried out on 30 patients with recurring head and neck cancers previously treated by radiotherapy and surgery. The good tolerance and the initial results justified applying this protocol to previously untreated cases. The second study involved 40 patients with stage III and IV tumours. After 3 cycles of combined radio- and chemotherapy followed by a conventional radiotherapy, 78% were good responders (51% in complete remission). Oropharynx and oral cavity, without base of tongue, have a 51% actuarial survival at 3 years when they achieved an early complete remission.


Predicting chemical ecotoxicity by learning latent space chemical representations.
In silico prediction of chemical ecotoxicity (HC50) represents an important complement to improve in vivo and in vitro toxicological assessment of manufactured chemicals. Recent application of machine learning models to predict chemical HC50 yields variable prediction performance that depends on effectively learning chemical representations from high-dimension data. To improve HC50 prediction performance, we developed an autoencoder model by learning latent space chemical embeddings. This novel approach achieved state-of-the-art prediction performance of HC50 with R2 of 0.668 ± 0.003 and mean absolute error (MAE) of 0.572 ± 0.001, and outperformed other dimension reduction methods including principal component analysis (PCA) (R2 = 0.601 ± 0.031 and MAE = 0.629 ± 0.005), kernel PCA (R2 = 0.631 ± 0.008 and MAE = 0.625 ± 0.006), and uniform manifold approximation and projection dimensionality reduction (R2 = 0.400 ± 0.008 and MAE = 0.801 ± 0.002). A simple linear layer with chemical embeddings learned from the autoencoder model performed better than random forest (R2 = 0.663 ± 0.007 and MAE = 0.591 ± 0.008), fully connected neural network (R2 = 0.614 ± 0.016 and MAE = 0.610 ± 0.008), least absolute shrinkage and selection operator (R2 = 0.617 ± 0.037 and MAE = 0.619 ± 0.007), and ridge regression (R2 = 0.638 ± 0.007 and MAE = 0.613 ± 0.005) using unlearned raw input features. Our results highlighted the usefulness of learning latent chemical representations, and our autoencoder model provides an alternative approach for robust HC50 prediction.


Preoperative pulmonary vascular resistance and neutrophil-to-lymphocyte ratio predict the demand of extracorporeal membrane oxygenation after pulmonary endarterectomy.
Acute respiratory and circulatory collapse might occasionally happen after pulmonary endarterectomy (PEA). We aimed to investigate the utilization of extracorporeal membrane oxygenation (ECMO) after PEA and potential risk factors. Demographic characteristics, clinical and surgical data were collected for all patients who underwent PEA from December 2016 to June 2022. All factors were compared between patients in the ECMO group and those in the other group. The most characteristic risk factors were obtained by least absolute shrinkage and selection operator regression and support vector machine machine learning, and receiver operating characteristics (ROC) Curve analysis was performed to verify the diagnostic value of the obtained risk factors. A total of 117 patients underwent PEA, and 8 (6.8%) of them received ECMO treatment intraoperatively or postoperatively. There were significant differences between the two groups in terms of cardiac function, pulmonary vascular resistance (PVR), preoperative inflammation and cardiopulmonary bypass time. The PVR and neutrophil-to-lymphocyte ratio (N/L ratio) were the most characteristic risk factors with an area under the ROC curve of 0.847 (95% confidence interval [CI] = 0.7517-0.9420, p = .005) and 0.896 (95% CI = 0.803-0.989, p = .001), respectively. The ECMO group had higher PVR (1549.4 ± 600.7 vs. 952.9 ± 466.9 dyn.s.cm-5 , p = .004) and N/L ratio (6.3 ± 5.6 vs. 2.4 ± 1.7, p = .001). PVR and N/L ratio can correctly predict who is likely to receive ECMO treatment after PEA. Therefore, addressing the preoperative inflammatory status might be beneficial but further research is needed.


Organisational factors that facilitate research use in public health policy-making: a scoping review.
Although important syntheses and theoretical works exist in relation to understanding the organisational factors that facilitate research use, these contributions differ in their scope and object of study as well as their theoretical underpinnings. Therefore, from an exploratory angle, it may be useful to map out the current literature on organisational factors of research use in public health policy-making when revisiting existing theories and frameworks to gain further theoretical insights. Herein, a scoping review technique and thematic content analysis were used to bring together findings from both synthesised and empirical studies of different types to map out the organisational factors that facilitate research use in public health policy-making. A total of 14 reviews and 40 empirical studies were included in the analysis. These were thematically coded and the intra-organisational factors reported as enabling research use were examined. Five main categories of organisational factors that advance research use in policy organisations - (1) individual factors, (2) the management of research integration, (3) organisational systems and infrastructures of research use, (4) institutional structures and rules for policy-making, and (5) organisational characteristics - were derived as well as 18 subcategories and a total of 64 specific factors, where 27 factors were well supported by research. Using a scoping review methodology, the intra-organisational factors influencing research use in policy-making (including individual factors) were systematically mapped and the theories applied in this area of research were assessed. The review findings confirm the importance of an intra-organisational perspective when exploring research use, showing that many organisational factors are critical facilitators of research use but also that many factors and mechanisms are understudied. The synthesis shows a lack of studies on politicians and the need for more theoretically founded research. Despite increased efforts to update the existing evidential and theoretical basis of research use, we still need frameworks that combine different approaches and theories to help us grasp the complex organisational mechanisms that facilitate research use in policy settings.


The specific transmission of Grapevine fanleaf virus by its nematode vector Xiphinema index is solely determined by the viral coat protein.
The viral determinants involved in the specific transmission of Grapevine fanleaf virus (GFLV) by its nematode vector Xiphinema index are located within the 513 C-terminal residues of the RNA2-encoded polyprotein, that is, the 9 C-terminal amino acids of the movement protein (2BMP) and contiguous 504 amino acids of the coat protein (2CCP) [Virology 291 (2001) 161]. To further delineate the viral determinants responsible for the specific spread, the four amino acids that are different within the 9 C-terminal 2BMP residues between GFLV and Arabis mosaic virus (ArMV), another nepovirus which is transmitted by Xiphinema diversicaudatum but not by X. index, were subjected to mutational analysis. Of the recombinant viruses derived from transcripts of GFLV RNA1 and RNA2 mutants that systemically infected herbaceous host plants, all with the 2CCP of GFLV were transmitted by X. index unlike none with the 2CCP of ArMV, regardless of the mutations within the 2BMP C-terminus. These results demonstrate that the coat protein is the sole viral determinant for the specific spread of GFLV by X. index.


Effectiveness of school-based preventive programs in suicidal thoughts and behaviors: A meta-analysis.
Suicidal thoughts and behaviors (STBs) among adolescents have hardly decreased despite preventative efforts. School-based prevention programs could have a great reach, yet suicide prevention is not an easy topic to address. To increase acceptability of school-based suicide prevention, it is important to evaluate whether programs that target known risk factors of STBs, such as depression, could be equally effective. We conducted a systematic literature search in major electronic databases. Outcomes were suicidal ideation and behaviors. Multivariate random effects meta-regression-analyses were conducted. Eleven primary studies met the inclusion criteria, totalling 23,230 participants. The post-test effect size was small for both suicidal ideation (g = 0.15) and suicidal behaviors (g = 0.30). Meta-regression indicated that targeting known risk factors of STBs was not a significant modifier of effect size for ideation, indicating equal effectiveness. However, it was significant modifier of effect for behaviors, but only one intervention targeted know risk factors. Effects at follow-up (3-12 months) were also significant but small for both outcomes. Substantial heterogeneity between studies was noted. Only few and small sample size studies could be included that targeted known risk factors of STBs. Therefore, these results should be interpreted with caution. School-based prevention of STBs shows some promise within three months post-test assessments, and potentially also have effects that are sustained over time. More studies are needed to make conclusions regarding school-based interventions that target risk factors of STBs.


Direct evidence for glutathione as mediator of apoptosis in neuronal cells.
Recent evidence has focused attention on the role of oxidative stress in various acute and chronic neurodegenerative diseases. Particularly, a decrease in the level of the powerful antioxidant glutathione (GSH) and death of dopaminergic neurons in substantia nigra are prominent features in Parkinson's disease. The mode of neuronal death is uncertain; however, apoptosis has been hypothesized to be mediated through the induction of free radicals via oxidative pathways. An approach to determine the role of GSH depletion in neurodegeneration and apoptosis was to create a selective modulation of this antioxidant by metabolic manipulations in a clonal cell line of neuronal origin (mouse neuroblastoma NS20Y). Intracellular GSH levels was lowered by inhibiting its biosynthesis with L-buthionine-(S,R)-sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase. This treatment led to a GSH depletion of 50% after 1 h and 98% after 24 h. A direct cause/effect relationship between GSH depletion and apoptosis was evidenced in this neuronal cell type. GSH depletion induced the death of NS20Y and promoted nuclear alterations of apoptosis as demonstrated by the in situ staining of DNA fragmentation after 5 days of BSO treatment (by terminal-deoxynucleotide transferase-mediated dUTP-nick end labeling), and the appearance of DNA laddering on agarose gel. These results suggested that redox desequilibrium induced by GSH depletion may serve as a general trigger for apoptosis in neuronal cells, and are consistent with the hypothesis that GSH depletion contribute to neuronal death in Parkinson's disease.


Evidence for Cerebral Embolic Prevention in Transcatheter Aortic Valve Implantation and Thoracic Endovascular Aortic Repair.
Embolic stroke is a formidable complication of transcatheter aortic valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR). Mechanical strategies to reduce the risk of ischemic embolic lesions include embolic protection devices (EPDs) and carbon dioxide flushing (CDF). This study aims to assess the efficacy for EPD and CDF uses in TAVI and TEVAR. A literature review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis. All searches were performed via PubMed, OvidSP, MEDLINE, Web of Science Core Collection, and Cochrane Library. Conference abstracts and proceedings were included. Those that were out of scope of interest and review articles were excluded. Eighteen studies fulfilled the inclusion criteria of the 456 articles searched. Regarding EPD use in TAVI, systematic review comparing EPD with no-EPD showed smaller total volume of cerebral lesions and smaller volume per lesion in patients with EPD in all studies. They also performed better in postoperative neurocognitive assessments but could not demonstrate clinical prevention of embolic stroke in all studies. While for EPD use in TEVAR, capture of embolic debris and absence of early postoperative neurocognitive deficit were demonstrated in all cases of 2 prospective pilot studies. Concerning CDF in TEVAR, significant reduction in gaseous emboli released during stent-graft deployment was shown by 1 in vitro study. Successful CDF application in all patients, with only 1 case of postoperative nondisabling stroke, was also demonstrated by 1 cohort study. This systematic review of medical literature has demonstrated the safety and feasibility of EPD use in TAVI. Although improvements in clinical outcomes have yet been demonstrated, there was level I evidence showing reduced embolic lesions in imaging. The use of EPD and CDF in TEVAR was suggested, but evidence remained inadequate to support routine clinical use.


[Cardiac magnetic resonance imaging in the diagnosis of acute coronary syndrome. Basics and clinical value].
In contrast to chronic myocardial infarction, data concerning the value of cardiac magnetic resonance imaging in patients with acute onset of chest pain are still rare. Even in the presence of characteristic clinical parameters, cardiac magnetic resonance imaging might provide independent evidence especially in the absence of typical ECG alterations and prior to biomarker elevation. Besides the ability to demonstrate wall motion abnormalities cardiac magnetic resonance imaging gains additional potential as to the detection of myocardial edema, microvascular obstruction (no-reflow) and myocardial necrosis. However, cardiac magnetic resonance imaging is expensive and time-consuming, and therefore may not be cost-effective. At present, a lack of sufficient diagnostic and prognostic data would make cardiac magnetic resonance imaging unsuitable for routine stratification of chest pain patients in an emergency department.


Estimation of N2 fixation based on differences in the natural abundance of 15N among freshwater N2-fixing and non-N2-fixing algae.
The dynamics of nitrogen supply was investigated for blue-green and green algae from Smith Lake and other freshwaters of subarctic and arctic Alska. The natural abundance of 15N (defined as δ15N) of six N2-fixing blue-green algae was 1.0±%o(X±SE), indicating supply of metabolic nitrogen from atmospheric N2 (δ15N=0.0). The δ15N of six green algae showed an average of 6.6±4.5%o, which is significantly higher than δ15N of N2-fixing blue-green algae from the same waters, reflecting the utilization of dissolved inorganic nitrogen (DIN). Nitrogen-fixing algae also showed higher nitrogen content (7.1±2.1%) than non-N2-fixing algae (2.9±1.5%). The δ15N of a bloom-forming species, Anabaena flos-aquae (Lyngb.) Breb. in Smith Lake showed no significant interannual variations during a three-year study period. The changes in δ15N during each bloom were probably due to variations in the 15N composition of DIN and in the proportional uptake of DIN and N2 fixation. An estimation of the fractional contribution of atmosphere-derived nitrogen (ADN) from δ15N indicated that A. flos-aquae obtained 58-75% of its nitrogen by N2 fixation. This technique agreed with the result obtained using a 15N2 enrichment method. The δ15N of the presumed N2-fixing terrestrial plant was similar to that of the atmospheric N2, whereas the δ15N of the presumed non-N2-fixing terrestrial plants reflected their nitrogen sources.


Atezolizumab and pembrolizumab in triple-negative breast cancer: a meta-analysis.
The approval of anti-PD-L1 drugs, including atezolizumab/pembrolizumab in triple-negative breast cancer (TNBC), potentially improveme treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of atezolizumab/pembrolizumab for the treatment of TNBC in both the adjuvant and neoadjuvant settings. We calculated standardized mean difference (SMD) for the associations of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) to estimate objective response rate (ORR) and pathological complete response (pCR), using 95% confidence intervals (CIs). Six clinical trials comprising 3612 patients were included. For adjuvant therapies, the ORR (OR = 1.26, P = 0.04) of atezolizumab/pembrolizumab plus chemotherapy was higher in the intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (d = 1.55, P < 0.001). The atezolizumab plus chemotherapy group had a positive effect size for OS compared to control groups (d = 0.52, P < 0.001). In the neoadjuvant setting, patients in ITT arms had higher pCR rates than the control groups (OR = 1.61, P = 0.001). We collate evidence of atezolizumab/pembrolizumab as viable therapeutics among patients with TNBC with PD-L1 subgroups deriving higher benefits.


Vitamin E prevents buthionine sulfoximine-induced biochemical disorders in the rat.
Antioxidant therapy can improve the protection and metabolic activity of cells and tissues. In this study, the effect of vitamin E administration on buthionine sulfoximine (BSO)-induced glutathione (GSH) depletion in the rat lung and liver was investigated. Hepatic GSH was depleted by intraperitoneal administration of BSO (4 mmol kg(-1)), twice a day, for 30 days to rats. We also investigated whether the lung and liver mitochondrial GSH contents were influenced by BSO administration and whether an extracellular supply of vitamin E could prevent the changes caused by BSO-mediated GSH depletion. Glutathione levels in lung and liver tissues were depleted by 47% and 60%, respectively. Depletion of hepatic and pulmonary GSH in turn causes decline in the levels of mitochondrial GSH, leading to impaired antioxidant defence function of mitochondria. Both the cytosolic and mitochondrial glutathione disulfides (GSSG) were altered during BSO treatment, and led to drastic increase in GSSG/GSH redox status. One of the experimental groups was given vitamin E (65 mg (kg diet)(-1)) mixed with rat feed. The rats fed with vitamin E were found to have partially restored GSH levels in liver and lung, diminished levels of TBARS and minimized tissue damage. The current findings suggest that the impaired glutathione and glutathione-dependent enzyme status may be correlated with the elevated lipid peroxidation and mitochondrial membrane damage and that vitamin E therapy to the BSO-administered rats prevents the above changes. However, vitamin E did not have any effect on the activity of gamma-glutamyl cysteine synthetase (gamma-GCS).


The P300-based, complex trial protocol for concealed information detection resists any number of sequential countermeasures against up to five irrelevant stimuli.
We previously tested the P300-based Complex Trial protocol for deception detection against 2 and 4 countered of 4 irrelevant stimuli. The protocol detected 90-100% of these subjects with <10% false positives. We have also shown that Reaction Time (RT) to the first trial stimulus is increased (group effect) with countermeasure use. We also reported a new P900 component associated with countermeasure use when 2 of 4 irrelevants are countered. In the present study we report data from 4 new groups and re-present for comparison previously collected data to have 7 groups: an innocent control, a guilty group not using countermeasures, and 5 guilty/countermeasure groups who counter from 1 to all 5 stimuli presented (4 irrelevants plus a probe). Subjects were detected at rates varying from 92 to 100% in the 6 guilty groups (n = 12 or 13 per group). There was 1 false positive in 13 innocent subjects. Additionally, 41 of 60 CM users were identified with RT as using countermeasures. P900 appeared in the 2 groups using 2 and 3 countermeasures.


6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis.
Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of potency; while the presence of an aryl ester function at the 3-position was preferred to a thioester or an amide function to induce marked biological activity. This work confirms the interest of aryl esters of 6-substituted coumarin-3-carboxylic acids as potential new anti-cancer agents.


Advances in nanoparticle mediated targeting of RNA binding protein for cancer.
RNA binding proteins (RBPs) enact a very crucial part in the RNA directive processes. Atypical expression of these RBPs affects many steps of RNA metabolism, majorly altering its expression. Altered expression and dysfunction of RNA binding proteins lead to cancer progression and other diseases. We enumerate various available interventions, and recent findings focused on targeting RBPs for cancer therapy and diagnosis. The treatment, sensitization, chemoprevention, gene-mediated, and virus mediated interventions were studied to treat and diagnose cancer. The application of passively and actively targeted lipidic nanoparticles, polymeric nanoparticles, virus-based particles, and vaccine-based immunotherapy for the delivery of therapeutic agent/s against cancer are discussed. We also discuss the formulation aspect of nanoparticles for achieving delivery at the site of action and ongoing clinical trials targeting RBPs.


Bone marrow colony-formation in vitro after infection of genetically defined inbred mice with Candida albicans.
The effect of C. albicans infection on the production of haematopoietic precursor cells in the bone marrow of CBA/CaH and BALB/c mice was evaluated by assay of colony formation in vitro. In immunocompetent mice, neither systemic nor oral infection induced significant alterations in colony formation by bone marrow from the two mouse strains, and Candida infection did not alter the proportion of morphological cell types in the colonies. However, the number of neutrophil-like was relatively greater in colonies derived from acutely infected CBA/CaH nude mice than in those from BALB/c nude mice, whereas small mononuclear cells were present in higher proportions in the latter strain. In both strains of nude mice, there was an increase in colony formation at 6 days after oral infection, but at 8 weeks, when the infection had become chronic, the production of bone marrow cells by CBA/CaH nude mice was significantly less than that by BALB/c nude mice. Reconstitution of nude mice with syngeneic lymphocytes enhanced the production of bone marrow precursor cells by BALB/c, but not by CBA/CaH mice, suggesting that T cells can enhance host resistance by promoting the colony-forming response of the bone marrow in BALB/c mice that are genetically resistant to tissue damage, but not in CBA/CaH that are prone to severe lesions. Finally, culture with Candida antigen in vitro decreased the number of colony-forming cells in cultures from CBA/CaH, but not from BALB/c mice.


Prognostic value of left ventricular mechanical dyssynchrony indices in long-standing type II diabetes mellitus with normal perfusion and left ventricular systolic functions on SPECT-MPI.
To test whether phase analysis indices from SPECT-MPI for left ventricular mechanical dyssynchrony (LVMD) are predictors of major adverse cardiac events (MACEs) in long-standing diabetes mellitus (DM). A total of 136 DM patients with normal perfusion and left ventricular systolic functions were followed up for about two years and divided into two groups according to the presence and the absence of MACEs. Thirteen (9.5%) patients experienced MACEs during follow-up. Patients experiencing MACEs showed significantly higher phase standard deviation (PSD) and wider phase bandwidth (PBW) than those who did not. Moreover, both PSD and PBW showed significant correlations (r = 0.25 and 0.27; P < 0.05) with duration of DM. Logistic regression analysis revealed significant associations of DM duration, microvascular complications, and LVMD indices for predicting MACEs. Kaplan-Meier event-free survival analysis revealed significantly higher rate of MACEs (Logrank = 10.02; P = 0.001) in patients with high PSD and wide PBW. An overall fit model consisting of high-PSD and wide-PBW group was improved with the addition of microvascular complications (χ2 = 15.9; P = 0.03) and further by addition of DM duration of ≥ 15 years (χ2 = 24.3; P = 0.007) as variables. LVMD indices are novel prognostic markers in diabetic patients with normal perfusion and left ventricular systolic functions and their increases in magnitudes with DM-duration and in the presence of microvascular complications.


Management of bilateral adrenal metastases from hepatocellular carcinoma: a case report.
The adrenal glands rarely are an extrahepatic site for metastasis from hepatocellular carcinoma (HCC). Once identified, adrenal metastasis requires aggressive management, due to the risk of rupture and internal hemorrhaging. Disease management of adrenal metastasis from HCC is limited, given the relative lack of available knowledge, and the present report details our efforts in managing bilateral adrenal metastases from HCC. For this patient, we used radiation therapy and transcatheter arterial chemoembolization (TACE). The left adrenal tumor was treated by 3D conformal radiation therapy, following the failure of TACE. The size of the left adrenal tumor decreased and no evidence of recurrence after management was noted. One right adrenal tumor was treated using two sessions of TACE, and the size of the tumor did not decrease. We later observed that the right tumor actually progressively increased in size. The tumor was then treated by 3D conformal radiation therapy (total 5400 cGy), and the size decreased by 10 mm, 1 month after treatment. The patient's condition was stable and liver function was maintained at early stage liver cirrhosis (Child A). Renal function was maintained within normal ranges after diagnosis of HCC and throughout the entire follow-up period, and no complications secondary to radiation therapy were noted. Our experience may provide useful information in disease management for these patients.


Transcervical sterilization with use of methyl 2-cyanoacrylate and a newer delivery system (the FEMCEPT device).
The increasing use of sterilization as a means of permanent contraception prompts the search for simpler, safer methods. Methyl 2-cyanoacrylate 0.6 ml was administered to the uterocornual tubal junction with the use of the FEMCEPT transcervical delivery system in 35 healthy parous women aged 30 to 44 years. Hysterosalpingography 4 months after the procedure showed bilateral tubal occlusion in 88.2% of the study participants. There were no complications in the study group, and there were no pregnancies among those who demonstrated bilateral tubal occlusion. The technique, which is safe, effective, and simple, could consideraly reduce anesthetic and operative risk in sterilization.


Does silent reading speed in normal adult readers depend on early visual processes? evidence from event-related brain potentials.
Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in the FDT correlated with behavioral tests measuring silent reading speed. We suggest that reading speed performance can be at least partially accounted for by the extraction of essential structural information from visual stimuli, consisting of a domain-general and a domain-specific expertise-based portion.


PATTERN CLADISTICS OR EVOLUTIONARY CLADISTICS?
We can also put it like this. The introduction of an auxiliary hypothesis should always be regarded as an attempt to construct a new system; and this new system should then always be judged on the issue of whether it would, if adopted, constitute a real advance in our knowledge of the world-K. R. Popper.


Report from the International Commission on Radiation Units and Measurements.
A summary of the activities of the International Commission on Radiation Units and Measurements since 1973 is presented.


Long-term anti-inflammatory diet in relation to improved breast cancer prognosis: a prospective cohort study.
Inflammation-modulating nutrients and inflammatory markers are established cancer risk factors, however, evidence regarding the association between post-diagnosis diet-associated inflammation and breast cancer survival is relatively sparse. We aimed to examine the association between post-diagnosis dietary inflammatory index (DII®) and risks of all-cause and breast cancer-specific mortality. A total of 1064 female breast cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial prospective cohort, were included in this analysis if they had completed the diet history questionnaire (DHQ). Energy-adjusted DII (E-DIITM) scores were calculated based on food and supplement intake. Cox regression and competing risk models were used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by E-DII tertile (T) for all-cause and breast cancer-specific mortality. With median follow-up of 14.6 years, there were 296 (27.8%) deaths from all causes and 100 (9.4%) breast cancer-specific death. The E-DII was associated with all-cause mortality (HR T3 vs T1, 1.34; 95% CI, 1.01-1.81; P trend, 0.049, Table 2) and breast cancer mortality (HR T3 vs T1, 1.47; 95% CI, 0.89-2.43; P trend, 0.13; multivariable-adjusted HR for 1-unit increment: 1.10; 95% CI: 1.00-1.22). Non-linear positive dose-response associations with mortality from all causes were identified for E-DII scores (P non-linearity < 0.05). The post-diagnosis E-DII was statistically significantly associated with mortality risk among breast cancer survivors. Long-term anti-inflammatory diet might be a means of improving survival of breast cancer survivors.


Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era.
Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.


Synthetic hydrogels mimicking basement membrane matrices to promote cell-matrix interactions.
Naturally-derived materials have been extensively used as 3D cellular matrices as their inherent bioactivity makes them suitable for the study of many cellular processes. Nevertheless, lot-to-lot variability, inability to decouple biochemical and biophysical properties and, in some types, their tumor-derived nature limits their translational potential and reliability. One innovative approach to overcome these limitations has focused on incorporating bioactivity into cytocompatible, synthetic hydrogels that present tunable physicochemical properties. This review provides an overview of successful approaches to convey basement membrane-like bioactivity into 3D artificial hydrogel matrices in order to recapitulate cellular responses to native matrices. Recent advances involving biofunctionalization of synthetic hydrogels via incorporation of bioactive motifs that promote cell-matrix interactions and cell-directed matrix degradation will be discussed. This review highlights how the tunable physicochemical properties of biofunctionalized synthetic hydrogel matrices can be exploited to study the separate contributions of biochemical and biophysical matrix properties to different cellular processes.


Design and synthesis of piperidine derivatives as novel human heat shock protein 70 inhibitors for the treatment of drug-resistant tumors.
HSP70 is a potential target for tumour treatment. HSP70 plays significant roles in several biological processes, including the regulation of apoptosis. In this study, piperidine derivatives were designed as novel HSP70 inhibitors based on virtual fragment screening performed in Dock 4.0, Discovery Studio 2.5 and SYBYL 6.9. A total of 67 novel piperidine derivatives were synthesized. Cell viability assays were performed in 16 cancer cell lines. The emphasis was placed on lapatinib-resistant breast cancer cells (BT/Lap(R)1.0, MDA-MB-361, SK/Lap(R)1.0, and MDA-MB-453). The compounds HSP70-36/37/40/43/46 significantly inhibited the proliferation of human breast cancer cells. Compound HSP70-36 inhibited the growth of BT474 and BT/Lap(R)1.0 cells with IC50 values of 1.41 μM and 1.47 μM, respectively. The binding affinity of HSP70-36/HSP70 was evaluated by surface plasmon resonance and yielded Kd values of 2.46 μM. The LD50 was 869.0 mgkg(-1). These data suggest that HSP70-36 may be a potential candidate compound for tumour treatment.


Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling.
Opioid and beta-adrenergic receptors are recently shown to cross talk via formation of receptor heterodimers to control the growth and proliferation of breast cancer cells. However, the underlying cell signaling mechanism remained unclear. To determine the effect of the interaction of the two systems in breast cancer, we employed triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, CRISPR or chemical inhibition or activation of beta-adrenergic receptors (B2AR) and mu-opioid receptors (MOR) gene, and PCR array technology and studied aggressive tumor phenotype and signaling cascades. We show here that in triple-negative breast cancer cells, the reduction in expression B2AR and MOR by genetic and pharmacological tools leads to a less aggressive phenotype of triple-negative breast cancer cells in vitro and in animal xenografts. Genomic analysis indicates the glycogen synthase kinase 3 (GSK3) pathway as a possible candidate messenger system involved in B2AR and MOR cross talk. GSK3 inactivation in MDA-MB-231 and MDA-MB-468 cells induced similar phenotypic changes as the inhibition of B2AR and/or MOR, while a GSK3 activation by wortmannin reversed the effects of B2AR and/or MOR knockdown on these cells. GSK3 inactivation also prevents B2AR agonist norepinephrine or MOR agonist DAMGO from affecting MDA-MB-231 and MDA-MB-468 cell proliferation. These data confirm a role of B2AR and MOR interaction in the control of breast cancer cell growth and identify a possible role of the GSK3 signaling system in mediation of these two receptors' cross talk. Screening for ligands targeting B2AR and MOR interaction and/or the GSK3 system may help to identify novel drugs for the prevention of triple-negative breast cancer cell growth and metastasis.


Let's talk about faces: Identifying faces from verbal descriptions.
Face descriptions inform real-world identification decisions, for example when eyewitnesses describe criminal perpetrators. However, it is unclear how effective face descriptions are for identification. Here, we examined the accuracy of face identification from verbal descriptions, and how individual differences in face perception relate to producing and using descriptions for identification. In Study 1, participants completed a face communication task in pairs. Each participant saw a single face, and via verbal communication only, the pair decided if they were viewing the same person or different people. Dyads achieved 72% accuracy, compared to 81% when participants completed the task individually by matching face pairs side-by-side. Performance on the face communication and perceptual matching tasks were uncorrelated, perhaps due to low measurement reliability of the face communication task. In subsequent studies, we examined the abilities of face 'describers' (Study 2) and 'identifiers' separately (Study 3). We found that 'super-recognizers' - people with extremely high perceptual face identification abilities - outperformed controls in both studies. Overall, these results show that people can successfully describe faces for identification. Preliminary evidence suggests that this ability - and the ability use facial descriptions for identification - has some association with perceptual face identification skill.


Postoperative complication rate and survival of patients with gastric cancer undergoing immunonutrition: A retrospective study.
This study aimed to evaluate the effect of preoperative immunonutrition on the rate of postoperative complication and survival of patients with gastric cancer. A retrospective cohort was formed after data collection of patients hospitalized with gastric cancer. Postoperative complications classified according to the Clavien-Dindo classification system, length of hospital stay, readmissions, and rates of survival at 6 mo, 1 y, and 5 y were analyzed. A χ2 or Fisher's exact test, Student or Mann-Whitney t test, and Kaplan-Meier and Cox regressions were used in the statistical analysis. A total of 164 patients were included in the study, with 56 patients assigned to the immunonutrition group and 108 to the conventional group. There were no significant differences in postoperative complications between the immunonutrition and conventional groups (51.8% versus 58.3%; P = 0.423). The most frequent complications were fistula and surgical wound infection. Length of hospital stay did not differ between the groups (median of 7.0 d: P = 0.615) and the presence of readmissions did not differ either (12.5% versus 15.7%; P = 0.648). In the multivariate Cox regression, in a pooled model for group, age, sex, body mass index, Charlson comorbidity index, staging, neoadjuvant chemotherapy, and type of surgery, there was a significant difference in survival rates at 6 mo (P = 0.011), 1 y (P = 0.006), and 5 y (P < 0.001). Preoperative immunonutrition in patients with gastric cancer did not reduce postoperative complications or length of hospital stay. More studies are needed to confirm the benefit of immunonutriton supplementation for overall survival when associated with other protective factors.


Molecular, clinical, and pathologic comparison of two distinct strains of Haemobartonella felis in domestic cats.
To characterize 2 strains of Haemobartonella felis by use of molecular techniques. 35 specific-pathogen-free cats, 6 months to 4 years old. Intraperitoneal or IV inoculation with blood containing H felis small form (Hfsm, 18 cats) or H felis large form (Hflg, 11 cats); 6 cats were uninfected controls. Hfsm was evaluated for capability to cross-protect against the more virulent Hflg. Morphology of both strains was compared by light microscopy of Wright-Giemsa-stained blood smears, and the 16S rRNA genes were sequenced. Infection with Hflg induced signs of depression, fever, and severe macrocytic normochromic anemia with nucleated erythrocytes. More than 95% of erythrocytes were parasitized. Inoculation with Hfsm and uninfected control blood induced mild or no clinical signs and no hematologic abnormalities. Anti-H felis IgG was first detected on postinoculation day (PID) 21, and increased to maximal titer of 400 by PID 28. Reactivated infection was observed in 8 of 29 cats (4 Hfsm and 4 Hflg), with 5% parasitized erythrocytes during the later attack. On PID 8, Hflg-inoculated cats had positive results of polymerase chain reaction analysis (PCR) that persisted until cats were treated with doxycycline or oxytetracycline; Hfsm-inoculated cats had positive PCR results that persisted for duration of observation (3 months). Genetically and morphologically distinct strains of H felis infect cats in the field. The level of genetic difference suggested that these strains may be different species or genera. PCR is a critical diagnostic aid to detect occult Haemobartonella spp infection, as well as response to treatment and clearance of the organism.


Age-aware constitutive materials model for a 3D printed polymeric foam.
Traditional open or closed-cell stochastic elastomeric foams have wide-ranging applications in numerous industries: from thermal insulation, shock absorbing/gap-filling support cushions, packaging, to light-weight structural and positional components. Recent developments in 3D printing technologies by direct ink-write have opened the possibility of replacing stochastic foam parts by more controlled printed micro-structures with superior stress-distribution and longer functional life. For successful deployment as mechanical support or structural components, it is crucial to characterize the response of such printed materials to long-term external loads in terms of stress-strain behavior evolution and in terms of irreversible structural and load-bearing capacity changes over time. To this end, here we report a thermal-age-aware constitutive model for a 3D printed close-packed foam structure under compression. The model is based on the Ogden hyperfoam strain-energy functional within the framework of Tobolsky two-network scheme. It accurately describes experimentally measured stress-strain response, compression set, and load retention for various aging times and temperatures. Through the technique of time-temperature-superposition the model enables the prediction of long-term changes along with the quantification of uncertainty stemming from sample-to-sample variation and measurement noise. All aging parameters appear to possess the same Arrhenius activation barrier, which suggests a single dominant aging mechanism at the molecular/network level.


Unraveling the Reaction Mechanism of FeS2 as a Li-Ion Battery Cathode.
Iron pyrite (FeS2) is a promising lithium-ion battery cathode material because of its low cost and ultrahigh energy density (1671 Wh kg-1). However, its reaction mechanisms are still controversial. In this work, we find that different from the conventional belief that an intermediate phase Li2FeS2 is formed followed by Fe/Li2S composites at the initial discharge, it undergoes a one-step reaction (FeS2 → Fe + Li2S) or a two-step reaction (FeS2 → FeS + Li2S → Fe + Li2S), which depends on the current rate and temperature. In the charge process, it undergoes a two-step reaction: phase transition Fe + Li2S → FeS at about 1.74 V and generation of elemental sulfur (Li2S → S, 2.30 V). FeS is a mackinawite phase that is formed on the interface of Li2S via heteroepitaxial growth. Subsequent cycles involves a combination reaction of FeS and S. The reaction mechanism suggests that FeS2 suffers from the demerits of both FeS and S, such as a large volume change, voltage hysteresis, and polysulfide dissolution. These findings would help us to understand the intrinsic capacity fading of FeS2 and provide guidelines to improve its electrochemical performances.


4D flow MRI assessment of extracranial-intracranial bypass: qualitative and quantitative evaluation of the hemodynamics.
Our aim was to assess the feasibility of using time-resolved 3D phase-contrast (4D flow) MRI to characterize extracranial-intracranial (EC-IC) bypass. We enrolled 32 patients who underwent EC-IC bypass (15 men, 17 women; mean age 66.4 years). In all, 16 underwent radial artery graft (RAG) bypass and 16 underwent superficial temporal artery (STA) bypass. 4D flow MRI, time-of-flight (TOF) magnetic resonance angiography (MRA), and computed tomography angiography (CTA) were performed. Bypass patency, flow direction, and blood flow volume (BFV) of each artery were determined by 4D flow MRI. Arterial diameters were measured by TOF-MRA and CTA. We compared RAG and STA bypasses by evaluating the flow direction and BFV of each artery. We evaluated the correlation between arterial diameters (measured by CTA or MRA) and the BFV and the detectability of flow direction (measured by 4D flow MRI) of each artery. 4D flow MRI confirmed the patency of each bypass artery. Flow direction of the M1 segment of the middle cerebral artery and BFV in the bypass artery differed between RAG and STA groups (p < 0.01). BFV in the bypass slightly correlated with the diameters on CTA (p < 0.05, R (2) = 0.287). Of the 29 arteries in the circle of Willis, nine were not depicted on 4D flow MRI. Cutoff values for arterial diameters on CTA and TOF-MRA for detecting the artery on 4D flow MRI were 2.4 and 1.8 mm, respectively. 4D flow MRI provided unique information for characterizing EC-IC bypasses, although this detectability is limited when addressing small arteries with slow flow.


Effect of blood in the cerebrospinal fluid on the accuracy of cerebral oxygenation measured by near infrared spectroscopy.
Near infrared spectroscopy (NIRS) is an optical technique used to examine the oxygenation state of tissues such as the brain in patients, including those with brain injury. We have examined the effect of a cerebrospinal fluid (CSF) contaminant, specifically haemoglobin, on the sensitivity of cerebral NIRS signals through computer simulation. Previous models of light transport in the head have shown that the clear CSF layer has a profound effect on the sensitivity profile of the NIRS signal due to its low absorbing, low scattering qualities. In subarachnoid haemorrhage, which may accompany brain injury, the principal near infrared chromophore, haemoglobin, is released into the CSF. Sensitivity was measured through forward modeling and the presence of haemoglobin within the CSF was modeled by increasing the absorption coefficient of the layer, with sensitivity quantified in terms of the partial pathlength of light within the brain. The model demonstrated that increases in the CSF absorption led to a marked decrease in the sensitivity to changes in the brain layer. This suggests that blood or other contaminants in the CSF may have a significant effect on the utility of NIRS for measurement of cerebral oxygenation, and merits further investigation.