Assessment of coronary artery bypass graft patency by multidetector computed tomography and electron-beam tomography.
This case report describes the use of retrospectively ECG-gated 16-slice multidetector computed tomography (MDCT) and electron-beam tomography (EBT) for assessing bypass graft patency in two patients with recurrent angina after coronary artery bypass graft surgery. The results of each tomographic modality were compared to the findings of traditional coronary angiography. In the first patient MDCT showed occlusion of the left internal mammary artery (LIMA) and saphenous vein graft after the second anastomosis. Coronary angiography confirmed these findings. In the second patient EBT showed patency of the LIMA and saphenous vein graft. After the first anastomosis of the saphenous vein graft, the connected vessel filled poorly. Coronary angiography confirmed both grafts to be patent, and detected an occlusion distal to the first anastomosis. These findings support the evidence that both MDCT and EBT are suitable techniques for establishing bypass graft patency by non-invasive means.


Nucleotide sequences of feline retroviral oncogenes (v-fes) provide evidence for a family of tyrosine-specific protein kinase genes.
The nucleotide sequences encoding the transforming polyproteins of the Snyder-Theilen and Gardner-Arnstein strains of feline sarcoma virus (FeSV) have been determined. These sequences include a viral transforming gene (v-fes), derived from cellular proto-oncogene sequences (c-fes) of domestic cats by recombination with feline leukemia virus (FeLV). The v-fes sequences are predicted to encode a polypeptide domain strikingly similar to that specified by the transforming gene (v-fps) of the avian Fujinami sarcoma virus. In addition, the 3' 0.8 kilobase pairs of v-fes encode amino acid sequences homologous to the carboxy-terminal portion of pp60src, the transforming protein encoded by the avian Rous sarcoma virus src gene. Thus different feline and avian retroviral transforming genes, all of which encode functionally related proteins with associated tyrosine-specific kinase activities, must be derived from divergent members of the same proto-oncogene family.


The impact of fractionation in SBRT: analysis with the linear quadratic model and the universal survival curve model.
Since the impact of fractionation in SBRT has not been systematically investigated, this modelling study was performed to see how the therapeutic window is affected for a range of fractions at target doses commonly administered in SBRT. Isoeffective tumour-doses (constant cell survival) were calculated with the linear quadratic (LQ) and the universal survival curve (USC) models for 2-20 fractions. The isoeffective tumour-regimes (with α/β = 10 Gy) were used to calculate the sparing of normal tissues (with α/β = 3 Gy) for an increasing number of fractions. Sparing was calculated as an increase in cell survival and decrease in normal tissue complication probability (NTCP) as compared to a common scheme with 3 fractions of 22 Gy to the centre of the target [(15 Gy to the periphery of the planning target volume (PTV)]. At a high dose per fraction, above about 15 Gy, the USC model predicted much lower fractionation sensitivity than the LQ model. This holds true for both tumour and normal tissues. The USC model also predicted greater sparing of normal tissues outside the PTV as compared to the LQ model. Especially at dose levels of the order of 30-50% to that in the centre of the target. The decrease in NTCP predicted by the USC model was of the order of 30% for 10 fractions as compared to the NTCP for 3 fractions. With the LQ model the corresponding decrease was of the order of 10%. The USC model generally predicts a larger therapeutic window than the LQ model for an increasing number of fractions than today's practice in SBRT.


CEO-TMT overseas experience differences and firm performance: A self-categorization theory perspective.
Based on upper echelons and self-categorization theories, this study empirically examines the relationship between CEO-top management team (TMT) overseas experience differences and firm performance and the moderating effects of hometown connectedness, ownership nature, and environmental dynamics. We use data on Chinese manufacturing listed companies from 2012 to 2021. The results show that CEO-TMT overseas experience differences significantly and negatively affect firm performance. Hometown connectedness positively moderates this relationship; as CEO-TMT hometown connectedness increases, the negative impact of CEO-TMT overseas experience differences on firm performance decreases. Finally, state ownership and higher environmental dynamics mitigate the negative relationship between CEO-TMT's overseas experiences and firm performance.


Spinal dissemination following operation on cerebral oligodendroglioma.
This paper concerns two cases of cerebral oligodendroglioma (intraventricular in one case, right temporal in the other), with spinal dissemination (cervical and upper thoracic respectively), manifested clinically 2 years and 14 months respectively after removal of the cerebral tumour. Anatomical examination confirmed the diagnosis of disseminated oligodendroglioma in the leptomeninges in both cases and also in the parenchyma in the second case.


Reduction of adverse acute cardiovascular actions of 6-hydroxydopamine in dogs by adrenergic receptor blockade.
Injection of dogs with 50 mg/kg of 6-hydroxydopamine (6-OHDA) caused large increases in blood pressure and heart rate, followed after 1 or 2 hr by severe hypotension. Prior administration of the adrenergic receptor blocking agents phentolamine and propranolol attenuated both the hyper- and hypotensive phases of 6-OHDA. Phentolamine and propranolol did not prevent depletionof norepinephrine or development of the characteristic morphological changes induced in adrenergic fibers by 6-OHDA.


Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder.
Lower serotonin transporter (5-HTT) binding (BP(P)=f(P)B(avail)/K(D)) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD). 5-HTT binding was quantified using positron emission tomography (PET) with [(11)C]McN5652 in 19 currently depressed subjects with MDD and 41 healthy controls. Depressed subjects received open, naturalistic antidepressant treatment. Remission status was determined one year after PET scan and treatment initiation. Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p=0.057). The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome. Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.


Protein kinase C activator phorbol 12, 13-dibutyrate inhibits platelet activating factor-stimulated Ca2+ mobilization and phosphoinositide turnover in neurohybrid NG108-15 cells.
The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu) dose-dependently inhibited platelet-activating factor (PAF)-induced [Ca2+]i elevation and inositol monophosphate (IP1) accumulation in neurohybrid NG108-15 cells with IC50 values of 162 nM and 35 nM, respectively. Pretreatment of NG108-15 cells with PKC inhibitor H-7 partially prevented the inhibitory effect of PDBu on PAF-induced [Ca2+]i elevation as well as PI metabolism in NG108-15 cells. Pretreatment of the cells with pertussis toxin (PTX) resulted in a dose-dependent inhibition of PAF-induced IP1 and IP3 accumulation but only slightly affected PAF-induced [Ca2+]i elevation in NG108-15 cells. The results reveal that PAF receptor-mediated Ca2+ mobilization and PI metabolism in NG108-15 cells are regulated by PKC while a PTX-sensitive G protein is coupled to PAF receptor for inducing activation of phospholipase C.


The effects of arachidonic acid, indomethacin and SC-19220 on guinea-pig tracheal muscle tone.
The effects on guinea-pig tracheal muscle of a prostaglandin synthesis inhibitor, indomethacin, antagonist, SC-19220, and precursor, arachidonic acid have been studied in order to investigate the possible role of prostaglandins in the maintenance of respiratory smooth muscle tone. Indomethacin reduced the resting tone of the muscle, and increasing concentrations reduced the response to arachidonic acid without affecting the response to acetylcholine. Prostaglandins E2 and F2alpha caused contractions of indomethacin-relaxed muxcle, and tachyphylaxis was induced by repeated exposure of the muscle to these agonists, but not to arachidonic acid. The prostaglandin antagonist, SC-19220 relaxed the muscle and abolished its response to a standard dose of prostaglandin E2. Increasing concentrations of SC-19220 reduced the responses to both arachidonic acid and large doses of prostaglandin E2. The responses of tracheal muscle to arachidonic acid are concluded to be partly due to prostaglandin synthesis, supporting the hypothesis that this process maintanins tracheal muscle tone.


Effect of ethanol on nucleolar structure: a cytological indication of change in RNA/protein synthesis.
The effects of chronic ethanol ingestion on an organelle known to be involved in protein synthesis were studied cytologically in nerve cells of the adult hamster. Twenty-six animals were administered standard laboratory chow and either tap water (controls) or a 15% ethanol solution (experimentals) for a period of 7 weeks. Brains were perfusion-fixed, sectioned transversely, and stained with buffered thionin for microscopic analysis. Reported here are changes in an RNA-rich intranucleolar body (INB) seen in facial motor neurons and cerebellar Purkinje cells of the golden hamster. After chronic ethanol ingestion, the size and frequency of the INB increased significantly in both cell populations. Theoretical considerations are discussed concerning the correlation between this apparent storing of nucleolar RNA/RNP and the biochemical evidence of other investigators for ethanol-induced alterations in RNA/protein synthesis and utilization in neurons.


Neuromyoblastoma in the rat.
We report three tumours arising in the brain stem or adjacent cranial nerves of the Alderly Park rat. Light microscopy with special stains, immunocytochemistry and electron microscopy supported the conclusion that both neuronal and myoid differentiation occurred in all neoplasms. This was shown by the presence in neural cells of axon-like cell processes and in myoblastic cells of striated myofibrils. Although medulloblastomas occur in man and rats the tumours reported here were not related to the cerebellum. We have termed this tumour neuromyoblastoma.


Insights into in vitro phenotypic plasticity, growth and secondary metabolites of the mycobiont isolated from the lichen Platygramme caesiopruinosa.
The choice of inoculum for successful isolation and establishment of axenic lichen mycobiont culture is a key step towards eliminating endolichenic and lichenicolous fungi and other microbial contamination. The nutritional requirements of each lichen species are unique. This work reports on the isolation, phenotypic plasticity, growth and secondary metabolites from mycobiont culture of the pantropical lichen Platygramme caesiopruinosa. Media composition [Malt yeast extract (MY), Modified Murashige and Skoog (MMS) and Lilly and Barnett (LB) media] was optimized to determine nutritional requirements for optimal growth of this species as assessed by dry biomass and the occurrence of secondary metabolite. Furthermore, the role of different carbon sources in affecting growth, growth stages, phenotypic plasticity, biomass and spectrum of secondary metabolites produced of this mycobiont was examined. The molecular identity of the mycobiont culture was confirmed by amplifying mitochondrial small subunit (mtSSU) sequences. Cultures showed optimum biomass production in MY medium with 10% sucrose. The secondary metabolite profiles for each culture treatment were characterized using High-performance Thin-Layer Chromatography (HPTLC) and Gas Chromatography with Mass Spectrometric (GC-MS) analysis. The HPTLC spectral comparison, phenolic and iodine confirmatory analysis revealed the absence of phenolic metabolites and the presence of non-phenolic metabolites in mycobiont extracts, while GC-MS analysis revealed the biosynthesis of side chain fatty acids, hydrocarbons and sugar alcohol in mycobiont cultures treated with 10% supplemented sucrose as a carbon source.


Reference intervals of D-dimer during the pregnancy and puerperium period on the STA-R evolution coagulation analyzer.
Pregnant women are at a hyper-coagulable state with a higher risk of deep venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC), which could be life threatening. We established gestational age-specific reference intervals for D-dimer, and estimate the role of D-dimer test in ruling out VTE and DIC in pregnant women. We followed 1343 healthy pregnant women and 1042 uncomplicated postpartum women to establish gestational age-specific reference intervals of D-dimer during normal pregnancy. Eighty uncomplicated non-pregnant women were chosen as control group. D-dimer testing was also performed among the patients with pregnancy-related complications. D-dimer concentration increased progressively during the pregnancy and peaked at the first postpartum day, and then it began to decrease steadily and reach to non-pregnant concentrations on the 42nd postpartum day. The results of several cases that had clinical suspicion of VTE were compared with those of the reference group. The study provides reference intervals of D-dimer during the pregnancy and postpartum period for women of Chinese Han ethnicity using latex-based immunoturbidimetry on the STA-R evolution coagulation analyzer. Further studies are needed to validate these reference ranges and assess the clinical utility of the reference intervals for D-dimer.


Measurement of the 15N/14N ratio of phenylalanine in fermentation matrix by isotope ratio mass spectrometry.
To determine the origin of 15N-labeled phenylalanine in microbial metabolic flux analysis using 15N as a tracer, a method for measuring phenylalanine δ15N using HPLC coupled with elemental analysis-isotope ratio mass spectrometry (EA-IRMS) was developed. The original source of the 15N-labeled phenylalanine was determined using this new method that consists of three steps: optimization of the HPLC conditions, evaluation of the isotope fractionation effects, and evaluation of the effect of pre-processing on the phenylalanine nitrogen stable isotope. In addition, the use of a 15N-labeled inorganic nitrogen source, rather than 15N-labeled amino acids, was explored using this method. The method described here can also be applied to the analysis of metabolic flux.


Morphine administration and short-term pulmonary outcomes among ventilated preterm infants.
The use of opioid therapy for sedation and analgesia among ventilated infants varies among care providers. The impact of opioid therapy early in the neonatal course of respiratory distress syndrome (RDS) on pulmonary outcomes is not known. We tested the hypothesis that preterm neonates randomized to the morphine infusion group would have improved ventilatory outcomes, measured as shorter durations of ventilator or oxygen therapy, fewer air leaks, and lower incidence of bronchopulmonary dysplasia. All 898 subjects (gestational age [GA] of > or =23 to < or =32 weeks) who were enrolled in the Neurologic Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial formed the study cohort (morphine: 449 patients; placebo: 449 patients). Subjects received the masked study drug until they were weaned from the ventilator or for 14 days, whichever occurred earlier. Outcome measures included air leaks, duration of ventilation or oxygen therapy, hospitalization, bronchopulmonary dysplasia, and death. Subjects in the 2 groups had similar baseline characteristics (mean +/- SD, morphine versus placebo: GA: 27.3 +/- 2.3 vs 27.4 +/- 2.3 weeks; birth weight: 1037 +/- 340 vs 1054 +/- 354 g). Infants in the morphine group required ventilator therapy significantly longer, compared with the placebo group (median [interquartile range]: 7 days [4-20 days] vs 6 days [3-19 days]). This difference in ventilation duration was significant for infants with GA of 27 to 29 weeks (6 days [4-12 days] vs 5 days [2-9 days]) and 30 to 32 weeks (4 days [3-6 days] vs 3 days [2-5 days]). Infants who received additional analgesia with intermittent morphine doses in both groups were sicker than those who were not given open-label morphine. After adjustment for birth weight, Clinical Risk Index for Babies scores, maternal chorioamnionitis, RDS requiring surfactant, and patent ductus arteriosus in a logistic regression model, the use of additional analgesia with morphine was associated independently with increased air leaks and longer durations of high-frequency ventilation, nasal continuous positive airway pressure, and oxygen therapy. Morphine infusions do not improve short-term pulmonary outcomes among ventilated preterm neonates. Additional morphine doses were associated with worsening respiratory outcomes among preterm neonates with RDS.


NMR propagator measurements on flow through a random pack of porous glass beads and how they are affected by dispersion, relaxation, and internal field inhomogeneities.
We flow water through a pack of porous glass beads and employ NMR to measure molecular displacement distributions--the propagators--in the Stokes flow regime. Fluid is flowed over several evolution times to attain fixed mean displacements, and the time dependence of the resulting propagators is analyzed for the effects of diffusion, NMR relaxation, and signal loss due to internal fields. We delineate and illustrate the experimental regimes in which these different effects make their presence felt. Simulations on a simple model system reproduce the essential features of our experimental results and provide insight into the mechanisms shaping the propagators.


A robust composite hydrogel consisting of polypyrrole and β-cyclodextrin-based supramolecular complex for the label-free amperometric immunodetection of motilin with well-defined dual signal response and high sensitivity.
The label-free amperometric immunosensor is a simple, convenient and reliable method for the detection of diseases markers. Its performance heavily relies on the properties of the sensing substrate. In this paper, we proposed a robust composite hydrogel that consists of polypyrrole and vinyl ferrocene/mono-aldehyde β-cyclodextrin (β-CD) complex as a sensing and immobilizing substrate. Surprisingly, it was observed that the microstructure of the hybrid hydrogel could be well regulated by the feed ratio of vinylferrocene and so are the electrochemical properties. Depending on the dual electrochemical active compositions, a large loading capacity of antibodies and meanwhile the excellent conductivity, the square wave voltammetry results of the optimized immunosensor for the detection of motilin exhibited a well-defined dual signal response, with a wide linear range both from 10 pg mL-1 to 100 ng mL-1 for motilin, and an ultralow limit of detection of 6.29 pg mL-1 and 2.73 pg mL-1. More importantly, the immunosensor exhibited an especially sensitive response with the slope value as high as 31.342 and 25.751 respectively, which makes great sense in the practical diagnosis.


Association between 14 bp insertion/deletion HLA-G functional polymorphism and insulin resistance in a cohort of Italian children with obesity.
The non-classical HLA-class I molecule-g (HLA-G) gene shows a deletion/insertion (del/ins) polymorphism of a 14-base-pair sequence (14 bp) in the exon 8 at the 3' untranslated region. The presence of the 14 bp insertion allele has been associated to lower soluble HLA-G protein production, a protein with anti-inflammatory activities. So far, no studies have investigated the relationship between HLA-G 14 bp del/ins polymorphism and metabolic features of obese children and adolescents. We aimed to assess if the HLA-G ins/del polymorphism, and in particular the HLA-G ins/ins genotype determining lower sHLA-G production, is associated to insulin resistance (evaluated by homeostasis model assessment [HOMA]) in a population of obese children. We enrolled 574 obese children and adolescents. Anthropometric and laboratory data were collected. The white blood cell (WBC) count was evaluated as surrogate marker of inflammation. C-reactive protein (CRP) was available in 48 patients. HOMA was calculated. Patients were genotyped for the HLA-G del/ins polymorphism. Subjects carrying the HLA-G ins/ins genotype, presented with higher HOMA, WBC and CRP values, compared to del/ins and del/del genotypes (P ≤ 0.0009, ≤0.02 and ≤0.0001, respectively). Comparison of the regression line slopes, performed for HOMA and WBC on the basis of HLA-G genotypes, showed that subjects carrying the HLA-G ins/ins genotype presented with a stronger correlation between HOMA and WBC, compared to the other genotypes (Model r2 3.13%, P ≤ 0.006). We showed a strong association between HLA-G 14 bp ins/ins genotype and HOMA in obese children and adolescents. This association could be hypothetically modulated by subclinical inflammation.


Impact energy of everyday items used for assault.
Blunt force is a frequently used type of violence especially because it can be performed with basically every object of our daily lives or with bare hands or feet. The injuries and medical consequences have been widely examined, whereas the forces and especially the energies acting on impact have rarely been analyzed. The aim of the present study is to provide the impact energy and its ranges of four longish everyday items with different characteristics for male and female offenders. Additionally, the moment of inertia (MOI) for all the objects was calculated and its influence on the energy determined. A combination wrench, aluminum pipe, golf club, and spade were chosen as representatives of the four categories short, medium length with the center of mass (COM) in the middle, medium length with the COM close to the hitting point, and long and heavy. A total of 880 strikes have been performed by 11 volunteers. The results show the mean energy values of wrench, pipe, golf club, and spade for men of 51.1, 74.4, 93.5, and 166.7 J. For women, the results are 33.0, 41.0, 56.5, and 76.8 J. Knowing the energy thresholds for certain fractures and injuries, these results help to assess whether a claimed hit may have caused the fracture or injury or not.


Isoindolinone enantiomers having affinity for the dopamine D4 receptor.
PD 108635 (1) was identified as a potent dopamine D4 ligand and we wanted to replace the benzylic alcohol with a metabolically more stable moiety. Investigations led to the discovery of a series of isoindolinones having D4 affinity.


Identification of complement factor H variants that predispose to pre-eclampsia: A genetic and functional study.
The objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia. In a case-control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre-eclampsia. No variants were identified in controls. Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal-fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven. We genotyped 609 pre-eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts. Complement-based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type. Secretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations. We identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre-eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V. These results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre-eclampsia.


Three-dimensional (3D) system versus two-dimensional (2D) system for laparoscopic resection of adrenal tumors: a case-control study.
Laparoscopy is the standard technique for resecting adrenal tumors worldwide. The main drawbacks of conventional 2D laparoscopy are limited depth perception and tactile feedback. Currently available high-quality 3D laparoscopy systems might improve surgical outcomes for adrenalectomy. We compare the safety and efficacy of 3D versus 2D laparoscopy in the treatment of adrenal tumors. This case-control study analyzed prospectively collected data from patients with benign or malignant adrenal tumors treated laparoscopically at a single academic medical center between April 2003 and March 2020. We collected demographic, diagnostic, preoperative, and operative variables, and used multiple linear and logistic regression to analyze differences in various short-term outcomes between the two approaches while adjusting for potential confounders. We included 150 patients: 128 with benign tumors and 22 with malignant tumors; 95 treated with 3D laparoscopy (case group); and 55 with 2D laparoscopy (control group). After adjustment for patient, surgical, and tumor characteristics, a 2D vision was associated with a longer operative time (β = 0.26, p = 0.002) and greater blood loss (β = 0.20, p = 0.047). There was no significant difference in rates of conversion to open surgery (odds ratio [OR] = 1.47 (95% CI 0.90-22.31); p = 0.549) or complications (3.6% vs. 2.1%; p = 0.624). With experienced surgeons, laparoscopic adrenalectomy was safer and more feasible with the 3D system than with the 2D system, resulting in less operative blood loss and shorter operative time with no differences in rates of conversion to open surgery or postoperative complications. For adrenal tumors, 3D laparoscopy offers advantages over 2D laparoscopy.


Clinicopathologic Differences in Patients with Gallbladder Cancer According to the Presence of Anomalous Biliopancreatic Junction.
Anomalous biliopancreatic junction (ABPJ) is a risk factor for gallbladder cancer (GBC). This study investigated the significance of ABPJ in patients with GBC. Of the 453 patients with GBC underwent surgery at Seoul National University Hospital between 2000 and 2014, the 401 patients who can be assessed for the presence of ABPJ with radiologic image were analyzed. The 401 patients with GBC included 183 (45.6 %) males and 218 (54.4 %) females. ABPJ was identified in 69 (17.2 %) patients, 22 (31.9 %) males and 47 (68.1 %) females. Choledochal cyst (CC) was identified in 18 (4.5 %) patients, all of whom had ABPJ. Curative surgery was accomplished in 68.1 %. A comparison of patients with and without ABPJ showed that mean age (59.9 vs. 65.1 years, p < 0.001) and association with gallbladder stone (8.7 vs. 24.7 %, p = 0.002) were significantly lower in the ABPJ group, while the proportion of female (68.1 vs. 51.5 %, p = 0.012), bile duct resection rate (47.8 vs. 18.4 %, p < 0.001), and curative resection rate (81.1 vs. 65.7 %, p = 0.003) were significantly higher in the ABPJ group. Overall 5-year survival rates were similar in the ABPJ and non-ABPJ groups (74.4 vs. 69.0 %, p = 0.533). In patients with ABPJ, the presence of CC did not have a significant effect on survival (p = 0.099). ABPJ was found in 17.2 % of patients with GBC. ABPJ is associated with younger age, female gender, absence of gallbladder stones, higher BDR rate, and higher curative resection rate. However, neither ABPJ nor CC was prognostic of survival in curatively treated patients with GBC.


Molecular adaptation and salt stress response of Halobacterium salinarum cells revealed by neutron spectroscopy.
Halobacterium salinarum is an extreme halophile archaeon with an absolute requirement for a multimolar salt environment. It accumulates molar concentrations of KCl in the cytosol to counterbalance the external osmotic pressure imposed by the molar NaCl. As a consequence, cytosolic proteins are permanently exposed to low water activity and highly ionic conditions. In non-adapted systems, such conditions would promote protein aggregation, precipitation, and denaturation. In contrast, in vitro studies showed that proteins from extreme halophilic cells are themselves obligate halophiles. In this paper, adaptation via dynamics to low-salt stress in H. salinarum cells was measured by neutron scattering experiments coupled with microbiological characterization. The molecular dynamic properties of a proteome represent a good indicator for environmental adaptation and the neutron/microbiology approach has been shown to be well tailored to characterize these modifications. In their natural setting, halophilic organisms often have to face important variations in environmental salt concentration. The results showed deleterious effects already occur in the H. salinarum proteome, even when the external salt concentration is still relatively high, suggesting the onset of survival mechanisms quite early when the environmental salt concentration decreases.


NY-ESO-1 is a sensitive and specific immunohistochemical marker for myxoid and round cell liposarcomas among related mesenchymal myxoid neoplasms.
Myxoid and round cell liposarcomas constitute approximately one-third of all liposarcomas, a relatively common group of fat-derived soft tissue sarcomas. The histomorphology is a continuum between highly differentiated myxoid and poorly differentiated round cell components. The gold standard of diagnosis is dependent on histomorphology and/or identification of t(12;16)(q13;p11) translocation by cytogenetics or demonstration of DDIT3 rearrangements by fluorescence in situ hybridization. There are currently no diagnostic immunohistochemical stains available. The broad range of myxoid neoplasms in the differential diagnosis includes a variety of sarcomas. Given the notable differences in disease biology among myxoid neoplasms, which range from benign to aggressive, an accurate diagnosis is imperative for proper treatment and prognostication. Prompted by our recent study showing frequent expression of the cancer testis antigen NY-ESO-1 in myxoid and round cell liposarcomas, we sought to evaluate the utility of NY-ESO-1 as an immunohistochemical marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms within the differential diagnosis. Formalin-fixed, paraffin-embedded blocks were obtained for the following mesenchymal myxoid neoplasms (n=138): myxoid and round cell liposarcoma (n=38); well-differentiated liposarcoma (n=12); lipoma (n=20; 4 with myxoid change); extra-cardiac soft tissue myxoma (n=39); extraskeletal myxoid chondrosarcoma (n=12); myxofibrosarcoma (n=10: 5 low grade, 2 intermediate grade, 3 high grade); and low-grade fibromyxoid sarcoma (n=7). Utilizing standard immunohistochemistry protocols, full sections were stained with NY-ESO-1 (clone E978), and staining was assessed for intensity (1-2+), percentage of tumor positivity, and location. In all, 36/38 (95%) of the myxoid and round cell liposarcomas demonstrated NY-ESO-1 immunoreactivity. The majority of the positive cases (34/36; 94%) showed strong, homogenous staining (>50% tumor positivity), and two cases (6%) showed weak (1+ intensity), patchy staining (20-30% tumor positivity). Immunoreactivity was predominantly cytoplasmic. All the other neoplasms evaluated were negative for NY-ESO-1. NY-ESO-1 appears to be a sensitive and a specific marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms. The assessment of NY-ESO-1 expression by immunohistochemistry in the appropriate setting provides a cheaper, faster, and more accessible confirmatory test.


Angioedema with normal laboratory values: the next step.
When faced with a patient with recurrent swelling, a thorough laboratory evaluation to determine the underlying etiology ensues. When the laboratory work-up is unrevealing, health care practitioners are frequently left in a quandary. This review will attempt to provide up-to-date information on how to approach the diagnosis and management of angioedema in a patient with normal laboratory values. The subtypes that will be reviewed in detail include: hereditary angioedema with normal C1 inhibitor (HAE with normal C1INH), drug-induced angioedema, and idiopathic angioedema. We present literature to aid the physician in the diagnosis and treatment of these disorders.


Fish proteins as potential precursors of taste-active compounds: an in silico study.
Fish protein is a good source of amino acids and peptides with sensory properties. Theoretically, the type of protein affects the taste quality of the protein hydrolysates. To better use fish protein in the food ingredients industry, an in silico approach was adopted to evaluate the potential of fish protein to release taste-active compounds. Six types of protein from seven commercial fishes were screened from the Uniprot knowledge base. The results showed that a remarkable number of umami fragments presented in myosin and parvalbumin (PB), such as glutamic acid (Glu), aspartic acid (Asp), and Asp- and Glu- containing peptides, whereas sweet amino acids and bitter peptides (e.g., Pro- and Gly- containing peptides) were mainly found in collagen (CGI) in all fish samples. After the in silico proteolysis by papain, a difference in the profile of taste-active fragments was observed among the six types of proteins. Amino acids were the main hydrolysis products of these proteins, especially umami, sweet, and bitter amino acids, significantly contributing to the taste formation of protein hydrolysates. Besides, the myosin and CGI hydrolysates were abundant in taste active peptides both in types and quantities. Myosin is a promising protein source for producing umami fragments, and CGI seems to be a good precursor of sweet and bitter fragments. Different types of protein have an essential effect on the taste of protein hydrolysates. © 2022 Society of Chemical Industry.


Structure and dynamics of photosystem II light-harvesting complex revealed by high-resolution FTICR mass spectrometric proteome analysis.
Structure and dynamics of membrane-bound light-harvesting pigment-protein complexes (LHCs), which collect and transmit light energy for photosynthesis and thereby play an essential role in the regulation of photosynthesis and photoprotection, were identified and characterized using high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). LHCs from photosystem II (LHCII) were isolated from the thylakoid membrane of Arabidopsis thaliana leaves after light stress treatment using sucrose density gradient centrifugation, and separated by gel-filtration into LHCII subcomplexes. Using reversed-phase high-performance liquid chromatography and two-dimensional (2D) gel electrophoresis, the LHCII proteins, Lhcb1-6 and fibrillins, were efficiently separated and identified by FTICR-MS. Some of the LHCII subcomplexes were shown to migrate from photosystem II to photosystem I as a result of short-term adaptation to changes in light intensity. In the mobile LHCII subcomplexes, decreased levels of fibrillins and a modified composition of LHCII protein isoforms were identified compared to the tightly bound LHCII subcomplexes. In addition, FTICR-MS analysis revealed several oxidative modifications of LHCII proteins. A number of protein spots in 2D gels were found to contain a mixture of proteins, illustrating the feasibility of high-resolution mass spectrometry to identify proteins that remain unseparated in 2D gels even upon extended pH gradients.


Effects of acute cortisol administration on response inhibition in patients with major depression and healthy controls.
Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition.


[Studies on experimental renal damage in rats. II. beta 2-microglobulin: purification, radioimmunoassay, and urine and serum levels in tubular nephropathy].
Beta 2-Microglobulin (beta 2-M) was purified from the urine of rats treated with cephaloridine by a combination of ammonium sulfate precipitation, gel chromatography, ion exchange chromatography, zone electrophoresis, and isoelectric focusing. The protein thus obtained was identified as beta 2-M by its molecular weight, electrophoretic mobility, and amino acid composition and was confirmed as a single protein through polyacrylamide gel electrophoresis, Ouchterlony immunodiffusion analyses, and immunoelectrophoresis using rabbit anti-rat beta 2-M sera. A radioimmunoassay was developed for the measurement of serum and urine beta 2-M levels. In rats given gentamicin (20 or 80 mg/kg/day, s.c.) for 10 days, serum beta 2-M was increased simultaneously with changes in common renal function parameters such as serum urea nitrogen, creatinine, and urinary protein. Urinary beta 2-M was elevated from the early stage of nephropathy and correlated with renal morphological change, indicating that urinary beta 2-M can be used as a sensitive and valuable index of renal tubular damage.


Static and dynamic body balance following provocation of the visual and vestibular systems in females with and without joint hypermobility syndrome.
Joint hypermobility syndrome (JHS) is a heritable disorder of the connective tissue characterized by excessive joint movement, musculoskeletal pain and neurophysiological deficits (i.e. decreased proprioceptive acuity, altered neuromuscular reflexes). Such deficits may affect body balance thus increasing the risk of injury. The present study aimed at examining static and dynamic body balance following challenge of the visual and vestibular systems in individuals with JHS. The sample consisted of 21 females with JHS and 20 controls without signs of JHS. Static body balance was assessed by the degree of anteroposterior and mediolateral deviation of the center of pressure, during 20-sec single-leg stances with eyes opened (EO), eyes closed (EC) and eyes opened with head extension (EO-HE) using a foot pressure platform. Dynamic body balance was assessed by the number of landing and balance errors committed during a multiple single-leg-hop-stabilization test. Nonparametric analysis showed that the JHS-group demonstrated significantly greater (a) mediolateral deviation during single-leg-stance with EO (p < 0.01), (b) mediolateral and anteroposterior deviation during single-leg-stance with EO-HE (p < 0.05), and (c) number of landing errors (p < 0.05) compared to the control group. Poor static balance following challenge of the vestibular system may be justified by vestibular deficiency and/or insufficient proprioceptive capabilities of the neck. Impairments of dynamic balance in individuals with JHS may be attributed to proprioceptive deficits, which can alter feedforward and feedback mechanisms.


Discrete pleural masses without effusion in a young man: an unusual presentation of tuberculosis.
Extensive tuberculous infection of the pleura presented radiographically as multiple discrete nodules, without associated effusion or lesions of lung parenchyma.


Suppressive actions of a gonadotropin-releasing hormone antagonist on luteinizing hormone, follicle-stimulating hormone, and prolactin release in estrogen-deficient postmenopausal women.
We investigated time- and dose-dependent actions of a gonadotropin-releasing hormone antagonist, the "Nal-Glu" peptide [Ac-D2Nal1, 4CIDPhe2, D3Pal3, Arg5, DGlu6(AA), DAla10], in nine healthy estrogen-withdrawn postmenopausal women. Gonadotropin-releasing hormone antagonist was administered subcutaneously at doses of 10, 30, 100, and 300 micrograms/kg. Suppression of immunoactive luteinizing hormone concentrations was achieved with a 30 micrograms/kg dose of antagonist. Suppression of immunoactive follicle-stimulating hormone levels was less (40%) even at the highest antagonist dose (300 micrograms/kg). Bioactive luteinizing hormone concentrations also significantly decreased (greater than 60%) at the two antagonist doses tested (30 and 300 micrograms/kg). However, the lower antagonist dose showed an "escape" of bioactive luteinizing hormone values after 18 hours. No suppressive effects of the antagonist on prolactin secretion occurred at any dose tested. We conclude that this gonadotropin-releasing hormone antagonist can achieve effective, potent, and long-lasting suppression of pituitary secretion of biologically active luteinizing hormone at higher doses, but secretion of biologically active luteinizing hormone may "escape" at lower doses.


Prospective Validation of PREDICT and Its Impact on the Transesophageal Echocardiography Use in Management of Staphylococcus aureus Bacteremia.
Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, "PREDICT," that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke's criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.


Periprosthetic fractures of the knee: a comprehensive review.
Demographic changes have resulted in an increase in the number of older patients diagnosed with degenerative joint disease. Developments in the field of joint arthroplasty allow a broader population to improve their lifestyles. An increased demand for knee arthroplasty has led to a rise in operations performed worldwide. Although there has been a constant propagation of technology and an increase in medical staffing at a professional level, many patients still encounter complications. Though rare, these factors may lead to life-threatening scenarios and a devastating effect on the success of the operation. One such rare complication includes periprosthetic fractures around the knee, a complex injury which requires a cautious and experienced approach. In this review, we analyze the prevalence, risk factors and classification, investigation and treatment options for periprosthetic fractures with total knee arthroplasty.


Incidence of spine surgery in the South African private healthcare sector: ten-year trends within a large open medical scheme.
Studies from developed countries suggest a dramatic increase in the utilization of spine surgery in recent decades, however less is known about spine surgery rates in the developing world. The aim of this study was to investigate ten-year trends in the incidence of spine surgery within South Africa's largest open medical scheme. This retrospective review included adult inpatient spine surgeries funded by the scheme between 2008 and 2017. The incidence of spine surgery was investigated by age group-overall and for degenerative pathologies, fusion and instrumentation. Surgeons per 100,000 members were determined. Trends were evaluated by linear regression and by crude 10-year change in incidence. A total of 49,575 spine surgeries were included. The incidence of surgery for lumbar degenerative pathology showed a significant upward trend among 60-79 year olds but declined among 40-59 year olds. The incidence of lumbar fusion and lumbar instrumentation declined significantly among 40-59 year olds with little change among 60-79 year olds. The ratio of orthopaedic spinal surgeons decreased from 10.2 to 6.3 per 100,000 members whereas the ratio of neurosurgeons decreased from 7.6 to 6.5 per 100,000. Spine surgery in the South African private healthcare sector bears some similarity to developed countries in that it is dominated by elective procedures for degenerative pathology. However, the findings did not reflect the marked increases in the utilization of spine surgery reported elsewhere. It is hypothesized that this may be partly related to differences in the supply of spinal surgery.


The roles of glucocorticosteroid and of fibrinolytic activity in the development of bilateral renal cortical necrosis in cycloheximide-treated mice challenged with a submicrogram dose of endotoxin.
Mice given cycloheximide and 0.2 microgram of endotoxin simultaneously developed ischaemic bilateral renal cortical necrosis as part of a fatal syndrome. Endotoxin given 2 h after cycloheximide, although fatal, failed to produce renal cortical necrosis. Investigation suggested that, following endotoxin challenge in cycloheximide-treated mice, the occurrence or non-occurrence of bilateral renal cortical necrosis was determined by the concentration of circulating glucocorticoids at the time of endotoxin challenge. Thus, below a certain, as yet undefined, glucocorticoid concentration, endotoxin does not cause renal cortical necrosis in cycloheximide-treated mice. Inhibition of the fibrinolytic system by epsilonaminocaproic acid (EACA) indicated that protection against renal cortical necrosis was directly mediated by increased fibrinolytic activity. Since this increased activity occurred during a period of profound cycloheximide-mediated inhibition of protein synthesis, it was postulated that pre-existing plasminogen activator was released from inhibition, and that this release could only occur when the glucocorticoid concentration fell below a certain critical value.


Anterior, posterior, and nonkeratometric contributions to refractive astigmatism in pseudophakes.
To investigate the relationship between measured anterior (ACA) and posterior (PCA) keratometric astigmatism and postoperative refractive astigmatism (RA) and to quantify noncorneal astigmatism (NCA) contributions to RA. Penn State College of Medicine, Hershey, Pennsylvania, USA. Retrospective consecutive case series. Consecutive eyes underwent preoperative biometry (IOLMaster 700) and tomography/topography using a dual Scheimpflug-placido disk-based device (Galilei G4), cataract surgery with implantation of a monofocal intraocular lens (IOL), and postoperative manifest refractions. RA was compared with keratometric astigmatism using the following methods: IOLMaster, SimK, CorT, SimK + measured PCA, total corneal power at the corneal plane (TCP2), and CorT(Total). An ocular residual astigmatism (ORA) vector was calculated between RA and each measured astigmatism. Analysis was based on 296 eyes. ORA centroids were 0.28 @ 179, 0.45 @ 001, 0.37 @ 001, 0.19 @ 003, 0.19 @ 001, and 0.23 @ 178 diopter (D) for the 6 aforementioned methods, respectively (P < .000001 [ORAx, ORAy]). Based on TCP2 measurements, eyes with against-the-rule ACA and with-the-rule (WTR) ACA had ORA centroids of 0.09 @ 082 and 0.58 @ 001 D (P < .000001 [ORAx, ORAy]), respectively. ORA was nonzero and not entirely explained by the cornea, especially in those with WTR ACA. Total keratometric astigmatism did not explain all ocular astigmatism. Noncorneal contributions were significant, especially in eyes with WTR ACA.


Quantitative assessment of gastric ischemic preconditioning on conduit perfusion in esophagectomy: propensity score weighting study.
Gastric ischemic preconditioning prior to esophagectomy has been studied as a method to improve gastric conduit perfusion and reduce anastomotic complications, without conclusive results. The aim of this study is to evaluate the feasibility and safety of gastric ischemic preconditioning in terms of post-operative outcomes and quantitative gastric conduit perfusion. Patients who underwent an esophagectomy with gastric conduit reconstruction between January 2015 and October 2022 at a single high-volume academic center were reviewed. Patient characteristics, surgical approach, post-operative outcomes, and indocyanine green fluorescence angiography data (ingress index for arterial inflow and ingress time for venous outflow, and the distance from the last gastroepiploic branch to the perfusion assessment point) were analyzed. Two propensity score weighting methods were used to investigate whether gastric ischemic preconditioning reduces anastomotic leaks. Multiple linear regression analysis was used to evaluate the conduit perfusion quantitatively. There were 594 esophagectomies with gastric conduit performed, with 41 having a gastric ischemic preconditioning. Among 544 with cervical anastomoses, leaks were seen in 2/30 (6.7%) in the ischemic preconditioning group and 114/514 (22.2%) in the control group (p = 0.041). Gastric ischemic preconditioning significantly reduced anastomotic leaks on both weighting methods (p = 0.037 and 0.047, respectively). Ingress index and time of the gastric conduit with ischemic preconditioning were significantly better than those without preconditioning (p = 0.013 and 0.025, respectively) after removing the effect of the distance from the last gastroepiploic branch to the perfusion assessment point. Gastric ischemic preconditioning results in a statistically significant improvement in conduit perfusion and reduction in post-operative anastomotic leaks.


Comparison of pre- and postcontrast 3D time-of-flight MR angiography for the evaluation of distal intracranial branch occlusions in acute ischemic stroke.
Three-dimensional time-of-flight (TOF) MR angiography is used routinely in stroke workup to detect arterial occlusions, but a major drawback is its inadequate depiction of vessels with slow or in-plane flow. We hypothesized that the use of contrast-enhanced MR angiography improves delineation of vessels with diminished or absent flow on precontrast MR angiograms. Pre- and postcontrast 3D TOF MR angiograms were acquired in 55 consecutive patients with acute stroke. Patency of 480 intracranial vessels was assessed on both the pre- and postcontrast angiograms. Diffusion-weighted (DW) and perfusion-weighted (PW) imaging data were also obtained and results correlated with those of pre- and postcontrast MR angiography. For 50 abnormal vessel segments seen on precontrast MR angiograms, postcontrast MR angiograms resulted in change in the vascular signal intensity in 70% (35 vessel segments); 94% of these changes showed a greater extent of vessel patency. Venous and soft-tissue contrast enhancement had no effect on assessment in 95% of all 480 vessels examined. Interobserver reliability was moderate, with postcontrast interpretation (kappa = 0.48) showing a slight improvement over precontrast interpretation (kappa = 0.41). Good agreement was found between the TOF results and the pooled DW and PW imaging results. Compared with precontrast 3D TOF MR angiograms, postcontrast 3D TOF angiograms improve assessment of intracranial vessel patency in acutely ischemic vascular territories. In some patients, an improved understanding of acute ischemic stroke was obtained by viewing the pre- and postcontrast images. Postcontrast MR angiography should be included in the MR evaluation of acute stroke.


The Quality Index for Nutrition in Nursing Homes (QUINN). A new tool for evaluating diet quality in long-term care homes.
Background: the assessment of diet quality (DQ) is fundamental to the study of disease-diet associations, and it is necesary to implement an easy to-apply tool in nursing homes (NHs). Our objective was to propose and apply a novel diet quality indicator (DQIn) using an a priori approach for NHs. Methods: the QUality Index for Nutrition in Nursing homes (QUINN) was implemented in a public NH located in Valladolid, Spain, during a 5-week period (n = 137 subjects). The choice of the QUINN components was based on a rapid review. The QUINN was based on 15 dietary components - 12 were basic (vegetables, fruits, legumes, olive oil, cereals, dairy, white fish and seafood, white-meat, eggs/positive; other fats, red and processed meat, and sweets/negative), and 3 were supplementary (fruits and vegetables variety, oily-fish, and whole-grains/positive). Each component was classified into 4-categories (0, 1, 2 o 3 points; range: 0-45 points). Results: the QUINN was tested on a menu offered by a NH giving a result of 34 points (good diet). The components with the highest scores were related to the Mediterranean diet (high consumption of legumes, olive oil, white fish and shellfish; low intake of other fats; and a wide variety of fruits and vegetables), together with cereals, white meat, dairy, and eggs. The components that required a major change were red- and processed-meats, sweets, and whole grains. Conclusion: the menu of this Spanish NH showed a good DQ according to the QUINN. The assessment of the DQ in NHs using QUINN will allow the proposal of interventions aimed at improving their diet.


Ecdysone differentially regulates metamorphic timing relative to 20-hydroxyecdysone by antagonizing juvenile hormone in Drosophila melanogaster.
In insects, a steroid hormone, 20-hydroxyecdysone (20E), plays important roles in the regulation of developmental transitions by initiating signaling cascades via the ecdysone receptor (EcR). Although 20E has been well characterized as the molting hormone, its precursor ecdysone (E) has been considered to be a relatively inactive compound because it has little or no effect on classic EcR mediated responses. I found that feeding E to wild-type third instar larvae of Drosophila melanogaster accelerates the metamorphic timing, which results in elevation of lethality during metamorphosis and reduced body size, while 20E has only a minor effect. The addition of a juvenile hormone analog (JHA) to E impeded their precocious pupariation and thereby rescued the reduced body size. The ability of JHA impeding the effect of E was not observed in the Methoprene-tolerant (Met) and germ-cell expressed (gce) double mutant animals lacking JH signaling, indicating that antagonistic action of JH against E is transduced via a primary JH receptor, Met, or a product of its homolog, Gce. I also found that L3 larvae are susceptible to E around the time when they reach their minimum viable weight. These results indicate that E, and not just 20E, is also essential for proper regulation of developmental timing and body size. Furthermore, the precocious pupariation triggered by E is impeded by the action of JH to ensure that animals attain body size to survive metamorphosis.


Flower-feeding specialization in wild bee and wasp communities in seasonal neotropical habitats.
Flower visitation records were obtained for 192 species of bees and 138 species of wasps in three neotropical habitats. Four indices of feeding specialization were calculated for common species, and similar patterns were observed using each index. Variation in specialization could be attributed to several factors: the habitat and season in which species were found, the degree of sociality of species, and whether species were bees or wasps. Important differences among habitats and seasons were the number of coexisting consumer species and the species richness and phenology of resource plants. Differences in average consumer specialization among habitats and seasons may have been the result of differences in competitive pressures and to a lesser extent, differences in the flowering strategies of local plants. Eusocial bees and wasps were much more generalized in feeding than solitary species, and bees were more generalized than wasps. Bees in these neotropical communities were much less specialized than their north temperate counterparts. This pattern is reflected by the near absence of species that feed at only one or two plant species in Guanacaste, as compared to a very high frequency of these extreme specialist species in north temperate areas. Temperate zone species of bees have less "even" visitation rates to their resources than tropical bees. Consequently, temperate zone bees are more specialized in both the variety of plant species visited and the dominance of visitation to each set of resource plants. Several hypotheses are examined as possible explanations for this apparent qualitative difference in community structure between neotropical and temperate communities.


The Effect of Polymetallic Pollution on Ion-Exchange Properties of Barley Root and Shoot Cell Walls.
For the first time we determined the ion-exchange properties of the cell walls (CWs) isolated from roots and shoots of barley plants grown in the conditions of polymetallic pollution. The content of all the types of cation-exchange groups in the CWs was found to be considerably higher in the shoots than in the roots, which resulted in higher metal-binding capacity of the shoot CWs and higher swelling capacity of CW polymers. It was shown for the first time that the heavy metal excess causes an increase in the content of demethylated pectins in the shoot CWs.


A preliminary investigation of daily variability of stuttering in adults.
Variability in frequency of stuttering has made the results of treatment outcome studies difficult to interpret. Many factors that affect variability have been investigated; yet the typical range of variability experienced by speakers remains unknown. This study examined the day-to-day variability in the percentage of syllables containing stuttered and nonstuttered disfluencies in the speech of six adult speakers in three spontaneous speaking situations and two reading tasks. The frequency of moments stuttering during the tasks were compared within and between speakers and days to document the degree of variability in stuttering frequency and explore whether there were any consistent patterns. The Stuttering Severity Instrument-Fourth Edition (SSI-4) and Overall Assessment of the Speaker's Experience of Stuttering for Adults (OASES-A) were also tested for day-to-day variability. Correlations between frequency, severity, and life impact were made. The primary result of this study was the large range over which frequency of stuttering varied from day to day for the same individual. This variability did not correlate with any measures of stuttering severity but did correlate with life impact as measured by the OASES-A. No global pattern was detected in variability from day to day within or between participants. However, there were significantly more nonstuttered disfluencies present during the spontaneous speaking tasks than during the reading tasks. The day-to-day variability in the life impact of the disorder (OASES-A) was less than the day-to-day variability in observable stuttering behavior (percentage of syllables stuttered and SSI-4). Frequency of stuttering varies significantly from situation to situation and day to day, with observed variability exceeding the degree of change often reported in treatment outcomes studies from before to after treatment. This variability must be accounted for in future clinical and scientific work.


Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae).
Schistosomiasis is one of the world's major public health problems, and its treatment is widely dependent on praziquantel (PZQ), the only available drug. Schistosoma mansoni ATP diphosphohydrolases are ecto-enzymes localized on the external tegumental surface of S. mansoni and considered an important target for action of new drugs. In this work, the in vitro schistosomicidal activity of the crude extract of Glycyrrhiza inflata roots (GI) and its isolated compounds echinatin, licoflavone A and licoflavone B were evaluated against S. mansoni adult worms. Results showed that GI (200 μg/mL) was active against adult schistosomes, causing 100% mortality after 24 h of incubation. Chromatographic fractionation of GI led to isolation of echinatin, licoflavone A and licoflavone B. Licoflavone B (25-100 μM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms, without affecting mammalian Vero cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after incubation with licoflavone B. Licoflavone B also showed high S. mansoni ATPase (IC50 of 23.78 μM) and ADPase (IC50 of 31.50 μM) inhibitory activities. Docking studies predicted different interactions between licoflavone B and S. mansoni ATPDase 1, corroborating with the in vitro inhibitory activity. This report demonstrated the first evidence for the schistosomicidal activity of licoflavone B and suggests that its mechanism of action involve the inhibition of S. mansoni ATP diphosphohydrolases.


[Spasmophilia in children and the anticonvulsant properties of a new Ukrainian preparation containing a pyrimidine derivative].
Tablets valcophen, which are containing the pyrimidine's derivative, have an acute anticonvulsive activity. Tablets valcophen and granules phenobarbital for children are having the same activity, which have been marked about lower intensity convulsions, quantity of a lived animals and also lengthening a time of deathing mice. These investigations are showing that tablets valcophen may be used for treatment convulsive state in children.


TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer.
Tetraspanin 8 (TSPAN8), a transmembrane glycoprotein, is implicated in various pathological conditions including human malignancies. However, the roles and underlying mechanisms of TSPAN8 in promoting gastric cancer(GC) progression are yet to be fully understood. Our study found that TSPAN8 expression was significantly elevated in GC tissues. We also observed a positive correlation between high TSPAN8 expression and various clinicopathological characteristics of GC, including tumor differentiation, invasion depth, lymph node metastasis, and clinical stage. Moreover, the elevated TSPAN8 expression was indicative of poor prognosis. Functionally, we observed that knockdown of TSPAN8 significantly attenuated while overexpression of TSPAN8 promoted GC cell migration and invasion. In vivo experiments, knockdown of TSPAN8 suppressed lung metastasis in nude mice. We further explored the underlying mechanisms of TSPAN8 and found that it regulated EGFR expression in GC cells by accelerating phosphorylation of EGFR and AKT. Our study reveals that TSPAN8 plays a significant role in promoting tumor metastasis by activating the EGFR/AKT pathway, indicating that it may serve as a promising therapeutic target of gastric cancer.


Examining cross-level effects in dyadic analysis: A structural equation modeling perspective.
The actor-partner interdependence (APIM) and common-fate (CFM) models for dyadic data are well understood and widely applied. The actor and partner coefficients estimated in the APIM reflect the associations between individual-level variance components, whereas the CFM coefficient describes the association between dyad-level variance components. Additionally, both models assume that the theoretically relevant and/or empirically dominant component of variability resides at the same level (individual or dyad) across the predictor and outcome variables. The present work recasts the APIM and CFM in terms of dyadic nonindependence, or the extent to which a given variable reflects dyad- versus individual-level processes, and describes a pair of hybrid actor-partner and common-fate models that connect variance components residing at different levels. A series of didactic examples illustrate how the traditional APIM and CFM can be combined with the hybrid models to describe mediational processes that span the individual and dyad levels.


[Diarrhea of the newborn animal: nature and mechanism of action of enteropathogenic Escherichia coli in the calf and piglet].
The present knowledge of the enteropathogenic characteristics of Escherichia coli (adhesion and toxinogenesis) is reviewed in the calf, and compared with piglet data. A pathogenic model of E. coli diarrhoea in the calf is proposed, taking into account the electromyographic, bacteriologic and physiologic data.


Infection recurrence factors in one- and two-stage total knee prosthesis exchanges.
Revision of infected total knee replacements (TKR) is usually delayed for a period in which the joint space is filled with an antibiotic-loaded acrylic spacer. In contrast, one-stage re-implantation supposes immediate re-implantation. Formal comparisons between the two methods are scarce. A retrospective multi-centre study was conducted to investigate the effects of surgery type (one-stage vs. two-stage) on cure rates. It was hypothesised that this parameter would not influence the results. All infected TKR, treated consecutively between 2005 and 2010 by senior surgeons working in six referral hospitals, were included retrospectively. Two hundred and eighty-five patients, undergoing one-stage or two-stage TKR, with more than 2-year follow-up (clinical and radiological) were eligible for data collection and analysis. Of them, 108 underwent one-stage and 177 received two-stage TKR. Failure was defined as infection recurrence or persistence of the same or unknown pathogens. Factors linked with infection recurrence were analysed by uni- and multi-variate logistic regression with random intercept. Factors associated with infection recurrence were fistulae (odds ratio (OR) 3.4 [1.2-10.2], p = 0.03), infection by gram-negative bacteria (OR 3.3 [1.0-10.6], p = 0.05), and two-stage surgery with static spacers (OR 4.4 [1.1-17.9], p = 0.04). Gender and type of surgery interacted (p = 0.05). In men (133 patients), type of surgery showed no significant linkage with infection recurrence. In women (152 patients), two-stage surgery with static spacers was associated independently with infection recurrence (OR 5.9 [1.5-23.6], p = 0.01). Among patients without infection recurrence, International Knee Society scores were similar between those undergoing one-stage or two-stage exchanges. Two-stage procedures offered less benefit to female patients. It suggests that one-stage procedures are preferable, because they offer greater comfort without increasing the risk of recurrence. Routine one-stage procedures may be a reasonable option in the treatment of infected TKR. III.


Stressful life events in countries of differing economic development: Nicaragua, Chile, and Spain.
the aim was to describe a study involving 481 psychology students in the last courses of their degrees (M age = 21.9 yr., SD=4.2; 94 men and 386 women) from Nicaragua, Chile, and Spain. The study examined the potential risk of experiencing certain stressful life events, the number of stressors, and their characteristics. Also were analyzed the strength of their relation to social class and stressful life events experienced. Greater presence of stressful life events were reported among people from less developed countries, Chile and Nicaragua, and among people belonging to lower social class.


Alterations in the glycosylation of secreted thyrotropin during ontogenesis. Analysis of sialylated and sulfated oligosaccharides.
We have examined the carbohydrate structure of thyrotropin (TSH) secreted in vitro by pituitaries from prenatal, perinatal, and mature rats using concanavalin A (ConA)-agarose chromatography and anion-exchange high performance liquid chromatography (HPLC). [3H]Glucosamine-labeled TSH was immuno-precipitated and treated with either Pronase to generate glycopeptides or a mixture of endo-beta-N-acetyl-glucosaminidase F and peptide:N-glycosidase F to release oligosaccharides. The percentage of secreted TSH glycopeptides not bound to ConA was greater in mature animals (47 +/- 3%) than in either prenatal (29 +/- 3%) or perinatal animals (29 +/- 6%), suggesting more multiantennary oligosaccharides in the older animals. These structural changes were characterized further by performing anion-exchange HPLC on released oligosaccharides. Secreted TSH from prenatal rats predominantly contained oligosaccharides with 1 and 2 negative charges, while TSH from mature rats contained these structures as well as 15% with 3 negative charges. In addition, the ratio of sialylated to sulfated oligosaccharides was greater in mature compared to prenatal animals for species with 1 negative charge (1.9-fold) as well as for species with 2 negative charges (4.3-fold). We also correlated the structural alterations noted by ConA analysis with anion-exchange HPLC. Oligosaccharides that bound to ConA and were eluted with alpha-methylglucoside, when analyzed by anion-exchange HPLC, consisted of species with 1 and 2 negative charges, whereas oligosaccharides that were unbound to ConA were predominantly species with three negative charges. Together, these data suggest that with maturation of the hypothalamic-pituitary-thyroid axis secreted TSH contains more negatively charged multiantennary oligosaccharides with increased sialylation and decreased sulfation.


Effect of respiratory protective devices on development of antibody and occupational asthma to an acid anhydride.
To determine whether the use of respiratory protective equipment would reduce the incidence of occupational asthma due to exposure to hexahydrophthalic anhydride (HHPA). Prospective cohort study. A facility that makes an epoxy resin product requiring HHPA for its manufacture. Sixty-six individuals newly hired at a facility that makes an epoxy resin product requiring HHPA for its manufacture. Employees who wished to use respiratory protective equipment could choose from three types of masks: dust mask, half-face organic vapor respirator, or full-face organic vapor respirator. Workers were evaluated annually for development of positive antibody to HHPA and occupational, immunologic respiratory disease, including occupational asthma. With use of respiratory protective equipment, the rate of developing an occupational immunologic respiratory disease was reduced from approximately 10 to 2% per year. Occupational asthma developed in only three individuals, and they were all in the higher exposure category. Statistically, one respirator was not superior to the others. Respiratory protective equipment can reduce the incidence of occupational immunologic respiratory disease, including occupational asthma, in employees exposed to HHPA.


Successively amplified electrochemical immunoassay based on biocatalytic deposition of silver nanoparticles and silver enhancement.
A successively signal-amplified electrochemical immunoassay has been reported on the basis of the biocatalytic deposition of silver nanoparticles with their subsequent enlargement by nanoparticle-promoted catalytic precipitation of silver from the silver-enhancer solution. The immunoassay was carried out based on a heterogeneous sandwich procedure using polystyrene microwells to immobilize antibody. After all the processes comprising the formation of immunocomplex, biocatalytic deposition of silver nanoparticles and following silver enhancement were completed, the silver on polystyrene microwells was dissolved and quantified by anodic stripping voltammetry (ASV). The effect of relevant experimental conditions, including the concentration of ascorbic acid 2-phosphate (AA-p) substrate and Ag(I) ions, the biocatalytic deposition time, and of crucial importance, the silver enhancement time, were investigated and optimized. The anodic stripping peak current was proportional to the concentration of human IgG in a dynamic range of 0.1-10 ng ml(-1) with a detection limit of 0.03 ng ml(-1). Scanning electron microscope (SEM) was applied to characterize the silver nanoparticles before and after silver enhancement on the surface of polystyrene microplates. By coupling the highly catalytic effect of enzyme and nanoparticles to successively amplify the analytical signal, the sensitivity of immunoassay was enhanced so dramatically that this approach would be a promising strategy to achieve a lower detection limit for bioassays.


Current progress in suicide gene therapy for cancer.
Standard chemotherapeutic agents and ionizing radiation destroy dividing cells. Because tumor cells divide more rapidly than normal cells, there is a therapeutic index in which damage to the cancer cells is maximized while keeping the toxicity to the normal host cells acceptable. Suicide gene therapy strives to deliver genes to the cancer cells, which convert nontoxic prodrugs into active chemotherapeutic agents. With this strategy, the systemically administered prodrug is converted to the active chemotherapeutic agent only in cancer cells, thereby allowing a maximal therapeutic effect while limiting systemic toxicity. A literature search was conducted using the MEDLINE database from 1990 to 2001 to identify articles related to suicide gene therapy for cancer. A number of suicide gene systems have been identified, including the herpes simplex virus thymidine kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine kinase gene, the nitroreductase gene, the Escherichia coli gpt gene, and the E. coli Deo gene. Various vectors, including liposomes, retroviruses, and adenoviruses, have been used to transfer these suicide genes to tumor cells. These strategies have been effective in cell culture experiments, laboratory animals, and some early clinical trials. Advances in tissue- and cell-specific delivery of suicide genes using specific promoters will improve the clinical utility of suicide gene therapy.


Application of internal wool lipids to hair.
Hair lipids can contribute to physicochemical phenomena such as diffusion, cell cohesion and mechanical strength, although lipids occur at much lower levels (1-6% dry weight) than proteins (>90%).Hair lipids can be diminished by hair washing and submission to chemical treatments. Studies have shown that internal wool lipids (IWL) resemble those membranes of other keratinic tissues such as human hair or stratum corneum. In this work, the IWL, in the form of liposomes or from an emulsion system, were applied to untreated hair fibres and also treated hair fibres. The results showed that application of IWL to pretreated hair samples lead to an improvement in mechanical strength properties of the fibres when the IWL were applied structured as liposomes. Differential scanning calorimetry studies demonstrated that the application of IWL to pretreated hair sample led to a slight increase in the crystalline material of the fibres. Moreover, scanning electron microscopy studies showed that application of IWL liposomes to damaged hair fibres lead to an improvement of the cuticle scale, demonstrating the importance of the use of a delivery vehicle with a bilayer structure similar to the one present in the hair fibre to restore the natural properties of the fibre.


Overlapping electron density and the global delocalization of π-aromatic fragments as the reason of conductivity of the biphenylene network.
Recently fabricated 2D biphenylene network is an astonishing solid-state material, which possesses unique metal-like conductive properties. At the same time, two-dimensional boron nitride network (2D-BN)-an isoelectronic and structural analogue of biphenylene network, is an insulator with a wide direct bandgap. This study investigates the relationship between the electronic properties and chemical bonding patterns for these species. It is shown that the insulating 2D-BN network possesses a strong localization of electron density on the nitrogen atoms. In turn, for a carbon-containing sheet, we found a highly delocalized electron density and an appreciable overlap of pz orbitals of neighboring C6 rings, which might be a reason for the conductive properties of the material.


Trajectory of PaO2/FiO2 Ratio in Shock After Angiotensin II.
High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO2/FiO2 and SpO2/FiO2 in patients in shock. Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO2, SpO2, and FiO2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO2 and SpO2/FiO2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO2 ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined. The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO2/FiO2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p < .001; hourly SpO2/FiO2 change -3.1/hr, 95% CI-3.7 to -2.4, p < .001). Ang-2 treatment was associated with significant improvements in PaO2/FiO2 and SpO2/FiO2 in the 48-h after initiation (hourly PaO2/FiO2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p = .003; hourly SpO2/FiO2 change +0.9/hr, 95% CI 0.5-1.2, p < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant (pinteraction < 0.001 for both PaO2/FiO2 and SpO2/FiO2). This improvement was associated with significantly fewer patients having a PaO2/FiO2 ≤ 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p = .011). Subgroup analysis found that patients with either a baseline PaO2/FiO2 ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement. Ang-2 is associated with improved PaO2/FiO2 and SpO2/FiO2. The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.


Hormonal regulation of transforming growth factor beta-2 expression in human prostate cancer.
We have previously shown that a transforming factor-beta species (TGF beta) is a hormonally regulated negative growth factor in estrogen responsive MCF-7 human breast cancer cells. We now demonstrate that androgen withdrawal leads to a significant stimulation of TGF beta-2 mRNA in the androgen-responsive human prostate carcinoma cell line LNCaP. These data indicate that TGF beta-2 is a marker of (anti)androgen action in human prostate cancer in vitro. Based on these results we addressed the question of whether TGF beta-2 represented a marker of (anti)androgen action in prostate cancer in vivo: expression of TGF beta mRNA was determined by RNAase protection analysis in normal and malignant prostate tissue obtained from 9 prostate carcinoma patients without endocrine therapy. In parallel, the nuclear dihydrotestosterone (DHT) concentration was measured as an indicator of androgen stimulation in the same tissues. The following results were obtained. Both normal and cancerous tissues show nuclear accumulation of DHT indicating a functional androgen receptor system. TGF beta-2 is equally expressed in both normal and cancerous tissue. Expression of TGF beta-2 and nuclear DHT concentrations are correlated in both benign and malignant tissue. We conclude that TGF beta-2 is a marker of (anti)hormonal action in androgen-dependent tissue.


Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides.
Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.


Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient.
Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).


A preliminary identification of PIN1 SNP linkage in patients with coronary heart disease from Handan, China.
Our aim was to perform an initial assessment of the polymorphic patterns of the PIN1 gene in patients with coronary heart disease (CHD). The PIN1-encoded protein (Pin1) suppresses eNOS-NO signaling and may impair cardiovascular function. Blood collection, DNA extraction, PCR amplification and gene sequencing were performed for thirty CHD participants living in central China, focusing on nine single nucleotide polymorphisms (SNPs). Their genetic linkages were revealed and their allele frequencies were compared with SNP data from the NCBI. Three major linkage patterns were identified: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs1077220-8.rs2287838] and [6.rs889162-7.rs2010457], suggesting correlated involvement in CHD and possible simultaneous genetic origin in ancient times. The frequencies of six SNPs are consistent with the NCBI data, while the frequencies of three SNPs (2.rs2233678, 4.rs1077220 and 9.rs4804461) are not consistent with the NCBI. Especially, the 3.rs2233679-4.rs1077220 linkage is different from other populations worldwide and may be an interesting genetic characteristic of Chinese CHD patients. Predictably, 1.rs2287839, 2.rs2233678, 3.rs2233679 and 5.rs2233682 may be strongly associated with CHD risk, although this requires future verification. The PIN1 SNP linkages lay a new genetic foundation for discovering novel molecular mechanisms of CHD and for exploring PIN1-based targeted treatment of CHD with nitric oxide regulatory therapies in clinical practice.


Nucleic acid sequences of primate type C viruses in normal and neoplastic human tissues.
Recent reports on the isolation of type C viruses from human cells have generated considerable controversy because of the close relationship of the viruses to the type C viruses of subhuman primates. These findings have been interpreted as evidence for contamination despite the repeated isolation of some type C viruses from separate clinical specimens or from separate frozen primary cell stocks of the same donor. Our laboratory has described a type C virus which is released from the HEL-12 strain of normal human embryonic lung fibroblasts. The HEL-12 virus is related immunologically to simian sarcoma (woolly monkey fibrosarcoma) virus (SiSV) and the endogenous type C viruses of baboons and domestic cats. To demonstrate that the HEL-12 virus is not an adventitious contaminant, fresh human tissues were examined for antigenic cross-reactivity with HEL-12 virus antigens. Some patients with myelogenous leukemia contain circulating immunoglobulins which specifically inhibit the reverse transcriptases of HEL-12 virus and primate type C viruses. In addition, the glomerular immune complexes in patients with systemic lupus erythematosus contain antigens related to HEL-12 virus proteins. Using the techniques of molecular hybridisation, we demonstrate here that HEL-12 cells contain proviral DNA sequences before antigen expression or spontaneous virus release can be detected. We also present evidence for the existence of nucleic acid sequences homologous to HEL-12 viral RNA in the DNAs from certain cancer patients.


The adaptive significance of alpine melanism in the butterfly Parnassius phoebus F. (Lepidoptera: Papilionidae).
The adaptive significance of alpine melanism, the tendancy for insects to become darker with increased elevation and latitude, was investigated using the butterfly Parnassius phoebus. The effects on temperature dependent activity of five components of overall wing melanism, as well as size, were examined. The components of wing melanism examined were the transparency of the basal hindwing and distal fore-wing areas, the width of the black patch in the basal hind-wing area and the proportion of black to white scales in that area, and the proportion of the distal fore-wing covered by predominantly black scaling.The body temperature of dead specimens was correlated with air temperature, solar radiation, the width of the black patch at the base of the wings, and the proportion of black to white scales at the base of the wings. The minimum air temperatures and solar radiation levels required for initiation of flight did not vary with wing melanism of P. phoebus, in contrast to the results found for Colias butterflies by Roland (1982). However, under environmental conditions suitable for flight initiation, males with a higher proportion of black to white scales in the basal area of the hind-wing, and wider basal black patches, spent a greater proportion of time in flight at low air temperatures and low insolation. Increased basal wing melanism was also associated with increased movement of males within a population. In contrast, melanism in the distal area of the wings has no effect on activities which are dependant on body temperature. The amount of time spent feeding did not vary with differences in wing melanism. I suggest that in dorsal basking, slow-flying butterflies (Parnassius) basal wing color affects body temperature primarily during flight (rather than while basking), such that butterflies with darker wing bases cool down less rapidly because they absorb more solar radiation during flight.


Poly(lactic-co-glycolic acid) nanosphere as a vehicle for gene delivery to human cord blood-derived mesenchymal stem cells: comparison with polyethylenimine.
Polyethylenimine (PEI) is one of the most extensively studied non-viral vectors but its cytotoxicity limits its clinical value. PLGA nanospheres are biocompatible and can facilitate sustained release of plasmid DNA. This study compares the cytotoxicity and long-term transgene expression between PLGA nanosphere and PEI. PLGA nanospheres were significantly less cytotoxic than PEI at various concentrations. PLGA nanospheres induced significantly higher transgene expression in vitro for a longer duration (21 days) than PEI. We conclude that PLGA nanospheres have potential as gene delivery vehicles for use in gene therapy for diseases in which a long-term therapeutic gene expression regimen is necessary.


Effect of quinoid redox mediators during azo dye decolorization by anaerobic sludge: Considering the catalyzing mechanism and the methane production.
The effects of quinoid compounds on azo dyes decolorization were studied. Compared with other quinones, menadione was the most effective at aiding azo dye decolorization. Sodium formate was a suitable carbon source for the anaerobic decolorization system. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis indicated that the microbial structure changed in response to varying carbon sources. Phylogenetic analysis showed that the anaerobic sludge was consisted mainly of nine genera. The mechanism studies showed that the biotransformation of menadione to its hydroquinone form was the rate-limiting step in the dye decolorization process. Moreover, study of the electron transfer mechanism of quinone-mediated reduction showed that azo dye decolorization is not a specific reaction. The NADH chain was involved in the decolorization process. The methane production test indicated that azo dyes had an inhibitory effect on methane production. However, supplementation with a redox mediator could recover the inhibited methanogenesis. High-throughput sequencing analysis revealed that the methanogenic archaeal community was altered in the anaerobic sludge with or without azo dyes and the redox mediator.


Current status of brain protection during surgery for congenital cardiac defect.
The long-term neurodevelopmental outcome has been a great concern for cardiac surgeons although it is still unclear. There are some risks regarding the neurological and neuropsychological deficits before, during and after cardiovascular surgery. Current status of brain protection during congenital heart surgery could be reported. The incidence of neurologic outcome and the appropriate CPB strategy for brain protection are stated, and the latest data of neurodevelopmental outcome after pediatric cardiac surgery are clarified.


Effect of ionic additives on the elution of sodium aryl sulfonates in supercritical fluid chromatography.
Addition of a small amount of polar solvent (i.e., modifier) to CO2 in packed column supercritical fluid chromatography (SFC) has shown major improvements in both polar analyte solubility and interaction of the polar analyte with the stationary phase. Recently, the addition of an ionic component (i.e., additive) to the primary modifier by one of us has been shown to extend even further the application of SFC to polar analytes. In this work, the effect of various ionic additives on the elution of ionic compounds, such as sodium 4-dodecylbenzene sulfonate and sodium 4-octylbenene sulfonate, has been studied. The additives were lithium acetate, ammonium acetate, tetramethylammonium acetate, tetrabutylammonium acetate, and ammonium chloride dissolved in methanol. Three stationary phases with different degrees of deactivation were considered: conventional cyanopropyl, deltabond cyanopropyl, and bare silica. The effect of additive concentration and additive functionality on analyte retention was investigated. Sodium 4-dodecylbenzene sulfonate was successfully eluted using all the additives with good peak shape under isocratic/isobaric/isothermal conditions. Different additives, however, yielded different retention times and in some cases different peak shapes.


The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness.
Growing evidence linked inflammation with sleep. This study aimed to evaluate the associations and causal effects of sleep traits including insomnia, excessive daytime sleepiness (EDS), and sleep duration (short: <7 h; normal: 7-9 h; long: ≥9 h), with levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins. Standard procedures of quantitative analysis were applied to estimate the expression differences for each protein in compared groups. Then, a two-sample Mendelian randomization (MR) analysis was performed to explore their causal relationships with published genome-wide association study summary statistics. The inverse-variance weighted was used as the primary method, followed by several complementary approaches as sensitivity analyses. A total of 44 publications with 51 879 participants were included in the quantitative analysis. Our results showed that the levels of CRP, interleukin-1β (IL-1β), IL-6, and TNF-α were higher from 0.36 to 0.58 (after standardization) in insomnia compared with controls, while there was no significant difference between participants with EDS and controls. Besides, there was a U/J-shaped expression of CRP and IL-6 with sleep durations. In MR analysis, the primary results demonstrated the causal effects of CRP on sleep duration (estimate: 0.017; 95% confidence intervals [CI], [0.003, 0.031]) and short sleep duration (estimate: -0.006; 95% CI, [-0.011, -0.001]). Also, IL-6 was found to be associated with long sleep duration (estimate: 0.006; 95% CI, [0.000, 0.013]). These results were consistent in sensitivity analyses. There are high inflammatory profiles in insomnia and extremes of sleep duration. Meanwhile, elevated CRP and IL-6 have causal effects on longer sleep duration. Further studies can focus on related upstream and downstream mechanisms.


Targeted immunotherapy strategies in ANCA-associated vasculitis.
Targeted immunotherapy is substantially improving the management of ANCA-associated vasculitides (AAV), which include granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). This article reviews the current role for targeted immunotherapy in AAV, its validated indications, and avenues for further development. Rituximab is a validated induction treatment for GPA and severe MPA. Rituximab in these indications is not less effective than cyclophosphamide and is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide. Rituximab is more effective than cyclophosphamide for treating relapses. For remission maintenance therapy, which is indispensable, rituximab has been proven superior over conventional immunosuppressive treatment. Rituximab is licensed in the USA and in Europe for the induction treatment of severe forms of GPA and MPA. An extension study for remission maintenance therapy is ongoing. In EGPA, although maintenance treatment with the interleukin-5 antagonist mepolizumab is effective in decreasing glucocorticoid requirements and in alleviating asthma and sinonasal symptoms, its efficacy on the vasculitis remains somewhat unclear. Mepolizumab is licensed for use in EGPA, and rituximab is also being evaluated as an induction and maintenance agent. Immunoglobulins can be helpful as an adjuvant treatment for active AAV with severe immunedepression, notably when infections occur. Plasma exchange is indicated in AAV with advanced renal dysfunction and, perhaps, in the event of alveolar hemorrhage, a possibility that will be assessed in 2018 in a large international study.


Simultaneous double toe transfer for severely disabled hands.
Two cases are presented in which a severely damaged hand was reconstructed by the simultaneous transfer of two toes using microvascular techniques. A two year evaluation of the functional result is made in both cases. Conventional reconstructive methods have little place in the reconstruction of these severe disabilities.