Comparison of postpartum anti-Xa levels following enoxaparin administration to prevent venous thromboembolism using 2 weight-based protocols: a randomized controlled trial.
During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophylactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxaparin administration is superior (once daily weight categories vs 1 mg/kg body weight). This study aimed to compare the efficacy in reaching prophylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols. A randomized open-label controlled trial was conducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (≤90 kg, 40 mg; 91-130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addition, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated. Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respectively (P<.0001). The mean anti-Xa levels on day 2 were 0.34±0.09 and 0.19±0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanalysis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage. Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels without leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the preferred protocol for postpartum venous thromboembolism prophylaxis.


Metabolic crosstalk between host and pathogen: sensing, adapting and competing.
Our understanding of bacterial pathogenesis is dominated by the cell biology of the host-pathogen interaction. However, the majority of metabolites that are used in prokaryotic and eukaryotic physiology and signalling are chemically similar or identical. Therefore, the metabolic crosstalk between pathogens and host cells may be as important as the interactions between bacterial effector proteins and their host targets. In this Review we focus on host-pathogen interactions at the metabolic level: chemical signalling events that enable pathogens to sense anatomical location and the local physiology of the host; microbial metabolic pathways that are dedicated to circumvent host immune mechanisms; and a few metabolites as central points of competition between the host and bacterial pathogens.


High-performance liquid chromatographic methods with fluorescence detection for the determination of branched-chain amino acids and their alpha-keto analogues in plasma samples of healthy subjects and uraemic patients.
High-performance liquid chromatographic (HPLC) methods have been developed for the quantification of branched-chain amino acids (BCAA) and their keto analogues (BCKA). Amino acids and their keto analogues were derivatized with o-phthalaldehyde, 2-mercaptoethanol and o-phenylenediamine sulphate prior to HPLC. Both separations were performed on a reversed-phase column, using a multi-step gradient system with two solvents and a fluorescence detector. These methods are simple and sensitive and give highly reproducible results. By using an automatic system, the instability problem is avoided and the reaction kinetics are controlled. The use of a simple clean-up procedure with preparative cation-exchange chromatography before BCKA analysis concentrates the dilute plasma sample. The methods were applied to the determination of BCAA and BCKA in plasma samples of healthy volunteers and patients with chronic renal disorders. The relationship between the concentrations of BCAA and BCKA in plasma for these two groups is shown.


Brain ion and amino acid contents during edema development in hepatic encephalopathy.
Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of ammonium acetate (AAc) or thioacetamide (TAA), respectively. Serum and brain ammonia increased to similar levels (200 and 170% of control, respectively) in both experimental groups. Serum transaminase activities increased 10-fold in animals injected with TAA but were unchanged in animals given AAc injections. In both experimental groups glutamine was elevated in cerebral white matter, cerebral gray matter, and basal ganglia, whereas brain tissue specific gravity decreased in all brain regions, indicating edema formation. In the AAc group, we observed a decrease in glutamate and taurine contents concomitant with the development of brain edema. In these animals, cerebral gray matter specific gravity and taurine contents returned to control levels 24 h after the third AAc injection. TAA-injected animals demonstrated similar decreases in brain tissue specific gravity, whereas glutamine, glutamate, and taurine contents were all elevated. During hepatic encephalopathy, ammonia-induced changes in brain amino acid content may contribute to brain edema development.


Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer.
To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer. Retrospective cohort study. United States inpatient and outpatient hospital services. Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy. The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost. Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping. Among 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001). The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone. SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.


Draft Genome Sequence of Aspergillus tubingensis WU-2223L, a Citric Acid-Producing Filamentous Fungus Belonging to Aspergillus Section Nigri.
Aspergillus tubingensis WU-2223L, belonging to the section Nigri, is a hyperproducer of citric acid. Here, we present the high-quality draft (35 Mb) and mitochondrial (32.4 kb) genome sequences of this strain, which consisted of 16 scaffolds in total. The draft and mitochondrial genome sequences comprised 11,493 and 15 genes, respectively.


Post-High School Daily Living Skills in Autism Spectrum Disorder.
Daily living skills (DLS) are a predictor of positive outcomes in youths with autism spectrum disorder (ASD), yet little is known about trajectories of DLS in adults with ASD. This study investigated the impact of high school exit on participants' trajectories of daily living skills age equivalent (DLS-AE) scores from ages 2 to 26 and the relationship between DLS-AE trajectories and employment and education outcomes. Participants were 98 adults with ASD drawn from an ongoing longitudinal study. The Vineland Adaptive Behavior Scales were administered 8 times from ages 2 to 26. Employment and education data were compiled from parent report demographic forms. DLS-AE trajectories modestly increased with age before exiting school, at which point DLS-AE trajectories plateaued, then declined. A significant (p < .01) decrease occurred in the slope of DLS-AE trajectories following school exit. High DLS-AE scores predicted participation in postsecondary education (χ25 [n = 73] = 27.83, p < .001). Autism symptom severity predicted participation in employment (χ25 [n = 58] = 27.54, p < .001). These findings provide evidence that DLS decline in adults with ASD, specifically after school exit, and highlight the importance of DLS in normative adult outcomes. Future work should examine the trajectories of DLS in middle and later adulthood and consider intervention targets for bolstering DLS following school exit.


Cycling of carbon and oxygen in layers of marine microphytes; a simulation model and its eco-physiological implications.
A mathematical simulation model was used to ascertain the relation between the diffusion of oxygen and inorganic carbon into layers of marine microphytes and the carbon metabolism of these microphytes. The simulation model included physiological and physico-chemical parameters and was validated using the few data available from the literature on production determinations, on oxygen and pH values, and on growth dynamics of natural populations. The model was tested with various modifications to mimic experiments with suspended algae and algal films on inert substrates, and also to simulate microphytobenthos in sediment cores with or without grazing. The simulated variations in oxygen concentrations and pH values over time scales of min and days were consistent with field and experimental observations. The model predicted upper limits of primary production and biomass observed in well developed natural populations; these limits are caused by a combination of oxygen accumulation and depletion of inorganic carbon resulting from diffusion limitations and the recirculation of organic carbon in photosynthetic, respiratory and excretory processes. The model calculations were used to check on the adequacy of the various methods used to determine the primary production of benthic microphytes.


Absence of simulation evidence for critical depletion in slit pores.
Recent Monte Carlo simulation studies of a Lennard-Jones fluid confined to a mesoscopic slit pore have reported evidence of "critical depletion" in the pore local number density near the liquid-vapor critical point. In this Brief Report we demonstrate that the observed depletion effect is in fact a simulation artifact arising from small systematic errors associated with the use of long range corrections for the potential truncation. Owing to the large near-critical compressibility, these errors lead to significant changes in the pore local number density. We suggest ways of avoiding similar problems in future studies of confined fluids.


A Penetrating Foreign Body with Sphenoid Sinus extension- A Case Report.
Introduction: Foreign bodies in the paranasal sinuses are rare and can result from high velocity trauma. Here, we report a case of a 12 year old child, who sustained a penetrating injury to the left eye with a tree branch while playing. On CT scan, the wooden foreign body was found to extend into sphenoid sinus. Patient was posted for removal of foreign body in emergency OT under antibiotic coverage. The foreign body was mobilised from surrounding structures and was removed by giving strong traction. Primary closure of the wound was done and patient recovered with a stable post-op course. Discussion: Prompt and complete removal of wooden foreign body in the paranasal sinus is important due to their close proximity to vital structures. Their location and nature can be difficult to diagnose as they can have diverse appearances on imaging. Conclusion: Foreign bodies in close proximity to the sphenoid sinus should be removed by a multi-specialist team with good knowledge of head and neck anatomy in a tertiary care centre to avoid complications.


The development of a zonula occludens in peripheral myelin of the chick embryo. A freeze-fracture study.
Sciatic nerves of chick embryos, 12 to 18 days incubation, were examined in freeze-fracture replicas with special emphasis placed on the development of tight junctional contacts in the myelin sheaths. In stages of beginning myelination short isolated particulate chains (focal tight junctions) appear in fracture faces of the adjacent membranes in the outer myelin lamellae, i.e., the outer mesaxon. In stages of progressing myelination these tight junctional elements elongate and become more numerous. They can also be found in the membranes of the inner mesaxons, the paranodal loops and the intramyelinic cytoplasmic inclusions. In fibers of advanced myelinogenesis a fusion of these isolated tight junctions--either end-to-end or at an angle--gives rise to continuous zonulae occludentes. This contact zone extends in the mesaxonal membranes along the direction of the fiber, whereas in paranodal myelin it acquires a helical course joining the membranes of the paranodal loops. It is proposed that this zonula occludens, which seals the cytoplasmic border of the Schwann cell, separates an intramyelinic from an extramyelinic, extracellular space already during the developmental stages of myelinogenesis.


Can Mushrooms and Their Derivatives Be Efficient Bioalternatives to Conventional Synthetic Insecticides? (Review).
Annual losses in both agricultural and economic sectors have increased dramatically because of insect pests; hence, the effects of these pests pose a major global threat. In addition, some control methods currently used to combat insect pests are no longer as effective due to the continuous evolution in resistance and to the serious damage of these control approaches on the ecological system. Therefore, there is an urgent need to find new avenues that are more effective and environmentally friendly. In the search for novel, effective, and natural insecticides, many mushroom species are substantial sources of biologically active compounds, including those that possess insecticidal activities. This review illustrates the potential role of mushrooms as promising and powerful bioinsecticidal agents.


Self-collected HPV testing improves participation in cervical cancer screening: a systematic review and meta-analysis.
HPV testing has emerged as an effective cervical cancer screening test. The use of HPV self-testing has the potential to address many barriers to screening and reach at-risk women through engagement in screening. However, there is a need to examine the evidence for whether offering self-collected HPV testing in practice increases screening compliance. The objective of this review is to determine to what extent providing self-collected HPV testing increases screening participation in women who are never or underscreened for cervical cancer. A systematic literature review conducted in the databases Medline and Embase identified articles examining the use of HPV self-testing on cervical cancer screening participation. A meta-analysis using a random-effects model was used to calculate the relative compliance, with an intent-to-treat analysis of HPV self-testing compared to Pap testing, with 95% confidence intervals (CI). All statistical tests were two-sided. Ten studies were reviewed, with 8 being European and 2 North American. Of the 10 studies, 9 employed a randomized design. In all studies, the relative compliance of HPV self-collected testing compared to Pap testing was significantly greater than 1.0 (p<0.01). The overall relative compliance was 2.14 (95% CI 1.30-3.52). There was large heterogeneity of screening compliance between studies for both HPV self-testing and Pap testing. HPV self-collected testing significantly improved the participation of women who did not routinely attend cervical cancer screening programs. New approaches to HPV self-test delivery should be considered as HPV testing becomes more widely incorporated as a primary screening tool.


Overexpression of natural killer group 2 member D ligands predicts favorable prognosis in cholangiocarcinoma.
The natural killer group 2 member D (NKG2D) receptor and its ligands are important mediators of immune responses to tumors. NKG2D ligands are overexpressed in several malignant tumor types; however, the prognostic value of these ligands is unclear. Here, we aimed to elucidate the role of NKG2D ligands in extrahepatic cholangiocarcinoma (EHCC). We therefore investigated the expression of the NKG2D receptor and its ligands MHC class I chain-related proteins A and B (MICA/B), unique long 16 binding protein (ULBP) 1, and ULBP2/5/6 in resected specimens from 82 patients with EHCC. All NKG2D ligands were highly expressed in EHCC. High expression of MICA/B or ULBP2/5/6 correlated with overall and disease-free survival. In contrast, high expression of ULBP1 was significantly associated with improved overall survival, but not disease-free survival. Concurrent high expression of multiple NKG2D ligands revealed significantly better overall and disease-free survival than that observed with the overexpression of any one NKG2D ligand. Co-expression of multiple NKG2D ligands was an independent prognostic indicator of improved survival. Furthermore, co-overexpression of multiple NKG2D ligands was significantly correlated with high expression of the NKG2D receptor. Inhibiting interactions between multiple NKG2D ligands and the NKG2D receptor might be a promising approach for controlling cancer progression and improving patient prognosis in EHCC.


Identification and validation of Birc5 as a novel activated cell cycle program biomarker associated with infiltration of immunosuppressive myeloid-derived suppressor cells in hepatocellular carcinoma.
Preclinical studies and clinical trials have demonstrated that tumor-intrinsic activation of the cell cycle program impedes anticancer immunotherapy. Identification of cell cycle-related biomarkers may provide novel therapeutic targets to augment the efficacy of immunotherapy in hepatocellular carcinoma (HCC). Based on the genes related to cell cycle program, two clusters (Cluster 1 and Cluster 2) were detected in HCC patients via non-negative matrix factorization algorithm. Multivariable-adjusted Cox regression analysis indicated that the cell cycle gene-based classification was a significant prognostic factor for predicting the clinical outcome of HCC patients. Cluster 1 showed shorter overall survival time and progression-free interval time was associated with activated cell cycle program, higher infiltration of myeloid-derived suppressor cells (MDSCs) and less sensitivity to immunotherapy. A three-gene prognostic model, including BIRC5, C8G, and SPP1, was constructed to characterize the cell cycle-based classification of HCC, which had strong robustness and a stable predictive performance. Notably, Birc5 was positively correlated with CD11b expression (a MDSC marker) in HCC tissue. Concordant high expression of Birc5 and intratumor infiltration level of MDSCs were correlated with worse prognosis of HCC patients. In vitro, hepatocellular Birc5 overexpression promoted immunosuppressive CD11b+ CD33+ HLA-DR- MDSC expansion from human peripheral blood mononuclear cells. Genetically modified animal model of liver cancer revealed that Birc5 depletion upregulated the genes related to lymphocyte-mediated immunity, natural killer cell-mediated immunity, interferon-gamma production, T-cell activation, and T-cell-mediated cytotoxicity. These results suggest an immunosuppressive function of Birc5 in HCC. Birc5 was a potential biomarker and inducer of intratumor infiltration of MDSCs, which led to T cell exclusion or dysfunction in tumor immune microenvironment, consequently resulting in reduced response to ICIs in HCC.


Permeability, phase-boundary potential and conductance in a cholinergic channel without constant field.
A potassium-selective, chemically excitable channel, whose characteristics cannot be accurately described by constant-field theory, is studied by a new approach based on diffusion theory but with no need for the classical assumptions of constant field, homogeneous membrane, and equal phase-boundary potentials at both interfaces. Permeability is defined, free of these constraints, and the Goldman coefficient is demonstrated to be a special case useful only when the constraints apply. Permeability can be evaluated directly from current-voltage data, and it is found not to be a parameter in this channel, but rather a function of both the voltage and the concentration of the permeant ion. However, it becomes concentration-independent when the membrane voltage is equal to the sum of the phase-boundary potentials. That sum can therefore be determined from these data, and it is -65 mV in this channel. The permeability at that potential is a channel parameter, and equal to 8.66 X 10(-6) cm/s for this channel. A constant field is shown not to exist in this channel and the Goldman coefficient not to be a parameter but a function of potential and concentration. Although errors introduced into this coefficient by nonconstant field and unequal surface potentials partially cancel each other, the coefficient is nevertheless not a correct measure of permeability.


[A preliminary study of screening assay for thyroid hormone disruptors in vivo].
To study the biological effects of thyroid induced by N',N-methylene-bis (2-amino-5-sulfhydryl-1, 3, 4-thiadianole), discussing whether this agent is a thyroid hormone disruptor. Sixty Wistar rats were divided into 2 groups, including one experiment group and one control. The rats of experiment group were fed with this agent at 50 mg/kg. Whole animals were weighed, then they were sacrificed by bleeding from femoral artery on the fifth, 10th, 20th day, respectively; at the same time, serum T4 and TSH concentrations were examined and the thyroids were taken out and weighed for coefficient of thyroid gland weight; the pathological changes of thyroids were observed under light microscope; the enzyme activity of succinate dehydrogenase and thyroidperoxidase, and the positive expression of PCNA in thyroid gland were examined by histochemistry. Increased coefficient of thyroid gland weight, proliferation of thyroid epithelium, increased enzyme activity of SDH and TPO, and increased positive cells of PCNA were observed in the experiment group. N',N-methylene-bis (2-amino-5-sulfhydryl-1, 3, 4-thiadianole) is likely to be a thyroid hormone disruptor.


Phase behavior and domain size in sphingomyelin-containing lipid bilayers.
Membrane raft size measurements are crucial to understanding the stability and functionality of rafts in cells. The challenge of accurately measuring raft size is evidenced by the disparate reports of domain sizes, which range from nanometers to microns for the ternary model membrane system sphingomyelin (SM)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol (Chol). Using Förster resonance energy transfer (FRET) and differential scanning calorimetry (DSC), we established phase diagrams for porcine brain SM (bSM)/dioleoyl-sn-glycero-3-phosphocholine (DOPC)/Chol and bSM/POPC/Chol at 15 and 25°C. By combining two techniques with different spatial sensitivities, namely FRET and small-angle neutron scattering (SANS), we have significantly narrowed the uncertainty in domain size estimates for bSM/POPC/Chol mixtures. Compositional trends in FRET data revealed coexisting domains at 15 and 25°C for both mixtures, while SANS measurements detected no domain formation for bSM/POPC/Chol. Together these results indicate that liquid domains in bSM/POPC/Chol are between 2 and 7nm in radius at 25°C: that is, domains must be on the order of the 2-6nm Förster distance of the FRET probes, but smaller than the ~7nm minimum cluster size detectable with SANS. However, for palmitoyl SM (PSM)/POPC/Chol at a similar composition, SANS detected coexisting liquid domains. This increase in domain size upon replacing the natural SM component (which consists of a mixture of chain lengths) with synthetic PSM, suggests a role for SM chain length in modulating raft size in vivo.


The rise of oxygen and aerobic biochemistry.
Analysis of conserved protein folding domains across extant genomes by Kim et al. in this issue of Structure provides insights into the timing of some of the earliest aerobic metabolisms to arise on Earth.


Arthroscopic anatomic glenoid reconstruction has a lower rate of recurrent instability compared to arthroscopic Bankart repair while otherwise maintaining a similar complication and safety profile.
The primary purpose of this study was to determine the frequency and type of complications, including subluxation, infection, hardware complication, graft/glenoid fracture, chondrolysis, neurovascular deficits and stiffness following an Arthroscopic Bankart Repair (ABR) or an Arthroscopic Anatomic Glenoid Reconstruction (AAGR) using a distal tibia allograft for recurrent anterior shoulder instability. Secondary purposes were to determine the frank dislocation rate and the associations of post-operative complications with demographic patient factors. Demographic and clinical data were reviewed using means ± standard deviations or frequencies in patients with recurrent anterior shoulder instability who underwent either an ABR or an AAGR. Post-operative patient records were analysed to identify any post-operative complications. The numerical variables of the two groups were compared using the independent t-test or Mann-Whitney U test. Categorical variables and complications were tested using the chi-square test, Fisher's exact test, or the two-sided Monte Carlo test with a significance level of 0.05. We included 174 patients in this cohort, with 61.5% of patients receiving ABR and 38.5% receiving AAGR. Most of our patients were male (70.1%) with an average age of 23.41 ± 8.26 years in the ABR group and 29.37 ± 13.54 years in the AAGR group (p = 0.001). The two groups were similar with respect to their post-operative complication rates when excluding frank dislocation (ABR: 11%, AAGR: 12%). The AAGR group had statistically significantly higher rates of hardware removal compared to the ABR group (p = 0.004). The ABR group had 25 post-operative frank dislocations, with none reported in the AAGR cohort (p < 0.001). The total complication rate for each procedure was found to be 35% for ABR and 12% for AAGR. AAGR has a comparable safety profile to the ABR when assessing post-operative complications such as subluxation, infection, graft/glenoid fracture, chondrolysis, neurovascular deficits and stiffness. AAGR is superior to ABR with respect to rates of recurrent instability and should be considered as a first-line treatment in certain patients with specific risk factors such as younger age, competitive contact sports participation, and higher number of instability events pre-operatively. Level III.


Pachytene mapping of the C9 and acrocentric bivalents in the human oocyte.
Provisional maps are presented for all acrocentric bivalents and bivalent 9, according to their chromomere patterns at pachytene in the human oocyte. Each G band is subdivided into several sub-bands whose numbers varies according to the degree of chromosomal compacting. Chromomere number and sequence are in basic agreement with those observed in late prophase mitotic chromosomes. Thus, metaphase G bands of mitotic chromosomes result from progressive compressing together of smaller chromomeres whose individuality disappears as chromosomal condensation increases with progression of prophase.


A form of human basic fibroblast growth factor with an extended amino terminus.
The amino acid sequence of a human placental bFGF was determined by a combination of protein and cDNA sequencing. The placental bFGF consists of 157 amino acid residues with a calculated molecular weight of 17,464 and is highly homologous to bovine pituitary bFGF. The human protein contains an amino terminal extension when compared to the sequence established for bovine bFGF (Esch et al., 1985) and to the sequence of the predicted translation product based on human bFGF cDNA clones (Abraham et al., 1986).


Role of the fourth complement component (C4) in the regulation of contact sensitivity. I. Analysis in mice with high and low C4 levels.
Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride are able to immunize naive recipients by hapten-IgM immuno complexes. These cells ("4-day" cells) activate the early components of the classical pathway of complement from mice of the H-2 Sd haplotype (high-C4), but fail to activate the classical pathway of complement from mice of the H-2 Sk haplotype (low-C4). Incubation of "4-day" cells in complement from mice with high-C4 levels abolishes the induction of contact sensitivity, probably as a consequence of the solubilization of membrane-bound immuno complexes caused by complement activation. The presence of "4-day" cells is determined by the levels of C4. In fact, using strains of mice which differ only at the S region of the H-2 complex, we found that mice of the H-2 Sd (and perhaps H-2 Sb) haplotype (high-C4 levels) lack "4-day" cells in their lymph nodes and this is due to the activation of the early components of the classical complement pathway which occurs in vivo in these mice during sensitization with picryl chloride. The finding that contact sensitivity reaction to picryl chloride in H-2 Sk mice lasts about 21 days, whereas H-2 Sd mice show a contact sensitivity reaction until 7 days after sensitization, strongly suggests that the S region, and in particular C4 levels, controls the persistence of "4-day" immunogenic cells, and so play a role in the duration of the contact sensitivity reaction to picryl chloride in the mouse.


Extramedullary plasmacytoma of the orbit: case report with results of immunocytochemical studies.
Orbital involvement as the initial manifestation of primary extramedullary plasmacytoma is rare. The case presented in this article illustrates several interesting aspects of the disease. The neoplastic process involved monoclonal B-lymphocytes that produced IgG-lambda chains.


Significantly Improving the Crystal Growth of a Cu2ZnSn(S,Se)4 Absorber Layer by Air-Annealing a Cu2ZnSnS4 Precursor Thin Film.
The crystal quality of a Cu2ZnSn(S,Se)4 (CZTSSe) thin film is crucially important to a high-performance CZTSSe solar cell. After selenization, a bilayer CZTSSe thin film consisting of a large-grain top layer and a small-particle bottom layer is usually observed according to the literature. In this work, a facile air-annealing pretreatment is conducted for a Cu2ZnSnS4 precursor thin film prior to selenization, which can lead to sodium diffusion into the CZTS precursor thin film and surface oxidization of the CZTS thin film. Our experimental results revealed that the Na prediffusion and the surface oxidation of the CZTS precursor thin film can significantly promote the crystal growth of the CZTSSe thin film, which can completely remove the small-particle bottom layer and form a large-grain-spanned CZTSSe thin film. As a result, a photoelectric conversion efficiency of 9.80% was achieved by this method.


Effect of hyperthermic vesical irrigation with bleomycin on the ultrastructure of the well-differentiated tumour and non-tumorous mucosa of the human urinary bladder.
Bladder tumours and non-tumorous bladder mucosa were studied by scanning and transmission electron microscopy in seven patients who had undergone hyperthermic vesical irrigation with bleomycin. The treatment induced sloughing of the outermost tumour cells, an increase of blebs and a decrease of cytoplasmic processes of the deeply located tumour cells as well as cellular degeneration. Although less severe, non-tumorous mucosa showed similar changes. Microvilli also appeared on the superficial cells of non-tumorous mucosa after the treatment. This treatment is effective by inducing cell degeneration and desquamation but not selective to the bladder tumour.


Helmet treatment for plagiocephaly and congenital muscular torticollis.
Plagiocephaly usually originates in late fetal life through aberrant constraint of the fetal head and is often associated with sternocleidomastoid torticollis. In some patients the obligue head shape may become a permanent, cosmetic disability. Individually fitted plastic helmets, similar in style to football helmets, have been successfully used to remold the deformed heads of four infants. Each helmet is designed to fit snugly against the prominent aspects of the infants' cranium and to be loose fitting where the head is shallow. As the brain grows, the head is molded to fit the helmet and thus acquires a more usual shape. The treatment has been safe and effective. When torticollis is persistent after the initiation of treatment, rubber straps can be fixed to the outside of the helmet and attached to the side rails of the crib. While the infant sleeps, the straps can be tightened to stretch the shortened sternocleidomastoid muscle.


[Cervical ripening with balloon catheter for scared uterus: a three-year retrospective study].
To evaluate, for women with scared uterus, the mechanical cervical ripening with balloon catheter. We conducted a retrospective study of our practice of ripening for scared uterus from january 2010 to august 2012. Feasibility, Bishop's score, birth modalities and complications for mothers and babies during this ripening were studied. Thirty-nine medical files were analysed. All patients could have mechanical ripening independently of the internal os status (open or not). The cervical ripening with balloon catheter improved Bishop's score before induction of labour, from 3.54 ± 1.23 to 5.38 ± 1.47 (p=0.02). 64.1% of women had a vaginal delivery. Concerning the predictive factors for vaginal delivery, we only found significant influence of a body mass index less than 30kg/m² (p=0.03). We didn't find any maternal or neonatal complications in our population. Mechanical ripening for scared uterus seems to be a useful option to improve vaginal delivery without increasing maternal and foetal morbidity. Anyway, these results have to be confirmed by a randomized controlled trial on a specific scared uterus population.


Deposition, clearance, and translocation of chrysotile asbestos from peripheral and central regions of the rat lung.
We investigated the pulmonary deposition, clearance, and translocation of chrysotile asbestos in the context of our previously developed model of asbestosis in the rat. Adult male rats were exposed for 3 hr to an aerosol of chrysotile asbestos. Subgroups were sacrificed up to 29 days postexposure and the lungs of the animals fixed. Peripheral and central regions of the left lung were resected, digested, and analyzed for fiber content by scanning electron microscopy. Pulmonary deposition did not differ between peripheral and central regions. There was no evidence of translocation of fibers from central to peripheral regions. The average diameter of retained fibers decreased over time, consistent with longitudinal splitting. The average length of retained fibers increased over time, consistent with slower clearance of longer fibers. We employed a novel counting scheme to ensure accurate fiber number measurements, allowing the calculation of clearance rates for fibers 0.5 to greater than or equal to 16 microns in length. Fibers of length greater than or equal to 16 microns were cleared slowly, if at all. These findings could have important implications for the pathogenesis of asbestos-related pleural disease. Many fibers are deposited in the peripheral region, and the longest (greater than or equal to 16 microns) will persist there for extended periods.


Accurately evaluating for a small bowel obstruction using an abdominal radiograph, by a new method: The Bowel-Spine Ratio.
A well-established method does not exist to rule out a small bowel obstruction using an abdominal xray series with significant accuracy. The hypothesis of the study is that the ratio of an average small bowel diameter to lumbar spine diameter over 0.5 is most likely a small bowel obstruction. An x-ray abdominal series measurement technique was applied to 41 subjects with a chief complaint of "abdominal pain" as part of a randomized retrospective case review to predict an obstruction v. non obstruction. A total number of 81 abdominal pain subjects with a mean age of 46.7 years were selected with 40 excluded due to normal small bowel gas pattern. The subject's medical information was unknown to the authors when reading their images. The measurement technique involved averaging the largest and smallest small bowel short axis diameters with comparison to the lowest clearly visible lumbar body width. The subjects' medical course as described in the medical chart or subsequent computed tomography scans were used as the referencing standard to determine presence of obstruction vs non-obstruction. This method, called the Bowel-Spine Ratio (BSR), resulted in a sensitivity of 0.882 (0.622-0.979; 95% CI), specificity of 0.957 (0.760-0.998; 95% CI), accuracy of 94.7% (80.9%-99.1%; 95% CI) and a positive likelihood ratio of 21 for predicting a small bowel obstruction. The abdominal series Bowel-Spine Ratio is a simple yet effective technique to screen for a small bowel obstruction using limited resources and to avoid unnecessary computed tomography scans with the potential to reduce health care costs. Clinicians could have increased confidence in utilizing abdominal radiographs to evaluate for small bowel obstruction.


A sensitive and accurate method to simultaneously measure uric acid and creatinine in human saliva by using LC-MS/MS.
To establish a method to simultaneously measure uric acid (UA) and creatinine (Cr) in human saliva. By using HPLC-MS/MS, we developed and validated a fast, sensitive and accurate method to simultaneously determine UA and Cr in human saliva. The determination range for Cr and UA is of 10-5000 ng/ml with the R2 for both calibration curves over 0.999. The accuracy, precision and recovery of Cr and UA were all acceptable. By using the established method, the Cr and UA levels in saliva from 28 healthy volunteers were measured as 2.9 ± 0.8 µM and 46.8 ± 18.2 µM, respectively. This method can simultaneously determine Cr and UA in saliva for clinical and translational study.


Pathomorphology of postinfarction myocardial ischemia during atherosclerotic obstruction of coronary arteries.
Pathomorphological criteria of early postinfarction angina included segmentary atherosclerotic obstruction of the upper segments of the coronary artery supplying the infarction area, recurrent acute myocardial infarction, maximum decrease in vascularization of the left posterior ventricular wall; and individual changes in angioarchitectonics of the heart promoting hibernation of the myocardium. Pathognomonic morphological criteria of silent postinfarction myocardial ischemia included diffuse extensive atherosclerotic obstruction of lower segments in the coronary artery supplying the infarction area and total hypervascularization of the myocardium, first acute myocardial infarction of the left ventricular anterior wall, and maximum decrease in vascularization of the anterior and posterior wall in the left ventricle. These coronary-myocardial relationships contribute to stunning of the myocardium. Zones of hypokinesia and akinesia were revealed in the left ventricle, which reflects the phenomenon of resting myocardium associated with isolation of heart angioarchitectonics.


Transverse sinus thrombosis in a living donor: a case report.
Liver transplantation is among the treatment options for end-stage liver disease. Limited organ donation in our country has resulted in an increased performance of living donor liver transplantations. This case report describes a left transverse cerebral venous sinus thrombosis diagnosed in a living donor hepatectomy patient. A 45-year-old man underwent right lobe hepatectomy of a 330-g graft for living donor liver transplantation to his 55-year-old hepatitis B virus-positive brother. On the first postoperative day, without any surgical problems he presented with loss of consciousness. Previous medical history was unremarkable. Neurology consultation revealed lethargy and an acute confusional state. Cerebral magnetic resonance imaging venography showed signal alterations in the left transverse sinus wherein thrombosis was diagnosed. Heparin infusion initiated for antithrombotic treatment was adjusted to provide a 1.5 to 2-fold increased baseline activated partial thromboplastin time. On the second day of treatment has clinical status improved and he was discharged on the, fifth day on oral anticoagulant (warfarin) therapy for outpatient follow-up. Cerebral venous sinus thrombosis is a rare disease with variable clinical onsets. Surgical procedures are among risk factors. An early diagnosis is essential to achieve low mortality and morbidity rates.


Oral vaccination of dogs fed canine adenovirus in baits.
Six groups of 5 dogs each were fed dilutions of canine adenovirus-2, either as raw liquid or after insertion into cornmeal baits. By the fourth week after vaccination, 29 of the 30 dogs developed high titers of serum-neutralizing antibodies to the virus.


Coupling a Live Cell Directed Evolution Assay with Coevolutionary Landscapes to Engineer an Improved Fluorescent Rhodopsin Chloride Sensor.
Our understanding of chloride in biology has been accelerated through the application of fluorescent protein-based sensors in living cells. These sensors can be generated and diversified to have a range of properties using laboratory-guided evolution. Recently, we established that the fluorescent proton-pumping rhodopsin wtGR from Gloeobacter violaceus can be converted into a fluorescent sensor for chloride. To unlock this non-natural function, a single point mutation at the Schiff counterion position (D121V) was introduced into wtGR fused to cyan fluorescent protein (CFP) resulting in GR1-CFP. Here, we have integrated coevolutionary analysis with directed evolution to understand how the rhodopsin sequence space can be explored and engineered to improve this starting point. We first show how evolutionary couplings are predictive of functional sites in the rhodopsin family and how a fitness metric based on a sequence can be used to quantify the known proton-pumping activities of GR-CFP variants. Then, we couple this ability to predict potential functional outcomes with a screening and selection assay in live Escherichia coli to reduce the mutational search space of five residues along the proton-pumping pathway in GR1-CFP. This iterative selection process results in GR2-CFP with four additional mutations: E132K, A84K, T125C, and V245I. Finally, bulk and single fluorescence measurements in live E. coli reveal that GR2-CFP is a reversible, ratiometric fluorescent sensor for extracellular chloride with an improved dynamic range. We anticipate that our framework will be applicable to other systems, providing a more efficient methodology to engineer fluorescent protein-based sensors with desired properties.


Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition.
Decreased cerebrospinal fluid (CSF) beta-amyloid 42 (A beta 42) concentration, but not A beta 40 concentration, is a biomarker for Alzheimer disease. This A beta 42 concentration decrease in CSF likely reflects precipitation of A beta 42 in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease. To estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF A beta 42 concentration in adults with normal cognition across the life span. The CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF A beta 42 and A beta 40 concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method. Subjects One hundred eighty-four community volunteers with normal cognition aged 21 to 88 years. The CSF A beta 42, but not the A beta 40, concentration decreased significantly with age. There was a sharp decrease in CSF A beta 42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A beta 42 concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele. These CSF A beta 42 findings are consistent with acceleration by the APOE*4 allele of pathogenic A beta 42 brain deposition starting in later middle age in persons with normal cognition.


Presence of an H+/Quinidine Antiport System in Madin-Darby Canine Kidney Cells.
We have recently found an H+/quinidine antiport system in human kidney HEK 293 cells. The aim of the present study was to evaluate whether the H+/quinidine antiport system is expressed in Madin-Darby canine kidney (MDCK) cells. We investigated the uptake and efflux of quinidine in MDCK cells. The uptake of 100 µM quinidine into MDCK cells was decreased by acidification of extracellular pH or alkalization of intracellular pH. In addition, the uptake of quinidine was highly temperature sensitive, but was extracellular Na+ and membrane potential independent. Furthermore, tetraethylammonium, a typical substrate of renal organic cation transporters, did not inhibit the uptake of quinidine in MDCK cells. On the other hand, lipophilic cationic drugs, such as clonidine, bisoprolol, diphenhydramine, pyrilamine, and imipramine, significantly decreased the uptake of quinidine in MDCK cells. The uptake of quinidine was saturable, and the Michaelis-Menten constant was estimated to be approximately 0.5 mM. In addition, the efflux of quinidine from MDCK cells was increased by the acidification of extracellular pH, suggesting that the transport system mediates not only the uptake, but also secretion of quinidine. The present findings suggested that the renal new antiport system is involved in the bidirectional membrane transport of quinidine in MDCK cells.


Hydrophobic interaction adsorption of whey proteins: effect of temperature and salt concentration and thermodynamic analysis.
The adsorptive behavior of bovine serum albumin (BSA) and beta-lactoglobulin (beta-lg) on hydrophobic adsorbent was studied at four temperatures and different salt concentrations. The Langmuir model was fitted by experimental equilibrium data showing that an increase in temperature and salt concentration results in an increase on the capacity factor of both proteins. A thermodynamic analysis coupled with isotherm measurements showed that salt concentration and temperature affected the enthalpic and entropic behavior of the adsorption process of both proteins, mainly to the beta-lg. The fast variation in the Z value for temperature over than 303.1K suggest a great conformational change occurring in the beta-lg structure, which almost duplicated the maximum adsorption capacity of this protein.


Enhancing fixation strength in periprosthetic femur fractures by orthogonal plating-A biomechanical study.
Orthogonal plate osteosynthesis enhances fixation stability in periprosthetic femur fractures. Another option are locking attachment plates (LAP) allowing bicortical locking screw placement lateral to the prosthesis stem. Stability of lateral plate osteosynthesis with two LAP (2LAP) was compared to anterolateral orthogonal plate osteosynthesis (OP) with one LAP in a periprosthetic femur fracture model. In six pairs of fresh frozen human femora with cemented Charnley hip prosthesis, a transverse osteotomy was set distal to the tip of the prosthesis simulating a Vancouver type B1 fracture. Each pair was instrumented using a plate tensioner with either one lateral plate and two LAP, or two orthogonal anterolateral plates and one LAP. Stiffness was determined in a four-point-bending test prior to cyclic testing (2Hz) with physiologic profile and progressively increasing load up to catastrophic construct failure. Paired t-test and Wilcoxon-signed-rank test were used for statistical evaluation at a level of significance p = 0.05. The OP construct exhibited a significantly higher number of cycles and load to failure (39,627 cycles ± 4,056; 4,463 N ± 906) compared to the 2LAP construct (32,927 cycles ± 3,487; 3,793 N ± 849), p < 0.01. Mediolateral bending and torsional stiffness of the OP (1610 N/mm ± 249; 16.9 Nm/mm ± 6.3) were significantly higher compared to 2 LAP (1077 N/mm ± 189; 12.1 Nm/mm ± 3.9), p = 0.03 for both comparisons. Orthogonal plate osteosynthesis is a valuable option in periprosthetic fracture surgery, offering increased stability compared to a single lateral plate fixed with two LAP.


Interventions to support mental health in people with long COVID: a scoping review.
Long COVID (LC) is a multisystem disease with symptoms lasting weeks or months beyond the acute COVID-19 infection. Several manifestations are reported by people with LC, including effects on mental health, with varying degrees of psychological distress and disturbances to daily activities. Research conducted to identify effective interventions to support mental health among people with LC has been limited by the breadth and scope of studies. This review aims to identify interventions being tested to support mental health of people with LC. A scoping review was conducted by searching five databases for articles published between January 2020 and early October 2022 to identify research evaluating interventions focused on improving mental health symptoms associated with LC. Results from all sources were checked for eligibility by two reviewers, and agreements were resolved by discussion. Gray literature and reference list of included studies and relevant reviews were scrutinised to identify any additional studies. Data extraction was conducted by one reviewer and checked by another reviewer for accuracy. Of the 940 studies identified, 17 were included, the design of which varied but included mainly case studies (n = 6) and clinical trials (n = 5). Several interventions were described, ranging from single interventions (e.g., pharmacologic) to more holistic, comprehensive suites of services (pharmacologic and non-pharmacologic). Several mental health outcomes were measured, mostly anxiety and depression. All included studies were reported to be associated with improvements in participants' mental health outcomes. This scoping review identified studies reporting on a variety of interventions to support mental health among people with LC. Although positive changes were reported by all studies, some were case studies and thus their findings must be interpreted with caution. There is a need for more research to be conducted to identify the impact of interventions on mental health of people with LC.


Clinical Experience With a Coordinated Multidisciplinary Approach to Treating Prosthetic Joint Infection.
The successful treatment of prosthetic joint infection (PJI) is difficult, requiring coordination across multiple specialties. In 2017, we formed a collaboration between our infectious disease clinicians and our orthopaedic arthroplasty surgeons in an effort to optimize care, accommodate patients, and expedite clinical decision-making in the treatment of PJI. The model consisted of combined infectious disease and arthroplasty clinics, standardized lab results, and planned staged revision procedures. We named this the arthroplasty infection service. Our early experience with a defined multidisciplinary approach to PJI was positive. Although the impact of the arthroplasty infection service on PJI outcomes is yet to be determined, we believe this is a step forward in the management of this complex patient population. With an increasing burden of PJI in the United States, this model could be emulated at many institutions that regularly treat these challenging cases.


Feasibility and validation of virtual autopsy for dental identification using the Interpol dental codes.
Virtual autopsy is a medical imaging technique, using full body computed tomography (CT), allowing for a noninvasive and permanent observation of all body parts. For dental identification clinically and radiologically observed ante-mortem (AM) and post-mortem (PM) oral identifiers are compared. The study aimed to verify if a PM dental charting can be performed on virtual reconstructions of full-body CT's using the Interpol dental codes. A sample of 103 PM full-body CT's was collected from the forensic autopsy files of the Department of Forensic Medicine University Hospitals, KU Leuven, Belgium. For validation purposes, 3 of these bodies underwent a complete dental autopsy, a dental radiological and a full-body CT examination. The bodies were scanned in a Siemens Definition Flash CT Scanner (Siemens Medical Solutions, Germany). The images were examined on 8- and 12-bit screen resolution as three-dimensional (3D) reconstructions and as axial, coronal and sagittal slices. InSpace(®) (Siemens Medical Solutions, Germany) software was used for 3D reconstruction. The dental identifiers were charted on pink PM Interpol forms (F1, F2), using the related dental codes. Optimal dental charting was obtained by combining observations on 3D reconstructions and CT slices. It was not feasible to differentiate between different kinds of dental restoration materials. The 12-bit resolution enabled to collect more detailed evidences, mainly related to positions within a tooth. Oral identifiers, not implemented in the Interpol dental coding were observed. Amongst these, the observed (3D) morphological features of dental and maxillofacial structures are important identifiers. The latter can become particularly more relevant towards the future, not only because of the inherent spatial features, yet also because of the increasing preventive dental treatment, and the decreasing application of dental restorations. In conclusion, PM full-body CT examinations need to be implemented in the PM dental charting protocols and the Interpol dental codes should be adapted accordingly.


Ischemic preconditioning and the gene expression of enteric endothelial cell biology of rats submitted to intestinal ischemia and reperfusion.
To investigate the effects of ischemic preconditioning (IPC) on the expression of pro and anti-apoptotic genes in rat endothelial cells undergoing enteric ischemia (I) and reperfusion (R). Thirty rats underwent clamping of the superior mesenteric vessels. Sham group (GS) laparotomy only; Ischemia (GI): intestinal ischemia (60 min); Ischemia and Reperfusion (GIR): ischemia (60 min) and reperfusion (120 min); Ischemia and intestinal ischemic preconditioning (GI + IPC) : 5 minutes of ischemia followed by 10 min of reperfusion before sustained ischemia (60 min) ischemia and reperfusion and IPC (GIR + IPC): 5 min ischemia followed by 10 min of reperfusion before sustained ischemia (60min) and reperfusion (120 min). Rat Endothelial Cell Biology (PCR array) to determine the expression of genes related to endothelial cell biology. Gene expression of pro-apoptotic markers (Casp1, Casp6, Cflar, Fas, and Pgl) was down regulated in GI+IPC and in GIR + IPC. In contrast, the expression of anti-apoptotic genes (Bcl2 and Naip2), was up-regulated in GI + IPC and in GIR + IPC. Ischemic preconditioning may protect against cell death caused by ischemia and reperfusion.


Do Differences in Programmatic Resource Investments Result in Different 3-Year Pass Rates on the U.S. National Physical Therapy Examination?
The rising cost of health professions education is well documented and a growing concern among educators; however, little is known about the implications of resource investment on student success. The objective of this study was to determine whether programs with higher National Physical Therapist Exam (NPTE) pass rates invested significantly more on programmatic resources. This observational study used data from the Commission on Accreditation in Physical Therapy Education's (CAPTE) Annual Accreditation Report including all accredited physical therapist programs from the United States who graduated physical therapist students in 2011. Resource expenditures were recorded as both raw and as an index variable (resources per student). Descriptive statistics and comparisons (using chi-square and t-tests) among programs with <100% and 100% pass rates were analyzed from 2009-2011. An ANCOVA was used to determine differences in raw resource expenditures and resource expenditures per student. There were no differences in raw resource expenditures between programs with <100% and 100% pass rates. Programs with 100% pass rates were provided more resource expenditures per student for personnel, overall budget, and core faculty. The results of this study suggest programs with 100% pass rates invested significantly more per student for selected resources.


A novel procedure for the identification of chaos in complex biological systems.
We demonstrate the presence of chaos in stochastic simulations that are widely used to study biodiversity in nature. The investigation deals with a set of three distinct species that evolve according to the standard rules of mobility, reproduction and predation, with predation following the cyclic rules of the popular rock, paper and scissors game. The study uncovers the possibility to distinguish between time evolutions that start from slightly different initial states, guided by the Hamming distance which heuristically unveils the chaotic behavior. The finding opens up a quantitative approach that relates the correlation length to the average density of maxima of a typical species, and an ensemble of stochastic simulations is implemented to support the procedure. The main result of the work shows how a single and simple experimental realization that counts the density of maxima associated with the chaotic evolution of the species serves to infer its correlation length. We use the result to investigate others distinct complex systems, one dealing with a set of differential equations that can be used to model a diversity of natural and artificial chaotic systems, and another one, focusing on the ocean water level.


Coenzyme A dithioesters: synthesis, characterization and reaction with citrate synthase and acetyl-CoA:choline O-acetyltransferase.
Acyl dithioesters of CoA have been synthesized by transesterification. The alpha-hydrogens have a spectrally determined pKa of 12.5 +/- 0.14. The hydroxide catalyzed enolization rate is estimated to be 600 M-1.s-1. The absorbance of the dithioester, lambda max = 306 nm, can be used to monitor both the condensation and transesterification reactions that use CoA-Ac as a substrate. For citrate synthase at pH 7.4 Vmax = (4.0 +/- 0.4).10(-4) s-1 and Km = 53 +/- 7.5 microM, which are 2.10(-6) and 3.3-times the Vmax and Km values observed for CoAS-Ac, while for Ac-CoA: choline O-acetyltransferase (EC 188.8.131.52) at pH 7.0 Vmax = (1.1 +/- 0.2).10(-2) mumol.s-1.(mg protein)-1 and Km = 83 +/- 33 microM, which are 0.077 and 10-times the values observed with CoAS-Ac, respectively. The CoA dithioesters are stable at low pH, but hydrolyze with a second-order rate constant of 8.2.10(-2) M-1.s-1 at pH 11.4. The spectral properties of these dithioesters should allow these analogs to be used as probes of the structure of enzyme bound intermediates.


Heterogeneity of helper T cell subsets in Peyer's patches.
The OX22 monoclonal antibody recognizes the high molecular weight form of the CD45 molecule on rat T cells encoded by the CD45RC exon of the leukocyte common antigen gene. Its expression on CD4+ T cells is associated with virgin unprimed cells and primed cells which produce IL-2 and IFN-gamma on stimulation and participate in cell-mediated immune reactions. This suggested that CD45RC expression may be useful as a phenotypic marker for cells expressing Th1 function. In view of our previous data indicating heterogeneity of T-cell helper function in different lymphoid compartments in the gut, the helper activity of OX22-enriched or OX22-depleted cell populations prepared from Peyer's patches (PP) of rats was compared. Following intestinal immunization with keyhole limpet haemocyanin, PP cells were isolated and separated by panning. Recovery data indicated that the majority of T cells in rat PP express the OX22+ phenotype and, after separation, the OX22-enriched population contained 4 times as many cells as the OX22-depleted population. Functional studies revealed that both subsets were capable of providing cognate help for secondary IgM, IgG and IgA antibody responses indicating that on this basis the CD45RC marker does not correlate with Th1 function in rats.


A computerized discriminator for action potentials.
A system for recognizing extracellular action potentials in the presence of noise and other pulses was developed for a PDP11/23 computer. Data can be processed either on-line or off-line from a tape recorder. There are 4 parts: (1) An RC bandpass filter attenuates noise. (2) The data input program digitizes the signal every 55 mu sec. If the signal exceeds a threshold, 12 samples of the signal and the time are written onto the disk. Up to 300 pulses/sec can be processed. (3) The pulse discriminating program recognizes an action potential by fitting the 12 points with this function: v(t) = (a + bt + ct2) exp(-t/tau). It is biphasic, has two zeroes, and decays to zero at long times. There are 4 parameters, a, b, c and tau. The operator chooses a value of tau giving good fits for all pulses of this neuron. For each pulse the computer determines values of a, b and c by the least squares technique. The zeroes of v(t) are computed. For acceptance, the total pulse height (difference between extreme voltages), the position of the first zero, and the time between zeroes must be within limits. The 12 points and v(t) can be displayed. Summary statistics and histograms are printed. It takes 80 msec/pulse for these off-line computations. (4) Occasionally a pulse may be missed or an extra one recorded. The pulse insertion-deletion program edits the disk files. The instantaneous-interspike-frequency plot is displayed and the operator moves cursors to insert or delete pulses.


Development and characterization of blends formulated with banana peel and banana pulp for the production of blends powders rich in antioxidant properties.
The food product industry is increasingly looking for foods with nutritional properties that can provide health benefits. Additionally, a challenge for the food industry is the use of all raw materials. For these reasons, banana peel that is a raw material from Banana (Musa spp.) fruit emerges as potential for new food product development. Here, we developed powder blends using a lyophilization process for the preparation of flour to potential use in cookies, bread, and pasta products. Three formulations were designed; the main difference in the formulations was the use of banana peel concentration. Our results showed that blends produced with banana peel presented physical-chemical properties considered suitable for use in food industry. Moreover, the evaluated morphological parameters reveal the properties of the powders. The blends formulated with banana peel have more antioxidant properties, showing that the banana peel may be an attractive option to generate powders with high antioxidant properties.


Thromboembolism after COVID-19 Vaccination: A Systematic Review of Such Events in 286 Patients.
Development of vaccines with high efficacy against COVID-19 disease has ushered a new ray of hope in the fight against the pandemic. Thromboembolic events have been reported after administration of vaccines. We aim to systematically review thromboembolic events reported after COVID-19 vaccination. The available literature was systematically screened for available data on thromboembolic events after COVID-19 vaccination. Data were extracted from selected studies and analyzed for site of thromboembolism as well as other risk factors. All data were pooled to determine cumulative incidence of thromboembolism at various sites after vaccination. A total of 20 studies were selected for the final analysis. The mean age of the population was 48.5 ± 15.4 years (females - 67.4%). The mean time to event after vaccination was 10.8 ± 7.2 days. Venous thrombosis (74.8%, n = 214/286) was more common than arterial thrombosis (27.9%, n = 80/286). Cerebral sinus thrombosis was the most common manifestation (28.3%, n = 81/286) of venous thrombosis followed by deep vein thrombosis (19.2%, n = 49/254). Myocardial infarction was common (20.1%, n = 55/274) in patients with arterial thrombosis followed by ischemic stroke (8.02%, n = 22/274). Concurrent thrombosis at multiple sites was noted in 15.4% patients. Majority of patients had thrombocytopenia (49%) and antiplatelet factor 4 antibodies (78.6%). Thromboembolic events were mostly reported after the AstraZeneca vaccine (93.7%). Cerebral sinus thrombosis was the most common among thromboembolic events reported after the AstraZeneca vaccine. Among the reported cases, mortality was noted in 29.9% patients. Thromboembolic events can occur after COVID-19 vaccination, most commonly after the AstraZeneca vaccine. Cerebral sinus thrombosis is the most common manifestation noted in vaccinated individuals.


Ifosfamide given as a 24-h infusion with mesna in patients with recurrent ovarian cancer: preliminary results.
The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapy-resistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5-41 months). No patients who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4-12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2-13+ months) and that in the remaining group was 13 months (ranges 3(+)-24 months) (P less than 0.05). This treatment was moderately well tolerated. Grade 3 nausea and vomiting occurred in 27% of cycles and grade 3-4 leukopenia was observed in 47%, but thrombocytopenia was hardly ever found. In eight patients there was a deterioration of renal function. Among a total of 131 cycles, the dose was reduced for only 9 due to myelotoxicity and for 3 due to nephrotoxicity. IFX seems to be active only in patients who have relapsed after responding to previous cytotoxic treatment.


Development of pullulan/chitosan/salvianolic acid ternary fibrous membranes and their potential for chemotherapeutic applications.
This study investigates the feasibility of centrifugal spinning for producing fibrous membranes containing pullulan, chitosan, and danshen extract. The danshen extract is composed of 20 wt% salvianolic acid B (SA). Citric acid was added to the mixture as a crosslinking agent to promote its use in the aqueous medium. The influence of the danshen concentration (25 wt% and 33 wt%) on fiber morphology, thermal behavior, and the biochemical effect was analyzed. Developed fiber-based membranes consist of long, continuous, and uniform fibers with a sparse scattering of beads. Fiber diameter analysis shows values ranging from 384 ± 123 nm to 644 ± 141 nm depending on the concentration of danshen. The nanofibers show adequate aqueous stability after crosslinking. Thermal analysis results prove that SA is loaded into nanofibers without compromising their structural integrity. Cell-based results indicate that the developed nanofiber membranes promote cell growth and are not detrimental to fibroblast cells. Anticancer studies reveal a promising inhibition to the proliferation of HCT116 colon cancer cells. The developed systems show potential as innovative systems to be used as a bioactive chemotherapeutic drug that could be placed on the removed tumor site to prevent development of colon cancer microdeposits.


Binding mode of new (thio)hydantoin inhibitors of fatty acid amide hydrolase: comparison with two original compounds, OL-92 and JP104.
Substituted (thio)hydantoins (2-thioxoimidazolidinones and imidazolidinediones) were reported as new potential reversible inhibitors of fatty acid amide hydrolase (FAAH). Their binding mode to FAAH was explored to rationalize their activity and give idea to design highly active inhibitors. Starting from the crystal structure of one of these molecules, docking studies provide us with rational basis for the design of new inhibitors within the thiohydantoin family.


Mapping of jumping, rearing, squealing and switch-off behaviors elicited by periaqueductal gray stimulation in the rat.
Rats readily learn to escape from a stimulation applied to most mesencephalic periaqueductal gray (PAG) sites. In the present study, we tried to find out to what extent the differential effects induced by such stimulations actually reflect the existence of intraPAG functional subdivisions. To that end, a row of five electrodes was implanted into the PAG of each of 29 rats. Two kinds of effects were analyzed, the stimulation-elicited overt behaviors and the generalization of switch-off responding from one stimulation site to the others. Further, switch-off latency versus interpulse interval (IPI) relationships were established and both the threshold IPIs and the ceiling switch-off latencies were determined. The most commonly elicited behaviors (jumping, rearing and squealing) as well as the threshold IPIs and the ceiling switch-off latencies were mapped within the PAG. Switch-off behavior was elicited from all the stimulation sites studied. However, in the dorsal PAG the switch-off latency was found to decrease more steeply with decreasing IPI than it did in the ventral PAG. Switch-off generalization was less frequently observed between dorsally located stimulation sites. Jumps were most often elicited from dorsally and rostrally located PAG sites while squeals were more frequently elicited from the caudal part of the PAG and rearings from PAG subareas surrounding the aqueduct.


Effects of food deprivation on cocaine base smoking in rhesus monkeys.
Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio than increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Foe to frenemy: predacious ant nest beetles use multiple strategies to fully integrate into ant nests.
Ant nest beetles (Carabidae, Paussinae, Paussini; Paussus) are renowned myrmecophiles, mostly known for their bizarre and diverse antennal shape. While little is known about their development, behavior and host range, we do know they spend most of their lives inside ant nests, feeding upon the hemolymph of ant brood and teneral workers. Recent findings suggest these beetles use a surprisingly complex strategy for interacting and deceiving ants. They have managed to break into multiple communication channels that ants use to recognize and communicate with one another in order to deceive the ants and profit from the rich resources of the nest. Mounting evidence from structural, chemical, acoustic, and behavioral studies support the hypothesis that Paussus is among the most highly integrated parasite of social insects known to date.


Quantification and control of gaseous emissions from solid waste landfill surfaces.
Landfilling is the most common option for solid waste disposal worldwide. Landfill sites can emit significant quantities of greenhouse gases (GHGs; e.g., methane, carbon dioxide, and nitrous oxide) and release toxic and odorous compounds (e.g., sulfides). Due to the complex composition and characteristics of landfill surface gas emissions, the quantification and control of landfill emissions are challenging. This review attempts to comprehensively understand landfill emission quantification and control options by primarily focusing on GHGs and odor compounds. Landfill emission quantification was highlighted by combining different emissions monitoring approaches to improve the quality of landfill emission data. Also, landfill emission control requires a specific approach that targets emission compounds or a systematic approach that reduces overall emissions by combining different control methods since the diverse factors dominate the emissions of various compounds and their transformation. This integrated knowledge of emission quantification and control options for GHGs and odor compounds is beneficial for establishing field monitoring campaigns and incorporating mitigation strategies to quantify and control multiple landfill emissions.


A capripoxvirus pseudogene whose only intact homologs are in other poxvirus genomes.
Equivalent regions from within the inverted terminal repeats (ITRs) of the genomes of two capripoxviruses, KS-1 and InS-1, were sequenced. The sequence from KS-1 DNA covers the major part of three contiguous open reading frames (ORFs), which match three contiguous ORFs from within the genomic ITRs of the leporipoxvirus Shope Fibroma Virus (SFV). The sequenced region of InS-1 DNA contains only two of the three ORFs. The region homologous to the third ORF has no coding potential due to the presence of several stop codons, resulting from small frameshifting deletions and insertions. The significance of a degenerate poxvirus gene, intact homologs of which are only found in other poxvirus genomes, is discussed.


Pure-tone hearing thresholds in otologically healthy 5-year-old children in Finland.
We measured the pure-tone air and bone conduction hearing of 359 randomly selected otologically normal urban preschool children in Finland at the average age of 5.2 years. Children with otoscopically verified middle ear pathology or abnormal impedance audiometry were not included in this sample. The mean air conduction thresholds varied from 16.6 dB at 0.125 kHz to 6.6 dB at 2 kHz, and the mean bone conduction thresholds from 6.0 dB at 0.25 kHz to 0.7 dB at 4 kHz. The pure-tone average (of air conduction thresholds at 0.5, 1 and 2 kHz) of all the ears was 7.6 dB. The distribution of single air conduction hearing thresholds at the frequencies from 0.25 kHz to 4 kHz showed that 66%-75% were at the 5-10 dB level.


Hemobilia in childhood.
During a 10-year period we have encountered three cases of hemobilia among children after blunt abdominal trauma. All patients had the classical symptoms with varying degrees of severity. One of the patients, a 5-year-old boy, had several episodes of severe gastrointestinal bleeding, abdominal pain, and jaundice during a 2-month period. He was treated with selective arterial embolization of the left hepatic artery. The symptoms ceased instantly, and the patient has remained healthy during an observation period of more than 2 years. In cases of hemobilia, selective arterial embolization is a safe method with no serious complications. Arterial collaterals develop very quickly and the risk of liver dysfunction is small. We suggest that embolization of hepatic arteries may be the treatment of choice even in small children with hemobilia.


Clinicopathological and oncological significance of persistent prostate-specific antigen after radical prostatectomy: A systematic review and meta-analysis.
To investigate the association of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) with clinicopathological features and long-term oncological prognosis for the development of a potential management strategy. A systematic literature search was performed using PubMed and Web of Science up to June 2021 to identify the eligible studies focusing on understanding the impact of persistent PSA in patients who underwent RP for localized prostate cancer. Meta-analyses were performed on parameters with available information. A total of 32 RP studies were identified, of which 11 included 26 719 patients with consecutive cohorts and the remaining 21 comprised 24 177 patients with cohorts carrying specific restrictions. Of the 11 studies with consecutive cohorts, the incidence of persistent PSA varied between 3.1% and 34.6% with a median of 11.0%. Meta-analyses revealed patients with persistent PSA consistently showed unfavorable clinicopathological features and a more than 3.5-fold risk of poorer biochemical recurrence, metastasis, and prostate cancer-specific mortality prognosis independently, when compared to patients with undetectable PSA. Similarly, cases with persistent PSA in different specific patient cohorts with a higher risk of prostate cancer also showed a trend of worse outcomes. We found that the frequency of persistent PSA was about 11.0% in consecutive RP cohorts. Persistent PSA was significantly associated with unfavorable clinicopathological characteristics and worse oncological outcomes. Patients with persistent PSA after RP may benefit from early salvage treatment to delay or prevent biochemical recurrence, improving oncological outcomes for these patients. Further prospective randomized controlled trials are warranted to understand optimal systemic therapy in these patients.


Differential expression of the LFA-1 molecule on the human peripheral blood mononuclear cell subpopulations.
The expression of leukocyte function associated antigen 1 (LFA-1) was studied on human peripheral blood mononuclear cells (PBMNC) by a double immunofluorescence method. Monoclonal antibodies IOT18 (recognizing the beta chain, 95 kDa, CD18) and SPVL7 (recognizing the alpha chain, 180 kDa, CD11a) were used. These antibodies revealed the same heterogeneous distribution of the LFA-1 molecule among peripheral blood mononuclear cells. A bimodal profile characterized the lymphocytes, whereas the monocyte subpopulation presented a unimodal profile. NK cells, including CD16, CD8 dim, expressed the LFA-1 with a high density. B cells expressing the CD19 phenotype showed surface LFA-1 at a low level, whereas it appeared with an intermediate intensity on the T helpers/inducers (CD4 cells). Among the cytotoxic cells (CD8) and the immunoregulatory subpopulations associated with an immunosuppressive response (CD8+ CD11b+, CD8+ CD11b- and CD8+ leu8+) or with a contrasuppressive response (Vicia villosa cells), an heterogeneous LFA-1 expression was observed, discriminating the LFA-1 dim and the LFA-1 bright cells. Anti LFA-1 antibodies also allowed us to define three novel subsets among the CD8 cells: the CD8 dim LFA-1 bright, the CD8 bright LFA-1 bright, and the CD8 bright LFA-1 dim cell subpopulations. This heterogeneous distribution of LFA-1 among PBMNC may be associated with different functions of the different cell subsets analyzed in this study.


Liver Transplantation After Hematopoietic Stem Cell Transplant for the Treatment of Sickle Cell Disease: A Case Report.
Sickle cell anemia is the most common of the hemoglobinopathies, in which the abnormal hemoglobin formed in deoxygenation states undergoes a polymerization process with consequent erythrocyte deformation and vaso-occlusive events. The need for multiple blood transfusions, prolonged ineffective erythropoiesis, hemolysis, and increased iron absorption can cause iron overload in the liver, leading to liver fibrosis. Hematopoietic stem cell transplantation (HSCT) is currently the only treatment with a curative potential for this disease and can establish normal complete or partial donor-derived erythropoiesis and stabilize or restore function in affected organs, preventing further deterioration of function. However, it does not reverse preexisting liver fibrosis and siderosis. One of the possible complications of patients who undergo HSCT is chronic liver disease, which has a multifactorial cause, with iron overload being an important factor. In the long term, the prevalence of chronic liver disease in HSCT patients, including cirrhosis and its complications, can be significant. Solid organ transplantation after allogeneic hematopoietic cell transplantation for end-organ failure remains a very rare event. It may offer a valuable treatment strategy in selected recipients, although it is associated with significant morbidity and mortality. We report the case of a patient with sickle cell anemia who underwent HSCT and developed severe liver dysfunction requiring liver transplantation 13 years after the procedure. We found no previous report in the literature of orthotopic liver transplant after HCT for the treatment of sickle cell disease.


Myogenically differentiated mesenchymal stem cell insulin sensitivity is associated with infant adiposity at 1 and 6 months of age.
In adults, skeletal muscle insulin sensitivity (SI ) and fatty acid oxidation (FAO) are linked with a predisposition to obesity. The current study aimed to determine the effects of maternal exercise on a model of infant skeletal muscle tissue (differentiated umbilical cord mesenchymal stem cells [MSCs]) SI and FAO and analyzed for associations with infant body composition. Females <16 weeks' gestation were randomized to either 150 min/wk of moderate-intensity aerobic, resistance, or combination exercise or a nonexercising control. At delivery, MSCs were isolated from umbilical cords and myogenically differentiated, and SI and FAO were measured using radiolabeled substrates. Infant body fat percentage (BF%) and fat-free mass were calculated using standard equations at 1 and 6 months of age. MSCs from infants of all exercisers had significantly (p < 0.05) higher SI . MSC SI was inversely associated with infant BF% at 1 (r = -0.38, p < 0.05) and 6 (r = -0.65, p < 0.01) months of age. Infants with high SI had lower BF% at 1 (p = 0.06) and 6 (p < 0.01) months of age. MSCs in the high SI group had higher (p < 0.05) FAO. Exposure to any type of exercise in utero improves offspring SI and could reduce adiposity in early infancy.


[Fibrin(ogen degradation product concentration (SFP) as a diagnostic parameter for the differentiation of artifical and essential blood in cerebrospinal fluid].
The fibrin(ogen) degradation product concentration is another differential-diagnosis parameter for distinguishing between artificially blood-stained and essentially blood-stained CSF. Determination of the fibrin(ogen) degradation product concentration has been found to be a reliable method of recognizing natively and artificially blood-stained CSF as being different.


Some consequences of the Auger effect: fluorescence yield, charge potential, and energy imparted.
The potential energy produced by the Auger cascade due to the charging of atoms is evaluated and incorporated into conventional treatment of energy deposition. A straightforward method for calculating this energy is presented. For the photoelectric interaction the potential energy is shown to be at least as important as L-shell fluorescence in calculating the electron kerma. For radioactive decay by electron capture or internal conversion, it is shown that, for small (less than 100 nm) targets containing the decay, the atomic charging can be the dominant contribution to the total energy deposited in the target.


Ascending spinal projections to the optic tectum, facial and vagal lobes in the goldfish, Carassius auratus.
Using biotinylated dextran-amines as tracer, we observed prominent ascending spinal projections to three unreported areas in the gold fish brain viz. the optic tectum (OT), facial (FL) and vagal (VL) lobes. From the lateral spinal lemniscus (LSL), some fiber tracts separated off and extended mediodorsally, fanned out and innervated the FL. The VL was clearly laminated and showed three layers-the inner primary motor neuron and fiber layer (PMNF), outer secondary neuron layer (SN) and middle primary and secondary fiber layer (PSF). The PMNF received maximal innervation. Besides several fibers extending directly into the SN from the LSL, a few fibers extended dorsolaterally from the PMNF and innervated the SN. Several ascending fibers extended into the torus semicircularis, thalamic and pretectal areas and innervated the OT. The possible functional significance of the spinal innervation of these brain areas has been discussed.


Fracture of the penis: surgical management.
Fracture of the penis is a rare injury, only 135 patients having been reported by 1985. Our recent experience with six patients who underwent emergency surgery, has been documented. The results of treatment were excellent with complete recovery of function. The study recommends operative management as the treatment of choice.


[Crystallographic investigation of distraction callus (author's transl)].
Physical examination using electron diffraction and thermogravimetry was performed on the distraction callus of six metacarpal bones of sheep. Brushite was observed in this callus beside apatite, and the number of crystals found was less than in physiological nature bone. From the crystallographic point of view the distraction callus was found similar to the callus known in fracture healing.


G-Rh4 improves pancreatic β-cells dysfunction in vivo and in vitro by increased expression of Nrf2 and its target genes.
The aim of this study is to investigate the hypoglycemic mechanism of ginsenoside Rh4 (G-Rh4) in vivo and in vitro models. Our results showed that G-Rh4 markedly improved the symptoms of diabetes, normalized glucose metabolism, and promoted insulin secretion which contributed to attenuate symptoms of hyperglycemia in high-fat diet/streptozocin induced type 2 diabetes mellitus mice. This positive effect was associated with increased expression of Nrf2 by G-Rh4. Further results demonstrated that G-Rh4 promoted Nrf2 nucleus translocation as well as up-regulated the expression of HO-1, NQO1 and GCLC. Furthermore, we also found that G-Rh4 increased insulin secretion by activating the signal pathway of PDX-1, GLUT2 and GCK. More importantly, the protective effects of G-Rh4 on alloxan-induced upregulation of Nrf2 target gene and insulin secretion were abolished by Nrf2 knockdown. Finally, we explored the mechanism of G-Rh4 associated with Nrf2 activation and found that the Akt deficiency inhibited G-Rh4-mediated Nrf2 nuclear translocation. Altogether, we present evidence that G-Rh4 increased expression of Nrf2 and results in increased antioxidant gene, as well as a rise in insulin secretion in vivo and in vitro. Exploiting the Nrf2 pathway may show great potential as a therapeutic strategy to improve pancreatic β-cells dysfunction in the diabetic population.


Emergency surgery for complicated colorectal cancer. A two-decade trend analysis.
Emergency procedures for colorectal cancer have worse outcomes than elective resections. Temporal trends in emergency surgery are analyzed by comparing two decade-related series of colorectal cancer patients. The clinical data of 985 patients undergoing colorectal cancer surgery were collected during two decades (1975-1984 and 1995-2004). Rates of emergency surgery, operative mortality, 5-year cancer-related and overall survival were compared retrospectively. The rate of emergency surgery decreased from 81 out of 513 cases (16%) during 1975-1984 to 41 out of 471 cases (9%) during 1995-2004 (p = 0.005). Over the same time, the rate of curative resections in emergency increased from 46% (37/81 cases) to 76% (31/41 cases) (p < 0.001), while patient and tumor characteristics remained similar. Operative mortality after emergency procedures decreased from 14% (11 deaths) to 5% (2 deaths) and cancer-related survival increased from 21 to 42% (p = 0.03). However, when excluding palliative procedures, survival after emergency surgery increased from 52 to 58%, while after elective treatment it increased from 56 to 78% (p < 0.001). Frequency and operative mortality of emergency colorectal cancer surgery decreased substantially from 1975-1984 to 1995-2004. No significant improvement in long-term survival was observed when curative emergency resections only were considered. Further efforts are needed to reverse the diverging trend of long-term outcomes between emergency and elective curative procedures.


An effort to assess the relation between productivity loss costs and presenteeism at work.
This study assesses potential presenteeism costs and the association of these with a company's business figures. We conducted the questionnaire surveys in alternate years between 2003 and 2007 and linked them to sickness absence register data. Perceived work ability levels were assessed and converted into presenteeism days using the Presenteeism Scale tool. Sickness absence and presenteeism days were converted into monetary figures using median monthly salary information. The share of presenteeism costs was constant at about 1% of annual turnover and about 3.7% of personnel costs. The lowest annual presenteeism cost per employee was EUR 986 and the highest was EUR 1302. The lowest number of presenteeism days per employee in a year was 8.7 days and the highest number was 10.4 days. Estimated losses to a company due to sickness absences and presenteeism ranged from EUR 4.6 million to EUR 5.6 million annually. The potential presenteeism costs to the company and to Finnish society were vast. Presenteeism is a costly problem but more research is needed to reveal the connections between presenteeism and a company's turnover, personnel costs and profit.


Financialisation and income inequality: An investigation of the financial Kuznets curve hypothesis among developed and developing countries.
The Financial Kuznets Curve (FKC) is a variant of the renowned Kuznets Curve and a counterpart to the Environmental Kuznets Curve. In this paper, we examine the financial Kuznets curve hypothesis-based on annual data for 20 developed and developing countries-using the Phillips and Hansen (1990) fully modified ordinary least square (FMOLS) and the unobserved components model (UCM). The results correspond to the current divergence in the empirical literature and show support for the inverted U-shaped curve as well as the U-shaped curve, in more than half of the sample countries. The estimated turning points differ significantly across countries and depending on the measure of financialisation used. Overall, the findings of this research suggest that there is no uniform effect of financialisation on income inequality. The results vary according to the level of economic development, financial structure, and potentially other factors that have not been considered in the empirical analysis provided in this paper.


Oxidation of 3-hydroxykynurenine catalyzed by methemoglobin with hydrogen peroxide.
Methemoglobin (metHb) with H2O2 catalyzed the oxidation of 3-hydroxykynurenine (3-HKY) in the reaction mixture of metHb, 3-HKY, and H2O2. The spectrophotometric experiments suggest the following mechanism for the 3-HKY oxidation by metHb with H2O2. MetHb first reacts with H2O2 to form the ferryl complex of Hb. This species then oxidizes 3-HKY, while it returns to metHb. 3-HKY was more reactive with the ferryl complex than glutathione but less reactive than ascorbic acid. Scavengers of the hydroxyl radical, dimethyl sulfoxide and ethanol, scarcely inhibited the 3-HKY oxidation by metHb with H2O2. Desferrioxamine, a metal chelator, hardly suppressed the 3-HKY oxidation. These results indicate that the hydroxyl radical is not involved in the 3-HKY oxidation by metHb with H2O2.


The financial burden of out of pocket payments on medicines among households in Ethiopia: analysis of trends and contributing factors.
In Ethiopia, out-of-pocket (OOP) payment is the key means of healthcare financing, and expenses on medicines are a crucial component of such payment. This study aims to investigate the financial implications of OOP payments on medicines for Ethiopian households. The study involved a secondary data analysis of the national household consumption and expenditure surveys of 2010/11 and 2015/16. The "capacity-to-pay" method was used to calculate catastrophic OOP medicine expenditures. The extent of economic status related to catastrophic medicine payment inequity was calculated using concentration index estimation. The impoverishment consequences of OOP payment on medicine were estimated using poverty headcount and poverty gap analysis methods. Logistic regression models were used to identify the variables that predict catastrophic medicine payments. Medicines accounted for the majority of healthcare spending (> 65%) across the surveys. From 2010 to 2016, the total percentage of households facing catastrophic medicine payments decreased from 1% to 0.73%. However, the actual number of people expected to have experienced catastrophic medicine payments increased from 399,174 to 401,519 people. Payment for medicines pushed 11,132 households into poverty in 2015/16. The majority of disparities were explained by economic status, place of residence, and type of health services. OOP payment on medicine accounted for the majority of total health expenses in Ethiopia. A high medicine OOP payment continued to push households into catastrophic payments and impoverishment. Household seeking inpatient care, those with lower economic status and urban residents were among the most affected. Hence, innovative approaches to improve the supply of medicines in public facilities especially those in urban settings and risk protection mechanisms for medicine expenditures particularly for inpatient care are recommended.


2019 Update on Primary Immunodeficiency Disorders by the International Union of Immunological Societies.
International Union of Immunological Societies working group recently updated the human inborn errors of immunity. This classification includes 65 new disorders that have been added since the last classification in 2018. This article highlights the important aspects of new classification for the benefit of general pediatricians.


Comparison of interpolation methods of predominant cardiomyocyte orientation from in vivo and ex vivo cardiac diffusion tensor imaging data.
Cardiac electrophysiology and cardiac mechanics both depend on the average cardiomyocyte long-axis orientation. In the realm of personalized medicine, knowledge of the patient-specific changes in cardiac microstructure plays a crucial role. Patient-specific computational modelling has emerged as a tool to better understand disease progression. In vivo cardiac diffusion tensor imaging (cDTI) is a vital tool to non-destructively measure the average cardiomyocyte long-axis orientation in the heart. However, cDTI suffers from long scan times, rendering volumetric, high-resolution acquisitions challenging. Consequently, interpolation techniques are needed to populate bio-mechanical models with patient-specific average cardiomyocyte long-axis orientations. In this work, we compare five interpolation techniques applied to in vivo and ex vivo porcine input data. We compare two tensor interpolation approaches, one rule-based approximation, and two data-driven, low-rank models. We demonstrate the advantage of tensor interpolation techniques, resulting in lower interpolation errors than do low-rank models and rule-based methods adapted to cDTI data. In an ex vivo comparison, we study the influence of three imaging parameters that can be traded off against acquisition time: in-plane resolution, signal to noise ratio, and number of acquired short-axis imaging slices.