Intact retrieval inhibition in children's episodic recall.
Young children are assumed to be inefficient inhibitors in a number of cognitive tasks. In two experiments, we examined whether such deficits extend to children's episodic recall. We used two inhibition paradigms: retrieval-induced forgetting, the detrimental effect of retrieval practice with a subset of learned items on recall of the unpracticed items, and part-list cuing, the detrimental effect of the presentation of a subset of learned items on recall of the remaining items. In both experiments, the inhibitory effects were compared across three age groups: first or second graders, fourth graders, and young adults. The two children groups showed the same amounts of retrieval-induced forgetting and part-list cuing as the adult group, pointing to intact retrieval inhibition in young children's episodic recall. These results parallel very recent results on older adults' episodic recall, suggesting that both retrieval-induced forgetting and part-list cuing develop early in life and remain intact for the greater part of the lifespan.


The Metabolic Underpinnings of Ferroptosis.
Acute or chronic cellular stress resulting from aberrant metabolic and biochemical processes may trigger a pervasive non-apoptotic form of cell death, generally known as ferroptosis. Ferroptosis is unique among the different cell death modalities, as it has been mostly linked to pathophysiological conditions and because several metabolic pathways, such as (seleno)thiol metabolism, fatty acid metabolism, iron handling, mevalonate pathway, and mitochondrial respiration, directly impinge on the cells' sensitivity toward lipid peroxidation and ferroptosis. Additionally, key cellular redox systems, such as selenium-dependent glutathione peroxidase 4 and the NAD(P)H/ferroptosis suppressor protein-1/ubiquinone axis, are at play that constantly surveil and neutralize oxidative damage to cellular membranes. Since this form of cell death emerges to be the root cause of a number of diseases and since it offers various pharmacologically tractable nodes for therapeutic intervention, there has been overwhelming interest in the last few years aiming for a better molecular understanding of the ferroptotic death process.


Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia.
The results in this study confirm and expand previous reports that ischemia-modified albumin (IMA) is an early marker of ischemia in the setting of percutaneous coronary intervention (PCI). We observed that IMA levels are related to the number of inflations, inflation pressure, and duration of inflations. It is therefore likely that IMA reflects the magnitude and duration of ischemia induced during PCI.


Aedeagal divergence in sympatric populations of two sibling species of cactophilic Drosophila (Diptera: Drosophilidae): evidence of character displacement?
Aedeagal morphology of two sibling cactophilic species, Drosophila buzzatii Patterson & Wheeler and Drosophila koepferae Fontdevila & Wasserman, was analyzed in nine allopatric and three sympatric locations throughout South America. Morphological differences were detected for both aedeagus size and shape between sympatric and allopatric populations of D. buzzatii, despite the significant variability within both groups. Populations of D. buzzatii sympatric with D. koepferae displayed smaller aedeagus than the allopatric ones as well as more differentiated aedeagus shape. The shape differences were non-allometric and mainly consisted in a change of curvature of the dorsal margin of the aedeagus being more pronounced in males from populations sympatric with D. koepferae. It is concluded that aedeagal morphology presented some degree of character displacement in both size and shape in populations of D. buzzatii in sympatry with D. koepferae. These results might suggest the existence of mechanisms of interspecific recognition and hybridization prevention between these species that include the morphology of the male genitalia.


Investigating Male Presence at Antenatal and Choice of Place for Child Delivery in Ghana.
Male involvement in maternal health was introduced to improve and sustain maternal and child health in Ghana. The study utilized the 2014 Ghana Demographic and Health Survey data to investigate the relationship between male presence at antenatal and choice of place of childbirth among 1,167 males, 15-59 years. Descriptive and analytical statistical techniques were applied to the data. The binary logistic regression shows no association between male presence at antenatal and place of delivery (OR = 1.197; 95% CI = 0.808-1.773). However, age (OR = 2.647; 95% CI = 1.221-5.736, OR = 3.046; 95% CI = 1.345-6.896, OR = 3.513; 95% CI = 1.478-8.345), level of education (OR = 4.478; 95% CI = 1.412-14.1990, religion (OR = 0.473; 95% CI = 0.237-0.946), ethnicity (OR = 0.400; 95% CI = 0.182-0.877, OR = 0.425; 95% CI 0.194-0.935), marital status (OR = 5.682; 95% CI = 2.093-15.421, OR = 5.669; 95% CI = 1.448-22.198), place of residence (OR = 7.272; 95% CI = 4.231-12.499), and region of residence (OR = 11.515; 95% CI = 2.785-47.618) of males were found associated with health facility based delivery. Regarding policy to promote institutional delivery among women, these socio-demographic factors identified should be considered.


Relationship between tubal function, craniofacial morphology and disorder of deglutition.
26 children without hearing impairment have been examined by otolaryngologists and orthodontists. According to the tubal function test in a pressure chamber they were classifed into a group with good and poor tubal function. The E.N.T. examination was unconclusive for a possible relationship between rhinological findings, mode of breathing, sinusitis, size of tonsils, nasal airway resistance and tubal function. Adenoids proved to be a mechanical impairment for active tubal function as stated by many authors. The cephalometric analysis of lateral head films combined with a static and dynamic-functional evaluation of tongue posture revealed significant differences between children with good and poor tubal function. Subjects with a vertical craniofacial growth pattern seem to be predisposed for poor tubal function. Analysing static tongue posture in children with poor tubal function the tongue lies more retracted in a backward position. The back of the tongue is flattened in relation to the palatal arch. In children with good tubal function there is a much closer contact between the back of tongue and the hard palate. Subjects with poor tubal function have an increased incidence of abnormal deglutition combined with tongue-thrust, teeth-apart swallowing, lack of sealing off the anterior oral cavity and contraction of the circumoral musculature. In children with good tubal function one can find the somatic type of swallowing that means no contractions of the circumoral muscles, no tongue-thrust during deglutition but contact of the molars and contraction of the masseter muscle.


Chronic recurrent Goodpasture's syndrome.
A distinctive case of Goodpasture's syndrome characterized by multiple recurrences occurring over 14 years was observed. Each recurrence followed cessation of prednisone and azathioprine therapy, and reinstitution of this therapy resulted in prompt remission. Initially, both glomerulonephritis and hemoptysis were prominent clinical features. In recent years, hemoptysis has been the predominant clinical problem. This and other cases suggest that Goodpasture's syndrome may comprise a wider disease spectrum than generally appreciated.


[Effect of a large scale community-based distribution of artemether-lumefantrine on its therapeutic efficacy among children living in a rural area of Burkina Faso].
This study aimed to assess the effect of an integrated community case management of malaria and pneumonia programme (iCCMmp) on the efficacy of artemether-lumefantrine (AL). Thus, we carried out two open label and unique centre clinical trials, before and after the iCCMmp, on the therapeutic efficacy of AL. A total of 210 children aged 6-59 months, were included in the study, 105 before and 105 after the iCCMmp. The adequate clinical and parasitological response was 90.5% and 86.7% respectively before and after the iCCMmp (p value = 0.516). Our findings reported no effect of iCCMmp on the therapeutic efficacy of the AL.


Obstructive hydrocephalus due to a giant aneurysm of the internal carotid bifurcation.
A rare case of obstructive hydrocephalus associated with a giant aneurysm of the internal carotid artery is presented. The giant aneurysm, which was located in the prepontine cistern, was initially thought to be of basilar artery origin. Cerebral computed angiotomography had the most diagnostic value in disclosing the partially thrombosed giant aneurysm and its relationship with the surrounding arteries. After undergoing a ventriculoperitoneal shunt operation, the patient's clinical symptoms markedly improved.


Smoking in a popular German television crime series 1985-2004.
We aimed to study the prevalence of smoking in a popular German television crime series ("A case for two"), which has been internationally distributed in 59 countries, over a 20 year period. A content analysis of five randomly selected episodes per year of one crime series for the period 1985 to 2004 (100 episodes in total) was conducted. Smoking status of all major and minor series characters was assessed. Each episode was coded regarding one or more smoking occurrences, defined as active smoking or handling with tobacco products by a character. 97% of the episodes portrayed tobacco use with a median of 5 occurrences per episode. The series contained 1013 major and minor characters; the overall smoking prevalence was 17.1%. A downward trend in smoking occurrences and prevalence of major and minor characters who smoke from 1985 was followed by an increase in the last decade. Tobacco use is frequently portrayed in a popular prime-time German crime series, following a U curve over a 20 year period.


Acute spontaneous subdural hematoma of arterial origin.
Acute spontaneous subdural hematoma of arterial origin is very rare. We have encountered two such cases and verified the arterial origin of the bleeding at operation. Both patients had no history of head trauma and developed progressive neurological deficits, becoming comatose. The source of bleeding was identified as a cortical artery located on the temporal lobe near the Sylvian region. This type of lesion is reviewed in the literature and the etiology is discussed.


Mechanistic study of cobalt(I)-catalyzed asymmetric coupling of ethylene and enynes to functionalized cyclobutanes.
Density functional theory (DFT) calculations have been performed to gain insight into the reaction mechanism of the Co(I)-catalyzed asymmetric [2 + 2] cycloaddition reaction of enyne 1a with ethylene 2 to give the functionalized cyclobutene E-4a possessing a chiral, all-carbon quaternary center in the ring framework (Science, 361, 68-72). This study reveals that the whole catalysis can be characterized via three stages: (i) oxidative dimerization followed by reductive elimination gives the intermediate IM3, (ii) the alkenyl-Co(III) metallacycloheptene IM6 formation with the addition of another equivalent ethylene via an oxidative dimerization process, (iii) β-Hydrogen elimination and reductive elimination from IM6 to result in the final product E-4a and regenerate the active speices IM1 for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible for experimental realization under mild conditions, and the formation of the alkenyl-Co(III) metallacycloheptene IM6, with a barrier of 27.2 kcal mol-1 (i.e., IM2 → TS4), should be the rate-determining step (RDS) during the whole catalysis. In addition, the origins of enantioselectivity and regioselectivity of the product are discussed.


Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model.
Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process. Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 microg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 microg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured. Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.


Microbial Transport, Survival, and Succession in a Sequence of Buried Sediments.
Abstract Two chronosequences of unsaturated, buried loess sediments, ranging in age from <10,000 years to >1 million years, were investigated to reconstruct patterns of microbial ecological succession that have occurred since sediment burial. The relative importance of microbial transport and survival to succession was inferred from sediment ages, porewater ages, patterns of abundance (measured by direct counts, counts of culturable cells, and total phospholipid fatty acids), activities (measured by radiotracer and enzyme assays), and community composition (measured by phospholipid fatty acid patterns and Biolog substrate usage). Core samples were collected at two sites 40 km apart in the Palouse region of eastern Washington State, near the towns of Washtucna and Winona. The Washtucna site was flooded multiple times during the Pleistocene by glacial outburst floods; the Winona site elevation is above flood stage. Sediments at the Washtucna site were collected from near surface to 14.9 m depth, where the sediment age was approximately 250 ka and the porewater age was 3700 years; sample intervals at the Winona site ranged from near surface to 38 m (sediment age: approximately 1 Ma; porewater age: 1200 years). Microbial abundance and activities declined with depth at both sites; however, even the deepest, oldest sediments showed evidence of viable microorganisms. Same-age sediments had equal quantities of microorganisms, but different community types. Differences in community makeup between the two sites can be attributed to differences in groundwater recharge and paleoflooding. Estimates of the microbial community age can be constrained by porewater and sediment ages. In the shallower sediments (<9 m at Washtucna, <12 m at Winona), the microbial communities are likely similar in age to the groundwater; thus, microbial succession has been influenced by recent transport of microorganisms from the surface. In the deeper sediments, the populations may be considerably older than the porewater ages, since microbial transport is severely restricted in unsaturated sediments. This is particularly true at the Winona site, which was never flooded.


WholeCellViz: data visualization for whole-cell models.
Whole-cell models promise to accelerate biomedical science and engineering. However, discovering new biology from whole-cell models and other high-throughput technologies requires novel tools for exploring and analyzing complex, high-dimensional data. We developed WholeCellViz, a web-based software program for visually exploring and analyzing whole-cell simulations. WholeCellViz provides 14 animated visualizations, including metabolic and chromosome maps. These visualizations help researchers analyze model predictions by displaying predictions in their biological context. Furthermore, WholeCellViz enables researchers to compare predictions within and across simulations by allowing users to simultaneously display multiple visualizations. WholeCellViz was designed to facilitate exploration, analysis, and communication of whole-cell model data. Taken together, WholeCellViz helps researchers use whole-cell model simulations to drive advances in biology and bioengineering.


The positive frequency-dependent electrophysiological effects of the IKur inhibitor XEN-D0103 are desirable for the treatment of atrial fibrillation.
Selective inhibitors of Kv1.5 channels are being developed for the treatment of atrial fibrillation (AF). The purpose of this study was to investigate the effects of the highly selective Kv1.5 inhibitor XEN-D0103 on human atrial action potentials (APs) at high excitation rates and to assess safety. Intracellular APs (stimulation rates 1-5 Hz) were measured in right atrial trabeculae from patients in sinus rhythm (SR), chronic AF (cAF; AF of >6 months duration), and paroxysmal AF (pAF). The safety and tolerability of XEN-D0103 were tested in a double-blind, randomized, placebo-controlled phase 1 study. Depending on its concentration, XEN-D0103 elevated the plateau potential. At 1 Hz, XEN-D0103 (3 µM) shortened action potential duration at 90% repolarization (APD90) and effective refractory period (ERP) in SR preparations, but prolonged these parameters in cAF preparations. In SR and pAF preparations, the shortening effects on APD90 and ERP turned into prolongation at high rates. In cAF trabeculae, XEN-D0103 prolonged APD90 and ERP at 2 and 3 Hz. At high rates, more SR and pAF preparations failed to capture excitation in the presence of the drug than in its absence. XEN-D0103 (10 µM) did not significantly affect human ventricular APs. Even with plasma concentrations reaching 7000 ng/mL, XEN-D0103 did not increase ∆∆QTcF (QT interval corrected by the Fridericia formula) in the analysis of electrocardiograms of healthy volunteers, and no subjects receiving an active treatment had a QT or QTcF interval >450 ms, or increase in QTcF from baseline >30 ms. APD prolongation and suppression of APs by XEN-D0103 at high stimulation rates in SR and pAF tissue, but not cAF, could be of therapeutic benefit for reducing AF burden. This concept needs to be confirmed in clinical trials.


The hexa- and pentapeptide extension of proalbumin: lack of peptide-induced histamine-releasing activity by this hexapeptide in rat mast cells and human leucocytes.
It is well documented that small basic peptides with lipophilic counterparts induce non-cytolytic histamine release particularly from rat peritoneal mast cells, and to a lesser extent from human leukocytes. Since pro-albumin hexapeptide with its lipophilic core also exhibits a high percentage of basic amino acid residues, it was thought valid to investigate its potential histamine releasing activity using the above-mentioned cell systems. Results show that the peptide failed in both cell types to induce histamine release, or to inhibit IgE mediated or anaphylatoxin induced histamine release up to concentrations of 10(-4) M.


A review on recent developments in the adsorption of surfactants from wastewater.
The pollution of the world's water resources is a growing issue which requires remediation. Surfactants used in many domestic and industrial applications are one of the emerging contaminants that require immediate attention. Treating water contaminated with surfactants using adsorption provides better performance when compared to other techniques. A variety of materials have been developed for adsorbing surfactants. Activated carbon is the most suitable adsorbent for removing surfactants but is expensive to synthesize and difficult to regenerate. Therefore, a variety of new adsorbents such as zeolites, nanomaterials, resins, biomaterials and clays have been developed as alternatives. The developed adsorbents are promising but considerable research is still required to develop highly efficient, economical, environment friendly and sustainable adsorbents to replace activated carbon. This paper critically reviews the characteristics of adsorbents, the performance of adsorbents, kinetics, isotherms and thermodynamics, mechanisms of adsorption, regeneration of adsorbents and future perspectives in the adsorption of surfactants. Developing novel adsorbents, testing adsorbents in real wastewaters and recycling the adsorbents are required in future studies in the removal of surfactants.


Melagatran, a direct thrombin inhibitor, but not edoxaban, a direct factor Xa inhibitor, nor heparin aggravates tissue factor-induced hypercoagulation in rats.
There are concerns that some anticoagulants can paradoxically increase thrombogenesis under certain circumstances. We have shown that low-dose administration of a direct thrombin inhibitor, melagatran, significantly worsens the coagulation status induced by tissue factor injection in rats. We compared the effect of inhibition of thrombin and factor Xa for their potential to aggravate tissue factor-induced coagulation in rats. Hypercoagulation was induced by the injection of 2.8 U/kg tissue factor after administration of melagatran, heparin and edoxaban in rats. Blood samples were collected 10min after tissue factor injection. Platelet numbers, thrombin-antithrombin complex concentrations and plasma compound concentrations were measured. Though a high dose of melagatran (1mg/kg, i.v.) suppressed platelet consumption and thrombin-antithrombin complex generation induced by tissue factor, lower doses of melagatran (0.01, 0.03 and 0.1mg/kg, i.v.) significantly enhanced platelet consumption and thrombin-antithrombin complex generation. In addition, although melagatran (3mg/kg, i.v.) improved coagulation status when tissue factor was given 5min after the drug administration, and 2, 4 and 8h after melagatran dosing, it deteriorated coagulation status. These results were well explained by the plasma melagatran concentration. Low concentrations (15-234ng/ml) of melagatran aggravated coagulation status whereas it was mended by high concentrations (1190ng/ml or more) of the compound. In contrast, edoxaban and heparin did not show any exacerbation under these examination conditions. These results show that subtherapeutic concentrations of melagatran are associated with coagulation pathway activation, whereas factor Xa inhibition with edoxaban has a low risk of paradoxical hypercoagulation.


Planned preoperative irradiation in the management of clinical stage B2-C (T3) bladder carcinoma.
In recent years the role of planned preoperative irradiation in the management of clinical Stage B2-C (T3) bladder cancer has been questioned by a number of investigators. Much of the confusion regarding the efficacy of combined therapy results from studies that compare the results of treatment of pathological Stage B2-C patients treated by cystectomy alone versus clinical Stage B2-C patients treated by preoperative irradiation plus cystectomy. Such comparisons are biased because of (1) the exclusion of a large number of Stage D patients from cystectomy-alone series and their inclusion in preoperative irradiation plus cystectomy series and (2) the inclusion in the cystectomy-alone series of patients whose clinical stages were less than or equal to T2. The purpose of this paper is to compare the results of treatment in patients with clinical Stage B2-C bladder carcinoma following radical cystectomy alone versus preoperative irradiation plus cystectomy. This article reviews the rationale for administering preoperative irradiation, the effect of preoperative irradiation on the pathological specimen (including down-staging, the effect on regional lymph nodes, and radioresponsiveness according to tumor configuration, i.e., papillary vs. solid), the impact of preoperative irradiation on pelvic recurrence and 5-year survival, and the effect of preoperative irradiation on operative and postoperative complications. This paper cites all known literature on the subject in the English language. Data comparing 5-year survival results between radical cystectomy alone versus preoperative irradiation plus cystectomy are analyzed in three different ways: (a) retrospective comparisons of historical results, (b) review of the results of 6 randomized trials, and (c) comparison of concomitantly treated "modern-day" (1960-1980) series treated by either radical cystectomy alone versus preoperative irradiation plus cystectomy in 1185 patients. Preoperative results are also analyzed according to dose level (2000 rad versus 4000 rad versus 4500-5000 rad). The data presented indicate that the addition of preoperative irradiation to cystectomy for clinical Stage B2-C (T3) bladder cancer adds approximately 15 to 20 percentage points to the 5-year survival, leading to a survival figure that is approximately half-again that achieved by cystectomy alone.


Uncommon occurrence of fluoroquinolone resistance-associated alterations in GyrA and ParC in clinical strains of Chlamydia trachomatis.
Twenty-three clinical strains of Chlamydia trachomatis were isolated from men with chlamydial nongonococcal urethritis and examined for the presence of fluoroquinolone resistance-associated alterations in GyrA and ParC. The minimum inhibitory concentrations (MICs) of fluoroquinolones, erythromycin, and tetracycline were determined for 6 of the 23 isolates. In 12 of the 23 isolates, a single amino-acid change was found in GyrA, and in 1 isolate, two amino acids were changed. In all 23 isolates, an Arg-83-to-Gly substitution was observed in ParC, and in 3 isolates, an additional amino-acid change was found. Some changes occurred within the quinolone resistance-determining regions (QRDRs) of GyrA and ParC, but not at positions critical for fluoroquinolone resistance. Of the 6 isolates for which MICs of the agents were determined, 1 isolate had a Cys-66 --> Arg substitution in GyrA, and all had the Arg-83 --> Gly substitution in ParC. However, all 6 isolates were susceptible to fluoroquinolones. First-pass urine specimens were obtained from two men who were positive for C. trachomatis after levofloxacin treatment, and the gyrA and parC genes of C. trachomatis were amplified by polymerase chain reaction (PCR) and examined for fluoroquinolone resistance-associated mutations. Pre- and post-treatment C. trachomatis persisting in each of them had identical amino-acid sequences in the QRDR of GyrA and ParC. Further, the substitutions found in GyrA and ParC were not located at positions critical for fluoroquinolone resistance. The present study suggests that fluoroquinolone resistance-associated alterations in GyrA and ParC may be uncommon in clinical strains of C. trachomatis.


New horizons of adenosinetriphosphate energetics arising from interaction with magnesium cofactor.
MD DFT:B3LYP (6-31G** basis set, T = 310 K) method is used to study interactions [singlet (S) and triplet (T) reaction paths] between adenosinetriphosphate, ATP(4-), and [Mg(H(2)O)(6)](2+) in water environment, modeled with 78 water molecules. Computations reveal the appearance of low and high-energy states (stable, quasi-stable, and unstable), assigned to different spin symmetries. At the initial stage of interaction, ATP donates a part of its negative charge to the Mg complex making the Mg slightly charged. As a result, the original octahedral Mg complex loses two (S state) or four (T state) water molecules. Moving along S or T potential energy surfaces (PESs), Mg(H(2)O)(4 )or Mg(H(2)O)(2) display different ways of complexation with ATP. S path favors the formation of a stable chelate with the O1-O2 fragment of ATP triphosphate tail, whereas T path favors producing a single-bonded complex with the O2. The latter, being unstable, undergoes a further conversion into a spin-separated complex, also unstable, and two metastable S complexes, which finally arise in two stable, low-energy and high-energy, chelates. The spin-separated complex experiences rapid decomposition resulting in the production of a highly reactive adenosinemonophosphate ion-radical *AMP, early observed in the CIDNP experiment (Tulub 2006). Biological consequences of the findings are discussed.


Intrapleural low-dose silver nitrate elicits more pleural inflammation and less systemic inflammation than low-dose talc.
Several systemic effects have been described after talc pleurodesis. The aim of this study was to assess the systemic response induced by low, nonpleurodesis-inducing doses of talc and silver nitrate in an experimental model in rabbits. Groups of six rabbits were injected intrapleurally with talc, 100 mg/kg or 400 mg/kg, and silver nitrate, 0.1% or 0.5%. After 6, 24, or 48 h, samples of blood and pleural fluid were collected and assayed for leukocytes, percentage of neutrophils, lactate dehydrogenase, interleukin-8, and vascular endothelial growth factor (VEGF) levels. Preinjection blood samples were used as normal blood controls. Silver nitrate 0.1% induced a more intense pleural inflammation than that produced by talc 100 mg/kg. In contrast, talc 100 mg/kg induced a more pronounced acute systemic response with higher values of WBCs and neutrophils, whereas silver nitrate 0.1% produced no significant increases in leukocytes or neutrophils. The serum interleukin-8 and VEGF levels increased in all groups, and decreased with time only in the silver nitrate 0.1% group. The highest serum VEGF levels were observed in the talc 100 mg/kg group. In conclusion, 0.1% silver nitrate produced an intense pleural inflammatory response with a less evident systemic response in comparison to 0.5% silver nitrate and talc 100 mg/kg or 400 mg/kg.


O-GlcNAc modification of transcription factors, glucose sensing and glucotoxicity.
Regulation of proteins by O-GlcNAc modification is becoming a major area of research. This reversible modification depends on glucose concentrations and, therefore, constitutes a powerful mechanism to regulate protein activities according to glucose availability. Its importance in glucose-dependent gene transcription is underlined by its role in pancreatic insulin biosynthesis (through PDX-1 and NeuroD1 O-GlcNAc modifications) and leptin synthesis in adipose tissue (through Sp1 O-GlcNAc modification). Moreover, in chronic hyperglycaemia, O-GlcNAc modifications of Sp1, p53 and NFkappaB participate in glucotoxicity, resulting in cardiovascular and renal alterations. The recent discovery by two independent groups that FoxO1 is regulated by O-GlcNAc modification provides a potential mechanism by which hyperglycaemia promotes gluconeogenesis and worsening of glucose intolerance, opening new research perspectives in the field.


Transformed Xenopus embryos as a transient expression system to analyze gene expression at the midblastula transition.
The onset of transcriptional activity during embryogenesis in Xenopus laevis is at the 4000- to 8000-cell stage (stage 8-8.5) and is referred to as the midblastula transition (MBT). Most exogenous circular DNA that is microinjected into the fertilized egg also is expressed at the MBT. The transformed Xenopus embryo at these early stages was used as a transient expression system in order to determine the effects of (1) promoter strength, (2) physical conformation, (3) degree of replication, and (4) a regulatory molecule on the expression of an injected gene coding for chloramphenicol acetyl transferase. This gene linked to a relatively strong promoter (SV40 early promoter -pSV2CAT), a weak promoter (adenovirus early promoter -pE3CAT), or in circular or linear form is expressed at stage 8-8.5 following injection into fertilized eggs. pE3CAT coinjected with the E1a protein (enhances the transcription of the E3 promoter) is also expressed at stage 8.5, but expression is enhanced 2-7.6 fold. These data suggest that the inhibition of transcription prior to the MBT could not be perturbed by either the presence of different promoters or a positive regulatory molecule such as the E1a protein.


p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE-/- mice.
p-Cresyl sulfate (PCS) is a risk factor of cardiovascular disease in patients with chronic kidney disease. Here we tested whether serum PCS levels were related to the rate and evolution of carotid atherosclerosis in hemodialysis patients and identified a potential mechanism. A total of 200 hemodialysis patients were categorized as with or without carotid atherosclerotic plaque and followed for 5 years. Serum PCS levels were found to be higher in patients with than without carotid atherosclerotic plaque and positively correlated with increased total plaque area during follow-up. Multiple logistic regression and mixed effects model analyses showed that serum PCS levels were independently associated with the incidence and progression of carotid atherosclerotic plaque. PCS induced inflammatory factor and adhesion molecule expression in endothelial cells and macrophages. In addition, PCS triggered monocyte-endothelial cell interaction in vitro and in vivo through increased production of reactive oxygen species. Compared with controls, increase of PCS levels produced by gavage promoted atherogenesis in 5/6-nephrectomized apoE-/- mice; a process attenuated by NADPH oxidase inhibitors. Thus, increased serum PCS levels are associated with the occurrence and progression of carotid atherosclerosis in hemodialysis patients and promote atherogenesis through increased reactive oxygen species production.


The misleading choice for safer births in Brazilian's most developed region: a cross-sectional study.
To analyze the Cesarean Section (CS) rate in Brazilian women according to category of health insurance and individual characteristics associated with the mode of delivery. A cross-sectional study was performed in three maternity services (one public tertiary referral center, one maternity service for both public and private care, and one private maternity service) in Campinas city, Brazil. Eligibility criteria were: inpatient during the immediate postpartum period, hospital birth, single pregnancy, and live newborn. Sociodemographic and anthropometric data, reproductive history, pregnancy planning, and prenatal care information was obtained from participants. Comorbidities, type of birth, and newborn data were collected from medical records. The mode of delivery was categorized as either CS or vaginal delivery. A total of 1276 women were included in this study. The overall CS rate was 57.5%. CS rates were 41.6, 54.8, and 90.1% for public, mixed (public and private), and private maternity services, respectively. Mean age was higher in women who had a CS (28.0 ± 6.0 years versus 25.9 ± 6.5 years, p < .0001) as was the mean Body Mass Index (25.2 ± 5.3 kg/m2 versus 23.8 ± 4.5 kg/m2, p < .0001). CS was related to higher education, employment, white skin color, planned pregnancy, antenatal care in a private service, and primiparity. The overall CS rate was high (greater than 50%); in the private service, almost all participants had a CS delivery (90.1%). Better socioeconomic conditions and primiparity were associated with higher CS rates in Brazil. Political pressure for the management of unnecessary CSs is vital in Brazil. Together with the provision of real incentives for normal deliveries in public and, most importantly, private services.


Glycol methacrylate embedding of bone and cartilage for light microscopic staining.
A method is described for embedding bone and cartilage in glycol methacrylate (GMA) for light microscopy. Dehydration-infiltration of the hard tissue is with aqueous GMA solutions minimizing solvent and dehydration artefact, and polymerization is by UV light in the cold to minimize thermal damage. Over fifty stains, enzyme localizations and related histochemical methods for 0.5-3.0 micrometer thick sections of GMA embedded tissue are listed. The increased resolution plus the localization of cellular and extracellular chemical moieties is now easier and more accurate providing an improved method for the study of the musculo-skeletal system by light microscopy histochemistry.


Capillary hemangioma of the male urethra: case report with literature review.
The seventeenth case of hemangioma of the urethra is reported. A review of the literature supports our own experience that this growth tends to recur locally. It is our opinion that an initial wide resection should be performed. The margins of the removed lesion must be uninvolved or recurrence is almost certain.


Determination of tetramethylenedisulfotetramine in human urine with gas chromatograph-flame thermionic detection coupling with direct immersed solid-phase micro-extraction.
An analytical method for determination of tetramethylenedisulfotetramine (tetramine) in human urine by gas chromatography-flame thermionic detection (GC-FTD) coupling with a direct immersed solid-phase micro-extraction (DI-SPME) was developed. The enrichment effects of three fiber coatings of SPME for tetramine were compared. Results showed that the enrichment effect of polar 85 microm polyacrylate (PA) coating was better than that of apolar 100 and 7 microm polydimethylsiloxane (PDMS) coatings. Other experimental parameters, such as ionic strength, volume, temperature of sample solution and time for extraction, time and temperature for desorption, were also optimized. The correlation coefficient of the calibration curve was 0.9998 in the range of 0.082-41.0 ng/mL for tetramine. The limit of quantitation of tetramine in urine was 0.082 ng/mL. In this method, the sample pretreatment is simple and convenient. As a monitoring means, it has been successfully applied to detection of tetramine toxicosis in criminal cases, as well as clinical therapy of poisoned sufferer.


Synthesis and antibacterial in vitro activity of novel analogues of nematophin.
The synthesis and in vitro antibacterial activity of new derivatives and analogues of nematophin are described. It was shown that the unsubstituted amide NH-group is essential for bioactivity. Alkyl- or arylsubstitution at the 1-position results in a distinct increase of antibacterial activity. Addition of protein (blood or serum) to the culture media reduces the inhibitory activity on bacteria.


Morphine-induced immune alterations in vivo.
The high incidence of human immunodeficiency virus (HIV) seropositivity among drug abusers prompted us to examine in an animal model the effects of morphine on aspects of the immune system that may be specifically related to HIV infection. We now report a robust, sustained elevation in the ratio of CD4+/CD8+ cells in the spleen and thymus of mice chronically treated with morphine. Since CD4+ cells have been reported to be target cells for HIV, these alterations, in concert with a marked cellular atrophy that appears to be restricted to organs of the immune system, suggest that opiates may serve as cofactors in altering the immune status of the host and thus contribute to the increased susceptibility to HIV infection and eventual development of AIDS in opiate abusers.


Inference in conditioned dynamics through causality restoration.
Estimating observables from conditioned dynamics is typically computationally hard. While obtaining independent samples efficiently from unconditioned dynamics is usually feasible, most of them do not satisfy the imposed conditions and must be discarded. On the other hand, conditioning breaks the causal properties of the dynamics, which ultimately renders the sampling of the conditioned dynamics non-trivial and inefficient. In this work, a Causal Variational Approach is proposed, as an approximate method to generate independent samples from a conditioned distribution. The procedure relies on learning the parameters of a generalized dynamical model that optimally describes the conditioned distribution in a variational sense. The outcome is an effective and unconditioned dynamical model from which one can trivially obtain independent samples, effectively restoring the causality of the conditioned dynamics. The consequences are twofold: the method allows one to efficiently compute observables from the conditioned dynamics by averaging over independent samples; moreover, it provides an effective unconditioned distribution that is easy to interpret. This approximation can be applied virtually to any dynamics. The application of the method to epidemic inference is discussed in detail. The results of direct comparison with state-of-the-art inference methods, including the soft-margin approach and mean-field methods, are promising.


Identification of the Active Sites on Metallic MoO2-x Nano-Sea-Urchin for Atmospheric CO2 Photoreduction Under UV, Visible, and Near-Infrared Light Illumination.
We report an oxygen vacancy (Vo )-rich metallic MoO2-x nano-sea-urchin with partially occupied band, which exhibits super CO2 (even directly from the air) photoreduction performance under UV, visible and near-infrared (NIR) light illumination. The Vo -rich MoO2-x nano-sea-urchin displays a CH4 evolution rate of 12.2 and 5.8 μmol gcatalyst -1 h-1 under full spectrum and NIR light illumination in concentrated CO2 , which is ca. 7- and 10-fold higher than the Vo -poor MoO2-x , respectively. More interestingly, the as-developed Vo -rich MoO2-x nano-sea-urchin can even reduce CO2 directly from the air with a CO evolution rate of 6.5 μmol gcatalyst -1 h-1 under NIR light illumination. Experiments together with theoretical calculations demonstrate that the oxygen vacancy in MoO2-x can facilitate CO2 adsorption/activation to generate *COOH as well as the subsequent protonation of *CO towards the formation of CH4 because of the formation of a highly stable Mo-C-O-Mo intermediate.


Diagnostic challenges and case management of the first imported case of Plasmodium knowlesi in Sri Lanka.
Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider. Microscopy findings were suspicious of P. knowlesi infection as the smears showed parasite stages similar to both Plasmodium malariae and Plasmodium falciparum. Nested PCR at AMC confirmed Plasmodium genus, but not the species. In the absence of species confirmation, the patient was treated as a case of P. falciparum. The presence of P. knowlesi was later confirmed by a semi-nested PCR assay performed at the Environmental Health Institute, National Environmental Agency in Singapore. The parasite strain was also characterized by sequencing the circumsporozoite gene. Extensive case investigation including parasitological and entomological surveillance was carried out. Plasmodium knowlesi should be suspected in patients returning from countries in the South Asian region where the parasite is prevalent and when blood smear results are inconclusive.


Two cases of agenesis of the vermis of cerebellum, with fusion of the dentate nuclei and cerebellar hemispheres.
Two cases are reported of the rare anatomical abnormality of fusion of the cerebellar hemispheres with agenesis of the vermis. The cases are the more unusual since they show prolonged survival and the absence of other major fusion abnormalities in the nervous system.


Use and misuse of the gene ontology annotations.
The Gene Ontology (GO) project is a collaboration among model organism databases to describe gene products from all organisms using a consistent and computable language. GO produces sets of explicitly defined, structured vocabularies that describe biological processes, molecular functions and cellular components of gene products in both a computer- and human-readable manner. Here we describe key aspects of GO, which, when overlooked, can cause erroneous results, and address how these pitfalls can be avoided.


On the emerging relationship between the stratospheric Quasi-Biennial oscillation and the Madden-Julian oscillation.
A strong relationship between the quasi-biennial oscillation (QBO) of equatorial stratospheric winds and the amplitude of the Madden-Julian oscillation (MJO) during the boreal winter has recently been uncovered using observational data from the mid-1970s to the present. When the QBO is in its easterly phase in the lower stratosphere, it favors stronger MJO activity during boreal winter, while the MJO tends to be weaker during the westerly phase of the QBO. Here we show using reconstructed indices of the MJO and QBO back to 1905 that the relationship between enhanced boreal winter MJO activity and the easterly phase of the QBO has only emerged since the early 1980s. The emergence of this relationship coincides with the recent cooling trend in the equatorial lower stratosphere and the warming trend in the equatorial upper troposphere, which appears to have sensitized MJO convective activity to QBO-induced changes in static stability near the tropopause. Climate change is thus suggested to have played a role in promoting coupling between the MJO and the QBO.


Declining incidence of wound infection in cadaveric renal transplant recipient.
Over a five-year period 100 cadaveric renal transplants were performed. In 91 of these recipients, a prophylactic parenteral antibiotic (cefoperazone) was administered and closed wound drainage was used. Of these 91 patients, 33 received azathioprine/prednisone immunosuppression, whereas cyclosporine/prednisone with or without azathioprine was used in the remaining 58. The incidence of wound infections was significantly reduced from 12 per cent (4/33) in the azathioprine group to 1.7 per cent (1/58) in the cyclosporine group (p less than 0.01). When conventional immunosuppression (azathioprine/prednisone) is employed in renal transplantation, triple antibiotic prophylaxis that includes an aminoglycoside is most effective in preventing wound infections. A single non-nephrotoxic antibiotic, cefoperazone, offers similar protection in the cyclosporine/prednisone-treated renal transplant recipient.


Pathways to ovarian cancer diagnosis: a qualitative study.
Ovarian cancer is often diagnosed at a late stage, when survival is poor. Qualitative narratives of patients' pathways to ovarian cancer diagnoses may identify opportunities for earlier cancer detection and, consequently, earlier stage at diagnosis. We conducted semi-structured interviews of ovarian cancer patients and survivors (n = 14) and healthcare providers (n = 11) between 10/2019 and 10/2021. Interviews focused on the time leading up to an ovarian cancer diagnosis. Thematic analysis was conducted by two independent reviewers using a two-phase deductive and inductive coding approach. Deductive coding used a priori time intervals from the validated Model of Pathways to Treatment (MPT), including self-appraisal and management of symptoms, medical help-seeking, diagnosis, and pre-treatment. Inductive coding identified common themes within each stage of the MPT across patient and provider interviews. The median age at ovarian cancer diagnosis was 61.5 years (range, 29-78 years), and the majority of participants (11/14) were diagnosed with advanced-stage disease. The median time from first symptom to initiation of treatment was 2.8 months (range, 19 days to 4.7 years). The appraisal and help-seeking intervals contributed the greatest delays in time-to-diagnosis for ovarian cancer. Nonspecific symptoms, perceptions of health and aging, avoidant coping strategies, symptom embarrassment, and concerns about potential judgment from providers prolonged the appraisal and help-seeking intervals. Patients and providers also emphasized access to care, including financial access, as critical to a timely diagnosis. Interventions are urgently needed to reduce ovarian cancer morbidity and mortality. Population-level screening remains unlikely to improve ovarian cancer survival, but findings from our study suggest that developing interventions to improve self-appraisal of symptoms and reduce barriers to help-seeking could reduce time-to-diagnosis for ovarian cancer. Affordability of care and insurance may be particularly important for ovarian cancer patients diagnosed in the United States.


[Study of Siberian population movements: use of multiple markers].
To further explore early Eurasian steppe migration, we determined the Y chromosome and mitochondrial haplotypes of 26 ancient human specimens from the Krasnoyarsk area, dated between the middle of the second millennium BC and the fourth century AD. Our autosomal Y chromosome and mitochondrial DNA analyses reveal that, whereas few specimens seem to be related matrilineally or patrilineally, nearly all the subjects belong to haplogroup R1a1--M17, which is thought to mark the eastward migration of early Indo-Europeans. Our results also confirm that, during the Bronze and Iron Ages, southern Siberia was a region of overwhelming European settlement.


In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106.
The activation of microglia, in general, and the upregulation of the translocator protein (18 kDa) (TSPO) system, in particular, are key features of neuroinflammation, of which the in vivo visualization and quantitative assessment are still challenging due to the lack of appropriate molecular imaging biomarkers. Recent positron emission tomography (PET) studies using TSPO radioligands such as [11C]PK11195 and [11C]PBR28 have indicated the usefulness of these PET biomarkers in patients with neuroinflammatory diseases, including multiple sclerosis (MS). [18F]FEDAA1106 is a recently developed PET radioligand for the in vivo quantification of TSPO. In the present study, we aimed at investigating the diagnostic usefulness of [18F]FEDAA1106 in patients with MS. Nine patients (three on the interferon beta therapy and six without immunomodulatory therapy; seven females/two males; age 34.2 ± 9.1 years old) with relapsing-remitting MS in acute relapse and with gadolinium (Gd)-enhancing lesion(s) in the magnetic resonance imaging (MRI) scans and five healthy controls (four females/one male, age 38.0 ± 9.7 years old) were investigated in this study. Genetic information about the TSPO binding could not be obtained because knowledge about the importance of genetic background for TSPO binding was not available at the time the study was performed. Dynamic PET measurements were performed using an ECAT EXACT HR system (CTI/Siemens, Knoxville, TN, USA) for a total of 150 min, with a 30-min break after the injection of 153.4 ± 10.2 MBq of [18F]FEDAA1106. Metabolite-corrected arterial plasma samples were used to calculate the input function. PET data were analyzed in the following ways: (1) region-of-interest analysis for cortical and subcortical regions was performed using a two-tissue compartment kinetic model in order to estimate binding potentials (BPND) and distribution volume (VT), (2) the feasibility of the estimation of BPND and VT was investigated for MS lesions, and (3) VT parametric images by a Logan plot and standard uptake value (SUV) images were visually compared with the corresponding MRI, focusing on MRI-identified MS lesions. There were no significant differences in the BPND or VT values between patients with MS and healthy controls. Robust BPND and VT values could not be obtained for most MS lesions due to noisy time-activity curves. Visual inspection of VT and SUV images in all nine patients did not reveal high uptake of the radioligand inside and beyond MRI-identified active MS lesions with the exception of one Gd-enhanced MS lesion in the whole patient population. In our study, [18F]FEDAA1106 as a PET radioligand could neither differentiate patients with MS from healthy controls nor detect active plaques in the brain of MS patients. Stratification with respect to genetics and binder status might help to uncover the differences between the groups, which could not be detected here. ClinicalTrials.gov, NCT01031199.


Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma.
Despite decades of research, the early phases of metastatic development are still not fully understood. Canine osteosarcoma (OS) is a highly aggressive cancer, with a high metastatic rate (> 90%), despite a low overt metastatic prevalence at initial diagnosis (< 15%). Canine OS is generally regarded as a good clinically relevant model for human OS. The aim of this hypothesis-generating study was to evaluate a method to detect pulmonary micrometastases and study their prevalence in dogs with OS without macroscopic metastases. We prospectively enrolled dogs with OS that received no cancer-specific treatment (n = 12) and control dogs without cancer (n = 2). Dogs were necropsied and sampled immediately after euthanasia. The OS dogs were classified as having macroscopic metastases (n = 2) or not (n = 10). We immunohistochemically stained one tissue sample from each of the seven lung lobes from each dog with a monoclonal antibody (TP-3) to identify micrometastases (defined as clusters of 5-50 tumour cells), microscopic metastases (> 50 tumour cells) and TP-3 positive single cells (< 5 tumour cells). We showed that pulmonary micrometastases easily overseen on routine histology could be detected with TP-3. Pulmonary micrometastases and microscopic metastases were present in two dogs with OS without macroscopic metastases (20%). Micrometastases were visualised in three (43%) and four (57%) of seven samples from these two dogs, with a mean of 0.6 and 1.7 micrometastases per sample. Microscopic metastases were present in one (14%) and four (57%) of seven samples from the same two dogs, with a mean of 0.14 and 1.0 microscopic metastases per sample. There were four (57%) and two (29%) samples with neither microscopic metastases nor micrometastases for each of these two dogs. The prevalence of pulmonary micrometastases (20%) was significantly lower than expected (> 90%) based on commonly expected metastatic rates after amputation (P < 0.0001). There was no statistically significant difference in the number of TP-3 positive single cells in between groups (P = 0.85). Pulmonary micrometastases could be detected with TP-3 immunohistochemistry in a subset of dogs with OS before macroscopic metastases had developed. We propose that dogs with spontaneous OS represent clinically relevant models to study early micrometastatic disease.


Serial change of liver stiffness measured by acoustic radiation force impulse imaging in chronic liver disease: correlation with biochemical markers.
In patients with chronic diffuse liver diseases, liver fibrosis severity is an important element for prognosis and for selecting therapy. Acoustic radiation force impulse (ARFI) imaging techniques were recently developed to measure liver fibrosis, but their specificity is impaired by cholestasis, inflammation, or edema in acute hepatitis. Herein, our objectives were to evaluate serial changes in shear wave velocity (SWV) and to correlate these changes with biochemical activity. This study included 108 patients who underwent ARFI because of viral hepatitis [hepatitis B (HBV) or C (HCV)] with serial follow-up after 3-6 months at our institution between August 2011 and May 2013. Based on baseline and follow-up ARFI, we divided patients with HBV and HCV into two groups: a decreasing SWV group and a non-decreasing SWV group. We evaluated serial SWV changes and correlated these changes with biochemical activity changes. The patients were divided into SWV groups as follows: decreasing SWV group (HBV, n = 23; HCV, n = 7) and non-decreasing SWV group (HBV, n = 40; HCV, n = 38). In both HBV and HVC patients, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly decreased at follow-up in the decreasing SWV group. The liver stiffness value assessed by ARFI became lower over time in patients who had decreasing AST and ALT levels. According to this study, ARFI overestimates fibrosis grade in patients with high AST and ALT. Thus, assessment of liver fibrosis by ARFI elastography should include consideration of biochemical markers such as AST and ALT levels and additional follow-up using ARFI elastography.


Comparative genomics to examine the endophytic potential of Pantoea agglomerans DAPP-PG 734.
Pantoea agglomerans DAPP-PG 734 was isolated as endophyte from knots (tumors) caused by Pseudomonas savastanoi pv. savastanoi DAPP-PG 722 in olive trees. To understand the plant pathogen-endophyte interaction on a genomic level, the whole genome of P. agglomerans DAPP-PG 734 was sequenced and annotated. The complete genome had a total size of 5'396'424 bp, containing one circular chromosome and four large circular plasmids. The aim of this study was to identify genomic features that could play a potential role in the interaction between P. agglomerans DAPP-PG 734 and P. savastanoi pv. savastanoi DAPP-PG 722. For this purpose, a comparative genomic analysis between the genome of P. agglomerans DAPP-PG 734 and those of related Pantoea spp. was carried out. In P. agglomerans DAPP-PG 734, gene clusters for the synthesis of the Hrp-1 type III secretion system (T3SS), type VI secretion systems (T6SS) and autoinducer, which could play an important role in a plant-pathogenic community enhancing knot formation in olive trees, were identified. Additional gene clusters for the biosynthesis of two different antibiotics, namely dapdiamide E and antibiotic B025670, which were found in regions between integrative conjugative elements (ICE), were observed. The in-depth analysis of the whole genome suggested a characterization of the P. agglomerans DAPP-PG 734 isolate as endophytic bacterium with biocontrol activity rather than as a plant pathogen.


Phage Biocontrol Effectively Reduces Contamination of Wheat with Shiga Toxin-producing Escherichia coli O121 and O26 Without Adverse Effects on Flour Quality.
Contamination of wheat flours with Shiga toxin-producing E. coli (STEC) is a concern for the milling industry. Milling-specific interventions are needed to address this food safety hazard. The objectives for this study were to determine the efficacy of bacteriophage treatment in reducing wheat STEC contamination during tempering, and assess its effects on flour milling and baking quality. Bacteriophage solutions were prepared by mixing sterile water with the bacteriophage treatment at the following levels: 1 × 106 (0.1%), 2.5 × 106 (0.25%), 5 × 106 (0.5%), 1 × 107 (1.0%), and 1 × 108 (10%) PFU/g wheat dosage. Sterile water (0%) was used as the control. Predried wheat grains were inoculated with STEC (O121 and O26) at 5.0 and 6.0 log CFU/g to restore its original moisture content followed by resting for 24 h. Inoculated grains were then tempered (16% moisture, 24 h) using the prepared bacteriophage solutions. Grains were sampled at 0.5, 1, 2, 6, 12, 18, and 24 h during tempering to determine STEC concentration. The effects of the phage solutions on the flour milling and baking quality were also tested. Tempering time, bacteriophage dose, and their interaction had significant effects on phage efficacy (P < 0.05), with better reductions observed at longer tempering times and higher bacteriophage doses. The use of phage solutions reduced (P < 0.05) wheat STEC concentration after tempering, with the 10% treatment (3.2 logs) achieving ahigher reduction than the 1% (2.4 logs) treatment under similar phage preparation. Phage tempering (including at the highest concentration examined, i.e., 10%) produced wheat flours with comparable quality to the control. Phage-treated wheat flour resulted in breads with finer crumb structure, and comparable texture compared to the control. Phage tempering is a viable intervention for wheat milling as it reduced STEC loads of wheat with no detrimental effects to flour milling and baking quality.


Herpes simplex virus genome isomerization: origins of adjacent long segments in concatemeric viral DNA.
Herpes simplex virus type 1 DNA isomerization was studied by using a viral mutant, 5B8, lacking the unique SpeI site of its parent, SC16. In coinfected cells, SC16 genomic long segments flanked 5B8 genomes in all possible orientations with similar frequencies. Thus, recombination between progeny of different replication templates is sufficient to explain genomic isomerization.


Visualization of Ag-NOR proteins on nucleolar transcriptional units in molecular spreads.
Application of NOR silver staining to Pleurodeles oocyte nuclei showed selective silver deposits on the fibrillar part of the nucleoli in situ. This staining was adapted to nucleoli spread on grids, by a procedure which allowed the spreading of transcription units from both nucleoli and lampbrush chromosomes on the same grids. This permitted localization of the predominant nucleolar Ag-stained proteins on the nucleolar transcriptional units and not on the lampbrush chromosomes. These proteins were found exclusively on the transcribed part of the nucleolar genes and were not seen in apparently untranscribed spacer regions. The proteins seemed preferentially located on the DNP axis rather than on the RNP fibrils.


Connections between the ventral medullary swallowing area and the trigeminal motor nucleus of the sheep studied by tracing techniques.
The anatomical connections between two regions involved in swallowing, the medullary reticular formation around the nucleus ambiguous (ventral group of swallowing interneurons) and the trigeminal motor nucleus (NMV) were studied in sheep using anterograde and retrograde tracing techniques. [3H]leucine and HRP were injected into the ventral medulla and the NMV respectively. These injections were performed according to stereotaxic coordinates previously established by electrophysiological recording tests. The results show bilateral connections between the ventral medulla, 2-4 mm rostral to the obex, and the trigeminal motor nucleus. In addition, the same area of the ventral medulla is connected with the homologous contralateral region and with the facial, vagal and hypoglossal nuclei that are also involved in swallowing. Some connections between the ventral medulla and the NMV must be monosynaptic since aggregates of silver grains typical of axon terminals were observed on the cell bodies of trigeminal motoneurons. Obviously, the various connections shown to exist in this study may serve other functions than swallowing. Nevertheless, most of the results are consistent with the view that the ventral group of medullary swallowing interneurons are switching neurons that distribute the programmed swallowing excitation to the various motoneuron pools involved in deglutition.


Determinants of plasma alkylresorcinol concentration in Danish post-menopausal women.
Alkylresorcinols (AR), a group of phenolic lipids present in the outer parts of wheat and rye grain kernels, have been suggested as biomarkers of whole-grain wheat and rye intake. In this study, we investigated potential determinants of plasma AR concentration in a free-living population. Non-fasting samples from post-menopausal women enrolled in the Danish Diet, Cancer and Health study (n = 360) were selected. Diet was assessed using a semi-quantitative food frequency questionnaires (FFQ) and the association between food items likely to contain AR and relevant non-dietary factors were studied by analysis of covariance models. The median AR concentration was 78 nmol/l (interquartile range = 106.9 nmol/l). Intake of rye bread, identified as the main determinant, was associated with 87% higher plasma total AR concentration per 100 g of bread (95% confidence interval = 46-139%). About 8-12% of the total variation (depending on the AR homologue) in plasma AR concentration was explained by the selected dietary variables. At a nutrient level, total dietary fiber and cereal fiber were significantly associated with plasma total AR concentration (P = 0.05), but only ≈2% of the total plasma AR concentration was explained by the dietary fiber or cereal fiber intake. In the studied population, AR plasma concentration was mainly affected by rye bread intake among investigated determinants.


Atypical wound of entry and unusual presentation in a fatal stab injury.
Stab wounds encountered in medico-legal autopsies are usually caused by sharp pointed weapons. Peculiarities of the wound of entry in stab wounds, for example due to the hilt of the weapon, movement of the weapon and sometimes by the hand of the assailant holding the weapon are often described in literature. We report an unusual presentation in a fatal stab injury wherein a single atypical external wound was associated with multiple internal injuries to the organs. The exact cause of such peculiarities can never be accurately determined, rather that can be speculated upon at the time of the autopsy and recorded for the purpose of academic interest.


[Functional and audiological results of tympanoplasty type I using pure perichondrial grafts].
There are very few studies analyzing the functional und audiological results of tympanoplasty type I using pure perichondrium. Data of 80 randomly selected patients, who had tympanoplasty surgery between 1998 and 2008 with pure perichondrium were evaluated retrospectively. Average postoperative follow-up was 9 months. The preoperative- and postoperative status of tympanic membrane, air-bone gap (ABG) and influence of perforation size and perforation etiology on closure rate served as study parameters. The closure rate for tympanoplasty type I with pure perichondrium was 85% and the mean ABG reduction was 10.8±7.22 dB. Size and etiology of the perforation had no influence on operative results. Concerning closure rates pure perichondrium is very suitable for repairing tympanic membrane defects. Postoperative audiological results can be compared to other transplants, such as temporal fascia or combined cartilage-perichondrium grafts and the intraoperative handling and positioning seem to be more comfortable.


A do-it-yourself electrochemical cell based on pencil leads and transparency sheets: Application to the enzymatic determination of histamine.
The availability of more efficient analytical methods that answer the world's demands is a challenge and their development continues to be a difficult task. In this work the construction of an electrochemical cell, based on low-cost and accessible materials, that can be easily constructed and used for electroanalytical purposes, is described. Pencil leads were used as electrodes and a transparency sheet as the base. This cell was used as transducer for developing an amperometric biosensor for the quantification of histamine, which is the only biogenic amine regulated by law. The analysis was based on the use of diamine oxidase as biorecognition element, hexacyanoferrate(III) as electron-transfer mediator, and chronoamperometry, at +0.5 V during 100 s, to record the analytical signal. A linear relationship between histamine concentration and the analytical signal was established between 5.0 and 35 mg L-1 and a low limit of detection (1.0 mg L-1) was achieved. The analysis of different fish species (sardine and tuna) was performed, obtaining recovery values between 102% and 110%. The stability of the sensor is noteworthy: it maintained 95% of the initial analytical signal after 15 days.


The Bristol Radiology Report Assessment Tool (BRRAT): developing a workplace-based assessment tool for radiology reporting skills.
To review the development of a workplace-based assessment tool to assess the quality of written radiology reports and assess its reliability, feasibility, and validity. A comprehensive literature review and rigorous Delphi study enabled the development of the Bristol Radiology Report Assessment Tool (BRRAT), which consists of 19 questions and a global assessment score. Three assessors applied the assessment tool to 240 radiology reports provided by 24 radiology trainees. The reliability coefficient for the 19 questions was 0.79 and the equivalent coefficient for the global assessment scores was 0.67. Generalizability coefficients demonstrate that higher numbers of assessors and assessments are needed to reach acceptable levels of reliability for summative assessments due to assessor subjectivity. The study methodology gives good validity and strong foundation in best-practice. The assessment tool developed for radiology reporting is reliable and most suited to formative assessments.


The Role of Virtual Environment for Radiotherapy Training (VERT) in Medical Dosimetry Education.
Medical dosimetry is an important component in training of radiation therapist, yet it is not easy for student to understand the principle of treatment planning and to be familiar with the relationship of the clinical target volume (CTV), planned target volume (PTV), and the nearby organs at risk (OARs) by just imagination. This study is conducted to evaluate whether using VERT in teaching medical dosimetry can help student to improve their learning experience. Students of cohort 2015 and 2016 were taught under TPS mode and TPS + VERT mode respectively. Direct comparison was conducted through self-evaluation survey, between two groups of students, in terms of their understanding of the concept of medical dosimetry and their level of confidence in completing different types of plans after the course. Both groups of students were able to understand the concept of medical dosimetry and able to complete 3D conformal plans after taking the course. Though, the students received TPS mode reported that they had lower level of confidence in completing the planning and required longer time for self-study and practice compared to the students who received the TPS + VERT mode. This study demonstrated that including VERT into medical dosimetry education can improve students' learning experience, by improving their self-confidence, as well as reducing time required for their self-study and practice.


Cysteine Aminoethylation Enables the Site-Specific Glycosylation Analysis of Recombinant Human Erythropoietin using Trypsin.
Recombinant human erythropoietin (rhEPO) is an important biopharmaceutical for which glycosylation is a critical quality attribute. Therefore, robust analytical methods are needed for the in-depth characterization of rhEPO glycosylation. Currently, the protease GluC is widely established for the site-specific glycosylation analysis of rhEPO. However, this enzyme shows disadvantages, such as its specificity and the characteristics of the resulting (glyco)peptides. The use of trypsin, the gold standard protease in proteomics, as the sole protease for rhEPO is compromised, as no natural tryptic cleavage site is located between the glycosylation sites Asn24 and Asn38. Here, cysteine aminoethylation using 2-bromoethylamine was applied as an alternative alkylation strategy to introduce artificial tryptic cleavage sites at Cys29 and Cys33 in rhEPO. The (glyco)peptides resulting from a subsequent digestion using trypsin were analyzed by reverse-phase liquid chromatography-mass spectrometry. The new trypsin-based workflow was easily implemented by adapting the alkylation step in a conventional workflow and was directly compared to an established approach using GluC. The new method shows an improved specificity, a significantly reduced chromatogram complexity, allows for shorter analysis times, and simplifies data evaluation. Furthermore, the method allows for the monitoring of additional attributes, such as oxidation and deamidation at specific sites in parallel to the site-specific glycosylation analysis of rhEPO.


Application of LC and GC hyphenated with mass spectrometry as tool for characterization of unknown derivatives of isoflavonoids.
Polyphenols belonging to the class of secondary metabolites of plants and microorganisms play an important role as bioactive food constituents as well as contaminants. Structure elucidation of polyphenols in plant extracts or polyphenol metabolites, especially those arising during biotransformation, still represents a challenge for analytical chemistry. Various approaches have been proposed to utilize fragmentation reactions in connection with mass spectrometry (MS) for structural considerations on polyphenolic targets. We compiled and applied specific liquid chromatography (LC)-electrospray ionization in positive mode [ESI(+)]-tandem MS (MS/MS) and gas chromatography (GC)-(electron impact, EI)-MS/MS fragmentation reactions with a special focus on the analysis of isoflavones, whereby this technique was also found to be extendable to determine further polyphenols. For ESI(+)-MS the basic retro-Diels-Alder (rDA) fragmentation offers information about the substitution pattern in the A- and B-rings of flavonoids and the elimination of a protonated 4-methylenecyclohexa-2,5-dienone (m/z = 107) fragment can be used as a diagnostic tool for many isoflavanones. For GC-(EI)-MS/MS analysis after derivatization of the analytes to their trimethylsilyl ethers, the elimination of methyl radicals, tetramethylsilane groups or the combined loss of two methyl groups can be shown to be specific for certain substitution patterns in polyphenols. The applicability of the fragmentation reactions presented is demonstrated exemplarily for three derivatives of the isoflavone irilone. With the help of these fragmentation reactions of the two MS techniques combined, a reliable identification of polyphenols is possible. Especially in such cases where NMR cannot be utilized owing to low analyte amounts being available or prior to purification, valuable information can be obtained.


The production of cyanobacterial carbon under nitrogen-limited cultivation and its potential for nitrate removal.
Harmful cyanobacterial blooms (CyanoHABs) represent a serious threat to aquatic ecosystems. A beneficial use for these harmful microorganisms would be a promising resolution of this urgent issue. This study applied a simple method, nitrogen limitation, to cultivate cyanobacteria aimed at producing cyanobacterial carbon for denitrification. Under nitrogen-limited conditions, the common cyanobacterium, Microcystis, efficiently used nitrate, and had a higher intracellular C/N ratio. More importantly, organic carbons easily leached from its dry powder; these leachates were biodegradable and contained a larger amount of dissolved organic carbon (DOC) and carbohydrates, but a smaller amount of dissolved total nitrogen (DTN) and proteins. When applied to an anoxic system with a sediment-water interface, a significant increase of the specific NOX--N removal rate was observed that was 14.2 times greater than that of the control. This study first suggests that nitrogen-limited cultivation is an efficient way to induce organic and carbohydrate accumulation in cyanobacteria, as well as a high C/N ratio, and that these cyanobacteria can act as a promising carbon source for denitrification. The results indicate that application as a carbon source is not only a new way to utilize cyanobacteria, but it also contributes to nitrogen removal in aquatic ecosystems, further limiting the proliferation of CyanoHABs.


Detection rate of MR myelography without intrathecal gadolinium in patients with newly diagnosed spontaneous intracranial hypotension.
To evaluate the detection rate of magnetic resonance (MR) myelography without intrathecal gadolinium for cerebrospinal fluid (CSF) leakage in patients with newly diagnosed spontaneous intracranial hypotension (SIH) and to validate a published scoring system for predicting CSF leakage. This retrospective, observational, single-institution study included patients with newly diagnosed SIH between March 2015 and April 2021. Patients were included if they (a) had newly diagnosed SIH and (b) underwent initial brain MR imaging and preprocedural MR myelography with two- and three-dimensional turbo spin-echo sequences. Patients who underwent spine surgery or procedures including epidural injection and acupuncture were excluded. The detection rate was defined as the proportion of patients with a true-positive MR myelography result among all patients with confirmed CSF leakage. The interobserver agreement for the MR myelography results between two radiologists was analysed using weighted kappa statistics. A total of 136 patients (mean age, 48 years; 70 women) with suspected SIH were included. Of these patients, 120 (88%, 120/136) were confirmed to have CSF leakage. Of the patients with confirmed CSF leakage, 90 (75%, 90/120) had epidural fluid collection. The detection rate of MR myelography for CSF leakage was 88% (105/120). The interobserver agreement between the two readers for detecting CSF leakage (κ = 0.76) or epidural fluid collection (κ = 0.76) on MR myelography was high. Among 24 patients with normal brain MR imaging results, 16 had CSF leakage (67%, 16/24). Non-invasive MR myelography without intrathecal gadolinium should be considered to detect CSF leakage in patients with suspected SIH.


Multiple endocrine neoplasia type 1 (MEN 1) revisited.
Multiple endocrine neoplasia type 1 (MEN 1) is an inherited disease of the neuroendocrine cell system affecting primarily the parathyroids, pancreas, duodenum and the anterior pituitary. The pancreatic and duodenal tumours may metastasize, but generally have a low malignant potential. The diagnosis of MEN 1 is usually made in the second decade of life and based on the involvement of at least two organs and a family history. The recent discovery of the MEN 1 locus on the centromeric region of the long arm of chromosome 11 may become a further diagnostic criterion. The use of flanking DNA markers permits presymptomatic testing for MEN 1 in affected families.


Immobilization of α-amylase in ethylcellulose electrospun fibers using emulsion-electrospinning method.
α-Amylase encapsulated in water in oil (W/O) emulsion was prepared using poly ethylene glycol (PEG 10000) (2%w/v) as water phase and ethylcellulose (EC) in ethyl acetate as oil phase at the ratio of 10:90 v/v. Next, the electrospun fibers were prepared by mixing enzyme loaded emulsion with EC solution (20%w/v) in acetic acid/ethyl acetate (20:80 v/v) at the 2:1 ratio. The emulsion showed good physical stability. The immobilized enzyme showed high activity across a board range of pHs and temperatures. The storage stability of the immobilized enzyme was 2 fold of free enzyme activity after 45 days. The residual activity of immobilized α-amylase onto of fibers after 10 and 15 repeated cycles, was approximately 100% and 50%, respectively. The results of this study indicated that the α-amylase loaded EC fibers have acceptable activity against harsh conditions and excellent reusability.


The face of Olduvai Hominid 12.
Facial remains of Homo erectus are rare and their scarcity hinders our understanding of the variability and relationships in this taxon. Previously undescribed fragments of the peri-orbital region and unidentified matches between fragments of Olduvai Hominid 12 (OH 12) enhance comparison of the African H. erectus hypodigm. The newly reconstructed upper face and maxilla of OH 12 is most similar in size and shape to that of KNM-ER 3733, despite being as much as one million years younger than the Koobi Fora hominin. However, the posterior vault and mastoid region of OH 12 are most similar to OH 9. This combination of morphology suggests that the relationship between the Olduvai and Koobi Fora portions of the H. erectus hypodigm requires reconsideration.


[Pathology and molecular profile of differentiated thyroid carcinoma].
The clinical term of differentiated thyroid carcinoma (DTC) includes follicular (FTC) and papillary thyroid carcinomas (PTC). In diagnostic thyroid pathology, however, the term differentiated carcinoma (NOS) is used only very rarely for tumors with morphological features of both FTC and PTC. The current World Health Organization (WHO) classification of thyroid tumors introduced the entity of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). As a result, the diagnostic criteria for PTC had to be adjusted (compulsory histological demonstration of invasion and/or papillae), which also significantly limited the diagnostic potential of a fine needle biopsy (FNB) of the thyroid. The FTC is now divided into three distinct subgroups. Moreover, the WHO classification also established the diagnostic criteria of poorly differentiated thyroid carcinoma (PDTC), which has to be distinguished from both differentiated carcinomas and benign adenomas. This article also summarizes the current diagnostic status of molecular pathological analyses of thyroid tumors.


Decrease in peak heart rate with acute hypoxia in relation to sea level VO(2max).
The aim of this study was to evaluate the influence of arterial oxygen saturation ( SaO(2)) on maximal heart rate during maximal exercise under conditions of acute hypoxia compared with normoxia. Forty-six males were divided into three groups depending on their sea level maximal oxygen consumption ( VO(2max)): high [GH, VO(2max)=64.2 (3.3) ml x min(-1) x kg(-1)], medium [GM, 50.8 (3.9) ml x min(-1) x kg(-1)] and low [GL, 41.0 (1.9) ml x min(-1) x kg(-1)]. All subjects performed a maximal exercise test in two conditions of inspired oxygen tension ( PIO(2), (149 mmHg and 70 mmHg). Among the GM group, seven subjects performed five supplementary incremental exercise tests at PIO(2) 136, 118, 104, 92, and 80 mmHg. Measurements of VO(2max) and SaO(2) using an ear-oxymeter were carried out at all levels of PIO(2). The decrease in SaO(2 )and peak heart rate (HR(peak)) with PIO(2) became significant from 104 and 92 mmHg. SaO(2) correlated with the decrease in HR(peak). For PIO(2)=70 mmHg, the decrease in VO(2max), SaO(2) and HR(peak) was, respectively, 44%, 62%, and 17.0 bpm for GH, 38%, 68%, and 14.7 bpm for GM, and 34%, 68%, and 11.8 bpm for GL. During maximal exercise in hypoxia, SaO(2) was lower for GH than GM and GL ( p<0.01). Among subjects in GH, five presented exercise-induced hypoxemia (EIH) when exercising in normoxia. The EIH group exhibited a greater decrement in HR(peak) than the non-EIH group at maximal hypoxic exercise (21.2 bpm vs. 15.0 bpm; p<0.05). When subjects are exposed to acute hypoxia, the lower SaO(2), due either to lower PIO(2) or to training status, is associated with lower HR(peak).


Highly Loaded Independent Pt0 Atoms on Graphdiyne for pH-General Methanol Oxidation Reaction.
The emergence of platinum-based catalysts promotes efficient methanol oxidation reactions (MOR). However, the defects of such noble metal catalysts are high cost, easy poisoning, and limited commercial applications. The efficient utilization of a low-cost, anti-poisoning catalyst has been expected. Here, it is skillfully used N-doped graphdiyne (NGDY) to prepare a zero-valent platinum atomic catalyst (Pt/NGDY), which shows excellent activity, high pH adaptability, and high CO tolerance for MOR. The Pt/NGDY electrocatalysts for MOR with specific activity 154.2 mA cm-2 (1449.3 mA mgPt -1 ), 29 mA cm-2 (296 mA mgPt -1 ) and 22 mA cm-2 (110 mA mgPt -1 ) in alkaline, acid, and neutral solutions. The specific activity of Pt/NGDY is 9 times larger than Pt/C in alkaline solution. Density functional theory (DFT) calculations confirm that the incorporation of electronegativity nitrogen atoms can increase the high coverage of Pt to achieve a unique atomic state, in which the shared contributions of different Pt sites reach the balance between the electroactivity and the stability to guarantee the higher performance of MOR and durability with superior anti-poisoning effect.


Understanding multivariate brain activity: Evaluating the effect of voxelwise noise correlations on population codes in functional magnetic resonance imaging.
Previous studies in neurophysiology have shown that neurons exhibit trial-by-trial correlated activity and that such noise correlations (NCs) greatly impact the accuracy of population codes. Meanwhile, multivariate pattern analysis (MVPA) has become a mainstream approach in functional magnetic resonance imaging (fMRI), but it remains unclear how NCs between voxels influence MVPA performance. Here, we tackle this issue by combining voxel-encoding modeling and MVPA. We focus on a well-established form of NC, tuning-compatible noise correlation (TCNC), whose sign and magnitude are systematically related to the tuning similarity between two units. We show that this form of voxelwise NCs can improve MVPA performance if NCs are sufficiently strong. We also confirm these results using standard information-theoretic analyses in computational neuroscience. In the same theoretical framework, we further demonstrate that the effects of noise correlations at both the neuronal level and the voxel level may manifest differently in typical fMRI data, and their effects are modulated by tuning heterogeneity. Our results provide a theoretical foundation to understand the effect of correlated activity on population codes in macroscopic fMRI data. Our results also suggest that future fMRI research could benefit from a closer examination of the correlational structure of multivariate responses, which is not directly revealed by conventional MVPA approaches.


Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.
Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85 m s-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.


Discovery of novel N-aryl piperazine CXCR4 antagonists.
A novel series of CXCR4 antagonists with substituted piperazines as benzimidazole replacements is described. These compounds showed micromolar to nanomolar potency in CXCR4-mediated functional and HIV assays, namely inhibition of X4 HIV-1(IIIB) virus in MAGI-CCR5/CXCR4 cells and inhibition of SDF-1 induced calcium release in Chem-1 cells. Preliminary SAR investigations led to the identification of a series of N-aryl piperazines as the most potent compounds. Results show SAR that indicates type and position of the aromatic ring, as well as type of linker and stereochemistry are significant for activity. Profiling of several lead compounds showed that one (49b) reduced susceptibility towards CYP450 and hERG, and the best overall profile when considering both SDF-1 and HIV potencies (6-20 nM).


Concentration and distribution of sialic acid in human milk and its correlation with dietary intake.
This study evaluates the content, distribution, and changing trend of sialic acid in human milk and the correlation between dietary intake of sialic acid and that in human milk. The study included 33 mothers of full-term and exclusively breastfed infants. At least 2 ml of milk was collected on the 3rd, 8th, 30th, and 90th day after delivery, and 24-h diet recalls of the lactating mothers were obtained each time. The correlation of human milk sialic acid concentration with lactating women's dietary sialic acid intake during lactation was analyzed by statistical analysis software SPSS. The average concentration of sialic acid in colostrum, transition, and 1 and 3 months were 1,670.74 ± 94.53, 1,272.19 ± 128.74, 541.64 ± 55.2, and 297.65 ± 20.78 mg/L, respectively. The total sialic acid concentration in colostrum was about 5.6 times higher than that at 3 months (P < 0.001). The average dietary sialic acid intake of lactating mothers on the 2nd, 7th, 30th, and 90th day after delivery were 106.06 ± 7.51, 127.64 ± 8.61, 120.34 ± 10.21, and 95.40 ± 6.34 mg/day, respectively. The intake of sialic acid was relatively high on the 7th day, and there was no significant difference in dietary intake of sialic acid on different days (P < 0.05). In addition, there was no correlation between the intake of dietary sialic acid and the content of total sialic acid and various forms of sialic acid in milk (P < 0.05). During the lactation period, the distribution of sialic acid in breast milk is relatively stable and its content fluctuates greatly, which may not be affected by the mother's diet, but mainly depends on the self-regulation oft physiological needs.


An "abnormal" lymphoid proliferation simulating Hodgkin's disease in a burn patient.
A particularly exuberant and unusual lymphoid proliferation in the spleen of a burn patient is presented. Many Reed-Sternberg cell variants and occasional diagnostic Reed-Sternberg cells strongly suggested a diagnosis of Hodgkin's disease. The pattern of distribution and cytology of this lymphoid infiltrate, however, are incompatible with Hodgkin's disease or a non-Hodgkin lymphoma. Morphologic features in this case suggest that the Reed-Sternberg cell is a B lymphocyte. The most probable etiologies of this unusual lymphoid proliferation are reviewed.


Transplant of mesenchymal stem cells and hydroxyapatite ceramics to treat severe osteochondral damage after septic arthritis of the knee.
We describe a 21-year-old man with a large osteochondral defect of the knee after septic arthritis, successfully treated by transplant of mesenchymal stem cells (MSC) from bone marrow and a new type of interconnected porous hydroxyapatite ceramic (IP-CHA). We confirmed successful cartilage-like tissue regeneration by a second arthroscopy. Biopsy of the repaired tissue revealed cartilage-like regeneration and bone formation. We were able to regenerate new bone and cartilage-like tissue in a one-stage operation, without sacrificing autologous bone or other tissue. This cultured MSC and IP-CHA hybrid material transplant represents a novel treatment for a severe osteochondral defect after septic arthritis.


Anterior shoulder stabilization by Bristow-Latarjet procedure in athletes: return-to-sport and functional outcomes at minimum 2-year follow-up.
The aim of this study was to assess return-to-sport outcomes following the Latarjet-Bristow procedure. This retrospective study included all athletes <50 years old, who underwent a Latarjet-Bristow procedure for anterior shoulder instability in 2009-2012. Main criteria assessments were the number of athletes returning to any sport and the number returning to the same sport at their preinjury level. The main follow-up was 46.8 ± 9.7 months. Forty-seven patients were analyzed, 46 men/1 women, mean age 27.9 ± 7.9 years. Eighteen patients practiced competitive sports and 29 recreational sports. None of them were professional athletes. One hundred percent returned to sports after a mean 6.3 ± 4.3 months. Thirty/47 (63.8 %) patients returned to the same sport at the same level at least and 10/47 (21.3 %) patients changed sport because of their shoulder. Compared to patients who returned to the same sport at the same level, patients who changed sports or returned to a lower level had practiced overhead or forced overhead sports [OR = 4.7 (1.3-16.9), p = 0.02] before surgery, experienced avoidance behavior at the final follow-up (p = 0.002), apprehension (p = 0.00001) and had a worse Western Ontario Shoulder Instability Index score and sub-items (p = 0.003) except for daily activities (p = 0.21). At the final follow-up, 45/47 (95.7 %) patients were still practicing a sport. All the patients returned to sports, most to their preinjury sport at the same level. Patients who practiced an overhead sport were more likely to play at a lower level or to change sport postoperatively. IV, retrospective study-Case series with no comparison group.


Slipped capital femoral epiphysis (SCFE) following pelvic irradiation for rhabdomyosarcoma.
A 7-year-old child developed slipped capital femoral epiphysis (SCFE) 3 years following pelvic irradiation for rhabdomyosarcoma. The reasons for this occurrence are discussed. This is the second report of radiation-induced SCFE and it is anticipated that more such cases are likely to occur.


Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes.
Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network's hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions.


Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1.
Human melanin-concentrating hormone (hMCH) is a nonselective natural ligand for the human melanin-concentrating hormone receptors: hMCH-1R and hMCH-2R. Similarly, the smaller peptide encompassing the disulfide ring and Arg(6) of hMCH, Ac-Arg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Gly(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)-Pro(15)-Cys(16))-NH(2), Ac-hMCH(6-16)-NH(2), binds to and activates equally well both human MCH receptors present in the brain. To separate the physiological functions of hMCH-1R from those of hMCH-2R, new potent and hMCH-1R selective agonists are necessary. In the present study, analogs of Ac-hMCH(6-16)-NH(2) were prepared and tested in binding and functional assays on cells expressing the MCH receptors. In these peptides, Arg in position 6 was replaced with various d-amino acids and/or Gly in position 10 was substituted with various L-amino acids. Several of the new compounds turned out to be potent agonists at hMCH-1R with improved selectivity over hMCH-2R. For example, peptide 26 with d-Arg in place of L-Arg in position 6 and Asn in place of Gly in position 10, Ac-dArg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Asn(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)-Pro(15)-Cys(16))-NH(2), was a potent hMCH-1R agonist (IC(50) = 0.5 nm, EC(50) = 47 nm) with more than 200-fold selectivity with respect to hMCH-2R. Apparently, these structural changes in positions 6 and 10 results in peptide conformations that allow for efficient interactions with hMCH-1R but are unfavorable for molecular recognition at hMCH-2R.


Three new species of Pseudophanias Raffray from Japan and Taiwan Island, and synonymy of Chandleriella Hlaváč with Pseudophanias (Coleoptera, Staphylinidae, Pselaphinae).
The genus Pseudophanias Raffray, 1890 is discovered in Japan and Taiwan Island for the first time, with three new species: P. yaimensis Inoue, Nomura & Yin, sp. nov., P. nakanoi Inoue, Nomura & Yin, sp. nov., and P. excavatus Inoue, Nomura & Yin, sp. nov. It is the fifth tmesiphorine genus known from Japan and the first from Taiwan. The genus Chandleriella Hlaváč, 2000 is placed as a junior synonym of Pseudophanias, resulting in the following new combinations: P. termitophilus (Bryant, 1915), comb. nov., and P. yunnanicus (Yin, 2019), comb. nov. A list of world species, and a key to East and South Asian representatives of Pseudophanias is provided.