Coherently driven quantum features using a linear optics-based polarization-basis control.
Quantum entanglement generation is generally known to be impossible by any classical means. According to Poisson statistics, coherent photons are not considered quantum particles due to the bunching phenomenon. Recently, a coherence approach has been applied for quantum correlations such as the Hong-Ou-Mandel (HOM) effect, Franson-type nonlocal correlation, and delayed-choice quantum eraser to understand the mysterious quantum features. In the coherence approach, the quantum correlation has been now understood as a direct result of selective measurements between product bases of phase-coherent photons. Especially in the HOM interpretation, it has been understood that a fixed sum-phase relation between paired photons is the bedrock of quantum entanglement. Here, a coherently excited HOM model is proposed, analyzed, and discussed for the fundamental physics of two-photon correlation using linear optics-based polarization-basis control. For this, polarization-frequency correlation in a Mach-Zehnder interferometer is coherently excited using synchronized acousto-optic modulators, where polarization-basis control is conducted via a selective measurement process of the heterodyne signals. Like quantum operator-based destructive interference in the HOM theory, a perfectly coherent analysis shows the same HOM effects of the paired coherent photons on a beam splitter, whereas individual output intensities are uniform.


Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses.
Rituximab, a B cell-depleting therapy, is indicated for treating a growing number of autoantibody-mediated autoimmune disorders. However, relapses can occur after treatment, and autoantibody-producing B cell subsets may be found during relapses. It is not understood whether these autoantibody-producing B cell subsets emerge from the failed depletion of preexisting B cells or are generated de novo. To further define the mechanisms that cause postrituximab relapse, we studied patients with autoantibody-mediated muscle-specific kinase (MuSK) myasthenia gravis (MG) who relapsed after treatment. We carried out single-cell transcriptional and B cell receptor profiling on longitudinal B cell samples. We identified clones present before therapy that persisted during relapse. Persistent B cell clones included both antibody-secreting cells and memory B cells characterized by gene expression signatures associated with B cell survival. A subset of persistent antibody-secreting cells and memory B cells were specific for the MuSK autoantigen. These results demonstrate that rituximab is not fully effective at eliminating autoantibody-producing B cells and provide a mechanistic understanding of postrituximab relapse in MuSK MG.


Reversible interaction between androgen binding protein and testicular macromolecules causing inhibition of androgen binding activity.
Sertoli cells in culture isolated from immature rat testes secrete androgen binding protein (ABP) in the culture medium. Binding activity of ABP in concentrated medium was estimated with equilibrium dialysis against 1 nM dihydrotestosterone at 4 degrees C. The ABP protein activity was inhibited approximately 50% through addition of cytosol preparations from testis or liver, but not from brain tissue, to the concentrated culture medium; this inhibition remained constant for at least two days. The inhibitor is probably a macromolecule, because the activity could not be removed by charcoal treatment and dialysis. The percent inhibition of ABP binding activity was increased when increasing amounts of cytosol were added, it decreased in the presence of increased concentrations of androgens, but it was not influenced by variations of the concentration of ABP. Inhibition of androgen binding to ABP by cytosols in the presence of 1 nM testosterone could be reversed after dialysis in the presence of 10 nM testosterone. These results suggest a reversible competition between testosterone and the testicular macromolecule for ABP. The occurrence of this interaction between ABP and a testicular macromolecule can explain the variable results of estimated ABP binding activity in testis cytosol preparations.


The Kock pouch: initial experience and complications.
The modified Kock continent internal reservoir procedure has been performed on 15 patients at our medical center since December 1984: 13 underwent simultaneous anterior exenteration for pelvic malignancy, 1 had conversion from an ileal conduit and 1 underwent cystectomy for refractory interstitial cystitis. There was no operative mortality. There were 3 early complications: a urinary leak from the pouch in 2 patients that required re-exploration to close the defect, and an enteric-Kock pouch fistula in 1 that required resection of the small bowel fistula and repair of the pouch defect. All 3 patients are doing well. The late complication in 3 cases was urinary incontinence of the efferent nipple valve with difficulty in catheterization of the stoma. Two patients have undergone revision with a new efferent nipple valve added on to the pouch and creation of a new stoma. One patient is completely dry and continent, 1 has tolerable intermittent leakage and refuses a further operation, and 1 is awaiting revision. Although the initial experience is small, we are encouraged by these results and believe that this procedure is an alternative form of urinary diversion for the properly selected patient.


An eFace-Template Method for Efficiently Generating Patient-Specific Anatomically-Detailed Facial Soft Tissue FE Models for Craniomaxillofacial Surgery Simulation.
Accurate surgical planning and prediction of craniomaxillofacial surgery outcome requires simulation of soft-tissue changes following osteotomy. This can only be accomplished on an anatomically-detailed facial soft tissue model. However, current anatomically-detailed facial soft tissue model generation is not appropriate for clinical applications due to the time intensive nature of manual segmentation and volumetric mesh generation. This paper presents a novel semi-automatic approach, named eFace-template method, for efficiently and accurately generating a patient-specific facial soft tissue model. Our novel approach is based on the volumetric deformation of an anatomically-detailed template to be fitted to the shape of each individual patient. The adaptation of the template is achieved by using a hybrid landmark-based morphing and dense surface fitting approach followed by a thin-plate spline interpolation. This methodology was validated using 4 visible human datasets (regarded as gold standards) and 30 patient models. The results indicated that our approach can accurately preserve the internal anatomical correspondence (i.e., muscles) for finite element modeling. Additionally, our hybrid approach was able to achieve an optimal balance among the patient shape fitting accuracy, anatomical correspondence and mesh quality. Furthermore, the statistical analysis showed that our hybrid approach was superior to two previously published methods: mesh-matching and landmark-based transformation. Ultimately, our eFace-template method can be directly and effectively used clinically to simulate the facial soft tissue changes in the clinical application.


Potentiation of cocaine toxicity with calcium channel blockers.
Three calcium channel blockers were studied for efficacy in preventing seizures and death from cocaine intoxication. Rats were first pretreated with a test drug then subjected to high dose intraperitoneal cocaine. In this model, control animals developed seizures within six minutes, followed by death within ten minutes. Animals that were pretreated with diltiazem, nifedipine, or verapamil developed seizures significantly faster than controls, and at specific doses the death rate was higher than in controls for all three drugs. The potentiation of seizures and death by 2 mg/kg nifedipine pretreatment was further shown by challenge with three different doses of cocaine. This study fails to demonstrate a protective effect and suggests augmentation of cocaine toxicity by pretreatment with the three currently available calcium channel blockers. Several mechanisms by which calcium channel blockers may augment cocaine-induced toxicity are discussed.


Characterising the TP53-deleted subgroup of chronic lymphocytic leukemia: an analysis of additional cytogenetic abnormalities detected by interphase fluorescence in situ hybridisation and array-based comparative genomic hybridisation.
Deletion of the TP53 gene on chromosome 17p13.1 is the prognostic factor associated with the shortest survival in CLL. We used array-based comparative genomic hybridisation (arrayCGH) to identify additional DNA copy number changes in peripheral blood samples from 74 LRF CLL4 trial patients, 37 with >or=5% and 37 without TP53-deleted cells. ArrayCGH reliably detected deletions on 17p, including the TP53 locus, in cases with >or=50%TP53-deleted cells detected by fluorescence in situ hybridisation, plus seven additional cases with deleted regions on 17p excluding TP53. Losses on chromosomal regions 18p and/or 20p were found exclusively in cases with >or=5%TP53-deleted cells (p<0.001), 38% having one or both losses. The incidence of additional cytogenetic abnormalities, reflecting an increased chromosomal instability, was higher in >or=5%TP53-deleted cases (p=0.02). In particular, amplification of 2p and deletion of 6q were both more frequent. Cases with >20%TP53-deleted cells had the worst prognosis in the LRF CLL4 trial.


Interleukin-1α deficiency reduces adiposity, glucose intolerance and hepatic de-novo lipogenesis in diet-induced obese mice.
While extensive research revealed that interleukin (IL)-1β contributes to insulin resistance (IR) development, the role of IL-1α in obesity and IR was scarcely studied. Using control, whole body IL-1α knockout (KO) or myeloid-cell-specific IL-1α-deficient mice, we tested the hypothesis that IL-1α deficiency would protect against high-fat diet (HFD)-induced obesity and its metabolic consequences. To induce obesity and IR, control and IL-1α KO mice were given either chow or HFD for 16 weeks. Glucose tolerance test was performed at 10 and 15 weeks, representing early and progressive stages of glucose intolerance, respectively. Liver and epididymal white adipose tissue (eWAT) samples were analyzed for general morphology and adipocyte size. Plasma levels of adiponectin, insulin, total cholesterol and triglyceride (TG), lipoprotein profile as well as hepatic lipids were analyzed. Expression of lipid and inflammation-related genes in liver and eWAT was analyzed. Primary mouse hepatocytes isolated from control mice were treated either with dimethyl sulfoxide (DMSO) (control) or 20 ng/mL recombinant IL-1α for 24 hours and subjected to gene expression analysis. Although total body weight gain was similar, IL-1α KO mice showed reduced adiposity and were completely protected from HFD-induced glucose intolerance. In addition, plasma total cholesterol and TG levels were lower and HFD-induced accumulation of liver TGs was completely inhibited in IL-1α KO compared with control mice. Expression of stearoyl-CoA desaturase1 (SCD1), fatty acid synthase (FASN), elongation of long-chain fatty acids family member 6 (ELOVL6), acetyl-CoA carboxylase (ACC), key enzymes that promote de-novo lipogenesis, was lower in livers of IL-1α KO mice. Treatment with recombinant IL-1α elevated the expression of ELOVL6 and FASN in mouse primary hepatocytes. Finally, mice with myeloid-cell-specific deletion of IL-1α did not show reduced adiposity and improved glucose tolerance. We demonstrate a novel role of IL-1α in promoting adiposity, obesity-induced glucose intolerance and liver TG accumulation and suggest that IL-1α blockade could be used for treatment of obesity and its metabolic consequences.


Nup155 regulates nuclear envelope and nuclear pore complex formation in nematodes and vertebrates.
Nuclear envelope (NE) formation during cell division in multicellular organisms is a central yet poorly understood biological process. We report that the conserved nucleoporin Nup155 has an essential function in NE formation in Caenorhabditis elegans embryos and in Xenopus laevis egg extracts. In vivo depletion of Nup155 led to failure of nuclear lamina formation and defects in chromosome segregation at anaphase. Nup155 depletion inhibited accumulation of nucleoporins at the nuclear periphery, including those recruited to chromatin early in NE formation. Electron microscopy analysis revealed that Nup155 is also required for the formation of a continuous nuclear membrane in vivo and in vitro. Time-course experiments indicated that Nup155 is recruited to chromatin at the time of NE sealing, suggesting that nuclear pore complex assembly has to progress to a relatively late stage before NE membrane assembly occurs.


A cohort study of guselkumab in the treatment of psoriasis refractory to previous biologic therapies: effectiveness, safety and adherence.
Background Guselkumab is indicated for moderate-to-severe plaque psoriasis. Data from real-life clinical practice regarding its use are scarce, especially concerning patients who relapse after previous biologic therapies. Aim This study aimed to evaluate the effectiveness, safety, and adherence to guselkumab in psoriasis refractory to biologic therapies. Method This real-life, retrospective study included patients who initiated guselkumab between February 2019 and October 2020. The main objective was to assess effectiveness, expressed as the psoriasis area and severity index (PASI) ≤5, ≤2 and 0, at the first follow-up medical visit. As secondary effectiveness outcomes, we assessed the body surface area (BSA) and dermatology life quality index (DLQI). We also evaluated adverse events and adherence (using the medication possession ratio [MPR]). Results The study included 35 patients who had previously received a median of two biologic drugs. The median basal PASI score (IQR) was 11 (7.3-15.9), decreasing to 0 (0-1.4) at first follow-up medical visit. At this point, 32 patients (94.1%) reached PASI ≤5, 28 (82.4%) PASI ≤2 and 19 (55.9%) PASI 0. We also found statistically significant improvements in PASI, BSA and DLQI at first follow-up (p<0.001). Three patients developed adverse events. Most patients (N=29, 85.3%) had an MPR ≥90%. The MPR was not associated with PASI score at first follow-up. Conclusion Our study supports evidence that guselkumab is an effective and safe drug in psoriasis refractory to biologic therapies. Adherence to treatment is not related to effectiveness, suggesting that, in some cases, the interval between doses could be increased.


[Density distribution of human lymphocytes. II. Distribution patterns of malignant lymphocytes and their prognostic significance in patients with non-Hodgkin's lymphoma].
The aim of this study was to investigate the prognostic significance of density distribution profiles in non-Hodgkin lymphomas. Density profiles were evaluated by equilibrium centrifugation on linear polysucrose-metrizoat gradients. Biopsy cells from 44 untreated non-Hodgkin lymphomas in advanced stages according to their density patterns could be classified into one of two distinct groups: Group A lymphomas exhibited high to intermediate densities and resembled normal resting B or T lymphocytes; they showed low spontaneous proliferation and favourable histologies. Group B lymphomas exhibited light densities, resembling activated lymphocytes and frequently revealed high spontaneous proliferation and unfavourable histology. Within a minimal time of observation of 40 months only 28% of the group A but 75% of the Group B lymphomas died. Simultaneously performed surface marker studies excluded the possibility that variable proportions of normal lymphocytes contaminating the lymphoma suspensions are responsible for the two density groups. They rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into denser tumour clones with low spontaneous proliferation. We therefore conclude that analyses of density profiles from non-Hodgkin lymphomas represenmts a promising method for the prognostic classification of this disease.


Conformational aspects of the acid-induced fusion mechanism of influenza virus hemagglutinin. Circular dichroism and fluorescence studies.
Circular dichroism and tryptophan fluorescence spectroscopy have been used to investigate the structures of the influenza virus membrane glycoprotein hemagglutinin, acid-treated hemagglutinin, and fragments of hemagglutinin derived by proteolysis. The conformational change in hemagglutinin which occurs at the pH of membrane fusion (pH 5-6) was associated with a significant change of the environment of tyrosine residues, a change in the environment of tryptophan residues, but no changes in secondary structure. Tryptic digestion of the hemagglutinin in its low pH conformation which releases one of the subunit polypeptides (HA1) caused minimal changes in tyrosine and tryptophan environments but a small secondary structural change in HA1. The secondary structure of the remainder of the molecule (HA2) was very similar to that predicted from the known x-ray crystallographic structure of the native molecule. However, fluorescence spectroscopy indicated a tertiary change in structure in the coiled coil of alpha-helices which form the fibrous central stem of the molecule. These results are consistent with a conformational change required for membrane fusion which involves a decrease of HA1/HA1, HA1/HA2 interactions and changes in tertiary structure not accompanied by changes in secondary structure.


Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2.
The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the biological regulation of ASF/SF2 is unknown. Here, we report the crystal structure of an active fragment of human SRPK1 bound to a peptide derived from an SR protein. This structure led us to identify a docking motif in ASF/SF2. We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles. We further show that Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the C-terminal part of its RS domain. These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization.


Junctional epithelium and hemidesmosomes: Tape and rivets for solving the "percutaneous device dilemma" in dental and other permanent implants.
The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the "device"/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant - as a model percutaneous device - placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists.


Effective terminal sterilization using supercritical carbon dioxide.
Gentle alternatives to existing sterilization methods are called for by rapid advances in biomedical technologies. Supercritical fluid technologies have found applications in a wide range of areas and have been explored for use in the inactivation of medical contaminants. In particular, supercritical CO(2) is appealing for sterilization due to the ease at which the supercritical state is attained, the non-reactive nature, and the ability to readily penetrate substrates. However, rapid inactivation of bacterial endospores has proven a barrier to the use of this technology for effective terminal sterilization. We report the development of a supercritical CO(2) based sterilization process capable of achieving rapid inactivation of bacterial endospores while in terminal packaging. Moreover, this process is gentle; as the morphology, ultrastructure, and protein profiles of inactivated microbes are maintained. These properties of the sterilization process suit it for possible use on a wide range of biomedical products including: materials derived from animal tissues, protein based therapies, and other sensitive medical products requiring gentle terminal sterilization.


The use of amielle vaginal trainers as adjuvant in the treatment of vestibulodynia: an observational multicentric study.
To assess the effectiveness of a specific set of vaginal dilators (Amielle Comfort) as a part of vestibulodynia therapy. Fifteen women referred for vestibulodynia, localized vulvodynia, were advised to use vaginal dilators (Amielle Comfort) accompanied by standardized instructions, after previously receiving 1 or more therapies for the vestibulodynia. The post-treatment Marinoff scale for dyspareunia significantly improved in patients after vaginal dilator treatment compared with baseline values (2.2 +/- 0.4 vs 1.1 +/- 0.9; P < .01), and the Female Sexual Function Index scores were significantly improved compared with the prestudy values (16.3 +/- 5.5 vs 25.3 +/- 7.5; P < .01). Among women with previous therapy for vestibulodynia, vaginal dilator use was associated with improvement in symptoms. Vaginal dilators can play an important role in overcoming pelvic floor muscular responses that remain and sometimes increase after pain perception has decreased.


Infection ability of watermolds in some temperate fishes of Himalaya, India.
Infection ability tests of four species of the Saprolegniales viz., Brevilegnia subclavata Couch, Geolegnia inflata Coker & Braxton, Protoachlya oryzae Khulbe and Scoliolegnia centrica Khulbe were made by artificial inoculation experiments. Except Geolegnia inflata, all the three species parasitized the test fishes (Carassius auratus L., Puntius conchonius Ham., P. ticto Ham. and Nemacheilus rupicola). Two chemicals, namely boric acid and potassium permanganate were effective at 0.1 to 0.15 M concentrations against parasitic watermolds.


Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade.
Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling of inflammatory tumor microenvironments (TMEs) linked to immune-dependent control in mice. We found that early intratumoral accumulation of interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling of the TME and unleashed cytotoxic T cell (CTL)-mediated tumor eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 and EP4 receptors on NK cells, hampered the TME switch, and enabled immune evasion. Analysis of patient datasets across human cancers revealed distinct inflammatory TME phenotypes resembling those associated with cancer immune control versus escape in mice. This allowed us to generate a gene-expression signature that integrated opposing inflammatory factors and predicted patient survival and response to immune checkpoint blockade. Our findings identify features of the tumor inflammatory milieu associated with immune control of cancer and establish a strategy to predict immunotherapy outcomes.


Highly dispersed sulfur in a porous aromatic framework as a cathode for lithium-sulfur batteries.
Lithium-sulfur (Li-S) batteries are attractive candidates for transportation applications because of their high energy density (2600 W h kg(-1)). However, Li-S batteries have failed to achieve commercial success, due to the rapid capacity fading with cycling caused mainly by the "shuttle" phenomenon. Here, we report a feasible approach to mitigate this issue using a porous aromatic framework (PAF) as a hosting substrate in Li-S batteries. As a cathode material, the composite of PAF with sulfur exhibits high capacity and excellent cycling stability in both a sulfone electrolyte, 1.0 M LiPF6-MiPS, and an ionic liquid electrolyte, 0.5 M LiTFSI-MPPY·TFSI.


Spontaneously infarcted fibroadenoma of the breast in an adolescent girl: sonographic findings.
Spontaneous infarction in fibroadenoma unrelated to any known risk factors is extremely rare. Here, I present a case of a spontaneously infarcted fibroadenoma in an adolescent girl in whom no plausible predisposing factors were identified. High-resolution sonographic imaging showed a unique circumscribed, complex echoic mass containing a frondular solid portion.


Role of Oral Health, Frailty, and Minimal Hepatic Encephalopathy in the Risk of Hospitalization: A Prospective Multi-Center Cohort of Outpatients With Cirrhosis.
Hospitalizations are a sentinel event in cirrhosis; however, the changing demographics in patients with cirrhosis require updated hospitalization prediction models. Periodontitis is a risk factor for liver disease and potentially progression. The aim of this study was to determine factors, including poor oral health, associated with 3-month hospitalizations in a multi-center cohort of outpatients with cirrhosis. North American Consortium for Study of End-stage Liver Disease (NACSELD-3), a new study cohort, recruits outpatients with cirrhosis. Cirrhosis details, demographics, minimal hepatic encephalopathy (MHE), frailty, and comorbid conditions including oral health were collected. All patients were followed for 3 months for nonelective hospitalizations. Multi-variable models were created for this outcome using demographics, cirrhosis details, oral health, MHE, frailty, and comorbid conditions with K-fold internal validation using 25%/75% split. A total of 442 outpatients (70% men; 37% compensated; Model for End-stage Liver Disease-Sodium, 12; 42% ascites; and 33% prior HE) were included. MHE was found in 70%, frailty in 10%; and both in 8%. In terms of oral health, 15% were edentulous and 10% had prior periodontitis. Regarding 3-month hospitalizations, 14% were admitted for mostly liver-related reasons. These patients were more likely to be decompensated with higher cirrhosis complications, MHE, frailty and periodontitis history. Multi-variable analysis showed prior periodontitis (P = .026), composite MHE + frailty score (P = .0016), ascites (P = .004), prior HE (P = .008), and hydrothorax (P = .004) were associated with admissions using the training and validation subsets. In a contemporaneous, prospective, multi-center cohort study in outpatients with cirrhosis, poor oral health is significantly associated with 3-month hospitalizations independent of portal hypertensive complications, MHE, and frailty. Potential strategies to reduce hospitalizations should consider oral evaluation in addition to MHE and frailty assessment in practice pathways.


Amyloidosis.
Amyloidosis is an uncommon plasma-cell dyscrasia with an incidence of eight patients per million per year. It is often difficult to recognize because of the myriad symptoms and vague nature of the clinical presentation. Symptoms include fatigue, dyspnea, edema, paresthesias, and weight loss. Clinical syndromes at presentation include nephrotic-range proteinuria with or without renal insufficiency, cardiomyopathy, hepatomegaly, symptomatic peripheral neuropathy, and autonomic failure. Recent advances have occurred in evaluation of patients by using the free light chain assay and new prognostic assessments with cardiac biomarkers. Newly developed therapeutic strategies, involving high-dose and intermediate-dose chemotherapy, have evolved in the last 3 years. This paper reviews a diagnostic pathway clinicians can use to diagnose the disorder, assess a patient's prognosis, and logically plan a therapeutic strategy.


Accidental macular injury from short-term exposure to a handheld high-intensity LED light.
To report a case of macular injury caused by short-term exposure to a handheld high-intensity light emitting diode (LED) light. Interventional case report. A patient with macular injury caused by short-term exposure to the light of a handheld high-intensity LED device. The patient was examined and followed for 3 months after exposure with ophthalmologic examinations (including funduscopy, optical coherence tomography [OCT], fluorescein angiography [FA], and multifocal electroretinography [mfERG]). The injured eye was treated with one retrobulbar injection of 20 mg triamcinolone acetonide at 5 days after exposure. Visual acuity, ophthalmoscopic, and OCT findings. 3 days after exposure, the best corrected visual acuity (BCVA) of the right eye was 6/20. OCT revealed the acute stage of the injury with eminence of the retinal pigment epithelium (RPE). BCVA was improved to 16/20 and 20/20 at 19 and 33 days after exposure, respectively. OCT results of follow-ups at five days, 19 days, 33 days and 3 months after exposure have demonstrated the restoration process of the injury. Short-term exposure to high-intensity LED light may cause damage to the retina. As the expansion of LED use in modern life, education and supervision are of urgent need for public health.


Structure-Based Optimization of Coumarin hA3 Adenosine Receptor Antagonists.
Adenosine receptors participate in many physiological functions. Molecules that may selectively interact with one of the receptors are favorable multifunctional chemical entities to treat or decelerate the evolution of different diseases. 3-Arylcoumarins have already been studied as neuroprotective agents by our group. Here, differently 8-substituted 3-arylcoumarins are complementarily studied as ligands of adenosine receptors, performing radioligand binding assays. Among the synthesized compounds, selective A3 receptor antagonists were found. 3-(4-Bromophenyl)-8-hydroxycoumarin (compound 4) displayed the highest potency and selectivity as A3 receptor antagonist (Ki = 258 nM). An analysis of its X-ray diffraction provided detailed information on its structure. Further evaluation of a selected series of compounds indicated that it is the nature and position of the substituents that determine their activity and selectivity. Theoretical modeling calculations corroborate and explain the experimental data, suggesting this novel scaffold can be involved in the generation of candidates as multitarget drugs.


Genetic variations in serum lipid levels of inbred mice and response to hypercholesterolemic diet.
The serum lipid contents of a number of inbred and congenic strains of mice were measured. There were inter-strain variations in each of the lipid fractions in mice fed a normal diet. Male and female C3H mice had the highest total cholesterol level; AKR mice showed the lowest values. Serum phospholipids were correlated well with cholesterolemia. The greatest variations between strains were in the triglyceride levels. There also was significant variation in the high density lipoprotein cholesterol serum levels (from 73-88% of the total cholesterol). The response to a hypercholesterolemic diet (1% cholesterol) was tested in seven inbred strains. All strains showed changes in serum cholesterol and in the proportions of the lipoproteins fractions. There was a large increase in the low density lipoprotein + very low density lipoprotein fractions. Feeding the diet revealed marked interstrain differences in the responses of the serum cholesterol and electrophoretic lipoprotein profiles. The C57BL/6 and B10.D2 strains were hyperresponders to the hypercholesterolemic diet with 71% and 63% of their serum cholesterol in the low density lipoprotein plus very low density lipoprotein fractions, respectively.


A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes.
P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR's related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.


Pressure and temperature dependencies of air-perturbed O2 B-band line shapes.
The air-broadened lines from the oxygen B band were measured for the first time in controlled laboratory conditions with a high signal-to-noise ratio using frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) referenced to the optical frequency comb. Spectra measured at various pressures and temperatures were analyzed with an advanced line-shape model, considering the speed-dependence of collisional broadening and shift, and the effect of velocity-changing collisions. The temperature dependence of collisional broadening and shift is determined, whereas no significant temperature dependence of speed-dependent parameters and Dicke narrowing was observed. In addition, we have demonstrated that reasonable estimation of temperature dependence for pressure broadening is possible even from measurements done in single temperature where the speed dependence of pressure broadening was determined. New spectroscopic data improve the accuracy of the air-broadened oxygen B-band spectra description by an order of magnitude.


Pancreatitis and anomalous union of the pancreaticobiliary ductal system in childhood.
From January 1978 to December 1989, 48 patients were diagnosed as having anomalous union of the pancreaticobiliary ductal system (AUPBD) at the Second Department of Surgery, Kanazawa University Hospital and its affiliated hospitals. Among these 48 patients, 13 (28.1%) were children under 13 years of age. Four of these patients had acute pancreatitis. The clinical, radiological, and surgical features of these patients are presented. The chief presenting complaint was epigastric pain in all cases; three patients had recurrent episodes of epigastric pain and had been diagnosed as having autotoxicosis. AUPBD was clearly demonstrated in all patients, three by endoscopic retrograde cholangiopancreatography (ERCP) and one by operative cholangiography. At operation, macroscopic evidence of pancreatitis was recognized in all cases. In one case, roentogenolucent pancreaticolithiases were seen on ERCP. We consider AUPBD as an important cause of pancreatitis in children and advocate ERCP in children who are suspected having biliary tract or pancreatic disease. The diagnosis of AUPBD should be considered when children with abdominal pain and elevated serum or urinary amylase levels are evaluated.


Open pulmonary embolectomy for treatment of major pulmonary embolism.
Inadequate data exist regarding the management of acute major pulmonary embolism. Various modalities that are used, including thrombolytics and embolectomy, have not been shown to conclusively improve mortality when compared to heparin. In the past, open pulmonary embolectomy was reserved for patients with severe hemodynamic instability because of its high mortality rate. Our objective was to analyze our experience with early embolectomy as an alternative for the treatment of major pulmonary embolism. A retrospective review of charts of all patients undergoing pulmonary embolectomy at our institution over the last two years was performed. Patients were followed until their discharge from hospital. There were 13 patients (7 women and 6 men). Four had massive and 9 had submassive pulmonary embolism. There was one mortality. Postoperative echocardiography showed no evidence of pulmonary hypertension in 7. Open pulmonary embolectomy can be performed in patients with major pulmonary embolism with minimal mortality and morbidity. It may prevent the development of chronic thromboembolic pulmonary hypertension and should be a part of the algorithm in the treatment of major pulmonary embolism.


Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals.
The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY*A and FY*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals.


Pathogenesis and significance of urogenital mycoplasmal infections.
U. urealyticum and M. hominis can no longer be considered as harmless commensals of the lower genitourinary tract. Both can produce disease in humans. Diagnosis and management of infections due to these organisms must be based upon isolation of the organisms from the affected site and preferably the number of organisms present. Due to the frequent resistance of both organisms to tetracycline, treatment must be based upon appropriate antibiotic sensitivities. For a more detailed description of the basic biology of these organisms and isolation and identification and treatment, the reader is referred to several recent reviews.


The fate of methyl salicylate in the environment and its role as signal in multitrophic interactions.
Phytohormones emitted into the atmosphere perform many functions relating to the defence, pollination and competitiveness of plants. To be effective, their atmospheric lifetimes must be sufficient that these signals can be delivered to their numerous recipients. We investigate the atmospheric loss processes for methyl salicylate (MeSA), a widely emitted plant volatile. Simulation chambers were used to determine gas-phase reaction rates with OH, NO3, Cl and O3; photolysis rates; and deposition rates of gas-phase MeSA onto organic aerosols. Room temperature rate coefficients are determined (in units of cm3 molecule-1 s-1) to be (3.20 ± 0.46) × 10-12, (4.19 ± 0.92) × 10-15, (1.65 ± 0.44) × 10-12 and (3.33 ± 2.01) × 10-19 for the reactions with OH, NO3, Cl and O3 respectively. Photolysis is negligible in the actinic range, despite having a large reported near-UV chromophore. Conversely, aerosol uptake can be competitive with oxidation under humid conditions, suggesting that this compound has a high affinity for hydrated surfaces. A total lifetime of gas-phase MeSA of 1-4 days was estimated based on all these loss processes. The competing sinks of MeSA demonstrate the need to assess lifetimes of semiochemicals holistically, and we gain understanding of how atmospheric sinks influence natural communication channels within complex multitrophic interactions. This approach can be extended to other compounds that play vital roles in ecosystems, such as insect pheromones, which may be similarly affected during atmospheric transport.


Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis.
Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non-alcoholic steatohepatitis. To investigate the role of insulin sensitizers in the treatment of individuals with non-alcoholic steatohepatitis (NASH). A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 +/- 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment-insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 +/- 24.2 to 33.3 +/- 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 +/- 46.3 to 47.3 +/- 34.5 IU/L, P < 0.001] and histological features (median non-alcoholic fatty liver disease activity score: 5.0-3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 +/- 11.1 to 30.0 +/- 8.6 IU/L, P < 0.01; ALT: 66.9 +/- 28.9 to 42.0 +/- 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high-sensitivity C-reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.


Detection of P-glycoprotein-mediated multidrug resistance against anthelmintics in Haemonchus contortus using anti-human mdr1 monoclonal antibodies.
The "multidrug resistance" (MDR) system involves the action of transmembrane P-glycoproteins (Pgp) which may be responsible for failure of chemotherapy in both invertebrates and vertebrates. We previously obtained partial reversion of anthelmintic resistance in nematodes subjected to both anthelmintics and inhibitors of this system. The results presented here are able to describe more accurately the presence of Pgp in nematodes because of the use of C219 and UIC2 monoclonal antibodies, which are used for the detection of human and mouse mdr1 gene products. These antibodies demonstrated the presence of Pgp in eggshells. Their role in these structures, which are considered to be passive barriers, remains to be determined. Flow cytometry analyses of the UIC2 staining allowed determination of the resistance of individuals, which varied within the parasite population. UIC2 demonstrated both the presence and activity of Pgp in nematodes as has previously been shown in tumour cells. Resistance seems to be due to an increase in both the number of Pgp sites and parasites with high levels of Pgp.


Emerging solute-induced mineralization in Arctic rivers under climate warming.
Permafrost degradation under a warming climate is accelerating the hydrological processes in Arctic river basins. However, corresponding changes in river mineralization, riverine solute exports and their potential influencing factors are not fully understood. In this study, we selected six major Arctic rivers (Ob, Yenisei, Lena, Kolyma, Yukon and Mackenzie Rivers) with different permafrost extents, meteorological conditions and hydrological regimes to reveal the changes in river mineralization and riverine solute exports using ArcticGRO sampling data from 2003 to 2019. Our results indicate that solute-induced river mineralization has already been observed in the Lena, Yukon and Mackenzie Rivers during 2003-2019. The annual flux of total dissolved solids (TDS; a key parameter of drinking water quality), calculated by the Load Estimator (LOADEST) program, from these six rivers was approximately 295.24 ± 12.50 Tg, with the Ob, Kolyma and Yukon Rivers exhibiting significant increasing trends (p < 0.05) at rates of 4.38 Tg/10 yr, 1.62 Tg/10 yr and 3.03 Tg/10 yr, respectively. Climate-induced changes in hydrological regimes regulate riverine solute exports, with relatively higher TDS concentrations in the groundwater-dominated winter low-flow season and lower TDS concentrations under the dilution of groundwater by snowmelt spring floods and summer precipitation events. The riverine solute fluxes with higher TDS concentrations (e.g., those of the Yukon and Mackenzie Rivers) increased more rapidly (~0.14 Tg/km3) with changes in river discharge; however, the TDS concentrations were more sensitive to climate warming in continuous permafrost-dominated colder basins (i.e., the Kolyma and Lena River basins) than in other relatively warmer basins. Our results suggest that riverine solute exports are likely affected by permafrost thaw-induced changes in hydrogeological processes, which are tightly associated with increases in active layer thickness and enhanced groundwater discharge to rivers. Under a warming climate, riverine solute exports in Arctic rivers are expected to increase with intensifying groundwater-surface water exchanges.


[Conservative therapy of coronal fractures with reattachment of the original fragment: indications for periodontal treatment].
The AA, analyse the relation between dental fracture and relative parodontal tissues. A clinical case, treated with an intervention of parodontal surgery and with sticking of the coronal fragment, is shown.


Correction to: Parenting as a Mediator of Associations between Depression in Mothers and Children's Functioning: A Systematic Review and Meta-Analysis.
The original version of the article requires a correction to one of the sentences. Under the section 'Limitations', the last sentence 'Findings of no support for mediation was also deemed important as, for example, our findings suggest..' should read as below. Also important were where we found no support for moderation of the mediation model; for example, our findings suggest that parenting as a mediator of associations between depression and child functioning is concerning regardless of the ages of the children, for both sons and daughters, and for a broad range of aspects of children's functioning.


Effects of Carbamazepine in Bivalves: A Review.
Carbamazepine (CBZ) is among the ten most frequent pharmaceuticals that occur in the aquatic systems, with known effects on inhabiting organisms, including bivalves. Bivalves are important species in coastal ecosystems, often exhibiting a dominant biomass within invertebrate communities. These organisms play a major role in the functioning of the ecosystem and particularly in food webs (as suspension-feeders) and represent a significant fraction of the fisheries resource. They also have strong interactions with the environment, water and sediment and are considered good bioindicator species. The present paper reviews the known literature on the impacts of CBZ in biological endpoints of marine bivalves exposed to environmentally and non-environmentally relevant concentrations, highlighting differences in terms of biological responses, associated with exposure period, concentrations tested, and species used. Overall, the literature available showed that CBZ induces individual and sub-individual effects in marine bivalves (adults and life stages) and the most common effect reported was the induction of oxidative stress.


Functional genomics of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1.
Nitrate-reducing bacteria of the recently recognized Azoarcus/Thauera group within the Betaproteobacteria contribute significantly to the biodegradation of aromatic and other refractory compounds in anoxic waters and soils. Strain EbN1 belongs to a distinct cluster (new genus) and is the first member of this phylogenetic group, the genome of which has been determined (4.7 Mb; one chromosome, two plasmids) by [Rabus R, Kube M, Heider J, Beck A, Heitmann K, Widdel F, Reinhardt R (2005) The genome sequence of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1. Arch Microbiol 183:27-36]. Ten anaerobic and four aerobic aromatic-degradation pathways were recognized on the chromosome, with the coding genes mostly forming clusters. Presence of paralogous gene clusters (e.g. for anaerobic ethylbenzene degradation) suggests an even broader degradation spectrum than previously known. Metabolic versatility is also reflected by the presence of multiple respiratory complexes and is apparently controlled by an extensive regulatory network. Strain EbN1 is unique for its capacity to degrade toluene and ethylbenzene anaerobically via completely different pathways. Bioinformatical analysis of their genetic blueprints and global expression analysis (DNA-microarray and proteomics) of substrate-adapted cells [Kühner S, Wöhlbrand L, Fritz I, Wruck W, Hultschig C, Hufnagel P, Kube M, Reinhardt R, Rabus R (2005) Substrate-dependent regulation of anaerobic degradation pathways for toluene and ethylbenzene in a denitrifying bacterium, strain EbN1. J Bacteriol 187:1493-1503] indicated coordinated vs sequential modes of regulation for the toluene and ethylbenzene pathways, respectively.


Long-term Trends in Infection-Related Mortality in Adults Treated With Maintenance Dialysis.
Infection is 1 of the top 3 causes of death in patients receiving maintenance dialysis. We evaluated the trends over time and risk factors for infection-related deaths among people receiving dialysis. Retrospective cohort study. We included all adults who began dialysis between 1980 and 2018 in Australia and New Zealand. Age, sex, dialysis modality, and dialysis era. Infection-related death. Incidence was described and standardized mortality ratios (SMR) calculated for infection-related death. Fine-Gray subdistribution hazards models were fitted, with non-infection-related death and kidney transplantation treated as competing events. The study comprised 46,074 patients who received hemodialysis and 20,653 who were treated with peritoneal dialysis who were followed for 164,536 and 69,846 person-years, respectively. There were 38,463 deaths during the follow-up period, 12% of which were ascribed to infection. The overall rate of mortality from infection (per 10,000 person-years) was 185 and 232 for patients treated with hemodialysis and peritoneal dialysis, respectively. The rates were 184 and 219 for males and females, respectively; and 99, 181, 255, and 292 for patients aged 18-44, 45-64, 65-74, 75 years and over, respectively. The rates were 224 and 163 for those commencing dialysis in years 1980-2005 and 2006-2018, respectively. The overall SMR declined over time, from 37.1 (95% CI, 35.5-38.8) in years 1980-2005 to 19.3 (95% CI, 18.4-20.3) in years 2006-2018, consistent with the declining 5-year SMR trend (P<0.001). Infection-related mortality was associated with being female, older age, and Aboriginal and/or a Torres Strait Islander or Māori. Mediation analyses defining the causal relationships between infection type and infection-related death could not be undertaken as disaggregating the data was not feasible. The excess risk of infection-related death in patients on dialysis has improved substantially over time but remains more than 20 times higher than in the general population.


Impact of comorbidities on ischemic stroke outcomes in women.
We assessed the association of prestroke comorbidities with long-term stroke outcomes among women with ischemic stroke. Prestroke comorbid conditions in 133 women admitted with acute ischemic stroke were scored with the Charlson Index (CI). We assessed whether the CI and other specific conditions were associated with modified Rankin Score (mRS) at 90 days or more poststroke. After adjustment for initial NIHSS and age, higher CI was the sole factor independently associated with poorer 90 day mRS scores. When CI was excluded, coronary disease and diabetes were independently associated with poorer outcome. The extent of comorbidities as assessed by the CI is independently associated with 90-day mRS among women with ischemic stroke, but the individual comorbidities of CHD and DM were each associated with functional outcome.


What is the specificity of the response to the own first-name when presented as a novel in a passive oddball paradigm? An ERP study.
One's own first-name is a special stimulus: one's attention is more likely captured by hearing one's own first-name than by hearing another first-name. Previous event-related potential (ERP) studies demonstrated that this special stimulus produces differential responses both in active and in passive condition. Such results suggest that passively hearing one's own first-name triggers processing levels generally activated by the explicit detection of stimuli. This questions about the particular power of the own first-name to automatically orient attention, but no study investigated the specific response to this special stimulus in a paradigm designed to study automatic attention orienting. In this ERP study, we compared the responses elicited by the own first-name (OWN) and one unfamiliar first-name (OTHER) presented, rarely, randomly and at the same frequency among repetitive tones (i.e., as novel stimuli in an oddball paradigm) while subjects (N=36) were watching a silent movie with subtitles. We tested at what latency the responses to OWN and OTHER diverge, and whether OWN modulates the brain orienting response (novelty P3). Data analysis showed specific responses to OWN after 300 ms. OWN only evoked a central negativity (320 ms) and a parietal positivity (550 ms). However, OWN had no significant effect on the brain orienting response (260 ms). Our results confirm that the own first-name does elicit a late specific brain response. However, they challenge the idea that in passive condition, the own first-name is systematically more powerful than another first-name to orient attention when it is heard unexpectedly.


Accuracy of a 3D printed sleeveless guide system used for fiber post removal: An in vitro study.
The removal of fiber post is often a challenging task. A 3D printed assembled sleeveless system that guides the head of the handpiece instead of the drill was developed to address this issue. This study aimed to evaluate the accuracy of this novel guide system using an in vitro approach. A standard maxillary typodont was digitized. The right first molar, the right central incisor, the left first premolar, and the left second molar in the digitized dentition were virtually crown-amputated. Four cylinders (diameter: 6 mm, height: 12 mm) were positioned along the directions of the main roots of these teeth to establish the virtual test model. Ten copies of the test model were printed using light-polymerizing resin. Four assembled sleeveless guide systems targeting the cylindrical axes were designed and printed using titanium alloy. One senior prosthodontist performed the drilling task targeting each cylindrical axis aided by the guide system or freehand (20 teeth each). The drilled models were scanned. The coordinates of the centers of all perforations and circular bases on the coronal and apical surfaces were obtained. The linear and angular deviations between the actual drilling path and the cylindrical axis for each tooth were calculated and analyzed. The guided group exhibited significantly smaller linear and angular deviations than the freehand group (coronal linear deviation: 0.19 ± 0.09 mm vs. 0.35 ± 0.18 mm, p = 0.0012; apical linear deviation: 0.54 ± 0.19 mm vs. 1.71 ± 0.51 mm, p < 0.001; angular deviation: 2.67 ± 1.07° vs. 8.48 ± 2.86°, p < 0.001). The accuracy of the 3D printed assembled sleeveless guide system used for fiber post removal is superior to that of the freehand method within the limits of an in vitro design. For the removal of fiber posts, the present 3D printed sleeveless guide system can provide better accuracy that the conventional freehand method. This may justify the diffusion of the guided technique for fiber post removal.


An in vitro comparison of the Erbium: YAG laser and the carbon dioxide laser in laryngeal surgery.
This study compares the relative thermal damage caused by a surgical CO2 laser and the Erbium:YAG laser when used to incise the human vocal fold in vitro. Results show that charring is completely eliminated when using the Erbium:YAG laser. The depth of coagulative necrosis adjacent to an incision is reduced from 510 microns (+/- 75) using the CO2 laser to 23 microns (+/- 12) using the Ebrium:YAG laser and at the base is reduced from 125 microns (+/- 45) using the CO2 laser to 12 microns (+/- 8) using the Erbium:YAG laser. The potential advantages regarding post-operative healing after laryngeal surgery are discussed.


The iron link between malaria and invasive non-typhoid Salmonella infections.
Epidemiological studies have demonstrated an association between malaria and invasive non-typhoid Salmonella (NTS) infections, especially in children. We explore the role of iron as a possible cofactor in this association. Malarial disease, among others, is associated with enhanced erythrophagocytosis and inflammation, which increases the iron content of macrophages and thereby also the survival of Salmonella spp. within macrophages. Whether iron supplementation programs augment the risk of invasive NTS infections in malaria-endemic regions is an important global health issue that still needs to be determined.


Testing a single dominant gene theory without an accepted criterion variable.
In testing a single dominant gene hypothesis we often are not able directly to measure the inherited trait. A typical situation is one where we only have one or more fallible indicators of the trait under study. The statistical method proposed requires that we have measurements on several such indicators for each of the parents of probands known to possess the trait.


Trigger tool versus verbal inventory to detect surgical complications.
Traditionally, registering complications after surgery is based on voluntary reporting or incident reports. These methods may fail to detect the total number of complications. A trigger tool was developed to detect complications in hospitalized surgical patients. In this diagnostic study, we compared its sensitivity and specificity with the verbal inventory by surgical staff and residents. A set of 31 potential triggers was chosen based on a systematic review and availability in hospital databases. The trigger tool was developed using multivariable regression and Receiver Operating Characteristic (ROC) analyses. A reference standard consisted of 300 patients, 150 with and 150 without complications. Sensitivity and specificity of the trigger tool and verbal inventory were determined. The final trigger tool consisted of nine triggers. Sensitivities of the trigger tool and verbal inventory were 70.7 vs. 78.7%, respectively, while specificities were 70.0 vs. 100.0%, respectively. Sensitivity values to detect major complications were 97.2 vs. 80.6%, respectively. The proposed customized trigger tool for a university hospital to detect surgical patients with complications appeared as accurate as a verbal inventory and even more accurate to detect major complications.


Allergic reactions to raw, pasteurized, and homogenized/pasteurized cow milk: a comparison. A double-blind placebo-controlled study in milk allergic children.
Five children aged 12-40 months with IgE-mediated adverse reactions to cow milk (immediate onset clinical pattern of cow milk allergy) were orally challenged double-blind in random order with three different milk preparations processed from the same batch of milk 1) raw untreated cow milk, 2) pasteurized cow milk, 3) homogenized and pasteurized cow milk, and 4) Nutramigen (a commercial hypoallergenic infant formula based on hydrolysed casein) as placebo. Skin prick tests with the same preparations were also performed. On oral challenge the three different processed milk types provoked significant and similar allergic reactions in each child, and no adverse reactions followed the challenge with placebo (Nutramigen). Skin prick test with the same milk products were positive in all children and comparable to the results with an extract of purified raw cow milk protein (Soluprick), whereas Nutramigen did not elicit any skin reactions. A tendency towards a lower threshold of reaction and larger skin reactions induced by the processed milk preparations might indicate an increased ability of pasteurized and homogenized/pasteurized milk to evoke allergic reactions in patients allergic to milk.


Laboratory study highlights the key influences of stormwater sediment thickness and bioturbation by tubificid worms on dynamics of nutrients and pollutants in stormwater retention systems.
In urban area, the accumulation of polluted stormwater sediments (SWS) in retention ponds may be a source of dissolved pollutants and nutrients for the aquatic ecosystems. Our objective was to quantify the influence of the thickness of SWS layer and the occurrence of tubificid worms on organic matter processing (O(2) uptake and fluxes of NH(4)(+), NO(3)(-), PO(4)(3-), and dissolved organic carbon between sediment and water), releases of 17 PAHs and 4 heavy metals, and microbial characteristics. Results showed that oxidation of SWS organic matter (O(2) and NO(3)(-) uptakes) and releases of nutrients were significantly increased by the quantity of accumulated SWS and the worm bioturbation. Releases of acenaphtene and naphthalene from sediments were significantly increased by the thickness of the SWS layer. In contrast, tubificid worms did not promote the mobilization of pollutants. In conclusion, biological activities and stormwater sediment characteristics need to be assessed to quantify the fate of pollutants and nutrients in stormwater retention ponds.


Plasma exchange for paediatric kidney disease-indications and outcomes: a single-centre experience.
Outcome data in paediatrics regarding the use of plasmapheresis for immunological kidney disease are scarce. We aimed to evaluate the role of plasmapheresis in children presenting with severe renal impairment secondary to immunological kidney diseases. A retrospective chart review of children admitted between January 2009 and August 2013 to the Paediatric Nephrology Unit, Christian Medical College, Vellore, India, and requiring plasma exchange was undertaken. Demographic and clinical data were studied and descriptive statistics applied for analysis. Sixteen children underwent plasmapheresis with a male:female ratio of 10:6 and a mean age of 10.2 years (range 5-15 years). Twelve children had atypical haemolytic uraemic syndrome, two had anti-glomerular basement disease and one each had lupus nephritis with neurological manifestation and anti-nuclear cytoplasmic antibody-associated vasculitis. The mean serum creatinine at presentation was 6.52 [interquartile range (IQR) 4.96-7.85] mg/dL with a mean eGFR of 43 (IQR 27.54-56.7) mL/min/1.73 m(2). Other presenting features included nephrotic range proteinuria (69%), gross haematuria (27%), hypertension (94%) and seizures (37.5%). All children received 1.5 times plasma volume plasmapheresis (mean 11 sessions, range 5-26), dialysis and immunosuppressive therapy. The mean duration of follow-up was 4 months (range 2-24 months) with a majority of the children (15/16, 93.75%) surviving acute illness. One child died of overwhelming sepsis and another was lost to follow-up. Of the survivors, eight had eGFR >60 mL/min/1.73 m(2), while eGFR was 15-60 mL/min/1.73 m(2) in the remaining six children. Eight children were still requiring antihypertensive medications and two were continuing peritoneal dialysis at the last follow-up. Thus early introduction of plasmapheresis along with other supportive therapy in immunological kidney disease may improve outcome.


Cryptococcal meningitis in pregnancy.
Cryptococcal meningitis was diagnosed in a pregnant woman at 21 weeks' gestation. The availability of fetal tissues, blood, and amniotic fluid in such a patient receiving therapy with amphotericin B plus flucytosine afforded the opportunity to study the effects of the disease and therapeutic agents on the developing fetus. The amphotericin B concentration in amniotic fluid was 0.25 micrograms/ml and that of flucytosine was 168 micrograms/ml. The concentrations in cord blood were 0.3 micrograms/ml and 64.7 micrograms/ml, respectively. No evidence was found of amphotericin B or flucytosine toxicity in fetal tissues, although exposure of the fetus to these compounds was of brief duration.


Organotin contamination in sediments from the Western Mediterranean enclosures following 10 years of TBT regulation.
Organotin (OT) compounds, namely butyl and phenyl, were measured in 38 recent sediments collected in harbours of the Western Mediterranean Sea (Northern: 4 and Southern: 9) and domestic and industrial sewage disposal sites (Northern: 9 and Southern: 1). Butyltins were the predominant tin species identified as being tributyltin (TBT) widespread in the whole area which suggests recent inputs of OTs. The highest levels of TBT were detected in commercial harbours associated with inputs from large vessels (average value: 5.0 microg TBT g(-1). Moreover, relatively high TBT values were also detected in fishing and recreational boating areas (average level ca. 1.0 microg TBTg(-1)). Phenyltin derivatives occurred at lower levels than butyltins being the monophenyltin the predominant compound (average values 45-945 ng g(-1)). The large predominance of the phenyltin degradation products (i.e. mono and diphenyltin) over the parent compound (i.e. triphenyltin) suggests that there are almost no recent inputs of these compounds. Furthermore, a comparative study of the OT occurrence in the sewage sludge disposal sites offshore Barcelona and Almeria (domestic) and into the Tarragona harbour (industrial) shows that domestic primary sewage sludge effluents can contribute to coastal OT pollution (244ng TBT g(-1)). Nevertheless, sewage sludge is a secondary source of OT contamination in the coastal environment in comparison to commercial harbours. In a comparative study with previous data collected in the late 1980s, the present study reveals that OT regulations established in the Mediterranean region in 1991 on the use of TBT-based antifouling paints have been effective in marinas, but reveals a significant TBT contamination in commercial and fishing harbours.


Effect of S0/X0 ratio and acclimation on respirometry of activated sludge in the cometabolic biodegradation of phenolic compounds.
Aerobic batch biodegradation experiments and respirometric analysis were performed in order to investigate the effect of S(0)/X(0) (substrate/biomass) ratio and preliminary acclimation on bi-solute biodegradation of phenolic compounds. It was shown that 2-chlorophenol (2-CP) and 2-nitrophenol (2-NP) could be cometabolically biodegraded only with acclimated biomass in the presence of phenol as growth substrate. Acclimation resulted in domination of phenol oxidizing bacteria which could induce the necessary enzymes for cometabolic transformation of 2-CP and 2-NP. Biodegradation of the cometabolic compounds occurred even after depletion of phenol at resting cell conditions. Both compounds could be successfully biodegraded by the acclimated biomass at initial substrate concentrations as high as 300 mg/L. Respirometric analysis showed that the optimum S(0)/X(0) ratio ranged between 1.5 and 5.5mg COD(eq)/mg MLSS for cometabolic substrates 2-CP and 2-NP, whereas it was as high as 8.5mg COD(eq)/mg MLSS for phenol which corresponds to a phenol concentration of about 1500 mg/L.


Linear dichroism studies of binding site structures in solution. Complexes between DNA and basic arylmethane dyes.
The interaction between B-form DNA and twelve cationic triaryl-methane dyes was studied with respect to optical properties and stabilities, using linear dichroism (LD) and aqueous two-phase partition techniques. Monovalent dyes derived from crystal violet as a rule form a single strong complex (K1 ca 10(5) M-1; site density per nucleotide base n1 ca 0.1 at 0.1M ionic strength) in which the plane of the dye is at an angle of less than 50 degrees to the local DNA helix axis. The complex with fuchsin is weaker (10(4) M-1) but can be explained by a similar orientation. For some of the dyes (those with pseudo-C2v symmetry) the angular orientations of two molecule-fixed axes can be obtained. For the divalent methyl green a second complex appears to be formed at low ionic strength. Methyl green (and to some extent 2-thiophene green and malachite green) show exciton splitting in the LD spectrum and circular dichroism assignable to exciton coupling between transition dipoles roughly parallel to the helical strands, indicating a dye-dye interaction. The optical data, supported by fitting experiments with space-filling models, suggests a general structure for the binding site. The dye is not intercalated but is bound to exposed hydrophobic regions in the major groove. The ligand is in part (the charged amino groups) in contact with the phosphoribose chain but its main surface lies against the hydrophobic base-pair stack. For a diphenylmethane dye, Michler's hydro blue, a perpendicular orientation was observed, possibly due to intercalation.


[False positive troponinemia in patient with pneumothorax : a case report].
A 20-year-old patient is admitted to the emergency room for chest pain occurring in the context of recurrent left complete pneumothorax. Ultrasensitive troponinemia is elevated to 20 times normal. Myocardial distress is attributed to pneumothorax following the negativity of cardiological examinations (EKG, TTE, cardiac MRI). The pneumothorax is drained with a favorable evolution. This is the first reported case of pneumothorax associated with a significant elevation of troponin without ECG change, TakoTsubo syndrome, or myocardial inflammation. Several mechanisms are considered: rotation of the myocardium around its axis, increase in pulmonary vascular resistance with overload of right ventricular pressure, disturbance of coronary blood flow on significant mediastinal compression with decrease in systolo-diastolic myocardial perfusion.


Carpal and tarsal osteolysis.
This report describes the symptoms, clinical course and radiological features in three cases of idiopathic carpotarsal osteolysis. Before signs of extensive osteolysis were noted, one of our patients showed flattening, loss of harmonious curvature and minimal osteoporosis of carpal and tarsal bones, all early radiological signs which have not been described previously. We discuss the findings, classification and our ideas as to the cause of the disorder.


Bilirubin kinetic modeling for quantification of extracorporeal liver support.
To provide a measure of treatment dose for extracorporeal liver support (ELS). The kinetics of conjugated bilirubin were described by a two-compartment model (Vc, Vp) with central elimination (K) and constant generation rate (G). The transfer of solute between compartments was modeled by intercompartmental clearance (Kpc). The central compartment (Vc) was assumed as a constant fraction of total volume (Vc = 0.3*Vt). Eight patients were studied during 35 treatments lasting 6 h each. The average K, Vt, Kpc, G, and mass of conjugated bilirubin removed were 18.6 +/- 3.9 ml/min, 9.1 +/- 3.8 liters, 103 +/- 108 ml/min, 0.33 +/- 0.15 mg/min, and 641 +/- 275 mg, respectively. The reduction ratio (48 +/- 10%) measured as the change in post- to pre-treatment concentrations underestimated the modeled fraction of bilirubin mass removed (54 +/- 13%) essentially because of significant conjugated bilirubin appearance during treatments. Kinetic analysis provides an improved measure of treatment dose as generation, distribution, and elimination of conjugated bilirubin are jointly considered.


Distributions of soil branched glycerol dialkyl glycerol tetraethers from different climate regions of China.
Distributions of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from soil bacteria have been recently used for reconstructions of past soil pH and air temperature history. Here, we report the brGDGTs distribution patterns from different climate regions of China, using 42 novel brGDGT data from sub-tropical Chinese soils, compiled alongside previously-published data encompassing different environmental conditions across China. These patterns show high abundance of Ia fraction in soils from humid areas, and high abundance of IIa' and IIIa' fractions corresponds to semi-humid or semi-arid conditions, implying a possible relationship with precipitation. The abundance of IIa fraction appears negatively correlated with air temperature. Statistically, the soil pH and temperature factors represent 62% and 30% variations of the total variance respectively. For soils from humid and semi-humid regions, strong correlations between cyclization of branched tetraethers (CBT') index and soil pH (R2 = 0.89) and between methylation of branched tetraethers (MBT'5ME) index and mean annual temperature (MAT)(R2 = 0.82) exist. When soils from semi-arid regions are included, the correlations become slightly stronger with pH and significantly weaker with MAT. Our study confirms the usefulness of soil brGDGTs distributions for Quaternary palaeo-climate reconstructions.


Interactions of the RAD7 and RAD23 excision repair genes of Saccharomyces cerevisiae with DNA repair genes in different epistasis groups.
The RAD7 and RAD23 genes of S. cerevisiae affect the efficiency of excision repair of UV-damaged DNA. We have examined the UV survival of strains carrying the rad7 and rad23 deletion mutation in combination with deletion mutations in genes affecting different DNA repair pathways. As expected, the rad7 delta and rad23 delta mutations interact epistatically with the excision repair defective rad1 delta mutation, and synergistically with the rad6 delta and rad52 delta mutations that affect the postreplication repair and recombinational repair pathways, respectively. However, the rad7 delta rad6 delta and the rad23 delta rad6 delta mutants exhibit the same level of UV sensitivity as the rad1 delta rad6 delta mutant. This observation is of interest since, in contrast to the rad7 delta or the rad23 delta mutations, the rad1 delta mutant is very UV sensitive and highly excision defective. This observation suggest that RAD6 and RAD7 and RAD23 genes complete for the same substrate during DNA repair.


Association between oocyte donors' or recipients' BMI with clinical outcomes after first single blastocyst transfers. The uterus is the mostly affected.
To assess if high BMI in either oocyte donors or recipients is associated with poorer outcomes after first single blastocyst transfers. Retrospective study including 1394 first blastocyst single embryo transfers (SETs) conducted by 1394 recipients during oocyte donation cycles with the gametes retrieved from 1394 women (Jan2019-July2021). Four BMI clusters were defined for both donors and recipients (underweight: <18.5; normal weight: 18.5-24.9; over-weight: 25-29.9; obese: ≥30). 1394 recipients, 42.4±4.0 years old and with a BMI 23.2±3.8, and 1394 donors, 26.1±4.2 years old and with a BMI 21.9±2.5. All oocytes were vitrified at two egg banks and warmed at eight IVF clinics part of the same network. ICSI, blastocyst culture and either fresh or vitrified-warmed SETs were conducted. Putative confounders were investigated, and the data adjusted through regression analyses. The primary outcome was the live birth rate (LBR) per SET according to donors' and/or recipients' BMI. The main secondary outcome was the miscarriage rate (<22nd gestational weeks) per clinical pregnancy. The LBR per blastocyst SET showed no significant association with donors' BMI. Regarding recipients' BMI, instead, the multivariate-OR was significant in obese versus normal weight recipients (0.58, 95%CI 0.37-0.91, p=0.019). The miscarriage rate per clinical pregnancy was also significantly associated with recipients' obesity with a multivariate-OR of 2.31 (95%CI 1.18-4.51, p=0.014) versus normal weight patients. A Generalized Additive Model (GAM) method was used to represent the relationship between predicted LBR or miscarriage rates with donors' or recipients' BMI; it pictured a scenario where the former outcome moderately but continuously decreases with increasing recipients' BMI to then sharply decline in the BMI range 25-35. The miscarriage rate, instead, increases almost linearly with respect to both donors' and recipients' increasing BMI. Obesity mostly effects the uterus, especially due to higher miscarriage rates. Yet, poorer outcomes can be appreciated already with a BMI of 25 in both oocyte donors and recipients. Finer markers of nutritional homeostasis are therefore desirable, recipients should be counselled about poorer expected outcomes in case of overweight/obesity, and oocyte banks should avoid assigning oocytes from overweight donors to overweight/obese recipients.


Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects.
Betaine comes from the diet and from choline, and it is associated with vascular disease in some patient groups. Betaine supplementation lowers plasma total homocysteine. We compared the acute effects of dietary and supplementary betaine and choline on plasma betaine and homocysteine under standard conditions and after a methionine load. In a randomized crossover study, 8 healthy men (19-40 y) consumed a betaine supplement (approximately 500 mg), high-betaine meal (approximately 517 mg), choline supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and -choline meal (approximately 517 mg betaine, approximately 622 mg choline), or a low-betaine and -choline control meal under standard conditions or postmethionine load. Plasma betaine, dimethylglycine, and homocysteine concentrations were measured hourly for 8 h and at 24 h after treatment. Dietary and supplementary betaine raised plasma betaine concentrations relative to control (P < 0.001) under standard conditions. This was not associated with raised plasma dimethylglycine concentration, and no significant betaine appeared in the urine. A small increase in dimethylglycine excretion was observed when either betaine or choline was supplied (P = 0.011 and < 0.001). Small decreases in plasma homocysteine 6 h after ingestion under standard conditions (P < or = 0.05) were detected after a high-betaine meal and after a high-betaine and high-choline meal. Dietary betaine and choline and betaine supplementation attenuated the increase in plasma homocysteine at both 4 and 6 h after a methionine load (P < or = 0.001). Dietary betaine and supplementary betaine acutely increase plasma betaine, and they and choline attenuate the postmethionine load rise in homocysteine concentrations.


MR imaging of intralabyrinthine schwannoma, labyrinthitis, and other labyrinthine pathology.
This article reviews recent imaging developments in various diseases of the membranous labyrinth. Membranous labyrinth is the initial receptor for acoustic stimuli. Exciting progress has been made in the imaging evaluation of the normal and diseased labyrinth. Structures of the membranous labyrinth, such as the cochlea, vestibule, semicircular canals, and endolymphatic duct and sac can be visualized on routine MR scans. Using high-resolution MR imaging techniques, researches have been able to visualize the cochlear duct, scala tympani, scala vestibuli, and even the otolithic mass. The sensitivity of gadolinium-enhanced MR imaging is such that labyrinthitis or other labyrinthine pathology, including small intralabyrinthine schwannomas, can be diagnosed on routine MR study.


VO2max prediction based on submaximal cardiorespiratory relationships and body composition in male runners and cyclists: a population study.
Oxygen uptake (VO2) is one of the most important measures of fitness and critical vital sign. Cardiopulmonary exercise testing (CPET) is a valuable method of assessing fitness in sport and clinical settings. There is a lack of large studies on athletic populations to predict VO2max using somatic or submaximal CPET variables. Thus, this study aimed to: (1) derive prediction models for maximal VO2 (VO2max) based on submaximal exercise variables at anaerobic threshold (AT) or respiratory compensation point (RCP) or only somatic and (2) internally validate provided equations. Four thousand four hundred twenty-four male endurance athletes (EA) underwent maximal symptom-limited CPET on a treadmill (n=3330) or cycle ergometer (n=1094). The cohort was randomly divided between: variables selection (nrunners = 1998; ncyclist = 656), model building (nrunners = 666; ncyclist = 219), and validation (nrunners = 666; ncyclist = 219). Random forest was used to select the most significant variables. Models were derived and internally validated with multiple linear regression. Runners were 36.24±8.45 years; BMI = 23.94 ± 2.43 kg·m-2; VO2max=53.81±6.67 mL·min-1·kg-1. Cyclists were 37.33±9.13 years; BMI = 24.34 ± 2.63 kg·m-2; VO2max=51.74±7.99 mL·min-1·kg-1. VO2 at AT and RCP were the most contributing variables to exercise equations. Body mass and body fat had the highest impact on the somatic equation. Model performance for VO2max based on variables at AT was R2=0.81, at RCP was R2=0.91, at AT and RCP was R2=0.91 and for somatic-only was R2=0.43. Derived prediction models were highly accurate and fairly replicable. Formulae allow for precise estimation of VO2max based on submaximal exercise performance or somatic variables. Presented models are applicable for sport and clinical settling. They are a valuable supplementary method for fitness practitioners to adjust individualised training recommendations. No external funding was received for this work.


Musashi-2 binds with Fbxo6 to induce Rnaset2 ubiquitination and chemokine signaling pathway during vascular smooth muscle cell phenotypic switch in atherosclerosis.
The objective of this study is to determine how Musashi-2 (MSI2) affects vascular smooth muscle cell (VSMC) phenotypic switch and contributes to atherosclerosis (AS). Primary mouse VSMCs were transfected with MSI2 specific siRNA and treated with platelet-derived growth factor-BB (PDGF-BB). The proliferation, cell-cycle, and migration of VSMCs were determined by CCK-8, flow cytometry, wound healing, and transwell assays. Western blot and qRT-PCR were conducted to analyze the protein and mRNA expression. Moreover, the correlation between MSI2, Fbxo6, Rnaset2, and chemokine signaling was predicted and verified using RNAct database, KEGG, wiki, RNA-binding protein immunoprecipitation and co-immunoprecipitation. Moreover, H&E and Oil Red O staining were employed for assessing necrotic core and lipid accumulation in AS mouse aorta tissues. The numbers of B lymphocytes and monocytes, and the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDL-C) in AS mice blood were investigated using flow cytometry and corresponding commercial kits, respectively. MSI2 was up-regulated in the PDGF-BB-treated VSMCs. Knockdown of MSI2 inhibited VSMC proliferation, cell-cycle, and migration. Moreover, MSI2 regulated VSMC phenotypic switch through binding with Fbxo6 to induce Rnaset2 ubiquitination. MSI2 knockdown inhibited chemokine signaling via regulating Fbxo6/Rnaset2 axis. In AS mice, knockdown of MSI2 inhibited the formation of necrotic core and atherosclerotic plaque, and inhibited chemokine signaling via regulating Fbxo6/Rnaset2 axis. Our findings demonstrated that MSI2 could bind with Fbxo6 to induce Rnaset2 ubiquitination and the activation of chemokine signaling pathway during VSMC phenotypic switch in AS.


Aggregation behavior of aqueous dioctadecyldimethylammonium bromide/monoolein mixtures: a multitechnique investigation on the influence of composition and temperature.
A recently described non-viral gene delivery system [dioctadecyldimethylammonium bromide (DODAB)/monoolein (MO)] has been studied in detail to improve knowledge on the interactions between lamellar (DODAB) and non-lamellar-forming (MO) lipids, as a means to enhance their final cell transfection efficiency. Indeed, the morphology, fluidity, and size of these cationic surfactant/neutral lipid mixtures play an important role in the ability of these systems to complex nucleic acids. The different techniques used in this work, namely dynamic light scattering (DLS), fluorescence spectroscopy, differential scanning calorimetry (DSC), cryogenic transmission electron microscopy (cryo-TEM), light microscopy (LM), and surface pressure-area isotherms, allowed fully characterization of the phase behavior and aggregate morphology of DODAB/MO mixtures at different molar ratios. Overall, the results indicate that the final morphology of DODAB/MO aggregates depends on the balance between the tendency of DODAB to form zero-curvature bilayer structures and the propensity of MO to form non-bilayer structures with negative curvature. These results also show that in the MO-rich region, an increase in temperature has a similar effect on aggregate morphology as an increase in MO concentration.


A fully continuous individual-based model of tumor cell evolution.
The aim of this work is to develop and study a fully continuous individual-based model (IBM) for cancer tumor invasion into a spatial environment of surrounding tissue. The IBM improves previous spatially discrete models, because it is continuous in all variables (including spatial variables), and thus not constrained to lattice frameworks. The IBM includes four types of individual elements: tumor cells, extracellular macromolecules (MM), a matrix degradative enzyme (MDE), and oxygen. The algorithm underlying the IBM is based on the dynamic interaction of these four elements in the spatial environment, with special consideration of mutation phenotypes. A set of stochastic differential equations is formulated to describe the evolution of the IBM in an equivalent way. The IBM is scaled up to a system of partial differential equations (PDE) representing the limiting behavior of the IBM as the number of cells and molecules approaches infinity. Both models (IBM and PDE) are numerically simulated with two kinds of initial conditions: homogeneous MM distribution and heterogeneous MM distribution. With both kinds of initial MM distributions spatial fingering patterns appear in the tumor growth. The output of both simulations is quite similar.


Single institution experience with Tru-Cut renal mass biopsy for diagnosing Wilms tumor.
To evaluate the efficacy of needle biopsy for diagnosing Wilms tumor (WT) before chemotherapy. We reviewed our institutional experience with Tru-Cut biopsy of pediatric renal masses in patients who subsequently underwent nephrectomy. We compared biopsy pathology with nephrectomy specimens to determine if biopsy accurately predicted final pathology. Seven children underwent Tru-Cut renal mass biopsy followed by surgical resection. In 4 patients, the final biopsy pathology was definitively read as WT and in 3 subjects, the pathology was read as WT versus hyperplastic nephrogenic rest. In all 7 patients, the nephrectomy pathology confirmed a diagnosis of WT. There were no complications after biopsy, and no patients have had local or regional recurrence. In our experience, pre-therapy Tru-Cut biopsy safely provides an adequate specimen for pathologic review in diagnosing WT.


Identification and Chemical and Biological Management of Phytopythium vexans, the Causal Agent of Phytopythium Root and Crown Rot of Woody Ornamentals.
Soilborne diseases caused by pathogens such as Phytophthora, Rhizoctonia, Fusarium, Verticillium, and Pythium species are the most important diseases of woody ornamentals. Ginkgo (Ginkgo biloba) and red maple (Acer rubrum 'October Glory') plants grown in containers and fields in Tennessee showed root and crown rot symptoms with dark brown to black lesions in 2017 and 2018. The objective of this research was to isolate and identify pathogens affecting ginkgo and red maple plants in Tennessee nurseries and to develop fungicide/biofungicide management recommendations for nursery producers. Isolations were made from the infected roots. Several Phytophthora-like colonies with spherical zoospores, filamentous to globose oogoni, and whitish mycelium were isolated on V8-PARPH medium. To confirm identity, total genomic DNA was extracted, followed by sequence analysis of the internal transcribed spacer regions, large subunit of nuclear rRNA, and cytochrome c oxidase subunits I and II of mitochondrial DNA. Based on morphological and molecular analysis, Phytopythium vexans was described as a causal agent of crown and root rot from the infected ginkgo and red maple plants. To complete Koch's postulates, a pathogenicity test was performed by drenching 100 ml of V8 agar medium slurry of Phytopythium vexans inoculum on 1-year-old potted ginkgo plant root systems as well as red maple October Glory. Necrotic lesion development was observed in the root system 45 days after inoculation and Phytopythium vexans was reisolated from the roots of both ginkgo and red maple. All control ginkgo and red maple plants remained disease free and no pathogen was reisolated. In addition, the efficacy of fungicides, biofungicides, fertilizer, and host plant defense inducers (traditionally recommended for management of oomycete diseases) for control of Phytopythium crown and root rot was evaluated on ginkgo and red maple October Glory seedlings in greenhouse and field trials. Fungicides such as Empress Intrinsic, Pageant Intrinsic, Segovis, and Subdue MAXX were effective in both greenhouse and field trials, and the biofungicide Stargus reduced disease severity caused by pathogen Phytopythium vexans on ginkgo and red maple plants in greenhouse trials. These results will help nursery producers make proper management decisions for newly reported Phytopythium crown and root rot disease of ginkgo and red maple plants.


Modified general affinity adsorbent for large-scale purification of penicillinases.
N-Acetyl-D-(-)-penicillamine as a stable second-generation biospecific affinity ligand has previously been suggested for purification of Bacillus cereus 569/H beta-lactamase I. A complex spacer arm is coupled with the matrix by using epichlorohydrin and phloroglucinol doubly activated with divinyl sulphone in the meta position. Coupling of D-(-)-penicillamine ligand resulted in an active affigel. However, we found that two affinity ligands in close proximity prevents simultaneous binding of two penicillinase molecules, therefore one ligand is superfluous. Our results show that: (1) shortening the spacer arm by direct activation of the matrix with divinyl sulphone is satisfactory to produce the affinity material with N-acetyl-D-(-)-penicillamine; (2) incorporation of 15 mumol of N-acetyl-D-(-)-penicillamine per ml of wet Sepharose 4B satisfies the maximum binding capacity requirements of the affigel (about half of the originally incorporated amount of ligand); (3) our simplified affinity adsorbent is generally applicable for large-scale purification of penicillinases to homogeneity from various bacterial sources by the convenient batch method without prior concentration of these enzymes; (4) reacetylation for four/five times can regenerate the original binding capacity of the affigel.


Assessing the effect on the generation of environmentally persistent free radicals in hydrothermal carbonization of sewage sludge.
Environmentally persistent free radicals (EPFRs) have attracted increasing research interest in recent years. Herein, the generation of EPFRs during the hydrothermal carbonization of sewage sludge (SS) was studied. First, the surface morphology, functional groups, constituent elements and free radicals were characterized for a holistic description of the raw SS and the selected hydrochar obtained from hydrothermal carbonization of SS (SHC). Then, the impact of hydrothermal temperature, residence time and initial pH on the formation of EPFRs was explored in detail through the investigation of g-factors and intensities of EPFRs identified in SHC. The results have shown that the formation of EPFRs was affected by the factors mentioned above, in which the impact of temperature is the greatest. Two types of EPFRs were spotted in the hydrochar, oxygen-centered (O-centered) and carbon-centered (C-centered) EPFRs, which were caught in 120-150 °C and 260-280 °C, respectively. Moreover, the intensities of Electron Paramagnetic Resonance (EPR) signals enhanced with increasing hydrothermal temperature. Whereas, residence time and initial pH only affected the amount of EPFRs in a manner. Additionally, the half-life of the O-centered EPFRs and the C-centered EPFRs was determined as long as 160.45 days and 401.10 days, respectively, indicating that EPFRs are stable in a long time.


Redox refunctionalization of steroid spiroketals. Structure correction of ritterazine M.
The structure of the North spiroketal moiety of ritterazine M has been corrected from 1a to 1b. This was accomplished by comparison of published spectra of the natural product with five synthetic spiroketal-alcohols. Synthesis of these models was efficiently accomplished by reductive cleavage of the spiroketal and Sharpless asymmetric dihydroxylation of an isopentyl, methyl 1,1-disubstituted olefin, followed by Suarez iodine[III] oxidative spirocyclization of monoprotected 1 degree,3 degree 1,2 diols.


Women's preventive screening in rural health clinics.
Despite the strong interest in health care quality, little is known about the quality of preventive care among women in rural primary care settings. We sought to assess the quality of screening practices in Rural Health Clinics (RHCs) as measured by the rates at which female patients received screening within national guidelines. A cross-sectional, retrospective chart review of 480 charts of female patients in 12 randomly selected RHCs was conducted. Data were collected on screening activities documented in >3,800 patient visits. Chart data was extracted by trained, standardized chart auditors using the Women's Primary Care Screening Form for patient data and the Revised National Rural Health Clinic Survey for RHC background data. The rates of receipt of 5 preventive screenings received by female patients in RHCs were determined using a standardized and reproducible method, and patient and clinic characteristics associated with women's receipt of these screenings were identified. Demographic characteristics of patients were similar to that of national rural comparisons. Screening rates for Pap tests (66%) and mammograms (55%) were lower than Healthy People 2010 estimates, but similar to other record audit data; screening rates for cholesterol with comorbidity (66%) were near the Healthy People 2010 estimate, and screening rates for cholesterol without comorbidity (61%) exceeded it; and rates of blood pressure screening (99%) exceeded Healthy People 2010 estimates of national rates. Screening rates for depression showed that 35% had received a formal or informal screening. Rates of screenings for insured and uninsured female RHC patients in this retrospective chart review were not significantly different. Methods to improve pap and mammogram screening rates are needed.


Donepezil induces ventricular arrhythmias by delayed repolarisation.
Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and IKr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.


WITHDRAWN: Complement dysregulation in AMD: RPE-Bruch's membrane-choroid.
The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.mam.2012.03.011. The duplicate article has therefore been withdrawn.


[Intra renal teratoma. Study of a case in an infant (author's transl)].
Solid, intra renal tumors of children and infants are in most cases nephroblastomas. All the other types of solid tumors, malignant or benign, are very rare. This observation seems to be the seventh case of intra renal teratoma in the literature. The entire upper pole of the left kidney had disappeared, being occupied by a large tumor which proved to be solid upon specific examinations. Anatomo-pathologic examination, following nephrectomy, proved it to be benign.