Estimating clandestine abortion with the confidants method--results from Ouagadougou, Burkina Faso.
Data on abortion in sub-Saharan Africa are rare and non-representative. This study presents a new method to collect quantitative data on clandestine abortion, the confidants method, applied in 2001 in Ouagadougou, Burkina Faso. Preliminary qualitative work showed that individuals are aware of their close friends' induced abortions: women usually talk to their peers about the unintended pregnancy and ask them for help in locating illegal abortion providers. In a survey of 963 women of reproductive age representative of the city of Ouagadougou, we asked respondents to list their close relations, and, for each of them, and for each of the 5 years preceding the survey, whether they had an induced abortion. According to these data, there are 40 induced abortions per 1000 women aged 15-49 in Ouagadougou annually, and 60 per 1000 women aged 15-19. Adverse health consequences followed 60% of the reported induced abortions, and 14% of them received treatment in a hospital. Extrapolating these results to the entire city, we estimate that its hospitals treat about 1000 cases of abortion complications a year. Hospital data indicate that these centers admitted 984 induced abortions (adding all "certainly", "probably" and "possibly" induced abortions in the WHO protocol) in 2001; the age distribution of patients admitted for induced abortion also corresponds to the confidants method's projections ("certainly" induced abortions only). At least two biases could affect the abortion rates estimated by the confidants method, pertaining to the selection of the sample of relations and to the varying number of third parties involved in the abortion process. The confidants method, which is similar in its principle to the sisterhood method used to estimate maternal mortality levels, might generate accurate estimates of illegal abortion in certain contexts if these two biases are controlled for. Further testing is necessary.


Effect of ethanol on lactic acid production by exercised normal muscle.
Several studies have suggested that muscle lactic acid production is defective in alcoholic myopathy. However, normal controls have not been evaluated. To study the effects of ethanol on the production of lactic acid in normal exercised muscle, oral ethanol (1 g per kg body weight, 20% v/v) was given to eight nonalcoholic subjects. Forearm ischemic exercise with a total work load of 7.2 kg-m/min was performed just before and 90 min after ingestion of ethanol. At the time of exercise, the serum ethanol level was 95.7 +/- 15.1 mg% (mean +/- SD). Resting serum lactic acid was significantly higher after ingestion of ethanol (15.7 +/- 4.5 mg%) than before (8.5 +/- 4.7 mg%). Lactic acid generation with ischemic exercise was significantly lower after ethanol ingestion. The mean peak serum lactic acid level (expressed as percentage elevation above resting) was 330.5 +/- 118.2% before and 127.9 +/- 75.1% after (p less than .05). These results indicate that a single oral dose of ethanol decreases lactic acid production by exercised muscle in normal subjects.


Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)-a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layer-and diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE. Histological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE. Eosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3-positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin-3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM. Eotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE.


Characteristics of adults with a medical cannabis license, reasons for use, and perceptions of benefit following medical cannabis legalization in Oklahoma.
Little is known about the risks and benefits associated with medical cannabis legalization. The current study was an online panel survey of adult Oklahomans recruited between September and October 2020 (N = 1898). Respondents with and without a medical cannabis license were compared on sociodemographic, substance use and health characteristics, and sub-analyses focused on the characteristics of licensed and unlicensed past 30-day cannabis users. Among all participants, 19.34% (n = 367) reported that they had a medical cannabis license, and 35.73% (n = 676) reported past 30-day cannabis use. Licensees were more likely to be younger (i.e., 18-35 years of age; p = 0.001), identify as a sexual minority (p < 0.001), and report past 30-day cannabis, cigarette, alcohol, and prescription opiate use (all p's ≤ 0.003). Licensed participants most commonly reported medically-recommended cannabis use for anxiety (42.51%), depression (33.24%), sleep problems (26.98%), chronic pain (24.25%), and arthritis (12.81%). The likelihood of medically-recommended cannabis use for anxiety, depression, and chronic pain differed by age group (all p's ≤ 0.028). Licensees were most likely to perceive that cannabis delivered "very much/extreme" relief from anxiety (78.57%), sleep problems (76.30%), nausea/vomiting (70.00%), and depression (67.05%). Compared to licensed past 30-day cannabis users (n = 308), unlicensed users (n = 368) were more likely to be non-White, to have ≤ high school education, to report an annual household income <$30,000, and to report current smoking (all p's ≤ 0.027). Findings provide initial information about the personal characteristics associated with having a medical cannabis license in Oklahoma, the reasons for medical cannabis use, and the perceived medical benefits.


Methyl jasmonate-induced emission of biogenic volatiles is biphasic in cucumber: a high-resolution analysis of dose dependence.
Methyl jasmonate (MeJA) is a key airborne elicitor activating jasmonate-dependent signaling pathways, including induction of stress-related volatile emissions, but how the magnitude and timing of these emissions scale with MeJA dose is not known. Treatments with exogenous MeJA concentrations ranging from mild (0.2 mM) to lethal (50 mM) were used to investigate quantitative relationships among MeJA dose and the kinetics and magnitude of volatile release in Cucumis sativus by combining high-resolution measurements with a proton-transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) and GC-MS. The results highlighted biphasic kinetics of elicitation of volatiles. The early phase, peaking in 0.1-1 h after the MeJA treatment, was characterized by emissions of lipoxygenase (LOX) pathway volatiles and methanol. In the subsequent phase, starting in 6-12 h and reaching a maximum in 15-25 h after the treatment, secondary emissions of LOX compounds as well as emissions of monoterpenes and sesquiterpenes were elicited. For both phases, the maximum emission rates and total integrated emissions increased with applied MeJA concentration. Furthermore, the rates of induction and decay, and the duration of emission bursts were positively, and the timing of emission maxima were negatively associated with MeJA dose for LOX compounds and terpenoids, except for the duration of the first LOX burst. These results demonstrate major effects of MeJA dose on the kinetics and magnitude of volatile response, underscoring the importance of biotic stress severity in deciphering the downstream events of biological impacts.


No difference in the association between birth weight and total cholesterol for males and females. A SHARP (Scottish Heart and Arterial Disease Risk Prevention) study.
We carried out a cohort study in a relatively young healthy working population to assess any difference between males and females in the association between birth weight and adult total cholesterol. Perinatal data came from the Walker database of babies born between 1952 and 1966 in Dundee, Scotland. This was record-linked to information from the SHARP (Scottish Heart and Arterial Risk Prevention) cohort who had undergone a cardiovascular risk screening between 1991 and 1993. There were 1158 individuals (56% male, mean age 32.1 years). For both males and females there was no association between birth weight and cholesterol either unadjusted or after adjustment for BMI and other potential confounders: B = -0.11 (95% CI -0.03, 0.04) for males, B = -0.15 (95% CI -0.31, 0.01) for females. All individuals together showed a slight decrease in cholesterol for 1 kg increase in birth weight but only after adjustment for BMI: B = -0.13 (95% CI -0.24, -0.01). These results suggest no difference in the relationship between birth weight and total cholesterol for males and females.


Modified alginate materials for wastewater treatment: Application prospects.
Sodium alginate is a natural macromolecule widely used because of its abundance, low cost of acquisition, and rich hydroxyl and carboxyl groups in the matrix. The physical modification of sodium alginate can be made by blending it with polymer materials. The so-yielded alginate complex is commonly unstable in an aqueous environment due to alginate backbones' high hydrophilicity. The chemical modification can remove its hydrophilic groups and introduce special functional groups or polymers onto the alginate backbones to provide excess reaction sites for specific reactions and effective complexation sites for accommodating antibiotics, dyes, heavy metal ions, and radioactive elements. Sodium alginate has been used in water treatment engineering under revised modification protocols. This article also reviews the latest modification protocols for sodium alginate and outlines the novel application of the modified materials. The limitations of modified sodium alginate materials are described, and research prospects are put forward.


Regional enteritis complicating malignant lymphoma.
We describe a patient presenting with palpable lymph nodes due to non-Hodgkin's lymphoma. Chemotherapy induced complete remission. One year later he complained of cramping abdominal pain, diarrhoea and bloody stools all due to Crohn's disease of the colon. There are only a few more patients described with a combination of inflammatory bowel disease and malignant lymphoma. So far there is no explanation for the co-incidence of the two diseases.


Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders.
PSD-95 associated PSD proteins play a critical role in regulating the density and activity of glutamate receptors. Numerous previous studies have shown an association between the genes that encode these proteins and schizophrenia (SZ) and autism spectrum disorders (ASD), which share a substantial portion of genetic risks. We sequenced the protein-encoding regions of DLG1, DLG2, DLG4, DLGAP1, DLGAP2, and SynGAP in 562 cases (370 SZ and 192 ASD patients) on the Ion PGM platform. We detected 26 rare (minor allele frequency <1%), non-synonymous mutations, and conducted silico functional analysis and pedigree analysis when possible. Three variants, G344R in DLG1, G241S in DLG4, and R604C in DLGAP2, were selected for association analysis in an independent sample set of 1315 SZ patients, 382 ASD patients, and 1793 healthy controls. Neither DLG4-G241S nor DLGAP2-R604C was detected in any samples in case or control sets, whereas one additional SZ patient was found that carried DLG1-G344R. Our results suggest that rare missense mutations in the candidate PSD genes may increase susceptibility to SZ and/or ASD. These findings may strengthen the theory that rare, non-synonymous variants confer substantial genetic risks for these disorders.


Progress in small-angle scattering from biological solutions at high-brilliance synchrotrons.
Small-angle X-ray scattering (SAXS) is an established technique that provides low-resolution structural information on macromolecular solutions. Recent decades have witnessed significant progress in both experimental facilities and in novel data-analysis approaches, making SAXS a mainstream method for structural biology. The technique is routinely applied to directly reconstruct low-resolution shapes of proteins and to generate atomistic models of macromolecular assemblies using hybrid approaches. Very importantly, SAXS is capable of yielding structural information on systems with size and conformational polydispersity, including highly flexible objects. In addition, utilizing high-flux synchrotron facilities, time-resolved SAXS allows analysis of kinetic processes over time ranges from microseconds to hours. Dedicated bioSAXS beamlines now offer fully automated data-collection and analysis pipelines, where analysis and modelling is conducted on the fly. This enables SAXS to be employed as a high-throughput method to rapidly screen various sample conditions and additives. The growing SAXS user community is supported by developments in data and model archiving and quality criteria. This review illustrates the latest developments in SAXS, in particular highlighting time-resolved applications aimed at flexible and evolving systems.


Multicenter prospective study of nonruptured abdominal aortic aneurysms. I. Population and operative management.
This article describes the patient population and operative management of 666 patients with nonruptured aneurysms of the abdominal aorta. Statistical significance of variables was determined by the chi-square test and logistic regression analysis. There were no statistically significant differences (p greater than 0.05) in mortality rate for abdominal aortic aneurysm (AAA) on the basis of indication for surgery (asymptomatic, 3.9%; asymptomatic but with evidence of enlargement, 4.9%; and symptomatic, 7.2%) or the urgency of operation (elective operation, 4.5%; and urgent operation, 7.1%). Characteristics of the 72 participating surgeons did not influence the operative mortality rate. A family history of AAA was documented in 6.1% of cases and was more common if the patient was female (p = 0.03) and less than 65 years of age (p = 0.04). Patients without clinical evidence of coronary artery disease had a 0.8% mortality rate from cardiac disease compared with 6.2% if any stigmata of coronary disease were present. Prior aortocoronary bypass surgery did not reduce the incidence of postoperative cardiac events or operative mortality rate. Patients having "routine" angiography did not have a less complicated operative course, fewer thrombotic complications, or lower mortality rate than those not having it. Those patients with an inflammatory AAA (4.5%) did not have a significantly higher incidence of pain. Heparin administration (84.8%) did not reduce the complications of graft thrombosis, "trash," distal thrombosis, and/or amputation. The 6.8% of patients requiring suprarenal aortic cross-clamping had a higher incidence of postoperative renal dysfunction (p = 0.02) and intraoperative blood loss (p less than 0.001), but cardiac events were not more frequent. When the aortic cross-clamping time was prolonged (more than 70 minutes), the requirement for crystalloid fluid administration increased (p less than 0.001) and postoperative myocardial infarction was more common (p = 0.004). After ligation of the left renal vein in 7.9%, renal damage or dialysis was more frequent (p = 0.01). Patients having an intra-abdominal graft (tube, 38.5% and biiliac, 30.7%) had fewer wound infections (p = 0.02) and graft thromboses (p less than 0.001) than the patients with a femoral anastomosis. When the internal iliac artery flow was interrupted bilaterally (12%), diarrhea (p = 0.03) and ischemic colitis (p = 0.03) were more frequent complications. Reimplantation of the inferior mesenteric artery was carried out in 4.8%. After renal artery bypass in 2.1%, the mortality rate was not increased, but the incidence of transient renal dysfunction was increased (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)


Uncovering the transition between hydrothermal carbonization and liquefaction via secondary char extraction: A case study using food waste.
Despite the ability to perform both processes in the same reactor, hydrothermal carbonization (HTC) and hydrothermal liquefaction (HTL) are considered two distinct processes differentiated by their reaction temperatures. As temperatures increase from the less severe HTC range into the HTL regime, the product distribution progressively favors an organic bio-oil phase relative to solid hydrochar. Solvents are commonly used to extract bio-oil from the solid residues produced during HTL, and to separate the amorphous secondary char from the coal-like primary char of HTC hydrochars. This suggests secondary char is a HTL biocrude precursor. Lipid-rich food waste was hydrothermally processed between 190 and 340 °C, spanning HTC to HTL conditions. Higher temperatures produce more gas, less liquid, and similar amounts of a progressively less oxygenated hydrochars, suggesting a gradual transition from HTC to HTL. However, analyses of ethanol-separated primary chars and secondary chars tell a different story. While the primary char is progressively more carbonized with temperature, the secondary char composition sharply changes at 250 °C. That is, lipid hydrolysis begins around 220 °C, but proceeds rather completely at 250 °C and above. A lower HTL temperature reduces the energy cost of the hydrothermal process, yet enables full lipid hydrolysis into long chain fatty acids while minimizing recondensation and repolymerization of fatty acids onto the primary char and their subsequent amidation. This maximizes the conversion of lipid-rich feedstocks into liquid fuel precursors with up to 70 % energy recovery.


Defects in tumor cell immunogenicity: lymphokine signals in in vitro cytolytic responses to tumor alloantigens.
The B16 melanoma of C57BL/6 mice illustrates a deficiency in immunostimulation which may be important in some host-tumor relationships. B16 immunizes very poorly, even against its own major histocompatibility complex (MHC) antigens. We have compared the anti-MHC cytolytic response induced in vitro by B16 and by other tumors of both lymphoid and nonlymphoid origin. We have also studied the role of indomethacin and exogenous lymphokines in facilitating these responses and examined the relationship of specific and nonspecific effector cells induced. In contrast to normal lymphoid cells and two lymphoid tumor cells (EL4 and WEHI-265), the three nonlymphoid tumors, B16, Lewis lung tumor (3LL), and MC-2 fibrosarcoma, failed to induce primary cytolytic responses by themselves. MC-2 and B16 represented two different defects in immunogenicity. MC-2, which we have shown previously to induce an in vivo cytolytic response, could also immunize in vitro provided that prostaglandin production was blocked with indomethacin. In contrast B16, which is poorly immunogenic in vivo, immunized in vitro only if a concanavalin A-induced lymphokine supernatant (CS) was added as an exogenous source of "signal 2." High concentrations of the interleukin 2-containing Con A-induced spleen cell culture supernatant-induced non-H-2b-specific lymphokine-activated killer (LAK) cells in the absence of B16 stimulator cells. However, lymphokine concentrations too low to induce LAK cells enabled the otherwise nonimmunogenic B16 cells to induce specific cytolytic activity.


DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway.
Epigenetic alterations such as DNA methylation and histone modifications are implicated in repressing several tumor suppressor genes in prostate cancer progression. In this study, we determined the anti-prostate cancer effect of a small molecule drug guadecitabine (gDEC) that inhibits/depletes the DNA methylation writer DNA methyltransferase 1 (DNMT1). gDEC inhibited prostate cancer cell growth and proliferation in vitro without activating the apoptotic cascade. Molecular studies confirmed DNMT1 depletion and modulated epithelial-mesenchymal transition markers E-cadherin and β-catenin in several prostate cancer cell lines (LNCaP, 22Rv1, and MDA PCa 2b). gDEC treatment also significantly inhibited prostate tumor growth in vivo in mice (22Rv1, MDA PCa 2b, and PC-3 xenografts) without any observed toxicities. gDEC did not impact the expression of androgen receptor (AR) or AR-variant 7 (AR-V7) nor sensitize the prostate cancer cells to the anti-androgen enzalutamide in vitro. In further investigating the mechanism of cytoreduction by gDEC, a PCR array analyses of 84 chromatin modifying enzymes demonstrated upregulation of several lysine-specific methyltransferases (KMTs: KMT2A, KMT2C, KMT2E, KMT2H, KMT5A), confirmed by additional expression analyses in vitro and of harvested xenografts. Moreover, gDEC treatment increased global histone 3 lysine 4 mono-and di-methylation (H3K4me1 and H3K4me2). In sum, gDEC, in addition to directly depleting the corepressor DNMT1, upregulated KMT activating epigenetic enzymes, activating terminal epithelial program activation, and prostate cancer cell cycling exits independent of apoptosis.


CMR detects extensive intracavitary thrombi as solitary clinical presentation of Antiphospholipid Syndrome: A case report.
Intracavitary thrombi are an important differential diagnosis of cardiac masses. Cardiac magnetic resonance imaging (CMR) allows their non-invasive characterization. This case highlights extensive cardiac thrombi detected by CMR as solitary presentation of antiphospholipid syndrome.


Improving the signal intensity and sensitivity of MALDI mass spectrometry by using nanoliter spots deposited by induction-based fluidics.
A new contact-free, small droplet deposition method using an induction-based fluidics (IBF) technique to dispense nanoliter drops is described and evaluated for sample preparation in matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The signal intensities available when using nanoliter spots are greater than those obtained with normal, microliter spots when the same amount of analyte is used. When using an ionic-liquid matrix, the improvement in sensitivity is equal to the concentration enhancement that was achieved by using smaller quantities of matrix. When using a conventional solid matrix, however, the increase in signal intensity shows a more complicated relationship to concentration. The approach of nanoliter deposition also supports multiple spotting to increase sample concentration and, thus, sample signal intensity. Nanoliter spotting not only improves the signal intensity and sensitivity achieved by MALDI-MS but also allows a major fraction of trace samples to be saved for other experiments, thus expanding the application of MALDI-MS to biological studies where sample quantity is limited.


Intercepted-Knoevenagel condensation for the synthesis of unsymmetrical fused-tricyclic 4H-pyrans.
4H-Pyrans (4H-Pys) and 1,4-dihydropyridines (1,4-DHPs) are important classes of heterocyclic scaffolds in medicinal chemistry. Herein, an indium(III)-catalyzed one-pot domino reaction for the synthesis of highly functionalized 4H-Pys, and a model of 1,4-DHP is reported. This alternative approach to the challenging Hantzsch 4-component reaction enables the synthesis of fused-tricyclic heterocycles, and the mechanistic studies underline the importance of an intercepted-Knoevenagel adduct to achieve higher chemoselectivity towards these types of unsymmetrical heterocycles.


Formative service evaluation of transfer of care service for care home residents after hospital discharge.
This study provides a service description and analysis of a pilot across two sites involving pharmacists aiming to support care home residents with their medications post-discharge. An interview with the pilot coordinator was undertaken to understand the pilot service. Service data (March 2020-June 2021) were analysed to investigate what was actually delivered to the care home residents. One hundred eighty-eight inpatients were referred and 132 received the post-discharge service. One hundred three residents received medicines reconciliation and 29 received an additional structured medication review. The latter cohort was significantly more likely to receive medicines and illness-related information and have medicines stopped. The service facilitates the provision of medicines information and medicines-related interventions. Further evaluation is required to evidence the value of medicines review alongside the medicines reconciliation.


Anti-insulin receptor antibodies inhibit insulin binding and stimulate glucose metabolism in skeletal muscle.
Autoantibodies against the insulin receptor are found in the serum of some patients with severe insulin resistance. The effects of one of these sera on insulin binding and on glucose transport and metabolism were investigated in the isolated mouse soleus muscle. Preincubation of muscles with the patient's serum resulted in an inhibition of subsequent 125I-insulin binding (half-maximal effect at 1:500 dilution) and in a two to three-fold stimulation of glucose transport and metabolism (half-maximal effect at 1:2000 dilution). The insulin-like effects were blocked by anti-human IgG, but not by anti-insulin antibodies. The magnitude of the serum effects on 2-deoxyglucose uptake and glycolysis was similar to that of insulin, but the effect on glycogen synthesis was smaller than that of insulin. It is suggested that the patient's serum and insulin promote glucose transport and glycolysis through a common pathway, but act differently on glycogen synthesis.


A biosynthetic pathway to aromatic amines that uses glycyl-tRNA as nitrogen donor.
Aromatic amines in nature are typically installed with Glu or Gln as the nitrogen donor. Here we report a pathway that features glycyl-tRNA instead. During the biosynthesis of pyrroloiminoquinone-type natural products such as ammosamides, peptide-aminoacyl tRNA ligases append amino acids to the C-terminus of a ribosomally synthesized peptide. First, [Formula: see text] adds Trp in a Trp-tRNA-dependent reaction and the flavoprotein AmmC1 then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, [Formula: see text] attaches Gly to the indole ring in a Gly-tRNA dependent fashion. Subsequent decarboxylation and hydrolysis results in an amino-substituted indole. Similar transformations are catalysed by orthologous enzymes from Bacillus halodurans. This pathway features three previously unknown biochemical processes using a ribosomally synthesized peptide as scaffold for non-ribosomal peptide extension and chemical modification to generate an amino acid-derived natural product.


Genetic toxicity of a standardized mixture of citrus polymethoxylated flavones.
Flavonoids are a ubiquitous family of phytochemicals that display a variety of biological effects, both beneficial and adverse depending on the individual compound. Certain flavonoids are genotoxic while others inhibit the genotoxicity of other mutagens. In the present studies, the mutagenicity of a mixture of polymethoxylated flavones (PMFs) purified from citrus peel oil was evaluated. The mixture consisted of nobiletin (32.5%), 3,3',4',5,6,7,8-heptamethoxyflavone (25.0%), tangeretin (14.0%), trimethylscutellarein (9.1%), sinensetin (3.9%), 5-demethyl-nobiletin (2.8%), hexa-O-methylquercetagetin (3.3%), 5-demethyl-tetramethylscutellarein (0.7%), 5-hydroxy-3,3',4',6,7,8-hexamethoxyflavone (0.7%), and a small quantity of unidentified flavonoid compounds (3.9%). In vitro addition of the PMF mixture over a concentration range that spanned four log doses (0.0005-5.0 mg/plate) did not reveal any evidence of mutagenicity in five bacterial tester strains (Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537) either in the absence or presence of S9 activation. The PMF mixture exhibited a statistically significant increase in mutagenicity of L5178Y tk(+/-) mouse lymphoma cells at 0.05 (38.5 x 10(-6); P<0.05) and 0.1 mg/ml (61 x 10(-6); P<0.01) compared with vehicle-treated controls (mutation frequency=19.7 x 10(-6)). However, these responses were within historical values observed in negative control cultures and extremely small compared to the positive control (EMS 0.5 microl/ml; 1685.3 x 10(-6)). Furthermore, in the presence of S9 there was no indication of genetic toxicity in L5178Y tk(+/-) cells. These results demonstrate that the PMF mixture is not genotoxic in in vitro assay systems.


Alcohol trajectories among biracial black subgroups: Testing the intermediate substance use hypothesis.
This study tests the intermediate biracial substance use hypothesis, which suggests that the prevalence of substance use among biracial individuals fall intermediate to their corresponding mononoracial counterparts. Using National Longitudinal Study of Adolescent and Adult Health (Add Health) data, we examine alcohol-use trajectories of a de-aggregated sample of biracial Black youth and compare them with the trajectories of the corresponding monoracial counterparts. The sample consists of 9421 adolescents and young adults who self-identified as 1 of 4 monoracial groups (i.e., Black, White, Hispanic, American Indian) or 1 of 3 biracial Black groups (i.e., Black-American Indian, Black-Hispanic, and Black-White). Study hypotheses are tested using latent growth curve modeling for first use, number of drinks, and binge drinking. We found partial support for the intermediate substance use hypothesis, with the alcohol use rates of biracial Blacks more closely resembling the non-Black corresponding group than the monoracial Black group. Black-American Indians face particularly high risk of problematic drinking. These findings demonstrate the need for additional research clarifying the onset and maintenance of alcohol use and misuse among biracial individuals and subgroups.


Transformation of cucumber tissues by microprojectile bombardment: identification of plants containing functional and non-functional transferred genes.
The microprojectile bombardment method was used to transfer DNA into embryogenic callus of cucumber (Cucumis sativus), and stably transformed cucumber plant lines were obtained. A total of 107 independently regenerated cucumber plants were assayed for the presence and expression of the transferred Nos-NPTII gene (encoding nopaline synthase-neomycin phosphotransferase II). Genomic blot hybridization analyses showed that a high percentage (16%) of the cucumber plants were transformed with Nos-NPTII; however, only about 25% of these transgenic plants expressed Nos-NPTII. Inactivity of Nos-NPTII in many of the transformed cucumber plants may be associated with the transfer of multiple copies of Nos-NPTII. PCR and genomic blot hybridization analyses were used to show that the transferred gene was inherited in the subsequent plant generation.


Effects of various pretreatments on the acute nephrotoxic potential of styrene in Fischer-344 rats.
The effects of various inducers and inhibitors of hepatic microsomal mixed-function oxidase (MFO) system and diethylmaleate treatment on styrene-induced acute nephrotoxicity in male Fischer-344 rats were studied. Groups of rats were pretreated with either 3-methylcholanthrene (15 mg/kg, i.p., 3 days), or phenobarbital (80 mg/kg, i.p., 3 days), or SKF525-A (50 mg/kg, i.p., 1 h), or piperonyl butoxide (300 mg/kg, i.p., 2 h), or diethylmaleate (400 mg/kg, i.p., 90 min) prior to an i.p. administration of styrene (0, 0.6 and 0.9 g/kg) in corn oil. The uptake of p-aminohippurate (PAH) by renal cortical slices, the morphology of renal cortices, as well as urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GT) of control and pretreated rats were examined 24 h after styrene. The inducers and inhibitors of MFO system failed to modify further the acute nephrotoxicity of styrene. On the other hand, diethylmaleate pretreatment not only reduced further the uptake of PAH, but also produced further significant increase in the urinary excretion of NAG and gamma-GT observed at the higher dose of styrene. Similarly, ultrastructural studies showed a moderate increase in the severity of kidney damage induced at the higher dose of styrene due to pretreatment with diethylmaleate. These data suggest that tissue glutathione concentrations and hence, corresponding conjugating activity might be important determinants of styrene nephrotoxicity. The results further indicate that a metabolic activation system not involving certain cytochrome P-450 might be responsible in styrene-induced nephrotoxicity.


Persistence conditions of symmetric social hybridogenesis in haplo-diploid hymenoptera.
In eusocial Hymenoptera species, females variably develop into either alate females (queens) or workers, and in most cases, caste differentiation is determined environmentally. Recently, however, female castes in two harvester ant species, Pogonomyrmex rugosus and P. barbatus, were found to be determined genetically in hybrid zones of these two species. In the hybrid populations, homozygous females (e.g. AA or BB) and heterozygous females (AB) develop into alate females and workers, respectively. This genetic caste determination system is called symmetric social hybridogenesis (SSH). It is clear that populations with SSH can persist only if all four genotypes (AA and BB females, and A and B males) coexist simultaneously. However, it is not obvious that these populations are always persistent when the four genotypes simultaneously exist. Here, we examined the stability and persistence of an SSH population using a simple mathematical model. According to the analysis of the model, the SSH population persists only when some conditions are satisfied: (1) each female mates with more than two males, and (2) male production increases less steeply than linearly with increasing numbers of workers in a colony, and alate female production increases more steeply than linearly with increasing numbers of workers, or (2') male production increases more steeply than linearly with increasing numbers of workers in a colony, and alate female production increases much more steeply than male production. Therefore, it is not obvious that SSH populations are maintained and are stable for long periods. We discuss whether these conditions are satisfied in real SSH populations.


Structure and stability of hcp iron carbide precipitates: A first-principles study.
Hexagonal close-packed (hcp) iron carbides play an important role in steel processing and in steel products. The recent discovery of novel ultrafine (2-5 nm) iron carbide (ε'-Fe2+xC) precipitates in TRIP steel sheds a new light on the hcp family of carbides. Here we present a first-principles study on the relative stability, and the electronic, magnetic properties of the ε'-Fe2C phases. Different stackings of Fe-sheets and orderings of C atoms were investigated and compared with experimental data and with Jack's model. We find very favorable formation enthalpies for these new members of the hcp family, and we present a first-principles-refined model for the crystal structure of the ultrafine Fe(C) precipitates. These findings are useful for the characterization of nano-sized iron carbide precipitates, for understanding their role in the microstructure of steels, and for the design of novel steels having even more desirable properties.


Hypoiodite mediated synthesis of isoxazolines from aldoximes and alkenes using catalytic KI and Oxone as the terminal oxidant.
Isoxazolines can be efficiently synthesized in good yields via a hypoiodite mediated catalytic oxidative cyclization of aldoximes and alkenes. This reaction involves active iodine species generated in situ from catalytic amounts of KI and Oxone.


Consequences of stabilising selection for polygenic variation.
A number of earlier authors have investigated the consequences for fitness of gene differences affecting the expression of a primary character where stabilising selection is acting in favour of an optimal expression. Assuming that the mean expression must be at or close to the optimum, deviations from the mean have been taken as measures of the deviation from the optimum, and the conclusion reached that, random drift apart, stabilising selection must ultimately lead to fixation of the commoner allele. It is now shown that this approach is incorrect: in an illustrative example the mean cannot be taken as synonymous with the optimum except in the trivial case where they have precisely the same value. Where the mean departs from the optimum, even by sampling variation only, continuing selection for it is effectively self-propagating and directional away from the optimum. Deviation from the optimum itself must be used in investigating the consequences of stabilising selection. The model used here is based on the biometrical description of the effects of a gene difference on a quantitative character as used by Mather and Jinks (1982). This includes a parameter, h, which allows dominance of any magnitude in either direction to be taken into account, and is adapted for the present purpose by introducing an additional parameter, m, measuring the departure from the optimum of the mid-point, or mid-parent, which is used biometrically as the origin for measurement of the gene effects. Assuming random mating and the absence of epistasis in the effects on the primary character, it is shown that stabilising selection acting on a pair of alleles (A and a) can have any one of three possible outcomes depending on the relative values of the m and h which characterise the effects of the gene difference on the primary character, viz: (i) a stable equilibrium in the population where in respect of the primary character Aa is nearer to the optimum than both homozygotes; (ii) fixation of the fitter allele where Aa is intermediate between the homozygotes in its departure from the optimum; (iii) a theoretical unstable equilibrium leading to fixation of the commoner allele, where Aa departs further from the optimum than both homozygotes. Only outcome (i) can lead to the conservation of variation in the population. Preliminary consideration is also given to the interaction in effect on fitness of two gene pairs affecting the same character and segregating simultaneously in the population.(ABSTRACT TRUNCATED AT 400 WORDS)


Altered hearing function in mice with implanted cranial windows.
The cranial window technique has proven to be an effective method for in vivo imaging of cortical activity. However, given the invasive nature of this procedure, possible side effects could be expected in the nervous system. In this study, we evaluated the effects of unilateral cranial window surgery on auditory function in C57BL6 mice using electrophysiological and behavioral approaches. We found that one week after implantation, mice exhibited both increased thresholds and decreased amplitudes of their auditory brainstem responses. These changes were accompanied by a decrease in distortion product otoacoustic emissions, indicating a deterioration in cochlear function. In addition, behavioral testing of these mice revealed reduced suppression of their acoustic startle response by gap prepulse, suggesting a deficit in auditory processing or possibly the presence of tinnitus. The changes in auditory function appeared to be only partially reversible within four weeks after surgery. Thus, our findings suggest that cranial window implantation causes long-term functional changes in the auditory system that should be considered when interpreting data from optical imaging techniques.


Initial clinical experience with full-length metal ureteral stents for obstructive ureteral stenosis.
Long-term ureteral stenting is used to ensure urinary drainage if a reconstructive approach or a release of an extrinsic obstruction is not possible. In this contribution, a long-term experience with a new full-length, metal indwelling stent is presented. Fourteen patients with ureteral obstruction received full metal indwelling stents in 18 collecting systems (benign disease in 5 and malignant disease in 13). Stent placement was performed cystoscopically under fluoroscopic guidance. Follow-up was done every 3 months with ultrasonographic examination, creatinine levels, and a visual analog pain score. Eight stents were removed, whereas eight are still in situ. One patient without stent-related problems died because of progressive rectal cancer 9 months after bilateral stent insertion. Mean stent duration (8 stents still in situ) is 8.6 months, whereas mean stent duration for benign and malignant disease is 11.8 (median 13) and 7.3 (median 6) months, respectively (p<0.05). All removed stents were extracted endoscopically without any problems and had no incrustation except two. Neither migration nor mechanical damage was observed. This novel stent is easy to insert and remove. It is an option for patients in which a surgical reconstruction of the obstructed ureter is not possible. Stents have been developed further and are now available in various lengths. This might result in a reduction of problems associated with inadequate stent length and should increase patient comfort and stent durability.


Effects of routine infant vaccination with the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization with streptococcus pneumoniae in children in Calgary, Canada.
All Streptococcus pneumoniae disease is preceded by nasopharyngeal (NP) colonization. We studied the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on colonization in healthy children. Routine PCV7 vaccination began in Alberta in 2002. Six point prevalence surveys were conducted from 2003 to 2005, in 7 community health centers in Calgary where children had their routine vaccinations. A questionnaire was administered and a single NP swab was obtained for culture. Serotyping was performed on all S. pneumoniae isolates. There were 3398 children with complete data, 1307, 1225, and 866 in 12-month, 18-month, and 4-6 year groups, respectively. None had received PCV7 in survey 1. From survey 2 onwards, 92-98% of 12-month-olds had 3 or more doses of PCV7, and from survey 3 onwards, 95-99% of 18-month-olds had 3 or more doses. By survey 6, only 4% of 4-6 year olds had 3 or more doses. The overall S. pneumoniae colonization rate was 20%. In all age groups, including unvaccinated 4-6 year olds, there were significant declines in PCV7 serotypes, and increases in non-PCV7 serotypes. The largest increases were serotypes 6A, 15C, and 11A. Multivariate analysis found that factors including age, siblings, daycare attendance, episodes of otitis media, and antibiotic use affected S. pneumoniae colonization but only PCV7 vaccination was associated with decreased PCV7 serotype colonization and increased non-PCV7 colonization. Routine PCV7 vaccination has led to significant changes in the predominant S. pneumoniae serotypes found in NP colonization in both vaccinated and unvaccinated children, indicating both a direct and herd effect.


Gelatinases (MMP-2 and MMP-9), TIMP-1 expression and the extent of neovascularization in aggressive non-Hodgkin's lymphomas.
The present study was carried out to clarify the role of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and the extent of neovascularization in the clinicopathologic behavior of non-Hodgkin's lymphomas. Paraffin-embedded histologic sections from 57 patients with aggressive non-Hodgkin's lymphomas were stained with MMP-2, MMP-9, TIMP-1, and factor VIII antibodies to correlate the expression of these markers to the clinical disease characteristics. Strong MMP-9 staining was found to be an adverse prognostic factor among patients with aggressive B-cell lymphomas, the probabilities for 5-yr disease-free survival being 73%, 63%, 50%, and 0% in patients with grades 0, 1, 2, and 3 staining, respectively. Among the patients with strong (grades 2 and 3) MMP-9 staining, however, positivity for TIMP-1 indicated a trend toward a more favorable prognosis. TIMP-1 expression also correlated with the immunoblastic and anaplastic lymphoma subtypes. The expression of the proteins for MMP-2 and factor VIII had no independent prognostic role. None of the study parameters correlated with disease stage, the occurrence of extranodal infiltrates, the occurrence of bulky tumor, or the IPI scores. Positivity for MMP-9 immunoreactive protein is an independent sign of an unfavorable prognosis in non-Hodgkin's lymphomas. This is not mediated through influences in tumor dissemination or neovascularization indicating it to carry other important biological functions.


Greener liquid chromatography using a guard column with micellar mobile phase for separation of some pharmaceuticals and determination of parabens.
In this research, a greener chromatography employing a short column, Zorbax SB C18 cartridge (12.5 × 4.6 mm, 5 μm) commonly used as a guard column in a reverse phase high performance liquid chromatography (RP-HPLC), was utilized as the analytical column in conjunction with a more eco-friendly micellar mobile phase of sodium dodecyl sulfate (SDS) for separation tertiary mixtures of local anesthetics and antihistamines; and binary mixture of colds drugs; and quaternary mixture of some parabens with different separation conditions. The chromatographic behavior of these analytes was studied to demonstrate separation efficiency of this guard column in a micellar mobile phase. Moreover, this column and SDS mobile phase was exploited for determination of parabens in 64 samples of cosmetic product, both those that were produced locally in the community and those that were commercially manufactured. Linear calibration graphs of the parabens as detected at 254 nm were obtained in the range of 1-100 μmol L(-1) with R(2)>0.9990. Percentage recoveries were 92.4-109.2 with %RSD<3, and the limit of detection and quantitation were 0.04-0.10 and 0.20-0.80 μmol L(-1), respectively. This analytical system is not only greener but also faster and employing simpler sample preparation than a conventional liquid chromatographic system.


Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the lung epithelium are thought to be critical drivers of disease progression, contributing to fibroblast activation, extracellular matrix remodeling, and subsequently loss of lung architecture and function. To date, Pirfenidone and Nintedanib are the only approved drugs known to decelerate disease progression, however, if and how these drugs affect lung epithelial cell function, remains largely unexplored. We treated murine and human 3D ex vivo lung tissue cultures (3D-LTCs; generated from precision cut lung slices (PCLS)) as well as primary murine alveolar epithelial type II (pmATII) cells with Pirfenidone or Nintedanib. Murine 3D-LTCs or pmATII cells were derived from the bleomycin model of fibrosis. Early fibrotic changes were induced in human 3D-LTCs by a mixture of profibrotic factors. Epithelial and mesenchymal cell function was determined by qPCR, Western blotting, Immunofluorescent staining, and ELISA. Low μM concentrations of Nintedanib (1 μM) and mM concentrations of Pirfenidone (2.5 mM) reduced fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and human 3D-LTCs as well as pmATII cells. Notably, Nintedanib stabilized expression of distal lung epithelial cell markers, especially Surfactant Protein C in pmATII cells as well as in murine and human 3D-LTCs. Pirfenidone and Nintedanib exhibit distinct effects on murine and human epithelial cells, which might contribute to their anti-fibrotic action. Human 3D-LTCs represent a valuable tool to assess anti-fibrotic mechanisms of potential drugs for the treatment of IPF patients.


The menisci and articular cartilage: a life-long fascination.
The menisci and articular cartilage of the knee have a close embryological, anatomical and functional relationship, which explains why often a pathology of one also affects the other.Traumatic meniscus tears should be repaired, when possible, to protect the articular cartilage.Traumatic articular cartilage lesions can be treated with success using biological treatment options such as microfracture or microdrilling, autologous chondrocyte transplantation (ACT), or osteochondral transplantation (OCT) depending on the depth and area of the lesion.Degenerative cartilage and meniscus lesions often occur together, and osteoarthritis is already present or impending. Most degenerative meniscus lesions should be treated first conservatively and, after failed conservative treatment, should undergo arthroscopic partial meniscus resection. Degenerative cartilage lesions should also be treated conservatively initially and then surgically; thereby treating the cartilage defect itself and also maintaining the axis of the leg if necessary.Tears of the meniscus roots are devastating injuries to the knee and should be repaired e.g. by transtibial re-fixation.The clinical role of 'ramp' lesions of the meniscus is still under investigation. Cite this article: EFORT Open Rev 2020;5:652-662. DOI: 10.1302/2058-5241.5.200016.


Different effects of exposure to penconazole and its enantiomers on hepatic glycolipid metabolism of male mice.
(±) - PEN is a chiral fungicide widely used to control powdery mildew in agriculture. Currently, only a few studies have investigated the toxic effects of (±) - penconazole ((±) - PEN) on non-target organisms, and whether (±) - PEN from the enantiomeric level have toxic effects remains unclear. In this study, we systematically evaluated the effects of exposure to (±) - PEN, (+) - PEN and (-) - PEN on liver function in mice. Biochemical and histopathological analyses showed that exposure to (±) - PEN and (-) - PEN led to significant liver damage and inflammation. However, exposure to (+) - PEN treatment did not cause no adverse effects on liver function and inflammation. 1H-NMR-based metabolomics revealed that exposure to (±) - PEN, (+) - PEN and (-) - PEN led to the animals developing liver metabolic disorder that was caused by changes in glycolipid metabolism. Quantitative analysis of genes regulating glycolipid metabolism revealed that expression of gluconeogenesis and glycolytic pathway genes were altered in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. We also found that (±) - PEN, (+) - PEN and (-) - PEN have different effects on lipid metabolism of the liver. Exposure to (±) - PEN and (-) - PEN resulted in significant accumulation of lipids by regulating fatty acid synthesis, triglyceride synthesis, and fatty acid β oxidation pathways. In summary, we found different toxicological effects in individuals exposed to (±) - PEN, (+) - PEN and (-) - PEN. The results of this study are important for assessing the potential health risks of (±) - PEN.


Editorial Commentary: Role of Synovial Biomarkers in Patient Outcomes After Knee Arthroscopy.
Humans are notably poor at predicting event outcomes. In "Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy," Cuellar, Cuellar, Kirsch, and Strauss show that some synovial fluid biomarkers (20 were sampled for the investigation) may predict operative findings at the time of arthroscopy and patient-reported outcome measures at follow-up. Further research will clarify the role of synovial biomarkers in knee pathology and, hopefully, narrow the choices to one or two pertinent markers that can be used to improve our ability to predict outcomes from arthroscopic knee surgery.


A common mechanism for microtubule destabilizers-M type kinesins stabilize curling of the protofilament using the class-specific neck and loops.
Unlike other kinesins, middle motor domain-type kinesins depolymerize the microtubule from its ends. To elucidate its mechanism, we solved the X-ray crystallographic structure of KIF2C, a murine member of this family. Three major class-specific features were identified. The class-specific N-terminal neck adopts a long and rigid helical structure extending out vertically into the interprotofilament groove. This structure explains its dual roles in targeting to the end of the microtubule and in destabilization of the lateral interaction of the protofilament. The loop L2 forms a unique finger-like structure, long and rigid enough to reach the next tubulin subunit to stabilize the peeling of the protofilament. The open conformation of the switch I loop could be reversed by the shift of the microtubule binding L8 loop, suggesting its role as the sensor to trigger ATP hydrolysis. Mutational analysis supports these structural implications.


Corrigendum: A GMC Oxidoreductase GmcA Is Required for Symbiotic Nitrogen Fixation in Rhizobium leguminosarum bv. viciae.
[This corrects the article DOI: 10.3389/fmicb.2020.00394.].


Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis.
Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon. The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57Bl/6 mice received zymosan (100 µg/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis. ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED50) was 100mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6h and 24h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-α production at 6h and CXCL1/KC and IL-1β production at 24h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day. Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation.


The bark of trees: thermal properties, microclimate and fauna.
The thermal properties of four different types of bark were investigated on twentyfour central European tree species using thermocouples. Tree species with white bark avoid overheating of their surface by reflection of the radiation. Species with fissured and scaly barks shade inner parts of their bark. Some tree species with fissured barks show high insulation across the bark. Smooth and thin barks show no adaptation to avoid overheating. These tree species (in central Europe e.g. Fagus sylvatica) have to form closed stands and are not able to occur in open stands as tree species with structured or white bark types.The arthropod fauna of the same bark types was studied on six tree species using three collecting methods. The microclimate on the bark determines the number per cm2 of some species, some are active during winter, and other tend to aptery and reproduce parthenogenetically. On smooth bark one species dominates, whereas a highly diverse fauna lives on fissured barks. The occurrence of species on bark is determined by the microstructure, microclimate and consistence of the epiphyts. If tree species alter within forest ecosystems the dominant species on bark will persist. Specialists of fissured barks will die out if tree species with smooth bark (Fagus sylvatica) form the central European forest.


Vacuole dynamics and popping-based motility in liquid droplets of DNA.
Liquid droplets of biomolecules play key roles in organizing cellular behavior, and are also technologically relevant, yet physical studies of dynamic processes of such droplets have generally been lacking. Here, we investigate and quantify the dynamics of formation of dilute internal inclusions, i.e., vacuoles, within a model system consisting of liquid droplets of DNA 'nanostar' particles. When acted upon by DNA-cleaving restriction enzymes, these DNA droplets exhibit cycles of appearance, growth, and bursting of internal vacuoles. Analysis of vacuole growth shows their radius increases linearly in time. Further, vacuoles pop upon reaching the droplet interface, leading to droplet motion driven by the osmotic pressure of restriction fragments captured in the vacuole. We develop a model that accounts for the linear nature of vacuole growth, and the pressures associated with motility, by describing the dynamics of diffusing restriction fragments. The results illustrate the complex non-equilibrium dynamics possible in biomolecular condensates.


Effects of Amphotericin B on the expression of neurotoxic and neurotrophic factors in cultured microglia.
Amphotericin B (AmB) is a polyene antibiotic and reported to have therapeutic effects on prion diseases, in which the microglial activation has been suggested to play important roles by proliferating and producing various factors such as nitric oxide, proinflammatory cytokines, and so on. However, the therapeutic mechanism of AmB on prion diseases remains elusive. In the present study, we investigated the effects of AmB on cellular functions of rat primary cultured microglia. We found that AmB, similarly as lipopolysaccharide (LPS), could activate microglia to produce nitric oxide via inducible nitric oxide synthase. Both AmB and LPS also induced mRNA expressions of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in microglia. AmB also changed the expression levels of neurotrophic factors mRNAs. AmB and LPS significantly down-regulated the level of ciliary neurotrophic factor mRNA. However, AmB, but not LPS, significantly up-regulated the level of glial cell-line derived neurotrophic factor mRNA in microglia. In addition, brain-derived neurotrophic factor mRNA expression level was tending upward by treatment with AmB, but not with LPS. Taken together, these results suggest that AmB regulates the microglial activation in different manner from LPS and that microglia may participate in the therapeutic effects of AmB on prion diseases by controlling the expression and production of such mediators.


Study of sleep-wakefulness states by computer graphics and cluster analysis before and after lesions of the pontine tegmentum in the cat.
A computerized method of quantification, graphic representation and classification of sleep-wakefulness data in the cat before and after pontine tegmental lesions has been presented. Electrophysiological signal features including average EEG amplitude, average EMG amplitude and PGO spike rate which are particularly important for the definition of sleep-wakefulness states have been quantified for each 1 min epoch in the day. The data were presented in a projected 3-dimensional data display, in which they formed clusters that are considered to be analogous to sleep-wakefulness states. A cluster analysis algorithm was employed for the automatic classification of these data, and this automatic classification was compared graphically and with contingency table analyses to traditional visual assessment of state from polygraphic records. Although there were systematic differences in the locations of state boundaries, total percent agreement between cluster analysis classification and traditional human classification was comparable to the percent agreement between any two human classifiers (about 90%). After pontine tegmental lesions involving both the gigantocellular and lateral tegmental fields, paradoxical sleep was eliminated, and the characteristics of slow wave sleep and wakefulness were altered. The elimination of the state of paradoxical sleep was evident in the computer display by the absence of the paradoxical sleep cluster, and alterations of the other states were indicated in the display by shifts in the positions of their respective clusters. Automatic classification of slow wave sleep and wakefulness after such lesions compared well with traditional classification, attesting to the validity of this approach.


Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction.
We recently identified a polymorphic Sp1 binding site in an enhancer at the tissue-type plasminogen activator (tPA) locus (tPA -7,351C/T), which was associated with vascular tPA release. Subjects homozygous for the -7,351C allele had twice the tPA release rate compared to subjects carrying the -7,351T allele. In this study we tested the hypothesis that the tPA -7,351C/T polymorphism is associated with myocardial infarction (MI). In a population-based prospective nested case-control study within northern Sweden, genotypes were determined among 61 MI cases and 120 controls. In a multivariate model, the tPA -7,351C/T polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31-5.50), tPA antigen (OR 1.16; 95% CI 1.07-1.25) and apo A-I (OR, 0.997; 95% CI 0.995-0.999) were independently associated with a first MI. These findings suggest that genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information.


The dynamic influence of commensal bacteria on the immune response to pathogens.
Alterations in the composition of commensal bacterial communities are associated with enhanced susceptibility to multiple inflammatory, allergic, metabolic and infectious diseases in humans. In the context of infection, commensal bacteria-derived signals can influence the host immune response to invasive pathogens by acting as an adjuvant to boost the immune response to infection or by providing tonic stimulation to induce basal expression of factors required for host defense. Conversely, some pathogens have evolved mechanisms that can utilize commensal bacteria to establish a replicative advantage within the host. Thus, examining the dynamic relationship that exists between the mammalian host, commensal bacteria and invasive pathogens can provide insights into the etiology of pathogenesis from an infection.


Trauma exposure and sexual revictimization risk: comparisons across single, multiple incident, and multiple perpetrator victimizations.
Although research demonstrates a link between child sexual abuse and sexual revictimization in adolescence or adulthood, less is known about specific mechanisms that increase women's vulnerability to reassault. This study examined experiential and outcome differences between survivors of a single assault, survivors of ongoing abuse by a single perpetrator, and survivors of multiple assaults by different offenders. Multiply victimized women differed from survivors of a single assault or of ongoing abuse on psychological distress, health, and nonsexual trauma variables. Revictimization by new perpetrators was predicted by an earlier age during a first sexual assault and by nonsexual trauma in childhood.


A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.
To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001). Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.


Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015.
We used the Swedish Inpatient Register (IPR) to analyze rates of brain tumors of unknown type (D43) during 1998-2015. Average Annual Percentage Change (AAPC) per 100,000 increased with +2.06%, 95% confidence interval (CI) +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC) 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Register the age-standardized incidence rate per 100,000 increased for brain tumors, ICD-code 193.0, during 1998-2015 with AAPC in men +0.49%, 95% CI +0.05, +0.94%, and in women +0.33%, 95% CI -0.29, +0.45%. The cases with brain tumor of unknown type lack morphological examination. Brain tumor diagnosis was based on cytology/histopathology in 83% for men and in 87% for women in 1980. This frequency increased to 90% in men and 88% in women in 2015. During the same time period CT and MRI imaging techniques were introduced and morphology is not always necessary for diagnosis. If all brain tumors based on clinical diagnosis with CT or MRI had been reported to the Cancer Register the frequency of diagnoses based on cytology/histology would have decreased in the register. The results indicate underreporting of brain tumor cases to the Cancer Register. The real incidence would be higher. Thus, incidence trends based on the Cancer Register should be used with caution. Use of wireless phones should be considered in relation to the change of incidence rates.


Recent progress in chemical synthesis of bacterial surface glycans.
With the continuing advancement of carbohydrate chemical synthesis, bacterial glycomes have become increasingly attractive and accessible synthetic targets. Although bacteria also produce carbohydrate-containing secondary metabolites, our review here will cover recent chemical synthetic efforts on bacterial surface glycans. The obtained compounds are excellent candidates for the development of improved structurally defined glycoconjugate vaccines to combat bacterial infections. They are also important probes for investigating glycan-protein interactions. Glycosylation strategies applied for the formation of some challenging glycosidic bonds of various uncommon sugars in a number of recently synthesized bacterial surface glycans are highlighted.


Antimicrobial activity of a chimeric enzybiotic towards Staphylococcus aureus.
Phage lytic enzymes (enzybiotics) have gained attention as prospective tools to eradicate Gram-positive pathogens resistant to antibiotics. Attempts to purify the P16 endolysin of Staphylococcus aureus phage P68 were unsuccessful owing to the poor solubility of the protein. To overcome this limitation, we constructed a chimeric endolysin (P16-17) comprised of the inferred N-terminal d-alanyl-glycyl endopeptidase domain and the C-terminal cell wall targeting domain of the S. aureus phage P16 endolysin and the P17 minor coat protein, respectively. The domain swapping approach and the applied purification procedure resulted in soluble P16-17 protein, which exhibited antimicrobial activity towards S. aureus. In addition, P16-17 augmented the antimicrobial efficacy of the antibiotic gentamicin. This synergistic effect could be useful to reduce the effective dose of aminoglycoside antibiotics.


The activity of the neuronal and extraneuronal catecholamine-metabolizing enzymes of the perfused rat heart.
In a comparative study the neuronal and extraneuronal metabolism of several 3H-catecholamines (all of which were tritiated in the C-7 position of the side chain only) was determined in isolated rat hearts perfused at a concentration of the 3H-amines of 50 nmol/l. While the neuronal MAO activity was determined after inhibition of extraneuronal uptake (100 mumol/l OMI) and COMT (10 mumol/l U-0521), the extraneuronal MAO activity was estimated after inhibition of neuronal uptake (30 mumol/l cocaine) and COMT. The extraneuronal COMT activity was determined under conditions of inhibition of both neuronal uptake and MAO (pretreatment with pargyline). Hearts were perfused with the 3H-catecholamines until the rate of appearance of the various 3H-metabolites in the venous effluent has reached a steady state. From these rates (vst-st) and the steady-state content of the unchanged 3H-catecholamines in the tissue (Si), the rate constants (Vmax/Km) for the unsaturated intracellular enzymes COMT (kCOMT) and MAO (kMAO) were calculated. The kCOMT values for all four catecholamines, (-)-noradrenaline, dopamine, (-)-adrenaline and (+/-)-isoprenaline exhibit a range from 0.24 to 0.78 min-1; the metabolism of the catecholamines by the COMT differs: (-)-noradrenaline = dopamine less than (-)-adrenaline less than (+/-)-isoprenaline. The extraneuronal MAO activity was low for all three catecholamines, (-)-adrenaline, (-)-noradrenaline and dopamine (range of kMAO from 0.05 to 0.28 min-1) and declined in the order.(ABSTRACT TRUNCATED AT 250 WORDS)


Transanal circular-stapled reanastomosis as a management alternative for anastomotic colonic strictures: a novel technique in the pediatric patient.
A 12-year-old male patient with a recalcitrant rectal anastomotic stricture following two failed endorectal pull-through (Soave) procedures for Hirschsprung's disease was satisfactorily managed with transanal resection using a circular stapling device. This is the first reported case of a benign colonic anastomotic stricture treated transanally with a circular stapling device in a pediatric patient.


Sequencing of peracetylated oligosaccharides by rotating-frame nuclear Overhauser enhancement spectroscopy.
A combination of two-dimensional total correlation spectroscopy (TOCSY) and rotating-frame nuclear Overhauser enhancement spectroscopy (ROESY) is suggested as the optimum strategy for determining the primary structure of peracetylated oligosaccharides.


[Relation between the resistance index obtained by the transfontanellar Doppler ultrasonography and the neurological development until the first year of life in term infants with mild or moderate hypoxic-ischaemic encephalopathy].
To evaluate the relation between the resistance index (RI) obtained by transfontanellar Doppler ultrasonography, and the neurodevelopment until one year of life, at term newborns with mild or moderate hypoxic-ischaemic encephalopathy due to intrapartum asphyxia. 20 term newborns, with mild or moderate hypoxic-ischemic encephalopathy, high values of resistance index in the first exam, and without cerebral morfologic abnormalities or other diseases. They were submitted to serial bimonthly transfontanellar Doppler ultrasonography, from the seventh day of life on, and monthly clinical neurodevelopment assessment until one year of life. There was a progressive normalization of RI values until the last examination. In five cases there were clinical neurologic normalization in the neonatal period after the first Doppler exam. Fifteen infants presented neurologic abnormalities, with normalization after the second trimester of life. There was a relation between the normal RI values with the normalization of the clinical assessment.


Partial trisomy 2q and familial translocation t(2;18)(q31;p11).
This report describes a malformed infant with distal 2q trisomy/distal 18p monosomy due to adjacent segregation of a familial t(2;18). The rearrangement was present in four generations, and linkage studies were performed.


Pre- and postoperative exercise testing of the child with coarctation of the aorta.
Exercise studies in patients with coarctation of the aorta (CoA) are reviewed. A brief survey of the natural history of unoperated CoA, the pioneers who reported the first operative repair, and comments on blood pressure measurements are provided. Preoperative and postoperative (postop) exercise studies of patients with CoA are also reviewed. The various etiological factors which may contribute to hypertension found in some post-op CoA patients are discussed.


The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma.
The Total (Peroxyl) Radical-trapping Antioxidant Parameter (TRAP) of six freshly prepared human plasma samples and 45 frozen plasma samples has been determined. It is shown that contributions from urate (35-65%), plasma proteins (10-50%), ascorbate (0-24%) and vitamin E (5-10%) to TRAP account for all of the peroxyl radical-trapping antioxidant activity in the majority of the samples. The changes in concentrations of the plasma antioxidants during peroxyl radical attack show that the first line of defense is provided by the plasma sulfhydryl groups, even urate being spared during the initial stages of the reaction. The modes of action of all of these plasma antioxidants and possible interactions between them are discussed, with particular emphasis on the abilities of the water-soluble antioxidants to regenerate or spare the only lipid-soluble antioxidant, vitamin E.


Handedness and locus of control.
Groups of 15 left-, 15 mixed-, and 39 right-handers were tested with Rotter's Locus of Control Scale. Contrary to prediction, it was found that both left- and right-handers scored significantly higher, i.e., were more externally controlled, than mixed-handers. Primarily these data suggest a complex relationship between handedness and personality and they serve to reinforce the need to include mixed-handers in research on handedness.


Lack of evidence of human papillomavirus-induced squamous cell carcinomas of the oral cavity in southern Germany.
The aim of the present study was to identify HPV-attributable SCC of the oral cavity (OSCC) in a cohort of patients from southern Germany. A sensitive PCR-enzyme immunoassay (EIA) was followed by a more specific in situ hybridization (ISH) to detect high risk human papillomavirus (HPV). An immunohistochemical dual-staining for p16(INK4a) and the proliferation marker Ki-67 was used to assess whether co-expression of p16(INK4a)/Ki-67 is a better surrogate marker for HPV in OSCC than p16(INK4a) alone, based on the hypothesis that combined p16(INK4a) and Ki-67 expression might specifically discriminate oncogene-induced p16(INK4a) expression from cell-cycle arrest-inducing senescence-associated p16(INK4a) expression. HPV-DNA by PCR-EIA could be detected in 25.1% (69/275) of the tumors, but ISH was negative in all of them. Diffuse p16(INK4a) overexpression was detected in 11 HPV PCR-positive tumors, but also in 6 HPV PCR-negative tumors. p16(INK4a)-expressing cells in diffusely positive tumors co-expressed Ki-67, irrespective of the HPV status. Neither the sole HPV status nor combined HPV/p16(INK4a) status nor the sole p16(INK4a) status was significantly associated with disease free or overall survival, however a trend towards better overall survival of patients whose tumor expressed p16(INK4a) in a focal pattern (=p16(INK4a)-positive/Ki-67-negative cells) compared to no p16(INK4a) expression (p=0.09) was observed. Viral DNA can be detected in some tumors by a sensitive PCR, but absence of ISH signals indicates that the HPV-attributable fraction is smaller than estimated from PCR positivity. p16(INK4a)/Ki-67 co-expression is detectable in a fraction of OSCC irrespective of the HPV status.


Bariatric Surgery Improves Renal Function: a Large Inner-City Population Outcome Study.
Bariatric surgery is associated with improved renal dysfunction in general population studies. The study examined the effects of bariatric surgery on renal function in a predominantly Hispanic and African American population at a community hospital in New York, USA. This retrospective study analyzed prospectively collected bariatric surgical data from 2247 patients (89% female) who underwent bariatric surgery at a single center. Changes in glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), micro- and macroalbuminuria, and hyperfiltration, which were measured preoperatively and then yearly for 3 years postoperatively, were evaluated with t tests and logistic regression analysis, after adjusting for confounding variables. The mean age of the patients at surgery was 37.1 years; the mean preoperative body mass index was 45 ± 7 kg/m2. The results obtained 3 years postoperatively showed the following significant improvements compared with the preoperative values: mean UACR decreased from 40.3 to 11.1 mg/g, mean eGFR improved from 79.4 to 87.3 mL/min, the prevalence of microalbuminuria decreased from 13.7 to 6.2%, the prevalence of macroalbuminuria decreased from 2.5 to 0%, and the prevalence of hyperfiltration decreased from 4.4 to 2.7% (all P < .0001). In adjusted multivariate regression analysis, these results remained significant after adjusting for age, sex, race, type of surgery, and presence of diabetes mellitus or hypertension. In this large study at an inner-city hospital, bariatric surgery was associated with significant improvements in renal dysfunction parameters. These results could assist with informed decisions regarding indications for bariatric surgery.


Three-Dimensional Reconstruction of the Genial Spinal Canal.
The aim of this anatomical study was to investigate the genial spinal canal histologically and to reconstruct it three-dimensionally to improve understanding of its anatomy and to reveal any differences between dentate and edentulous specimens. Two tissue blocks from the mandible between the left and right second incisors, one dentate and one edentulous, were fixed in 4.5% formaldehyde, decalcified and embedded in paraffin. Serial histological sections were prepared, stained with Azan and examined microscopically. Additionally, three-dimensional models of the blocks were reconstructed using microphotographs of the sections. The genial spinal canal in the dentate specimen contained a neurovascular bundle, which branched into a nerve innervating the incisor and a neurovascular bundle, whereas that in the edentulous specimen contained some nerves for vestibular gingival innervation and a vascular bundle. The results suggest differences in the genial spinal canal between dentate and edentulous mandibles. Further research is needed to confirm this finding. Clin. Anat., 33:1102-1108, 2020. © 2019 Wiley Periodicals, Inc.


Consequences of the spilled gallstones during laparoscopic cholecystectomy: a systematic review.
Complications secondary to spilled gallstones can be classified in the category of disease of medical progress because prior to advent of laparoscopic cholecystectomy very few reports published on the topic. The aim of the present study was to investigate the predisposing factors and the complication rate of spilled gallstones during laparoscopic cholecystectomy over the past 21 years. Embase, Pubmed, Medline, Google scholar and Cochrane library were systematically searched for pertinent literature. Seventy five out of 181 articles were selected including 85 patients; of those 38% were men and 62% women. The median age of the cohort was 64 years old and ranged between 33 and 87 years. Only 23(27%) of the authors reported the incident of spillage of the gallstones during the operation. Time of onset of symptoms varied widely from the second postoperative day to 15 years later. Ten of 85 patients were asymptomatic and diagnosed with spilled gallstones incidentally. The rest of the patients presented with complications of severe morbidity and almost, 87% of the patients needed to be treated with surgical intervention and 12% with US ± CT scan guidance drainage. Only one perioperative death reported. Symptomatic patients with lost gallstones present with severe morbidity complications and required mostly major surgical procedures. Therefore, standardisation of the management of spilled gallstones is needed urgently. Hospitals need to review their policy with audits and recommendations and clinical guidelines are needed urgently.


Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy.
An immunoperoxidase method was used to demonstrate expression of HLA-DR (a Class II major histocompatibility antigen) as an indicator of microglial activation in cases of hippocampal sclerosis derived from temporal lobectomy for intractable seizures. HLA-DR-immunoreactive microglia were increased approximately 11-fold in CA1 and 3-fold in CA3, compared to control autopsy hippocampus. The numbers of HLA-DR-immunoreactive perivascular cells were also significantly increased in hippocampal sclerosis cases (9-, 7- and 6-fold increases in CA1, CA3 and CA2, respectively). Since animal studies have found microglial activation to be an acute or subacute response to injury, the results presented here suggest that, contrary to the classical conception of human hippocampal sclerosis as an inert scar, neuronal injury continues to occur as a result of ongoing seizure activity.


Clinical characteristics of patients with suspected Alzheimer's disease within a CSF Aß-ratio grey zone.
The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß1-42/Aß1-40 ratio in cerebrospinal fluid. We analysed retrospective data from two cohorts (memory clinic cohort and ADNI) of patients (n = 63) with an Aß1-42/Aß1-40 ratio within a predefined borderline area-Q1 above the validated cut-off value(grey zone). We compared demographic, clinical, neuropsychological and neuroimaging features between grey zone patients and patients with low Aß1-42 (normal Aß ratio but pathological Aß1-42, n = 42) and patients with AD (pathological Aß, P-Tau, und T-Tau, n = 80). Patients had mild cognitive impairment or mild dementia and a median age of 72 years. Demographic and general clinical characteristics did not differ between the groups. Patients in the grey zone group were the least impaired in cognition. However, they overlapped with the low Aß1-42 group in verbal episodic memory performance, especially in delayed recall and recognition. The grey zone group had less severe medial temporal atrophy, but mild posterior atrophy and mild white matter hyperintensities, similar to the low Aß1-42 group. Patients in the Aß ratio grey zone were less impaired, but showed clinical overlap with patients on the AD continuum. These borderline patients may be at an earlier disease stage. Assuming an increased risk of AD and progressive cognitive decline, careful consideration of clinical follow-up is recommended when using dichotomous approaches to classify Aß status.


Quality of paper boards from arecanut leaf sheath.
A study was carried on utilizing arecanut leaf sheath for making paper boards. Paper boards were made with various combinations of arecanut leaf sheath with waste paper, 1:1, 1:2, 1:3, 3:1, 2:1, control (100% areca leaf sheath) and the qualities of these paper boards were tested as per the Bureau of Indian Standards (IS: 1060 (part-I)-1966). The paper boards made with more arecanut sheath materials had more resistance to water absorption. The addition of paper increased the substance weight of the paper boards. The 2:1 and 3:1 combinations of arecanut leaf sheath and waste paper had best tear strength, tensile strength, bursting strength and water resistance with minimum substance weight.


Congestive cardiomyopathy due to chronic tachycardia: resolution of cardiomyopathy with antiarrhythmic drugs.
A three-year-old child with arrhythmia-induced cardiomyopathy is presented. Drug treatment produced immediate symptomatic relief and subsequent reversion to normal cardiac size and function. This demonstrates that reduction of ventricular rate by drug treatment produces resolution of arrhythmia-induced cardiomyopathy and that surgical excision of atrial automatic focus is not always necessary.


Recycling of plastic wastes generated from COVID-19: A comprehensive illustration of type and properties of plastics with remedial options.
Plastic has contributed enormously to the healthcare sector and towards public health safety during the COVID-19 pandemic. With the frequent usage of plastic-based personal protective equipment (PPEs) (including face masks, gloves, protective body suits, aprons, gowns, face shields, surgical masks, and goggles), by frontline health workers, there has been a tremendous increase in their manufacture and distribution. Different types of plastic polymers are used in the manufacture of this equipment, depending upon their usage. However, since a majority of these plastics are still single-use plastics (SUP), they are not at all eco-friendly and end up generating large quantities of plastic waste. The overview presents the various available and practiced methods in vogue for disposal cum treatment of these highly contaminated plastic wastes. Among the current methods of plastic waste disposal, incineration and land filling are the most common ones, but both these methods have their negative impacts on the environment. Alongside, numerous methods that can be used to sterilize them before any treatment have been discussed. There are several new sorting technologies, to help produce purer polymers that can be made to undergo thermal or chemical treatments. Microbial degradation is one such novel method that is under the spotlight currently and being studied extensively, because of its ecological advantages, cost-effectiveness, ease of use, and maintenance. In addition to the deliberations on the methods, strategies have been enumerated for combination of different methods, vis-à-vis studying the life cycle assessment towards a more circular economy in handling this menace to protect mankind.


Phosphaturic mesenchymal tumor with an admixture of epithelial and mesenchymal elements in the jaws: clinicopathological and immunohistochemical analysis of 22 cases with literature review.
Information on the heterogeneity of phosphaturic mesenchymal tumor, a rare entity associated with tumor-induced osteomalacia, is limited. In this retrospective analysis of 222 phosphaturic mesenchymal tumors, 22 cases exhibited mixed mesenchymal and epithelial elements, which we propose to term "phosphaturic mesenchymal tumor, mixed epithelial, and connective tissue type." Phosphaturic mesenchymal tumor of the mixed epithelial and connective tissue type showed a distinctive and significant male predominance (male:female = 2.67:1), with most patients diagnosed at <40 years old. Moreover, all tumors were mainly located in the alveolar bone with focal invasion into surrounding soft tissue and oral mucosa, which could be detected preoperatively by oral examination. The mesenchymal component, composed of spindled cells resembling fibroblasts or myofibroblasts arranged in a storiform or fascicular pattern, exhibited a less prominent vasculature and lower cellularity than the typical phosphaturic mesenchymal tumor (mixed connective tissue type). The epithelial component was typically haphazardly and diffusely distributed throughout the tumor, forming small, irregular nests resembling odontogenic epithelial nests. All cases were immunoreactive for fibroblast growth factor-23, somatostatin receptor 2A, and NSE in both components. Mostly also demonstrated positive staining for CD99 (21/22, 96%), CD56 (16/22, 73%), Bcl-2 (21/22, 96%), and D2-40 (19/22, 86%) in one or both components. S100 was positive in both components in one of seven cases. Interestingly, immunoreactivity was typically stronger and more diffuse in the epithelial than in the paired mesenchymal components. The mesenchymal component was also diffusely positive for CD68 (17/17, 100%) and showed variable focal staining for SMA (15/22, 68%) and CD34 (9/19, 47 %). These results indicate that phosphaturic mesenchymal tumor of the mixed epithelial and connective tissue type has distinctive clinicopathological characteristics and a polyimmunophenotypic profile.


Inhibitory effects of class I and IV antiarrhythmic drugs on the Na+-activated K+ channel current in guinea pig ventricular cells.
Recently we have reported that class III antiarrhythmic drugs including amiodarone inhibit the Na+-activated K+ (KNa) channels in isolated cardiac cells. In this study effects of antiarrhythmic drugs having class I and/or IV properties on the single KNa channel current were examined in inside-out membrane patches of guinea pig ventricular cells by using patch clamp techniques. The KNa channel current, which was activated by increasing [Na+]i from 0 mM to 100 mM in the presence of 150 mM [K+]o, showed a large slope conductance (212 pS) and inward-going rectification. Quinidine (100 microM), mexiletine (100 microM) and flecainide (10 microM) were selected as representative of class Ia, Ib and Ic drugs, respectively. These drugs at relatively high concentrations incompletely inhibited the KNa channel by decreasing the open time (flickering block). The class IV drug verapamil inhibited the KNa channel current mainly by decreasing the open probability although the IC50 value of verapamil (3.36 microM) was higher than the therapeutic concentrations. Bepridil and SD-3212, antiarrhythmic drugs having both class I and IV properties, potently inhibited the KNa channel current by decreasing the open probability. The IC50 values of bepridil and SD-3212 for inhibiting the KNa channel current was 0.51 microM and 0.53 microM, respectively, both of which are within the therapeutic range. Most antiarrhythmic drugs inhibit cardiac KNa channels by different modes and at different concentrations. The KNa channel blocking action of bepridil and SD-3212 may partly contribute to the prolongation of the action potential duration by these drugs at rapid stimulation rates.


Membrane surface roughness promotes rapid initial cell adhesion and long term microalgal biofilm stability.
In biofilm membrane photobioreactors development, conscientious works revolving around the effect of external environment factors on microalgal biofilm growth were assessed but more comparative research about the role of carrier surfaces properties such as surface roughness is necessary. Thus, commercial polyethersulfone (PES) membranes with two different molecular-weight-cut-offs (1 kDa and 30 kDa) were selected as the main representatives of surface roughness in a 20 days long-term biofilm cultivation experiment under dynamic flow condition for the biofilm evolvement of three benthic diatoms (Amphora coffeaeformis, Cylindrotheca fusiformis and Navicula incerta). Results depicted that rougher 30 kDa PES enable higher cell attachment degree for C. fusiformis (25.85 ± 2.75 × 109 cells m-2), followed by A. coffeaeformis (11.86 ± 2.76 × 109 cells m-2) and N. incerta (10.10 ± 0.65 × 109 cells m-2). Bounded extracellular polymeric substances (bEPS) gathered were relatively higher than soluble EPS (sEPS) while bEPS accumulated at least 10% higher on smooth 1 kDa PES than rough 30 kDa PES for the purpose of enhancing the biofilm disruption resistivity under liquid flow. Moreover, cell adhesion mechanism was proposed via computational fluid dynamics in parallel with EPS analysis. Copious amount of asperities and stagnant zones present on rough 30 kDa surfaces accelerated biofilm development and the consistency of the results have a great valence for interpretation of microalgal biofilm lifestyle on porous surfaces.


Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway.
To examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. Population-based prospective pregnancy cohort study. The Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. 45,266 women with 51,748 singleton pregnancies. The association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. Children's language competence at age three measured by maternal report on a validated language grammar scale. Women reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and long-term symptoms, respectively. Prolonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect.


A fluorescence probe based on carbon dots for determination of dopamine utilizing its self-polymerization.
A rapid and sensitive strategy for sensing dopamine (DA) was proposed based on the fluorescence quenching effects of polydopamine (PDA) on carbon dots (CDs). The green-emission fluorescence CDs were synthesized via a facile one-pot hydrothermal approach by employing p-phenylenediamine and ethanol as reagents. In alkaline environments, DA would polymerize to form PDA on surface of CDs, resulting in the fluorescence quenching of the detection system owing to the effects of fluorescence resonance energy transfer (FERT) and inner filter effect (IFE). The proposed fluorescence probe exhibits good selectivity and sensitivity to DA in the concentration range of 0.1-15 μM, with a limit of detection (LOD) of 37 nM. Results of detecting DA in serum samples indicate the broad potential of the proposed strategy for future application in diagnosis of DA-related diseases.