Childhood Psychosocial Environment and Adult Cardiac Health: A Causal Mediation Approach.
This study used causal mediation analysis to assess the life-course associations of a favorable childhood psychosocial environment with left ventricular mass and diastolic function in adulthood and the extent to which adult health behaviors mediate these associations. The sample included 880 participants (56% women) from the Young Finns Study with data on the childhood environment from 1980, adult health behaviors (smoking, physical activity, diet, and BMI) from 2001 and an echocardiographic assessment of the left ventricular mass (g/m2.7) and diastolic function (E/e' ratio; higher values indicating a lower diastolic function) from 2011. The associations of the childhood environment with the left ventricular mass and E/e' ratio and mediation pathways through health behaviors were assessed using marginal structural models that were controlled for age, sex, and time-dependent confounding by adult socioeconomic position (measured as educational attainment) via inverse probability weighting. The data were analyzed in 2018-2019. The mean age in 2011 was 41 (range 34-49) years. Those above versus below the median childhood score had a 1.28 g/m2.7 lower left ventricular mass (95% CI= -2.63, 0.07) and a 0.18 lower E/e' ratio (95% CI= -0.39, 0.03). There was no evidence for indirect effects from childhood environments to left ventricular outcomes through adult health behaviors after controlling for time-dependent confounding by the adult socioeconomic position (indirect effect β= -0.30, 95% CI= -1.22, 0.63 for left ventricular mass; β= -0.04, 95% CI= -0.18, 0.11 for E/e' ratio). The results after multiple imputation were similar. A favorable childhood environment is associated with more optimal cardiac structure and function in adulthood. After accounting for socioeconomic positions, adult health behaviors explain little of the associations.


Seasonal and year-to-year differences in food selection by beavers.
Selection of trees for food by a colony of beavers in central Massachusetts was studied from September 1972 through April 1974. The beavers exhibited both seasonal and year-to-year differences in preference for certain genera. Pine was selected against during fall but not spring, and there was a switch in preference from birch during fall 1972 to oak and witch hazel in fall 1973. These differences may partly reflect greater seasonal stability in concentrations of stored nutrients in coniferous tree bark than in deciduous tree bark, and greater year-to-year stability in bark concentrations of stored nutrients in non-mast-seeding species than in mast-seeding species (1972 was a mast year for oaks in central Massachusetts).


Reliability of sagittal pelvic position assessments in standing, sitting and during hip flexion using palpation meter.
The objective of this study was to investigate reliability of assessing sagittal pelvic position using the palpation meter (PALM) in healthy subjects while sitting, standing and while in different hip flexion angles in standing. Twenty healthy subjects were assessed two times by the same examiner, with a 48-h interval between test sessions. Reliability indices of PALM measures (intraclass correlation coefficient, ICC), standard error of measurement (SEM) and smallest detectable change (SDC) were calculated. ICC values showed excellent intra-rater reliability for measurements of sagittal pelvic position in standing and sitting position and for both standing hip flexion angles (ICC = .89-.96). SEM values ranged from .5° (hip flexion 90°) to 1.5° (sitting position). SDC values ranged from 1.5° (hip flexion 90°) to 4.0° (sitting position). The results of this study showed excellent intra-rater reliability for assessing sagittal pelvic position in standing, sitting and hip flexion in healthy subjects using the PALM.


Notes on the occurrence of the tropical eel Anguilla bicolor bicolor in Peninsular Malaysia, Malaysia.
Previous studies indicated that a tropical freshwater eel Anguilla bicolor bicolor occurs in Africa, India, Sri Lanka, Bangladesh, Myanmar, Indonesia and Australia, but an intensive survey has indicated an extended distribution range for the species into Peninsular Malaysia. Thus, A. b. bicolor is a native subspecies of Malaysia.


Clinical Utility of the Limited Prosocial Emotions Specifier in the Childhood-Onset Subtype of Conduct Disorder.
Clinicians may specify the diagnosis of conduct disorder (CD) as "with limited prosocial emotions" (LPE). This specifier is thought to identify youths with particularly severe and stable symptomatology. However, few studies have examined the clinical usefulness of the LPE specifier among children with childhood-onset CD. The current study examines whether the LPE specifier distinguishes children with particularly severe and persistent symptoms among those with childhood-onset CD. The study also aims to test whether the LPE specifier aids in identifying children with subclinical CD whose conduct problems are at risk of increasing. Two hundred sixty-four children showing at least one CD symptom before age 10 were divided based on the presence of CD and the specifier. Children with and without the specifier were compared on number of CD symptoms (assessed at study inception) and trajectory of conduct problems (assessed over 4 years). The analyses controlled for oppositional defiant and attention deficit hyperactivity symptomatology. Compared with children with CD but without LPE, children with CD and the LPE specifier did not differ on likelihood of endorsing most symptoms nor on total numbers of symptoms. Moreover, they did not show a more stable pattern of conduct problems across the 4 years. Children with subclinical CD with and without the LPE specifier were also similar in terms of their symptoms, severity, and evolution of their problems. Among youths with childhood-onset CD, the specifier appears to offer limited value in identifying those with particularly severe and stable CD symptomatology.


Generation of human embryonic stem cells from abnormal blastocyst diagnosed with albinism.
Human embryonic stem cell (hESC) line chHES-478 was derived from abnormal blastocyst diagnosed with albinism after preimplantation genetic diagnosis (PGD) treatment. DNA sequencing analysis confirmed that chHES-478 cell line carried a compound heterozygous mutation, c.896G>A(p.Arg299His) and c.929_930insC(p.Pro310Glnfs*9), of TYR gene. Characteristic tests proved that the chHES-478 cell line presented typical markers of pluripotency and had the capability to form the three germ layers both in vitro and in vivo.


Relationship between the depth of facial wrinkles and the density of the retinacula cutis.
To identify whether there is a relationship between the depth of facial wrinkles and the density of the retinacula cutis in the subcutaneous tissue of the skin. Wrinkle depth was assessed with image analysis on the forehead and the lateral canthus of human cadavers. The density of the retinacula cutis was measured in Azan-Mallory-stained skin sections obtained around the wrinkles. Gross Anatomy Section, Kagoshima University Graduate School of Medical and Dental Sciences. Fifty-five male and female cadavers (35-93 years old). The maximum depth of each wrinkle was used to represent the wrinkle's degree. In the skin sections, the density of the retinacula cutis was measured around the deepest point of each wrinkle in a 1-mm-wide area (the wrinkle-specific area) and a 10-mm-wide area that included the wrinkle (the wrinkle-inclusive area). In both the wrinkle-specific and wrinkle-inclusive areas, the retinacula cutis densities became lower in the forehead and in the lateral canthus areas. When a wrinkle was shallow, the density was lower in the wrinkle-specific area than in the wrinkle-inclusive area. With wrinkle progression, the density difference between the wrinkle-specific and the wrinkle-inclusive areas gradually decreased until there was no apparent difference. Facial wrinkles seem to develop above sites of reduced lower retinacula cutis density. As a wrinkle develops, the density decreases in both the wrinkle-specific and the wrinkle-inclusive areas, whereas the density difference between those areas vanishes.


[Effect of danazol on heterozygous c protein coagulation deficiency exacerbated by Salmonella typhi sepsis].
The case of an 8-month-old male with heterozygous coagulation protein C deficiency is presented. Sepsis due to Salmonella typhi aggravated the protein C deficiency and resulted in arterial thrombosis of the distal third of the lower right limb. The patient was treated with both heparin and danazol, the levels of functional protein C increasing and the necrotic phenomenon resolving, thus making unnecessary amputation of the limb. The observation is discussed with the evidences of danazol being useful in the treatment of patients with protein C deficiency.


Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering.
Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.


A critical evaluation of predicting ocular irritancy potential from an in vitro cytotoxicity assay.
Numerous in vitro cytotoxicity assays have been proposed as potential alternatives to the Draize eye irritancy test. The results reported, based upon the rank correlation of ocular irritancy with cytotoxicity, have been encouraging. However, direct calibration of in vivo to in vitro data utilizing several categories of chemicals has not been reported. This study evaluated the use of in vitro cytotoxicity data for predicting the ocular irritancy potential of 24 chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics). BALB/c 3T3 cells were grown overnight, then exposed for 30 min to at least four different concentrations of each chemical (expressed as volume percentage). Linear regression analysis of the log concentration versus percentage of control growth was used to calculate the concentration of toxicant that inhibited the normal growth rate by 50% (GI50). The rank ordering of cytotoxicity based upon the GI50s was surfactants greater than aromatics greater than alcohols greater than ketones or acetates. The larger molecular weight representative of each series (i.e., 2-ethyl-1-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances. The GI50 values were then directly calibrated against in vivo ocular irritancy quantitated as percentage corneal swelling following exposure of rabbits to the same test chemicals. A significant linear correlation between cytotoxicity and ocular irritancy was established only for surfactants and alcohols. For acetates, ketones, and aromatics there was little correlation. The overall poor correlation between cytotoxicity and ocular irritancy was attributed to differences in mechanisms of irritancy. The lack of correlation illustrates that in vitro cytotoxicity data cannot be used to predict the ocular irritancy potential of a broad spectrum of chemicals.


Comparison between pediatric acute myeloid leukemia (AML) and adult AML in VEGF and KDR (VEGF-R2) protein levels.
We reported previously that high levels of vascular endothelial growth factor (VEGF) were associated with shorter survival in adult acute myeloid leukemia (AML) patients. In this study, cellular VEGF and its receptor, VEGF-R2 (kinase domain receptor (KDR)), were analyzed in 45 pediatric AML patients using Western blot and solid-phase radioimmunoassay (RIA). Cellular VEGF levels were significantly lower in pediatric AML compared to adult AML patients. In contrast, there was no significant difference in VEGF-R2 levels between adult and pediatric AML. Higher VEGF and VEGF-R2 levels in pediatric AML patients correlated with higher white blood cell (WBC). Unlike in adults, VEGF and VEGF-R2 levels in pediatric AML patients did not correlate with survival. This data suggest that the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from that in adult AML.


Expression of the Duffy antigen in K562 cells. Evidence that it is the human erythrocyte chemokine receptor.
The human malarial parasite Plasmodium vivax invades erythrocytes by binding to a cell surface protein identified as the Duffy blood group antigen. The molecular properties of the Duffy antigen, which was recently cloned, are very similar to those of a chemokine binding protein known as the human erythrocyte chemokine receptor. This has led to the suggestion that these two molecules are the same protein. To further investigate the suspected double identity of the Duffy antigen we have transfected it into a human erythroleukemic cell line, K562. Cells stably expressing the Duffy antigen were isolated and used to characterize the protein. K562 cells transfected with the Duffy antigen displayed specific 125I-melanoma growth-stimulating activity (MGSA) binding while mock transfected cells did not. Comparison of 125I-MGSA binding to the Duffy antigen and the human erythrocyte chemokine receptor showed that the specific 125I-MGSA binding to both proteins was displaced by excess unlabeled MGSA, interleukin-8, RANTES, monocyte chemotactic peptide-1, and platelet factor 4, but not by macrophage inflammatory protein-1 alpha or -1 beta. Scatchard analysis of competition binding studies with these unlabeled chemokines revealed high affinity binding to the Duffy antigen with KD binding values of 24 +/- 4.9, 20 +/- 4.7, 41.9 +/- 12.8, and 33.9 +/- 7 nM for MGSA, interleukin-8, RANTES, and monocyte chemotactic peptide-1, respectively. A monoclonal antibody, Fy6, to the Duffy antigen inhibited 125I-MGSA binding to K562 cells expressing the Duffy antigen. Cell membranes from K562 cells permanently expressing the Duffy antigen were chemically cross-linked with 125I-MGSA. SDS-polyacrylamide gel electrophoresis analysis of the cross-linked products showed covalent incorporation of radiolabeled MGSA into a protein of molecular mass 47 kDa, and cross-linking was inhibited in the presence of unlabeled MGSA. These studies provide evidence that the Duffy blood group antigen is the same protein as the human erythrocyte chemokine receptor.


Lichen planus and cicatrizing conjunctivitis: characterization of five cases.
To report the clinical and immunopathologic features and the response to therapy in a series of six patients with cicatrizing conjunctivitis due to lichen planus. Retrospective case series. All six patients were seen in an ocular pemphigoid clinic. Clinical, immunopathologic, and serologic features were evaluated and therapeutic response in each patient was monitored. All six patients had evidence of conjunctival scarring. Five patients had lichen planus of the oral mucosa and gingiva; one patient had involvement of the skin. Histologic findings consisted of thickened epithelium and an interface lymphocytic infiltrate along the lamina propria. In three patients, electron microscopy of the conjunctiva revealed thickening, fragmentation, and duplication of the basement membrane zone. Direct immunofluorescence examination of the conjunctiva and oral mucosa demonstrated linear and shaggy fibrinogen deposition along the basement membrane zone, confirming the diagnosis of lichen planus. All six patients were placed on immunosuppressive therapy with control of the disease. However, only one patient was able to discontinue the anti-inflammatory medication and have the lichen planus remain in remission. Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis. Performing appropriate investigations to distinguish conjunctival lichen planus from other autoimmune diseases such as mucous membrane pemphigoid is critical to managing the patient with cicatrizing conjunctivitis appropriately. Oral cyclosporine effectively controlled the conjunctival lichen planus in four of the six cases.


TIRF Microscopy-Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica.
There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biologically active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a ≈500 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small-molecule model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behaviour of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8-facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system-induced changes to cellular membrane permeation.


Varicella-zoster virus thymidine kinase. Characterization and substrate specificity.
The varicella-zoster virus (VZV) thymidine kinase (TK) EC 126.96.36.199) catalyzes the phosphorylation of many anti-VZV nucleosides. Purified, bacterially expressed VZV TK was characterized with regard to N-terminal amino acid sequence, pI value, pH optimum, metal ion requirement, phosphate donor and acceptor specificity, and inhibition by dTTP. Initial velocities of thymidine phosphorylation with variable MgATP concentrations fit a two-site model with apparent Km values for MgATP of 0.10 and 900 microM. dTTP was a noncompetitive inhibitor of thymidine phosphorylation but was competitive with MgATP. Phosphate donor and acceptor specificities of the bacterially expressed enzyme were indistinguishable from those of VZV TK purified from infected cells. Detailed studies of the nucleoside specificity with the bacterially expressed enzyme showed that, for a given sugar moiety, thymine nucleosides were the most efficient substrates followed by nucleosides of cytosine, uracil, adenine, and with some exceptions, guanine. For a given pyrimidine or purine (except guanine), 2'-deoxyribonucleosides were the most efficient substrates, followed by arabinosides, ribonucleosides, 2',3'-dideoxyribonucleosides, and the acyclic moiety of acyclovir.


Antibiotic sensitivity pattern in blaNDM-1-positive and carbapenemase-producing Enterobacteriaceae.
Some studies published in recent time revealed that many bacteria from Enterobacteriaceae group are multi-antibiotic-resistant because of the production enzymes carbapenemase particularly New Delhi metallo-beta-lactamase encoded by gene called blaNDM-1. Looking at public health importance of this issue there is a need for studies at other centers to confirm or refute published findings. This study was designed with the aim of exploring antibiotic resistance in Enterobacteriaceae group of bacteria and also to explore gene and enzyme responsible for it. Samples of Enterobacteriaceae were collected from wards and outpatient departments. Antibiotic sensitivity was checked by an automated system (VITEK 2 COMPACT). Carbapenemase production was assessed by Modified Hodge Test. Presence of blaNDM-1 was assessed by polymerase chain reaction. Frequency and percentage were used to describe the data. Frequency of sensitivity was compared between carbapenemase producers and noncarbapenemase producers by Fisher's exact test. Forty-seven percent bacteria were found to be producing carbapenemase enzyme. These bacteria were significantly less sensitive to cefoperazone, cefepime, and amikacin. Among carbapenemase-producing organisms, 3% and 6% were resistant to tigecycline and colistin, respectively. Forty percent bacteria were found to be having blaNDM-1 gene. There was a significant difference between blaNDM-1-positive and blaNDM-1-negative for sensitivity toward cefoperazone + sulbactam, imipenem, meropenem, amikacin, tobramycine, ciprofloxacin, and levofloxacin. Presence of carbapenemase enzyme and blaNDM-1 gene is associated with high level of resistance in Enterobacteriaceae group of bacteria and only few antibiotics have good sensitivity for these organisms.


Peritonitis due to Mycobacterium avium complex in patients with AIDS: report of five cases and review of the literature.
Mycobacterium avium complex (MAC) often causes disseminated infection in patients at an advanced stage of HIV infection; however, peritonitis associated with disseminated MAC infection is rare. In this report, we describe five cases of MAC peritonitis in AIDS patients at our hospital, and analyze these cases alongside 11 previously published cases found in the literature. Most of the AIDS patients with MAC peritonitis had CD4 counts of <50 cells/microl and elevated alkaline phosphatase levels. Other than ascites, MAC was also isolated from other sterile and non-sterile sites. Of note, six patients (37.5%) presented with chylous ascites. Despite therapy, MAC peritonitis is associated with a grave outcome.


Enigmatic in vivo GlcNAc-1-phosphotransferase (GNPTG) transcript correction to wild type in two mucolipidosis III gamma siblings homozygous for nonsense mutations.
Mucolipidosis (ML) III gamma is a rare autosomal-recessive disorder caused by pathogenic mutations in the GNPTG gene. GNPTG encodes the γ-subunit of GlcNAc-1-phosphotransferase that catalyzes mannose 6-phosphate targeting signal synthesis on soluble lysosomal enzymes. ML III gamma patients are characterized by missorting of lysosomal enzymes. In this report, we describe the probable occurrence of mRNA editing in two ML III gamma patients. Patients A and B (siblings) presented at the adult age with a typical clinical picture of ML III gamma, mainly compromising bone and joints, and high levels of lysosomal enzymes in plasma and low levels in fibroblasts. Both were found to be homozygous for c.-112C>G and c.328G>T (p.Glu110Ter) mutations in genomic DNA (gDNA) analysis of GNPTG. Analysis of complementary DNA (cDNA), however, showed normal genotypes for both patients. Low GNPTG mRNA expression was observed in both patients. The mRNA editing can explain the differences found in patients A and B regarding gDNA and cDNA analysis, and the mild clinical phenotype associated with homozygosity for a nonsense mutation. Our results suggest that mRNA editing can be more frequent than expected in monogenic disorders and that GNPTG analysis should be performed on gDNA.


Effect of cigarette smoking on major histological types of lung cancer in men.
This study examined the effect of cigarette smoking parameters such as intensity, duration, age at initiation, and quitting on the development of different histological types of lung cancer in men. We used data from a case-control study conducted in Philadelphia between 1985 and 1987. Cases included 482 men with histologically confirmed lung cancer diagnosed in 15 selected hospitals in Philadelphia. Controls were selected from a neighborhood survey of men in Philadelphia conducted concurrently to the case recruitment. Most aspects of smoking were associated with all the major histological types of lung cancer. Number of cigarettes smoked per day was the strongest predictor of risk of developing lung cancer. Early age at initiation of smoking significantly increased the risk of small cell carcinoma (odds ratio = 3.0; 95% CI, 1.1-8.4). Quitting smoking reduced the risk of squamous cell and adenocarcinoma; however, it did not affect the risk of small cell lung cancer. The findings of this study suggest the need for greater emphasis on smoking prevention programs, especially in adolescents.


Percutaneous Removal of Inferior Vena Cava Filter after Migration to Pulmonary Artery using an 8-Fr Multipurpose Catheter.
An inferior vena cava filter migrated to the left pulmonary artery during removal. The legs of the filter were not open adequately due to thrombus accumulating around the legs and resulted in the filter floating up and migrating to the pulmonary artery through the right atrium and ventricle. The hook for retrieval placed at the top of the filter faced proximal in the pulmonary artery and the legs of filter remained closed, consequently the filter could be removed safely from the pulmonary artery. An 8-Fr multipurpose catheter with its flexibility was useful to retrieve the filter from the pulmonary artery.


Detection and quantitation of genetically modified maize (Bt-176 transgenic maize) by applying ligation detection reaction and universal array technology.
We have applied the ligation detection reaction (LDR) combined with a universal array approach to the detection and quantitation of the polymerase chain reaction (PCR) amplified cry1A(b) gene from Bt-176 transgenic maize. We demonstrated excellent specificity and high sensitivity. Down to 0.5 fmol (nearly 60 pg) of PCR amplified transgenic material was unequivocally detected with excellent linearity within the 0.1-2.0% range with respect to wild-type maize. We suggest the feasibility of extending the LDR/universal array format to detect in parallel several transgenic sequences that are being developed for food applications.


Electrical potentials indicate stimulus expectancy in the brains of ants and bees.
In vertebrates, and in humans in particular, so-called 'omitted stimulus potentials' can be electrically recorded from the brain or scalp upon repeated stimulation with simple stimuli such as light flashes. While standard evoked potentials follow each stimulus in a series, 'omitted stimulus potentials' occur when an additional stimulus is expected after the end of a stimulus series. These potentials represent neuronal plasticity and are assumed to be involved in basic cognitive processes. We recorded electroretinograms from the eyes and visually evoked potentials from central brain areas of honey bees and ants, social insects to which cognitive abilities have been ascribed and whose rich-behavioral repertoires include navigation, learning and memory. We demonstrate that omitted stimulus potentials occur in these insects. Omitted stimulus potentials in bees and ants show similar temporal characteristics to those found in crayfish and vertebrates, suggesting that common mechanisms may underlie this form of short-term neuronal plasticity.


The catecholamine uptake inhibitor nomifensine depresses impulse activity of dopamine neurons in mouse substantia nigra.
Systemic administration of the catecholamine uptake inhibitor nomifensine (NOM) in doses of 20-36 mg/kg strongly depressed the discharge rate of dopamine (DA) neurons in the substantia nigra of mice for more than 2-3 h. This effect was fully reverted by the systemically administered DA receptor antagonist haloperidol. Impulse activity of most neurons showed a reduced rhythmicity under the influence of NOM, as assessed by autocorrelograms. It is suggested that the depression of discharge activity of DA neurons by NOM represents an indirect agonist action on the DA receptor, probably via reduced elimination of DA from the extraneuronal space.


Blueberry Supplementation Effects on Neuronal and Pathological Biomarkers in Subjects at Risk for Alzheimer's Disease: A Pilot Study.
There is a need to develop non-invasive practical lifestyle interventions for preventing Alzheimer's disease (AD) in people at risk, such as those with mild cognitive impairment (MCI). Blueberry consumption has been associated with reduced risk of dementia in some epidemiologic studies and with improvements in cognition in healthy aging adults. Blood-based biomarkers have emerged at the forefront of AD therapeutics research spurred by the development of reliable ultra-sensitive "single-molecule array" assays with 100-1000-fold greater sensitivity over traditional platforms. The purpose of this study was to examine the effect of blueberry supplementation in MCI on six blood biomarkers: amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), phosphorylated Tau181 (ptau181), neurofilament light (NfL), Glial Fibrillary acidic protein (GFAP), and Brain-Derived Neurotrophic Factor (BDNF). This was a 12-week, open-label, pilot trial of 10 participants with MCI (mean age 80.2 years + 5.16). Subjects consumed 36 grams per day of lyophilized blueberry powder in a split dose consumed with breakfast and dinner. Baseline and endpoint venous blood was analyzed using an ultrasensitive SIMOA assay. Our aim was to test if blueberry supplementation would particularly impact p-tau181, NfL, and GFAP elevations associated with the neurodegenerative process. There were no statistically significant (p < 0.05) changes from baseline to endpoint for any of the biomarker values or in the ratios of Aβ42 / Aβ40 and ptau181/ Aβ42. Adverse effects were mild and transient; supplementation was relatively well tolerated with all subjects completing the study. To our knowledge, this is the first study to prospectively examine the effects of blueberry supplementation on a panel of blood biomarkers reflecting the neurodegenerative process. Our findings raise two possibilities - a potential stabilization of the neurodegenerative process or a lack of a direct and acute effect on beta-amyloid/tau/glial markers. A larger controlled study is warranted.


Relation of brachial artery reactivity to nitroglycerin and heart rate recovery following exercise in healthy male volunteers.
The parasympathetic nervous system facilitates peripheral arterial vasodilation and is also responsible for a decrease in heart rate immediately after exercise (heart rate recovery [HRR]). The relation among parasympathetic tone measured by HRR after exercise, endothelium-mediated vasodilation, and nitroglycerin-mediated vasodilation (determined with brachial artery ultrasound) was assessed in 25 healthy young men. One-minute HRR was nonsignificantly related to endothelium-mediated vasodilation (r = -0.35, p = 0.08) but was significantly related to nitroglycerin-mediated vasodilation (r = -0.63, p = 0.0008), a finding that persisted after adjustment for heart rate at rest, insulin resistance, lipid variables, and blood pressure. This suggests that parasympathetic tone may be inversely related to the responsiveness of arterial smooth muscle to nitrates in healthy humans.


Hypoglycemia in cystic fibrosis: Prevalence, impact and treatment.
Hypoglycemia is a common and feared complication of insulin therapy. As in type 1 and type 2 diabetes, people with cystic fibrosis related diabetes are also at risk for hypoglycemia related to insulin therapy. Spontaneous hypoglycemia is also common in patients with CF without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF may also occur during or after an oral glucose tolerance test. In this review, we will discuss the definition, epidemiology, pathophysiology and impact of hypoglycemia, with a focus on people with cystic fibrosis. We will also review strategies to manage and prevent hypoglycemia.


Osteopontin-Rac1 on Blood-Brain Barrier Stability Following Rodent Neonatal Hypoxia-Ischemia.
Osteopontin (OPN) is a neuroprotective molecule that is upregulated following rodent neonatal hypoxic-ischemic (nHI) brain injury. Because Rac1 is a regulator of blood-brain barrier (BBB) stability, we hypothesized a role for this in OPN signaling. nHI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8 % oxygen for 2 h) in P10 Sprague-Dawley rat pups. Intranasal (iN) OPN was administered at 1 h post-nHI. Groups consisted of: (1) Sham, (2) Vehicle, (3) OPN, and (4) OPN + Rac1 inhibitor (NSC23766). Evans blue dye extravasation (BBB permeability) was quantified 24 h post-nHI, and brain edema at 48 h. Increased BBB permeability and brain edema following nHI was ameliorated in the OPN treatment group. However, those rat pups receiving OPN co-treatment with the Rac1 inhibitor experienced no improvement compared with vehicle. OPN protects the BBB following nHI, and this was reversed by Rac1 inhibitor (NSC23766).


Neurosurgical approach to treating pituitary adenomas.
The transsphenoidal route remains the dominant surgical approach to the management of pituitary adenomas. These tumors may present clinically with signs or symptoms related to hypersecretion, hypopituitarism, or mass effect; or they may be identified incidentally during neuroimaging for management of other disorders. Diagnostic and treatment strategies for pituitary adenomas are reviewed. In addition, we present outcomes data from a large number of patients treated over a 30-year period by a single neurosurgeon. In our experience, transsphenoidal surgery for pituitary adenomas is associated with low rates of morbidity, mortality, and disease recurrence.


Comparison of efficacy between uncovered and covered self-expanding metallic stents in malignant large bowel obstruction: a systematic review and meta-analysis.
Insertion of a self-expandable metallic stent (SEMS) can rapidly relieve colorectal obstruction. This study aimed to compare the efficacy between uncovered and covered SEMSs in the treatment of malignant colorectal obstruction. A systematic search in Medline, Embase, the Cochrane controlled trials register and bibliographies of retrieved articles was performed. Randomized controlled trials and other comparative studies comparing uncovered and covered SEMSs for treatment of malignant colorectal obstruction were selected for this systematic review and meta-analysis. The main outcome measures were technical success, clinical success, tumour ingrowth, tumour overgrowth, early migration (≤ 7 days), late migration (> 7 days), overall complications and the duration of stent patency. Compared with covered SEMSs, uncovered SEMSs were associated with a lower late migration rate (relative risk 0.25; 95% CI 0.08, 0.80; P = 0.02), a higher tumour ingrowth rate (relative risk 5.99; 95% CI 2.23, 16.10; P = 0.0004) and a prolonged stent patency (weighted mean difference 15.34 days; 95% CI 4.31, 26.37; P = 0.006). There was no significant difference in technical success, clinical success, tumour overgrowth, early migration, perforation or overall complications between the two groups. Tumour ingrowth occurred more frequently in the uncovered SEMS group, while late migration was more common in the covered SEMS group.


Lipid storage myopathy in von Gierke's disease: a case report.
An 18-year-old girl with von Gierke's disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierke's disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gower's sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization.


The effect of leukocyte- and platelet-rich fibrin on the bone loss and primary stability of implants placed in posterior maxilla: a randomized clinical trial.
In this study, we investigated the effects of leukocyte- and platelet-rich fibrin (L-PRF) on implant stability and alterations in the marginal bone surrounding posterior maxillary implants. This randomized clinical trial was conducted to compare the variable of L-PRF placement around maxillary implants. Resonance frequency analysis (RFA) was used to evaluate the implant stability immediately after surgery and at 1, 2, 4, 6, 8, and 12 weeks after surgery (t0 to t6, respectively). In addition, the amount of marginal bone changes around the implant at t6 was compared with the baseline using periapical radiography. The RFA outcomes were statistically significant within each group (P < 0.001, Eta2 = 0.322); however, in none of the follow-ups and immediately after the surgery, there was a significant difference between the two groups in terms of the implant stability quotient (ISQ) scores (P > 0.05). At t0, the test and control groups' respective mean levels of marginal bone loss around the implants were 0.4836 mm and 0.7343 mm, significantly different from the corresponding values at t6. On the other hand, marginal bone loss around the implant was not significantly different between the two groups in t0 and t6 (P = 0.532). L-PRF did not improve the RFA outcomes of implants three months after implant placement, and changes in the ISQ values over time were the same in both groups. In addition, L-PRF had no superior effect on the marginal bone loss around the implants. The research was registered in the Iranian Registry of Clinical Trials on 22 December 2020 (No: IRCT20200624047906N1), available at http://www.irct.ir.


Amino acid ionic liquid-based magnetic dispersive solid-phase extraction for benzimidazole residue analysis in fruit juice and human serum based on theoretical screening.
The theoretical screening and design of green solvents to reduce organic solvents and to develop green and efficient sample pretreatment methods have attracted extensive attention. Here, benzimidazoles (BZDs) with potential reproductive toxicity were used as target compounds, and amino acid ionic liquids (AAILs) were designed and selected via a theoretical calculation. With the functionalized AAIL as monomers, and POSS as the crosslinking agent, novel specific magnetic nanoparticles (Fe3O4@SiO2@MAPs@AAIL-POSS) were prepared and used to develop the magnetic dispersive solid-phase extraction (MDSPE) of trace BZDs from fruit juice and human serum. In the evaluation of the method, Fe3O4@SiO2@MAPs@AAIL-POSS showed specific adsorption, recyclable ability, high adsorption efficiency, a good recovery rate, and a low coefficient of variation. In addition, the adsorption behavior of Fe3O4@SiO2@MAPs@AAIL-POSS on BZDs was verified by investigating the kinetic and thermodynamic of the adsorption process. The study design provides ideas for green rapid detection methods of other food pollutants.


[Severe, refractory neonatal inflammatory syndrome as the manifestation of a systemic multivisceral and meningeal syndrome].
A neonate presented with an inflammatory syndrome with multisystemic manifestations. There was no remission until age 6 years, despite anti-inflammatory treatments. Neonatal onset and neuromeningeal manifestations identified a peculiar rare inflammatory syndrome, whose relationship with juvenile rheumatoid arthritis is discussed. In the case reported, renal, abdominal, deep lymphatic and cranial involvements were present: these have not been previously reported.


Humoral mechanisms of regulation of erythropoiesis during hypoxia.
We studied the dynamics of erythropoietin content and erythropoietic activity of the serum during hypoxia of different genesis and severity. Our results show that humoral factors play an important role in the regulation of erythropoiesis during oxygen deficiency. Serum erythropoietic activity underwent similar changes in different types of hypoxia associated with similar hematological shifts. A discrepancy was observed between erythropoietic activity and serum erythropoietin concentration.


Membranous nephropathy in a bone marrow transplant recipient.
A bone marrow transplant recipient is described who had development of nephrotic syndrome in association with chronic graft-versus-host disease (GVHD) and on cyclosporine (CsA) treatment withdrawal. Renal biopsy revealed a membranous glomerulonephritis (MG). The possible relationship between this autoimmune disorder, the immunological features of GVHD in experimental animals, and the influence of CsA is discussed.


Correction to: Influence of population mobility on the novel coronavirus disease (COVID-19) epidemic: based on panel data from Hubei, China.
[This corrects the article DOI: 10.1186/s41256-020-00151-6.].


Addiction disorders of New Jersey physicians.
The principles of treatment for addictive disorders are simple: Identify the disorder. Find skilled therapists to direct a treatment plan. Pursue the plan. Develop the skills to cope with life after addiction. Seek appropriate support from family and systems in the community.


Ag+-mediated DNA base pairing: extraordinarily stable pyrrolo-dC-pyrrolo-dC pairs binding two silver ions.
6-Substituted pyrrolo-dC-pyrrolo-dC mismatches selectively capture silver ions to form extraordinarily stable metal-mediated base pairs. One single modification in a 12-mer duplex causes a Tm increase of 36.0 °C relative to the metal-free mismatched duplex. Spectrophotometric titrations as well as ESI mass spectra confirmed the binding of two silver ions per base pair. The Ag(+)-mediated base pairs may permit the construction of metal-responsive DNA with a very high silver loading.


Impact of pulsed electric fields on vacuum drying kinetics and physicochemical properties of carrot.
The effect of pulsed electric fields (PEF) on the kinetics of vacuum drying (VD) and rehydration of carrot tissue was studied. The intensity of PEF treatment was E = 0.6 kV/cm and the total PEF treatment duration was tPEF = 0.1 s. The VD was performed at sub-atmospheric pressure p = 3.03 × 104 Pa for different temperatures Td = 25 °C and 90 °C. During VD, the kinetics of moisture removal and temperature evolution inside of untreated and PEF pretreated samples were studied. The color and structure of the samples were also investigated. PEF pretreatment enhanced VD kinetics at different studied temperatures. However, its effect on VD was more evident at lower drying temperatures. With the PEF pretreatment, the drying time was reduced by 55% and 33% at 25 °C and 90 °C respectively. After the drying and rehydration process, the change in color of PEF pretreated samples was less significant compared to untreated ones. After rehydration, the untreated and PEF pretreated samples were nearly restored to their initial form and size.


Periocular management in recent facial palsy patients treated with triple innervation technique: A retrospective case series.
Facial paralysis decreases eye protection mechanisms leading to ocular problems up to corneal ulceration, and blindness. This study aimed to evaluate the outcomes of periocular procedures for recent facial paralysis. Medical records of patients with unilateral recent complete facial palsy who did periocular procedures at the Maxillofacial Surgery Department of San Paolo Hospital (Milan, Italy) between April 2018 and November 2021 were retrospectively reviewed. 26 patients were included. All patients were evaluated 4 months after surgery. The first group included 9 patients who underwent upper eye lid lipofilling and midface suspension with fascia lata graft; they had no ocular dryness symptoms and no need for eye protection measures in 33.3% of cases, significant reduction of ocular symptoms and need for eye protection measures in 66.6% of patient, 0-2 mm lagophthalmos in 66.6% and 3-4 mm lagophthalmos in 33.3%. The second group of 17 patients who underwent upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy, had no ocular dryness symptoms and no need for eye protection measures in 17.6% of patient, significant reduction of ocular symptoms and need for eye protection measures in 76.4% of patient, 0-2 mm lagophthalmos in 70.5%, 3-4 mm lagophthalmos in 23.5% and one patient 5,8%had 8 mm lagophthalmos and persistent symptoms. No ocular complication, cosmetic complain or donner site morbidity were reported. Upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy decrease ocular dryness symptoms and need for eye protection measures and improve lagophthalmos: the association of the reinnervation with these complementary techniques is therefore highly recommended in order to immediately protect the eye.


Thumb joint flexion. What is normal?
The purpose of this study was to measure the amount of active flexion from a neutral position in normal thumb metacarpophalangeal and interphalangeal joints and compare the results with previously published reports. One hundred and nineteen subjects (238 thumbs) volunteered to have active flexion of the metacarpophalangeal (MP) and interphalangeal (IP) joints of the thumb measured with a computerized Greenleaf goniometer by a certified hand therapist. The mean MP flexion was 59 degrees and IP flexion was 67 degrees. The results of this study suggest that the accepted normal values of thumb flexion should be reconsidered, particularly as a guide for determining impairment.


The interventricular septum is functionally bilayered: a fresh look at a well known structure.
Increasingly sophisticated echocardiographic procedures are revealing previously unknown details of well known structures such as the interventricular septum.


The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis.
The purpose of this study was to identify prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) treated with resection and to investigate the effect of adjuvant chemotherapy (CT). Patients with ICC diagnosed between 2000 and 2015 treated at Hannover Medical School were included. Clinicopathologic characteristics were analyzed in univariate and multivariate analysis. In a matched pair survival analysis, patients with or without adjuvant CT were matched by these prognostic factors. Two hundred and ten patients were included. Median survival was 28.7 months, 1-, 3-, and 5-year survival rates were 72.8%, 29.6%, and 14.1%, respectively. In multivariate analysis, lymph node involvement (p = 0.006, HR 1.84), larger tumor size (p = 0.013, HR 1.79), vascular invasion (p = 0.038, HR 1.70), and prolongation of prothrombin time (p < 0.001, HR 4.20) were significantly related to poor survival. Thirty-nine patients received adjuvant CT of which 60% had lymph node involvement. Each 25 patients with and without adjuvant CT were matched to the identified prognostic factors. The median survival of patients with adjuvant CT was 33.5 months, compared to 18 months in the control group (p = 0.002). The 1-, 3-, and 5-year survival rates were 96, 36, and 12%, compared to 60, 4, and 0% in non-treated patients. We identified several prognostic factors for patients with ICC treated with resection. Our data support the use of adjuvant CT in patients with ICC. The results of prospective randomized controlled studies will clarify the role of adjuvant CT in the future.


Diffusion-weighted signal models in healthy and cancerous peripheral prostate tissues: comparison of outcomes obtained at different b-values.
To evaluate the dependence on the b-values adopted of apparent diffusion coefficient (ADC), perfusion fraction (PF), slow and fast diffusion coefficient (Dslow, Dfast), corrected diffusion coefficient (D) and kurtosis (K), in healthy peripheral (HP) and peripheral cancerous (PCa) prostate tissues. Patients who underwent multiparametric prostate MR examination were retrospectively evaluated for possible inclusion. ADC, PF, Dslow, Dfast, D, and K were estimated both in HP and PCa tissues, using three different ranges of b-values: 0-2300, 0-1800, 0-800 s/mm2 (group A, B and C, respectively). Analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis were performed, to establish differences among groups and to evaluate sensitivity and specificity of every parameter in distinguishing HP and PCa tissues when calculated with different b-values. In all, 57 patients were included. ANOVA showed significant differences of all parameters between group A-B vs. C, both in HP and PCa tissues. In ROC analysis K showed the best area under the curve (AUC) when calculated in groups A and B (0.87 and 0.86), while it was comparable with the ADC one in group C (both 0.82). A significant dependence on the adopted b-values of DWI parameters is shown. The best performance in distinguishing HP from PCa tissues was obtained by K, calculated using a high b-value sequence.


Effects of cyclopiazonic acid and aflatoxin singly and in combination on selected clinical, pathological and immunological responses of guinea pigs.
Cyclopiazonic acid (CPA) and aflatoxin are known sometimes to coexist in nature but little is known of possible biological interaction in mammals that consume mixtures of these two mycotoxins. Guinea pigs were dosed orally with CPA (2.2 mg/kg) or aflatoxin (0.045 mg B1/kg) singly or in combination. Effects of toxin consumption were determined on clinical health, body weight gain, pathological change, and several immunologically related parameters including delayed cutaneous hypersensitivity, antibody response, complement hemolytic titer, intracutaneous mitogen (PHA) and in vitro lymphocyte blastogenesis. In contrast to an earlier study by others, significant synergy between these two toxins was demonstrated in reduced rate of body weight gain, lethality and histologic changes (vacuolization) in hepatocytes. Reductions in complement titer, intradermal PHA, delayed cutaneous hypersensitivity response and in vitro lymphocyte blastogenesis were related to aflatin activity. No effects on antibody formation to Brucella abortus were observed with either toxin or the combination of toxins. Cyclopiazonic acid appeared to restore the suppressive effects of aflatoxin in delayed cutaneous hypersensitivity response and in vitro lymphocyte blastogenesis.


Growth of normal human ovarian surface epithelial cells in reduced-serum and serum-free media.
The human ovarian surface epithelium (OSE) is believed responsible for over 85% of ovarian cancers, yet little is known about the normal biology of these cells. To date, culture of OSE has only been reported in media with high serum supplements. We have developed two media, one with less than 1% of serum (OSEM-1) and the other comprised of highly purified and defined materials (OSEM-2), which allow us to study OSE under relatively defined conditions. By substituting 0.05% of Pedersen's fetuin for 15% fetal bovine serum (FBS) with Medium 199/MCDB105 basal medium, the cell numbers reached 50 to 60% of those in the presence of 15% FBS over 7 days. However, over several weeks, the total number of population doublings achieved were comparable to those in 15% FBS. Addition of insulin, transferrin, ethanolamine, lipoic acid, and phosphatidylcholine to the medium with Pedersen's fetuin (OSEM-1) enhanced growth up to 20% more than in their absence. Supplementation of M199/105 with highly purified (> 99%) fetuin, alpha 2-macroglobulin, and hydrocortisone resulted in a defined medium (OSEM-2) that permitted 1 to 2 doublings/7 days. In addition, cells maintained a more normal, epithelial-like morphology in culture for a longer period in the presence of Pedersen's or purified fetuin than in M199/105/15% FBS, thus increasing the number of morphologically normal cells available for experimentation. Addition of 0.05% Pedersen's fetuin to M199/105 in the presence of 6 to 8% FBS resulted in levels of growth equivalent to those in M199/105/15% FBS alone. We are now able to study the effects of various compounds on the growth and differentiation of OSE under defined conditions, and have reduced the requirement for FBS to produce large numbers of OSE cells.


Effect of seat positions on discomfort, muscle activation, pressure distribution and pedal force during cycling.
The aim of this study was to measure and analyse discomfort and biomechanics of cycling, i.e., muscle activation, centre of pressure of seat pressure profiles and pedal forces as a function of seat position. Twenty-one recreationally active individuals cycled for 10min at 100W on an ergometer cycle using five different seat positions. The neutral position was considered as basic seat position and was compared with upward, downward, forward and backward seat positions. The initial bout was repeated at the end of the recording session. Discomfort increased for upward and backward condition compared with neutral (P<0.05). Normalized surface electromyography from gastrocnemius decreased in the downward and forward position but increased in the upward and backward position. The minimum force became less negative for forward position compared with neutral seat position (P<0.05). The degree of variability of centre of pressure increased in the upward and backward position and the entropy of the centre of pressure of sitting posture for backward position decreased compared with neutral seat position (P<0.05). The present study revealed that consecutive changes of seat position over time lead to increase in discomfort as well as alterations of the biomechanics of cycling.


Is Andrographis paniculata extract and andrographolide anaphylactic?
Andrographis paniculata, "King of bitters" is a popularly known medicinal plant extensively used in many parts of the world for treatment of various diseases. Since recent past, anaphylactic/allergic type adverse events were reported upon A. paniculata usage, the study aimed to evaluate the anaphylactic and anaphylactoid potential of A. paniculata extract and andrographolide (a major phytoactive of A. paniculata). The anaphylactic potential was evaluated using active systemic anaphylaxis (ASA) assay in guinea pigs. Further, the release of allergic mediators was measured in immunoglobulin E (IgE) sensitized and non-IgE sensitized Rat Basophilic Leukemia (RBL-2H3) cell lines in-vitro. A. paniculata extract or andrographolide sensitized guinea pigs following the challenge antigen administration orally and intravenously did not demonstrate any clinical signs of anaphylaxis. IgE sensitized and non- IgE sensitized RBL-2H3 cells treated with A. paniculata extract did not induce release of allergic mediators. Whereas IgE sensitized and non- IgE sensitized RBL-2H3 cells treated with andrographolide demonstrated mild to moderate release of allergic mediators. A. paniculata extract has no anaphylactic and anaphylactoid potential in in-vivo and in-vitro studies. Whereas, andrographolide effects on allergic mediators in in-vitro studies needs to be scrutinized if they are of biologically important.


Comparative performance of human papillomavirus messenger RNA versus DNA screening tests at baseline and 48 months in the HPV FOCAL trial.
HPV FOCAL is a randomized trial comparing high-risk HPV [Hybrid Capture 2 (HC2)] vs. liquid-based cytology (LBC) for primary cervical screening. The present study objective was to compare Aptima HPV (AHPV) and HC2 assay performance at the intervention arm baseline and 48 mo. screens in relation to the rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Women enrolled after December 2010 (n = 3475) were screened at baseline with both AHPV and HC2 (AHPV was blinded). Women with CIN2+ exited the trial; HC2 negative (-) women and those HC2 positive (+) with <CIN2 returned for 48 mo. screening with AHPV, HC2, and LBC. At baseline, 7.2% were AHPV + vs. 8.4% for HC2 (p = 0.06). Round 1 AHPV CIN2+ sensitivity (relative to HC2) was 96.0% (95%CI: 86.5-99.0; p = 0.15) and 100% (95%CI: 82.4-100) for CIN3+. AHPV and HC2 specificities (<CIN2) were 94.1% vs. 93.0% respectively (p = 0.05). At 48 mo., 4.8% and 5.2% were AHPV+ and HC2+ respectively (p = 0.41), and both tests had the same CIN2+ and CIN3+ sensitivities (87.5% and 85.0% respectively). AHPV specificity (95.8%) was higher, but not significantly, than HC2 (95.3%; p = 0.38). Of 3226 baseline AHPV- women, 12/2,858 (0.4%) had CIN2+ vs. 13/2821 (0.5%) for the 3184 baseline HC2- women. There was no significant difference in CIN2+ detection for AHPV vs. HC2 at baseline or at 48 mo. Baseline AHPV- and HC2- women had similar CIN2+ rates at 48 mo., demonstrating the safety of a four year screening interval for AHPV- women.


Multiple-dose vaginal misoprostol and single-dose misoprostol plus oxytocin for termination of second-trimester pregnancy.
To compare 2 different methods-multiple doses of misoprostol and a combination of misoprostol and oxytocin-for termination of pregnancy in the second trimester. Between 2006 and 2008, 120 women undergoing termination of second-trimester pregnancy in 2 hospitals in Kermanshah, Iran, were enrolled in a randomized trial comparing 2 treatments. In each treatment group, an initial vaginal dose of 600 μg of misoprostol was placed in the posterior fornix. After 6 hours, an intravenous infusion of concentrated oxytocin was given to women in group A, and 400 μg of vaginal misoprostol was given every 6 hours to women group B, up to a maximum of 4 doses. The outcomes were compared via χ(2) and independent t tests. Within 30 hours, 96.7% of women in group A and 96.7% of women in group B delivered successfully. The average duration between induction and delivery time was 12.3±6.0 hours in group A and 12.1±6.0 hours in group B (P>0.05). The use of misoprostol with oxytocin, and multiple doses of misoprostol gave similar results for termination of pregnancy in the second trimester.


SCPM-Net: An anchor-free 3D lung nodule detection network using sphere representation and center points matching.
Automatic and accurate lung nodule detection from 3D Computed Tomography (CT) scans plays a vital role in efficient lung cancer screening. Despite the state-of-the-art performance obtained by recent anchor-based detectors using Convolutional Neural Networks (CNNs) for this task, they require predetermined anchor parameters such as the size, number, and aspect ratio of anchors, and have limited robustness when dealing with lung nodules with a massive variety of sizes. To overcome these problems, we propose a 3D sphere representation-based center-points matching detection network (SCPM-Net) that is anchor-free and automatically predicts the position, radius, and offset of nodules without manual design of nodule/anchor parameters. The SCPM-Net consists of two novel components: sphere representation and center points matching. First, to match the nodule annotation in clinical practice, we replace the commonly used bounding box with our proposed bounding sphere to represent nodules with the centroid, radius, and local offset in 3D space. A compatible sphere-based intersection over-union loss function is introduced to train the lung nodule detection network stably and efficiently. Second, we empower the network anchor-free by designing a positive center-points selection and matching (CPM) process, which naturally discards pre-determined anchor boxes. An online hard example mining and re-focal loss subsequently enable the CPM process to be more robust, resulting in more accurate point assignment and mitigation of class imbalance. In addition, to better capture spatial information and 3D context for the detection, we propose to fuse multi-level spatial coordinate maps with the feature extractor and combine them with 3D squeeze-and-excitation attention modules. Experimental results on the LUNA16 dataset showed that our proposed SCPM-Net framework achieves superior performance compared with existing anchor-based and anchor-free methods for lung nodule detection with the average sensitivity at 7 predefined FPs/scan of 89.2%. Moreover, our sphere representation is verified to achieve higher detection accuracy than the traditional bounding box representation of lung nodules. Code is available at: https://github.com/HiLab-git/SCPM-Net.


Organic form and evolution: the morphological problem in twentieth-century italian biology.
This paper examines the efforts in evolution research to understand form's structure that developed in Italy during the first half of the twentieth century. In particular, it analyzes how the organic approach in biology and the study of organic form merged in the morphological research agendas of Giuseppe Colosi (1892-1975) and Giuseppe Levi (1872-1965). These biologists sought to understand form's inner composition and structure. First, I will briefly outline the morphological practices and frameworks used to study form changes and structures in the early twentieth century. Second, I will discuss what the Italian biologist Antonio Pensa (1874-1970) called the morphological problem. Third, I will examine Colosi's response to the morphological problem. Fourth, I will analyze Levi's morphological research program. As a result, this paper paves the way for a more nuanced and varied picture of the so-called "organicism movement" in the first half of the twentieth century by calling attention to morphology as practiced in Italian-speaking biology. In fact, alongside dialectical materialism and holistic biology, two of the main strands within organicism, the architectural approach to evolution as practiced in Italy and elsewhere had a profound impact on twentieth- and twenty-first-century organicism specifically and on evolutionary biology generally.


The structure and function of periodontal ligament cells in acellular cementum in rat molars.
To elucidate the structure and function of periodontal ligament cells at the periodontal ligament-cementum interface in advanced acellular cementogenesis, the cervical regions of molars in rats aged 6 weeks were observed by light and electron microscopy. The light and transmission electron microscopy showed the periodontal ligament cells to be elongated between dense, well-developed principal fibers. The transmission and scanning electron microscopy showed that these cells extended wing-like projections from the lateral surface, forming cylindrical compartments surrounding the principal fibers. In addition, finger-like projections extended toward the cementum from the cementum-facing ends. The main results suggest the following: at the periodontal ligament-cementum interface, the periodontal ligament cells maintain the architecture of the principal fibers by means of extracellular compartments. The arrangement of finger-like projections results in the formation of acellular cementum containing only Sharpey's fibers as a fibrous component.


Phosphorylation site independent single R-domain mutations affect CFTR channel activity.
We investigated CFTR channel activity of mature R-domain mutants showing single alterations at sites other than the predicted phosphorylation sites. All mutations were found in cystic fibrosis (CF) patients (H620Q, E822K and E826K). The macroscopic CFTR chloride conductance induced by phosphorylation was significantly enhanced in Xenopus oocytes injected with mRNA of H620Q but reduced in the E822K and E826K mutants compared to wild type CFTR. The anion permeability sequence for all three mutants was the same as that of wild type CFTR. Cell attached single channel studies in COS cells revealed that both open channel probability and/or the number of functional channels were either higher (H620Q) or lower (E822K and E826K) than in wild type CFTR. Single channel conductances were unchanged in all mutants. Our results suggest that additional sites in the R-domain other than phosphorylation sites influence gating of CFTR channels.


The standard tangential fields used for breast irradiation do not allow optimal coverage and dose distribution in axillary levels I-II and the sentinel node area.
Recent data from ACOSOG Z0011 and NSABP B32 trials suggested no need for axillary lymph node dissection (ALND) in patients with micrometastatic involvement of the sentinel lymph node (SLN). The low rate of axillary recurrence was attributed to the axilla coverage by the tangential fields (TgFs) irradiation and systemic therapy. This study aimed to evaluate dose distribution and coverage of the axilla levels I-II and the SLN area. One hundred and nine patients were analyzed according to three groups: group 1 (50 Gy; n = 18), group 2 (60 Gy; n = 34) and group 3 (66 Gy; n = 57). Patients were treated using the standard (STgF; n = 22) or high (HTgF; n = 87) TgF. The median doses delivered to level I using HTgF versus STgF were 33 and 20 Gy (P = 0.0001). The mean dose delivered to the SLN area was only 28 Gy. Additionally, the SLN area was totally included in the HTgF in 1 out of 12 patients who had intraoperative clip placement in the SNL area. TgFs provide a limited coverage of the axilla and the SNLB area. This information should be considered when only TgFs are planned to target the axilla in patients with a positive SLN without ALND. Standardization of locoregional radiotherapy in this situation is urgently needed.


Nexuses between crude oil imports, renewable energy, transport services, and technological innovation: a fresh insight from Germany.
This research attempts to model the association of crude oil imports with several macroeconomic factors such as renewable energy, transport services, trade, industrial value-added, and patents, using Germany's annual data covering the period of 1990-2020. Employing the Autoregressive Distributed Lag model, this study finds a significant co-integration relationship among targeted variables. Moreover, this study provides empirical evidence on the influence of given macroeconomic factors in determining crude oil imports of Germany. Results reveal that transport services and industrial value-added positively and significantly influence crude oil imports in the long and short run. Similarly, trade is discovered to have a significant positive impact on oil imports only in the long run. In contrast, findings reveal a significant negative association of renewable energy with crude oil imports. Hence, this research implies that the transportation sector and industrial production strongly depend on crude oil consumption. At the same time, promoting renewable energy in these segments could significantly help economies control crude oil demand and achieve sustainability by reducing the economic burden and protecting the environment.


Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women.
This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.


Hemodynamic and perfusion variables during experimental septic shock treated with goal-directed fluid resuscitation.
Although fluid resuscitation guided by central venous oxygen saturation (SvcO2) is currently considered the gold standard in sepsis therapy, few studies have described hemodynamic and perfusion parameters during this procedure. This study aims to describe these parameters during septic shock without resuscitation and after 12 hours of goal-directed resuscitation. Thirteen anesthetized pigs (35-45 kg) had peritonitis caused by fecal inoculation (0.75 g/kg). After developing persistent hypotension, both groups were given antibiotics and randomized either to the control group (n=7) or the experimental group (n=6). In the control group, hemodynamic control was optimized to maintain a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and a mean arterial blood pressure above 65 mmHg. The experimental group received the above target therapy in addition to maintaining a SvO2 above 65%. The interventions included lactated Ringer's solution and norepinephrine for both groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or until death. Untreated sepsis was associated with significant reductions in SvO2, PvO2, cardiac output and central venous pressure in addition to increased arteriovenous oxygen saturation and veno-arterial CO2 differences. Following resuscitation, these parameters were corrected in both groups. Goal-directed resuscitation was associated with a better hemodynamic profile, characterized by higher SvO2, cardiac output and central venous pressure. Non-resuscitated sepsis showed a hemodynamic profile suggesting hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon fluid resuscitation. Goal-directed resuscitation is associated with significantly improved hemodynamic and perfusion parameters.


Center for Life provides accessible maternity care.
Providing good, comprehensive, accessible maternity care to the underserved can help solve a hospital's declining OB census and can support a pro-life philosophy.


Subcortical neurons in cerebellar tissue cultures: a Golgi study.
Subcortical neurons incorporated with mouse cerebellar explants were subjected to analysis with Golgi methods. Intracerebellar nucleus neurons included multipolar and spindle-shape cells with complex dendrites having both spinous and aspinous branches. Dorsal pontine neurons were multipolar, with generally long, spinous dendritic branches. The dendritic complexity of these neurons maintained in relatively isolated in vitro conditions is indicative of considerable intrinsic developmental capability.


Geographic and microgeographic genetic differentiation in two aphid species over southern England using the multilocus (GATA)4 probe.
Samples of the grain aphid Sitobion avenae (F.) and the rose-grain aphid Metopolophium dirhodum (Walker) were collected in late March from wheat fields and adjacent road-side grasses at a number of locations in southern England. Unparasitized aphids were DNA fingerprinted using the multilocus (GATA)4 probe. Over all locations, the fingerprints of individual S. avenae caught in wheat had lower overall average distances of band migration (ADBM) and shared a higher proportion of bands, than fingerprints of individuals caught in adjacent road-side grasses. The ADBM of fingerprints of S. avenae collected on road-side grasses altered significantly with geographical location, while the ADBM of fingerprints of S. avenae caught on wheat did not. A comparison of the fingerprints of individual M. dirhodum caught in wheat and neighbouring road-side grasses did not reveal any genetic differentiation. Fingerprints of M. dirhodum that were caught in the same host type did however, show significant variation in ADBM between different locations. With both S. avenae and M. dirhodum, spatial autocorrelation revealed that locations that were close together were no more likely to have individuals with similar ADBM than locations that were far apart. Our results suggest that (i) particular clones of S. avenae prefer to colonize wheat, and/or that (ii) particular clones of S. avenae perform better on wheat than other clones. It is unclear why M. dirhodum did not show any genetic structuring according to host type, but this species appears to engage in sexual reproduction much more frequently than S. avenae in southern England.(ABSTRACT TRUNCATED AT 250 WORDS)


Palladium-catalyzed C(sp(3))-H Arylation of N-Boc benzylalkylamines via a deprotonative cross-coupling process.
Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via CH functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic CH with in situ arylation by a NiXantPhos-based palladium catalyst (50-93 % yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling.


Preparation and properties of alpha 1-proteinase inhibitor concentrate from human plasma.
Alpha 1-proteinase inhibitor (alpha 1-PI) has been prepared as a concentrate in quantities large enough for clinical testing of its safety and efficacy in the treatment of emphysema and other disorders. The alpha 1-PI was purified from Cohn fraction IV-1 paste by polyethylene glycol precipitation and DEAE-Sepharose chromatography. The methods used in the purification are gentle and the resulting product behaves almost identically to the alpha 1-PI from plasma. The protein has been heat treated (60 degrees C, 10 h) to lower the risk of transmission of plasma-borne diseases. This resulted in some aggregation of the protein, but did not cause the generation of new antigenic sites. Half-life studies in animals showed that the protein behaved normally (catabolic t1/2 of 68 h).


Serum osteocalcin (bone Gla-protein) following corticosteroid therapy in postmenopausal women with rheumatoid arthritis. Comparison of the effect of prednisone and deflazacort.
In 28 postmenopausal women with rheumatoid arthritis, serum osteocalcin (OC) concentration decreased from 5.2 +/- 1.9 ng/ml to 3.0 +/- 1.6 ng/ml after 6 months therapy with corticosteroids (p less than 0.005). No differences, however, were found in a control group of 13 patients treated for 6 months with nonsteroidal anti-inflammatory drugs. In those patients with serial OC measurements, changes in serum OC were already evident within the first month of therapy. This suggests that a suppressed osteoblast function may be detectable early during corticosteroid therapy in rheumatoid arthritis. Fifteen patients treated with prednisone (5-25 mg once daily, mean 12.33 mg/day) showed a more marked decrease in serum OC than 13 patients treated with equivalent doses of deflazacort (p less than 0.005). Prednisone therapy at doses higher than 10 mg/day resulted in a severe suppression of OC values in most cases. The effect of deflazacort was, however, mild in the majority of patients treated with doses of up to 30 mg/day.


Deep inferior epigastric perforator flap for successful simultaneous breast and chest wall reconstruction in a Poland anomaly patient.
Breast reconstruction in female Poland anomaly remains a surgical challenge with variable chest wall deformity and nipple position. Pedicled latissimus dorsi myocutaneous flap with implant reconstruction may have several drawbacks and complications. Free deep inferior epigastric flap (DIEP) flap is a reliable option for postmastectomy breast reconstruction, but rarely reported in Poland anomaly. We presented a 52-year-old Poland anomaly patient who underwent successful reconstruction for breast and chest wall deformity using DIEP flap. Preoperative ultrasound Doppler study for internal mammary vessels is recommended for microsurgical anastomosis. Care should be taken with regard to the flap inset and the location of the nipple areolar complex.


Variables associated with the oral impact on daily performance of adults in the state of São Paulo: A population-based study.
This study aimed to assess the oral impact on daily performance and its association with sociodemographic characteristics, tooth pain, need for prosthesis, and periodontal disease of adults in the state of São Paulo, Brazil. This was a cross-sectional epidemiological study with secondary data obtained from the Oral Health Conditions Project- 2015 conducted in 163 municipalities in the state of São Paulo with the participation of 17,560 individuals. This study evaluated adults in the age-range between 35-44 years (n = 5,855), selected by means of probabilistic cluster sampling in two stages. The outcome variable was the OIDP (Oral Impacts on Daily Performances), obtained by using this instrument to assess daily activities (eating, speaking, oral hygiene, relaxation, sports practice, smile, study/work, social contact, and sleep). The independent variables were collected and grouped into three blocks: Block 1 (sex, age group, and ethnic group); Block 2 (household income and education); and Block 3 (tooth pain, need for prosthesis, bleeding, calculus, and periodontal pockets). A hierarchical multiple logistic regression analysis was performed considering the complex cluster sampling plan. Each observation was assigned a specific weight, depending on the location, which resulted in weighted frequencies adjusted for the effect of outlining. the female sex (p<0.0001), ethnic group black/mulatto (p<0.0001), low household income (p = 0.0112), up to 8 years of education (p<0.0001), tooth pain (p<0.0001), presence of bleeding (p<0.0001), and presence of periodontal pockets (p<0.0001) had greater oral impact on daily performance. sociodemographic characteristics, tooth pain, and presence of periodontal disease were associated with oral impact on daily performance of the adult population in the state of São Paulo, Brazil.


Morpho-functional effects of different universal dental adhesives on human gingival fibroblasts: an in vitro study.
To analyze the effects of four universal adhesives (Optibond Solo Plus-OB, Universal Bond-UB, Prime&Bond Active-PBA, FuturaBond M + -FB) on human gingival fibroblasts in terms of cytotoxicity, morphology and function. After in vitro exposure for up to 48 h, fibroblast viability was determined by the MTT assay determined, morphology by phase-contrast microscopy and migration by the scratch wound assay. Expression levels of IL1β, IL6, IL8, IL10, TNFα and VEGF genes were assessed by RT-PCR and their protein production by Western blot analysis. Apoptosis and cell cycle were analyzed by flow cytometry. OB and UB induced early morphological changes on fibroblasts (3 h) with extended cell death at 24 h/48 h. Gene expression of collagen type I and fibronectin increased fivefold compared with controls, elastin disappeared and elastase increased threefold, indicating gingival tissue tended to become fibrotic. Only UB and OB increased gene expression of inflammatory markers: IL1β at 3 and 48 h (up to about three times), IL6 and IL8 at 3 h (up to almost four times) which corresponded to the increase of the activated form NF-kB. All adhesives showed an effect on the functionality of fibroblasts with cytotoxic effect time and concentration dependent. Among all the OB and UB adhesives, they showed the greatest cell damage. The in-depth analysis of the effects of universal adhesives and possible functional effects represents an important information for the clinician towards choosing the most suitable adhesive system.


Prevention of heart disease in the young coronary candidate.
Coronary heart disease characteristically attacks with little warning--in more than half the cases, striking before evidence of target organ involvement is seen. Thus a distinct rationale exists for advocating preventive maintenance in young coronary candidates.


The probability of nodal metastasis in novel T-factor: the applicability of sublobar resection.
Recently sublobar resection is often indicated for small-sized peripheral lung cancer according to size or the consolidation/tumor ratio on CT; however, the T-factor classification drastically changed in the 8th version. We investigated the relationship between a novel clinical T-factor classification, which includes other clinical information and the pathologic N-factor, to evaluate the applicability of the novel T-factor classification to sublobar resection. From January 2013 to October 2017, 545 patients with cTis or cT1 lung cancer underwent surgery. Patients with non-peripheral type, induction treatment, cN≥1, cM1, and those without nodal dissection, preoperative evaluation by thin-sliced CT or FDG-PET were excluded. Finally, 325 patients were eligible for inclusion. All clinical parameters were prospectively collected and retrospectively analyzed. The 8th edition of TNM classification was utilized. Nodal metastasis was detected in 38 (11.7%) patients. Among cTis/1mi/1a/1b/1c patients (n=10/11/51/146/107), pN1 and pN2 were observed in 0/0/2/9/10 and 0/0/1/8/8, respectively. cT1b/c patients showed a significantly higher rate of nodal metastasis (P=0.024). Among 253 cT1b/c patients, solid-type tumors (n=177) were more frequently associated with nodal metastasis. A ROC curve analysis revealed that SUVmax 1.9 was the cutoff value (AUC=0.827) for the presence of nodal metastasis. Using the 2 parameters of solid-type or SUVmax ≥1.9, we could successfully exclude patients with nodal metastasis, for whom sublobar resection is not indicated. In terms of nodal metastasis, sublobar resection can be applicable for all cTis/1mi tumors; patients with cT1a/b/c tumors with mixed GGO and low SUVmax are candidates for sublobar resection.


Generation of excited species catalyzed by horseradish peroxidase or hemin in the presence of reduced glutathione and H2O2.
Horseradish peroxidase (HRP) (EC 184.108.40.206) catalyzes the oxidation of reduced glutathione. This reaction is accompanied by light emission, which is attributed to the generation of singlet oxygen. The chemiluminescence is directly related to thiyl radical formation, as deduced from the correlation between the time course of HRP-compound II formation and light emission in the presence of different amounts of H2O2. Superoxide dismutase has an inhibitory effect on the chemiluminescence without affecting the HRP-compound II formation. This indicates the direct involvement of superoxide radicals in the production of photoemissive species. Replacement of HRP by hemin is also accompanied by chemiluminescence.


Safety and tolerance of Lactobacillus reuteri supplementation to a population infected with the human immunodeficiency virus.
Probiotic supplementation may provide health benefits, especially for individuals with an underlying disease state that makes them more susceptible to infections. The purpose of this experiment was to evaluate the safety and tolerance of Lactobacillus reuteri ingestion by subjects infected with the human immunodeficiency virus (HIV). Thirty-nine subjects consumed a freeze-dried preparation of L. reuteri or a placebo for 21 days in a double-masked, parallel design experiment. Serum chemistry, haematology, immune profile, urinalysis, physical examination, gastrointestinal tolerance and faecal microbiota data were collected. No clinically significant changes were noted in any of the safety parameters measured. Overall, tolerance was good in both groups. Consumption of L. reuteri tended to increase faecal levels of L. reuteri on days 7, 14 and 21 of treatment feeding (P < 0.06, P < 0.11 and P = 0.05, respectively). However, faecal levels of L. reuteri and total Lactobacillus species were lower than levels previously observed in healthy male adults. Overall, this study documents that L. reuteri may be fed to HIV-positive individuals at 1 x 10(10) colony forming units/day without any clinically significant safety or tolerance problems.


Perceptual spatial frequency--orientation surface: psychophysics and line element theory.
We have investigated the discriminability of gratings which simultaneously vary in spatial frequency and orientation. Thirteen and nine reference gratings were used with two observers, and bivariate discrimination probability surfaces were determined around each grating. These data were then fitted to a general bivariate Gaussian function. The results clearly demonstrate local separability in this log frequency and orientation discrimination domain. Our results also show that the factor contributing most to the non-Euclidean nature of such frequency/orientation discrimination is orientation anisotropia, although we also find some evidence for smaller changes in the associated Riemannian line-element at different frequency ranges. These results cast doubt upon claims for a "pseudo line-element" for frequency discrimination based upon the nonlinear outputs of a fixed set of detectors.


Probing the lowest energy chlorophyll a states of photosystem II via selective spectroscopy: new insights on P680.
We present the wavelength dependence of homogeneous holewidths of persistent spectral holes burnt in O2-evolving Photosystem II core complexes isolated from spinach, in the temperature range 2.5-8 K. The data supports the assignment that those chlorophylls which undergo persistent spectral hole-burning are specific CP43 and CP47-trap states that transfer their excitation energy to the reaction center. The lifetime-limited holewidths show that when PS II is in the S1(QA -) (closed) state, the CP43/CP47-trap states have excited-state lifetimes in the range from 70 to 270 ps. These lifetimes correspond to excitation transfer rates to the reaction center, and are far slower than required for models in which the PS II reaction center (P680) acts as a 'shallow-trap' for excitations. For wavelengths at which both traps absorb, the hole shape is clearly a composite of two Lorentzians, corresponding to hole-burning in both states simultaneously. The temperature dependence of the homogeneous holewidth does not follow the usual T1.3 dependence found in many chlorophyll-protein systems. Our data indicates T 2 temperature dependence, typically found in crystalline systems where the chromophore is coupled to localized phonon modes.


Field experimental evidence of how social relations shape behavior that promotes energy conservation.
Energy demand-side management is essential for deep decarbonization. However, while we target people as discrete and isolated individuals, we ignore the fact that energy consumption occurs in intricate webs of pre-existing social relations. This study examines an emergency demand response (EDR) program in China involving more than 180,000 households based on relations with family members, communities, and identity. The results indicate that the existence of social relations can promote energy conservation behavior and there is a large degree of heterogeneity. Targeted relations, such as single-living residents, small-scale households, city dweller etc., show greater electricity savings with 12.35% increase in overall effect, which benefit when demographics change in the next few decades. Such heterogeneous changes put forward the pressing need for policymakers to focus on social relations as a unit in future intervention designs to decarbonize the energy system.


Case of hemorrhagic pancreatic pseudocyst in which ultrasound imaging was useful.
A 50-year-old man was admitted to our institution for upper abdominal pain. The diagnosis was chronic pancreatitis. A pseudocyst 3 cm in diameter had been detected in the head of the pancreas by ultrasonography a year and a half earlier. At the current hospitalization, ultrasound examination showed a mass 5 cm in diameter where the pseudocyst had been seen. This mass comprised an external hypoechoic lesion, a middle movable hyperechoic lesion, and an internal cystic lesion showing an arterial signal on Doppler ultrasound examination. Computed tomography showed a high-density area thought to be a hematoma in the head of the pancreas, and extravasation in the mass was demonstrated by rapid injection of a contrast medium. Our diagnosis was a bleeding pseudocyst. The patient suddenly vomited fresh blood and went into hypovolemic shock on the 11th hospital day. Emergency angiography and transcatheter embolization with steel coils was accomplished under a diagnosis of rupture of the bleeding pseudocyst into the duodenum. Ultrasonographic examination showed that the mass had decreased in size and the cystic lesion, showing an arterial signal, had disappeared after embolization. Although bleeding pseudocysts occur infrequently, they are a life-threatening complication of chronic pancreatitis. Early diagnosis and treatment are thus essential. Ultrasound examination with Doppler ultrasonography is strongly indicated when diagnosing bleeding pseudocysts and examining patients with chronic pancreatitis accompanied by abdominal pain, gastrointestinal bleeding, or both. Early treatment by transcatheter embolization should be used to avoid this potentially lethal complication.


Anti-inflammatory activity of the essential oils of Cymbopogon validus (Stapf) Stapf ex Burtt Davy from Eastern Cape, South Africa.
To evaluate the essential oil composition and the anti-inflammatory activity of Cymbopogon validus (C. validus) leaves and flowers. A total of 300 g of fresh or dry (leaves and flowers) of C. validus were cut into small pieces and subjected to hydro-distillation method for approximately 5 h using the Clevenger apparatus. The extracted essential oils were then used for testing the anti-inflammatory activity. The anti-inflammatory activity was evaluated by using egg albumin-induced paw edema. The extracted oils had the following yields 2.2% for fresh leaves, 2.0% for dry leaves and 2.4% v/w for dry flowers. GC-MS results revealed that the oils contained artemisia ketone (37.5%), linalool (3.2%-29.6%), northujane (4.4%-16.8%), verbenone (13.5%), naphthalene (1.7%-9.6%), δ-cadinene (0.5%-8.1%), hedycaryol (5.4%-7.6%) and α-eudesmol (6.5%-6.7%) as the major constituents. C. validus essential oils showed significant (P < 0.05) anti-inflammatory effects from the first 30 min after albumin injection compared to aspirin which had a later onset of effect. The findings of this study show that the essential oil extracted from C. validus fresh or dry leaves and flowers have anti-inflammatory properties; that might be associated with the major components and the minor components found in the essential oils.


Description of four Iolaus Hbner, 1819 species in the subgenus Philiolaus Stempffer amp; Bennett, 1958 from East Africa, assigned to the proposed I. maritimus species group (Lepidoptera, Lycaenidae, Theclinae).
Four new Iolaus Hbner, 1819 species are described in the subgenus Philiolaus Stempffer Bennett, 1958. They are assigned to the newly formed I. maritimus species group. Members of the group occur in the coastal forests of Kenya, submontane and montane forests in Tanzania and Mozambique, and are locally distributed in montane forests at the western shores of Lake Malawi, in southwestern Tanzania, and northern Zambia/Malawi.


A pathophysiological model of gait captures the details of the impairment of pace/rhythm, variability and asymmetry in Parkinsonian patients at distinct stages of the disease.
Locomotion in people with Parkinson' disease (pwPD) worsens with the progression of disease, affecting independence and quality of life. At present, clinical practice guidelines recommend a basic evaluation of gait, even though the variables (gait speed, cadence, step length) may not be satisfactory for assessing the evolution of locomotion over the course of the disease. Collecting variables into factors of a conceptual model enhances the clinical assessment of disease severity. Our aim is to evaluate if factors highlight gait differences between pwPD and healthy subjects (HS) and do it at earlier stages of disease compared to single variables. Gait characteristics of 298 pwPD and 84 HS able to walk without assistance were assessed using a baropodometric walkway (GAITRite®). According to the structure of a model previously validated in pwPD, eight spatiotemporal variables were grouped in three factors: pace/rhythm, variability and asymmetry. The model, created from the combination of three factor scores, proved to outperform the single variables or the factors in discriminating pwPD from HS. When considering the pwPD split into the different Hoehn and Yahr (H&Y) stages, the spatiotemporal variables, factor scores and the model showed that multiple impairments of gait appear at H&Y stage 2.5, with the greatest difference from HS at stage 4. A contrasting behavior was found for the asymmetry variables and factor, which showed differences from the HS already in the early stages of PD. Our findings support the use of factor scores and of the model with respect to the single variables in gait staging in PD.


Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.
The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.


Thermal and ultraviolet light inactivation of Mycobacterium africanum.
Mycobacterium africanum Yaoundé and Rwanda were more heat-resistant than the tubercle bacilli. The ultraviolet susceptibilities of M. africanum strains were within the range usually found in the mycobacteria (e-1 doses), however marked differences were found in the intersept numbers of the Yaounde and the Dakar types.


Physical activity participation according to the pyramidal, sensory, and cerebellar functional systems in multiple sclerosis.
The objective of the study was to examine the differences in physical activity participation with the pyramidal, cerebellar, and sensory functional systems in people with multiple sclerosis (PwMS). This cross-sectional study included 289 PwMS with a median EDSS of 2.0 (range 0-6.5) and a mean disease duration of 6.8 (SD = 8.4) years. The Godin leisure-time exercise questionnaire (GLTEQ) assessed physical activity participation. The sample was divided into seven groups according to the pyramidal, cerebellar, and sensory functional system scores derived from the EDSS data. Additionally, PwMS were divided into three physical activity subgroups (active, moderately active, and insufficiently active). Furthermore, PwMS were categorized into four levels of disability based on their global Expanded Disability Status Scale (EDSS) score [very mild (0-1.5), mild (2.0-3.5), moderate (4.0-5.5), and severe (6.0-6.5)]. In the physical activity subgroups, 159 (55.0%) were classified as insufficiently active, 59 (20.4%) as moderately active, and 71 (24.6%) as active. Pyramidal, cerebellar, and sensory impairments were demonstrated in 134 (46.4%), 73 (25.3%), and 85 (29.4%) patients, respectively. No differences were found for the GLTEQ scores for all seven functional system groups (P value = 0.168). As for the EDSS disability subgroups, the percentage of active patients (moderately at least) were 60%, 45.8%, 36.5%, and 15.4%, for the very mild, mild, moderate, and severe subgroups, respectively. This study found that participation in leisure-time physical activity is independent from the pyramidal, cerebellar, and sensory functional systems in PwMS.


Co-circulation of Hepatitis E Virus (HEV) Genotype 3 and Moose-HEV-Like Strains in Free-Ranging-Spotted Deer (Axis axis) in Uruguay.
Hepatitis E caused by hepatitis E virus (HEV) is considered an emerging foodborne zoonosis in industrialized, non-endemic countries. Domestic pigs and wild boars are considered the main reservoir of HEV. However, HEV can also infect an ever-expanding host range of animals, but they exact role in transmitting the virus to other species or humans is mostly unknown. In this work, we investigated the spread of HEV in free-living and captive spotted deer (Axis axis) from Uruguay in a 2-year period (2020-2022) and examined the role of this invasive species as a new potential reservoir of the virus. In addition, with the aim to gain new insights into viral ecology in the context of One Health, by using camera trapping, we identified and quantified temporal and spatial coexistence of spotted deer, wild boars, and cattle. In free-living animals, we detected an anti-HEV seropositivity of 11.1% (6/54). HEV infection and viral excretion in feces were assessed by RT-PCR. Thirteen of 19 samples (68.4%) had HEV RNA. Six samples were amplified using a broadly reactive RT-PCR and sequenced. No captive animal showed evidence of HEV infection. Additionally, HEV RNA was detected in a freshwater pond shared by these species. Phylogenetic and p-distance analysis revealed that zoonotic HEV genotype 3 strains circulate together with unclassified variants related to moose HEV whose potential risk of transmission to humans and other domestic and wild animals is unknown. The data presented here suggest that spotted deer (A. axis) may be a novel host for zoonotic HEV strains.