Assessing the environmental risk and mobility of cobalt in sediment near nonferrous metal mines with risk assessment indexes and the diffusive gradients in thin films (DGT) technique.
The Jialing River is the tributary of the Yangtze River with the largest drainage area. In recent years, the Jialing River has suffered a series of environmental problems, such as discharge of industrial effluent and sand mining activities, which have severely threatened the aquatic ecosystem of the river. In the present study, we employed risk assessment indexes, sequential extraction and the diffusive gradients in thin films (DGT) technique to assess environmental risks and study the remobilization of cobalt (Co) in sediments. The potential ecological risk index and risk assessment code results demonstrated that Co may pose a low environmental and ecological risk to the local aquatic environment. However, BCR sequential extraction showed that the sum of the F1, F2 and F3 fractions of Co still accounted for over 50% of the Co in the study areas, indicating that sediments may be a source of Co release. The DGT results showed an increasing trend for DGT-labile Co in deep sediments (-8 cm to -12 cm), and the calculated flux values ranged from 0.08 to 15.54 ng cm2·day-1, indicating that Co tends to transfer across the sediment-water interface at all sampling sites. Correlation analysis showed that F1-Co, F2-Co and F3-Co are the fractions readily captured by DGT and can be used for predicting Co remobilization in sediment. Sand mining activities contribute substantially to the release of Co from the F1 and F3 fractions as a result of strong stirring of sediments and introduction of oxygen into the sediments. The reductive dissolution of iron (Fe) and manganese (Mn) hydroxides or oxides causes the release of Co and Fe/Mn in the sediment, which leads to Co release from the reducible fraction. The above work suggests that sand mining in the Jialing River should be reasonably regulated to prohibit illegal sand mining activities.


Identification and characterization of a novel class of atypical dopamine receptor agonists.
The D3 dopamine receptor exhibits tolerance and slow response termination (SRT) properties that are not exhibited by the closely-related D2 dopamine receptor. We previously demonstrated that the induction of tolerance elicits a unique conformational change in the D3 receptor. Here we tested the hypothesis that the tolerance and SRT properties of the D3 receptor are ligand-dependent. We used pharmacophore modeling and in silico screening approaches coupled with electrophysiological and biochemical methods to identify and functionally characterize the novel dopamine receptor agonists. We identified cis-8-OH-PBZI (PBZI), FAUC73 and an additional novel compound, ES609, which although they are full D3 receptor agonists, do not induce the tolerance and SRT properties of the D3 receptor. In addition, PBZI has full intrinsic activity at D2L, is a partial agonist at D2S and exhibits functional selectivity at D4.2 dopamine receptors. ES609 is a partial agonist at D2S, D2L and D4.2 receptors, and exhibits functional selectivity at D2L and D4.2 dopamine receptors. We have discovered a novel class of atypical dopamine receptor agonists that include three structurally dissimilar compounds. These new agonists will help determine the physiological and pathophysiological relevance of D3 receptor tolerance and SRT properties.


FeII/III and MnII complexes based on 2,4,6-tris(2-pyridyl)-triazine: synthesis, structures, magnetic and biological properties.
Reaction of the polypyridyl ligand 2,4,6-tris(2-pyridyl)-s-triazine (tpt) with mono- and polynuclear Fe(iii) or Mn(ii) precursors, specifically tri- or hexanuclear Fe(iii) pivalates (piv-), [Mn6O2(piv)10(Hpiv)4] and Mn(ii) isobutyrate (ib-), in various solvents and under various reaction conditions showcase the ligand's surprising coordination characteristics. The reactions result in mononuclear [FeIII(tpt)(tptH)][FeIIICl4]4·2(thf)·0.23(H2O) (1), [FeIII(piv)(tpt)Cl2] (2), [FeII(tpt)Cl2]·2(H2O) (3a), dinuclear [FeIII 2O(tpt)2Cl4] (3), and heptanuclear [FeIII 7O4(piv)12(tpt-O)]·A [A = MeCN (4a) or 4(dioxane) (4b)] and [FeIII 7O4(piv)11(tpt-O)(i-PrO)(i-PrOH)]·0.75(i-PrOH) (5), as well as the mononuclear compounds [MnII(tpt)(NO3)(H2O)2](NO3) (6) and [MnII(tpt)(ib)(Cl)(MeOH)]·MeOH (7). Single-crystal X-ray diffraction analyses identify tpt as a tridentate NNN donor ligand that forms two five-membered metallocycles in 1-3, 6 and 7, whereas in 4 and 5 five tpt N atoms form coordinative bonds accompanied by an unusual metal-induced oxidation of one of the carbon atoms of the central triazine core. Magnetic properties of Fe(iii)-tpt (2-5), Fe(ii)-tpt (3a), and Mn(ii)-tpt (7) compounds show dominant antiferromagnetic coupling for polynuclear coordination cluster compounds. The Mn(ii)-tpt complexes 6 and 7 exhibit efficient catalytic properties in the production of enzymes by microorganisms, which concerns the synthesis of exocellular proteases in Fusarium gibbosum CNMN FD 12 or Trichoderma koningii Oudemans CNMN FD 15 fungi strains. Thus, compounds 6 and 7 can be used for producing proteolytic enzymes with wide applications including in the food, detergents and pharmaceutical industries.


Evolutionary and diagnostic implications of intragenomic heterogeneity in the 16S rRNA gene in Aeromonas strains.
Sequencing 16S rRNA genes (SSU) cloned from Aeromonas strains revealed that strains contained up to six copies differing by < or = 1.5%. The SSU copies from Aeromonas veronii LMG13695 clustered with sequences from four Aeromonas species. These results demonstrate intragenomic heterogeneity of SSU and suggest caution when using SSU to identify aeromonads.


Agreement between Pleth Variability Index and oesophageal Doppler to predict fluid responsiveness.
Optimisation of stroke volume using oesophageal Doppler is an established technique to guide intraoperative fluid therapy. The method has practical limitations and therefore alternative indices of fluid responsiveness, such as ventilator-induced variation in the pulse oximetric signal (Pleth Variability Index (PVI)) could be considered. We hypothesised that both methods predict fluid responsiveness in a similar way. Seventy-five patients scheduled for open major abdominal surgery were randomised to fluid optimisation using fluid bolus algorithms based on either PVI (n = 35) or Doppler (n = 39). All patients were monitored with both methods; the non-guiding method was blind. Primary endpoint was the concordance between the methods to predict fluid responsiveness. We also analysed the ability of each method to predict a stroke volume increase ≥ 10% after a fluid bolus, as well as the accumulated intraoperative bolus fluid volume. PVI indicated a need for fluid in one-third of the situations when Doppler did so, Cohen's kappa = 0.03. A fluid bolus indicated by the PVI algorithm increased stroke volume by ≥ 10% in half the situations. The same was found for the Doppler algorithm. The mean total bolus volume given was 878 ml when the fluid management was governed by PVI compared to 826 ml with Doppler (P = 0.71). PVI- and Doppler-based stroke volume optimisations agreed poorly, which did not affect the amount of fluid administered. None of the algorithms showed a good ability to predict fluid responsiveness. Our results do not support the fluid responsiveness concept.


Can we justify goal blood pressure of <140/90 mm Hg in most hypertensives?
Hypertension is a common disorder with well-recognized consequences on the heart, brain, and kidney as target organs. Guidelines espouse a treatment goal of blood pressure reduction to <140 mm Hg for the systolic pressure and <90 mm Hg for the diastolic pressure in most hypertensive patients. In this review, the basis for these recommendations, the practical achievement of these goals in various practice settings, and the risk versus the benefit of achieving such goals in most hypertensive patients are examined.


Evidence to support the classification of hyperglycemia first detected in pregnancy to predict diabetes 6-12 weeks postpartum: A single center cohort study.
Diagnostic criteria for type 2 diabetes mellitus (T2DM) applied to women with gestational diabetes mellitus (GDM) may predict postpartum T2DM but requires validation. Women with GDM aged ≥ 18-years were prospectively evaluated 6-12 weeks after delivery at Tygerberg Hospital, Cape Town, South-Africa (November 2015- December 2018). Glucose status at GDM diagnosis was categorized into i) International Association for Diabetes in Pregnancy Study Group (IADPSG) T2DM (fasting glucose ≥ 7 mmol/L and/or 2hr-glucose ≥ 11.1 mmol/L) or ii) modified National Institute for Care Excellence (NICE) GDM (fasting glucose ≥ 5.6 mmol/L-6.9 mmol/L and/or 2hr-glucose ≥ 7.8 mmol/L-11 mmol/L) and compared with postpartum OGTT. IADPSG T2DM and NICE GDM was present in 35% (n = 64) and 65% (n = 117) of the 181 women who completed the 8 ± 2 weeks postpartum evaluation respectively. Postpartum, the prevalence of T2DM and prediabetes was 26% (n = 47/181) and 15% (n = 28). Antenatal IADPSG T2DM categorization identified 31/47 women with postpartum T2DM (sensitivity 75%; specificity 48%). All of the modified NICE GDM category women who developed T2DM (n = 16/117) had elevations of both fasting and 2hr-glucose values antenatally. The utility of the IADPSG T2DM criteria to predict T2DM postpartum is confirmed. Women with both fasting and 2hr-glucose values above GDM cut-offs emerged as another high-risk category.


[Convergence of projections from various thalamic nuclei on the rat somatosensory cortex columns].
The method of primuline fluorochrome retrograde transport was used to study sources of thalamo-cortical projections on a separate somatic cortical neuronal column connected with C3 vibrissae of albino rat. Labeled cells were found in 8 thalamic nuclei: tv, tvd, tpo, pf, rh, tvm, tvl, tr. The intensity of neuron staining and cell quantity and density varied in different nuclei. Hence their axon branching in the rat cortex was also different. The majority of intensively stained and densely packed cells have been observed in tv nucleus. The observed convergence of different thalamo-cortical inputs on single somatic cortex column explains heterogeneity in functional properties of the same column neurons and makes it possible for the column to form several neuronal assemblies with different functions.


Identification of functional dopamine receptors in human teratocarcinoma NT2 cells.
In search of a cellular model suitable for studying molecular events contributing to brain disorders, we have characterised the expression and functionality of dopamine receptors in human teratocarcinoma NT2 cells. The cells were differentiated by a 4-week retinoic acid treatment, followed by a 3-week mitotic inhibitor treatment in the absence of retinoic acid. The messages of two D(2)-like family members, D(2L) and D(3), were expressed in undifferentiated NT2 cells. The retinoic acid treatment resulted in increased expression of both spliced variants of the D(2) receptor, D(2L) and D(2S) isoforms and a significant induction of D(1) and D(5) gene transcripts. The same treatment turned off expression of the D(3) gene. Further induction of the D(5) gene was observed in the post-mitotic NT2N neurons. The NT2N cells stained positively for D(2) and D(5) receptor proteins, and the intracellular cyclic AMP level increased in response to forskolin, dopamine and the D(1)-receptor agonist SKF-81297. Furthermore, dopamine was ineffective in the presence of the D(2) receptor agonist PPHT and the D(1) receptor antagonist cis-(z)-flupenthixol. These results indicated that upon ligand/agonist/antagonist binding, the receptors could be coupled to the adenylyl cyclase system, hence were functional. To our knowledge, NT2 is the only human immortalized cell line expressing functional dopamine receptors of both families.


Matrix effects of calcium on high-precision sulfur isotope measurement by multiple-collector inductively coupled plasma mass spectrometry.
Multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) has been successfully applied in the rapid and high-precision measurement for sulfur isotope ratios in recent years. During the measurement, the presence of matrix elements would affect the instrumental mass bias for sulfur and these matrix-induced effects have aroused a lot of researchers' interest. However, these studies have placed more weight on highlighting the necessity for their proposed correction protocols (e.g., chemical purification and matrix-matching) while less attention on the key property of the matrix element gives rise to the matrix effects. In this study, four groups of sulfate solutions, which have different concentrations of sulfur (0.05-0.60mM) but a constant sequence of atomic calcium/sulfur ratios (0.1-50), are investigated under wet (solution) and dry (desolvation) plasma conditions to make a detailed evaluation on the matrix effects from calcium on sulfur isotope measurement. Based on a series of comparative analyses, we indicated that, the matrix effects of calcium on both measured sulfur isotope ratios and detected (32)S signal intensities are dependent mainly on the absolute calcium concentration rather than its relative concentration ratio to sulfur (i.e., atomic calcium/sulfur ratio). Also, for the same group of samples, the matrix effects of calcium under dry plasma condition are much more significant than that of wet plasma. This research affords the opportunity to realize direct and relatively precise sulfur isotope measurement for evaporite gypsum, and further provides some suggestions with regard to sulfur isotope analytical protocols for sedimentary pore water.


Interference of raw milk autochthonous microbiota on the performance of conventional methodologies for Listeria monocytogenes and Salmonella spp. detection.
Pathogen detection in foods by reliable methodologies is very important to guarantee microbiological safety. However, peculiar characteristics of certain foods, such as autochthonous microbiota, can directly influence pathogen development and detection. With the objective of verifying the performance of the official analytical methodologies for the isolation of Listeria monocytogenes and Salmonella in milk, different concentrations of these pathogens were inoculated in raw milk treatments with different levels of mesophilic aerobes, and then submitted to the traditional isolation procedures for the inoculated pathogens. Listeria monocytogenes was inoculated at the range of 0.2-5.2 log CFU/mL in treatments with 1.8-8.2 log CFU/mL. Salmonella Enteritidis was inoculated at 0.9-3.9 log CFU/mL in treatments with 3.0-8.2logCFU/mL. The results indicated that recovery was not possible or was more difficult in the treatments with high counts of mesophilic aerobes and low levels of the pathogens, indicating interference of raw milk autochthonous microbiota. This interference was more evident for L. monocytogenes, once the pathogen recovery was not possible in treatments with mesophilic aerobes up to 4.0 log CFU/mL and inoculum under 2.0 log CFU/mL. For S. Enteritidis the interference appeared to be more non-specific.


A 5-HT4-like receptor in human left atrium.
The effects of 5-hydroxytryptamine (5-HT) on left atrial preparations obtained from 5 patients with terminal heart failure who were undergoing heart transplant surgery were investigated. The preparations were paced under isometric conditions. In the presence of (-)-pindolol 1 mumol/l (to block beta-adrenoceptors) and cocaine 6 mumol/l (to block tissue uptake of 5-HT) 5-HT increased contractile force with a pEC50 of 7.0. The maximum effect of 5-HT amounted to 24.5% of that caused by a maximally effective concentration of (-)-isoprenaline (200 mumol/l) and 25% of that caused by 6.75 mmol/l CaCl2. The effects of 5-HT were competitively antagonised by 3 alpha-tropanyl-1H-indole-3-carboxylate (ICS 205-930) with a pKB of 6.8. The effects of 5-HT on cyclic AMP levels and cyclic AMP-dependent protein kinase activity were also studied using left atrial tissues from one of the patients; 5-HT increased the cyclic AMP content and stimulated the kinase. The results are consistent with the existence of a human left atrial 5-HT receptor which is similar to the recently identified human right atrial 5-HT receptor that resembles the 5-HT4 receptor. The left atrial 5-HT4-like receptor is functional in tissues obtained from patients with terminal heart failure.


Long-term photosynthetic response in single leaves of A C3 and C4 salt marsh species grown at elevated atmospheric CO2 in situ.
Mono-specific communities of the C3 sedge, Scirpus olneyi and the C4 grass, Spartina patens, were exposed to normal ambient or elevated CO2, (ca. 680 μl l-1) throughout the 1987 and 1988 growing seasons in open-top field chambers located on a tidal marsh. Single stems of C3 plants grown in ambient or elevated CO2 showed an increased photosynthetic rate when tested at elevated CO2 for both seasons. This increase in photosynthetic response in the C3 species was maintained throughout the 1987 and 1988 growing season. The stimulation of photosynthesis with elevated CO2 appeared to increase as temperature increased and decreased as photosynthetic photon flux (PPF) increased. Analysis of the photosynthetic response of the C3 species during the 1988 season indicated that significant differences in light-saturated photosynthetic rate between ambient and elevated CO2 conditions continued until October. In contrast to the C3 sedge, the C4 grass showed no significant photosynthetic increase to elevated CO2 except at the beginning of the 1988 season.


Cutaneous T-cell lymphoma.
Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant helper T lymphocytes. Accurate diagnosis of early CTCL is difficult due to the varied clinical and histologic expressions of the disease.


Antimicrobial peptide scolopendrasin VII, derived from the centipede Scolopendra subspinipes mutilans, stimulates macrophage chemotaxis via formyl peptide receptor 1.
In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic migration of FPR1-transfected RBL-2H3 cells, but not that of vector-transfected cells; moreover, scolopendrasin VII directly binds to FPR1. Our findings therefore suggest that the antimicrobial peptide scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates macrophages, resulting in chemotactic migration via FPR1 signaling, and the peptide can be useful in the study of FPR1-related biological responses.


Ulcer Disease in the Excluded Segments after Roux-en-Y Gastric Bypass: a Current Review of the Literature.
Ulcer disease in excluded segments after Roux-Y gastric bypass (RYGB) is rare but can evolve into a life-threatening situation. The excluded segments exhibit a different behavior from that of non-altered anatomy; perforated ulcers do not result in pneumoperitoneum or free fluid, and therefore must be met with a low threshold for surgical exploration. The anatomical changes after RYGB impede routine access to the remnant stomach and duodenum. There are various options to address bleeding or perforated ulcers. While oversewing and drainage preserves the anatomy and forgoes resection, remnant gastrectomy offers a definitive solution. The importance of traditional risk factors such as smoking or use of non-steroidal anti-inflammatory drugs is unclear. Eradication of Helicobacter pylori and secondary prophylaxis with proton-pump inhibitors is advisable, albeit in double-dose.


Moraxella Keratitis: Analysis of Risk Factors, Clinical Characteristics, Management, and Treatment Outcomes.
To analyze the risk factors, clinical characteristics, management, and treatment outcomes of culture-proven cases of Moraxella keratitis at our center. Retrospective observational case series. Thirty-nine culture-proven cases of Moraxella keratitis (39 eyes) diagnosed and treated between January 2003 and April 2018 at the University of Pittsburgh Medical Center were identified and retrospectively reviewed for ocular and systemic risk factors, treatment modalities, and outcomes, as well as for antimicrobial sensitivity and resistance data. The mean age of the 39 patients was 63.0 (range 4-95 years) with median follow-up time of 170 days. Thirty-four of 39 patients (87.2%) had an ocular risk factor, the most common of which were blepharitis in 12 (30.8%), dry eyes in 12 (30.8%), and history of ocular surgery in 9 (23.1%). History of diabetes mellitus was found in 8 patients (20.5%). Thirty-six of 39 patients (92.3%) received a fluoroquinolone (92.3%) and 30 of 39 (76.7%) received topical fortified antibiotics. Resistance to fluoroquinolones, gentamicin, and tobramycin was seen in 1 patient each, respectively. Four patients (10.3%) required tarsorrhaphy, 6 patients (15.4%) required penetrating keratoplasty, and 1 patient required enucleation. Of the 35 patients for whom visual acuity information was available, 19 (54.3%) were count fingers or worse at most recent follow-up. Ocular risk factors, especially poor ocular surface, were identified in the vast majority of patients with Moraxella keratitis. Moraxella isolates in our study were susceptible to fluoroquinolones and aminoglycosides. Many patients required surgical intervention and the final visual acuity was often poor.


Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes, for intracranial haemorrhage risk in a non-atrial fibrillation population: the Chin-Shan Community Cohort Study.
The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication. We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged >35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database. Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3-7.6] and 1.9[1.1-3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67-0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p<0.05, compared to other four scoring schemes). The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.


A Multifaceted Campaign to Combat COVID-19 Misinformation in the Hispanic Community.
At the height of the COVID-19 pandemic, the Public Good Projects, Hispanic Communications Network and World Voices Media joined forces to launch a nationwide, multifaceted campaign which aimed to increase vaccine confidence and decrease misinformation on social media within Hispanic communities. We created a Spanish vaccine misinformation tracking system to detect and assess misinformation circulating in online Spanish conversations. We used our media monitoring findings to work with Hispanic social media (SM) influencers, volunteers, and celebrities to spread pro-vaccine messaging online. We created misinformation-responsive SM assets, newsletters, talking points and trainings for Hispanic-serving community-based organizations (CBOs) to help them respond to misinformation and increase vaccine uptake. We used our misinformation findings to inform the creation of mass media communications such as radio PSAs and op-eds. In Year 1, our new Spanish monitoring system captured and organized 35 M Spanish and 212.7 M English posts about COVID-19 misinformation. We recruited 496 paid influencers, 2 Hispanic celebrities and 1,034 digital volunteers. We sent 70 newsletters to an average of 1539 CBO subscribers, containing 206 talking points and 344 resources (SM assets, toolkits, videos) in English and Spanish to support their outreach. Our radio PSAs reached 26.9 M people and the op-eds reached 2.9 M people. This project shows the proliferation of misinformation circulating in online Spanish conversations. It also shows we were effective at reaching our target audience with fact-based COVID-19 misinformation prebunk and debunk messaging.


Increased chronic bowel complications with split-course pelvic irradiation.
To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy. A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out. Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009). This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.


High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: correlation with poor prognosis and CD4 expression on blast cells.
Although increased serum levels of soluble interleukin-2 receptor (sIL-2R) and their clinical importance are well known in mature type lymphoproliferative disorders (LD), little data is available about such information in acute type hematological malignancies. We examined the serum levels of sIL-2R in 57 adult patients with acute type leukemias: 32 with acute myeloid leukemia (AML), 14 acute lymphoblastic leukemia (ALL) and 11 chronic myelocytic leukemia in blast crisis (CMLBC), and in 29 adult patients with mature type LD, and assessed their cellular and clinical relevance in acute type leukemias. No significant differences were seen in the sIL-2R levels between acute type leukemias and mature type LD. In AML, serum sIL-2R levels were related to the cell surface CD4 expression on blast cells, and patients with higher levels ≧2000U/ml had a poorer prognosis (lower response to chemotherapy and shorter overall survival). These results suggest that serum sIL-2R level elevates in acute type leukemias like mature type LD, and increased sIL-2R levels in adult AML are correlated with certain biological and clinical characteristics.


Systematic review and meta-analysis: Association between liver fibrosis and subclinical atherosclerosis in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a liver disorder commonly associated with metabolic syndrome and cardiovascular disease (CVD). Atherosclerosis, a leading cause of CVD, has been linked to liver fibrosis. However, the evidence regarding this association is conflicting. To evaluate the link between liver fibrosis and subclinical atherosclerosis in patients with NAFLD METHODS: We conducted a comprehensive search of four databases from 1950 to February 2023 to identify eligible studies investigating the association between liver fibrosis and subclinical atherosclerosis among patients with NAFLD, utilising the PICOS framework. Two independent reviewers screened the studies; quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using the DerSimonian-Liard random-effects model, and subgroup analysis was conducted based on the severity of liver fibrosis, type of subclinical atherosclerosis diagnosis and geographic region. The meta-analysis included 12 studies with a total of 4725 patients. Overall pooled odds ratio (OR) for subclinical atherosclerosis was 2.18 (95% CI: 1.62-2.93), indicating a significant association with liver fibrosis in NAFLD. Subgroup analysis revealed higher ORs in patients with more severe fibrosis: 1.64 (95% CI: 1.22-2.20) in ≥F1, 2.22 (95% CI: 1.37-3.62) in ≥F2, and 3.42 (95% CI: 1.81-6.46) in ≥F3. However, there was no significant difference between the West versus East and various measurements of subclinical atherosclerosis. Any degree of fibrosis is significantly associated with subclinical atherosclerosis, with fibrosis severity amplifying the association.


Sorption and desorption of Sr onto a rough single fractured granite.
To investigate the migration behavior of Sr (strontium) in granite, a rough-walled single fracture of granite was prepared with the self-built rock splitting apparatus. Surface roughness angle and hydraulic aperture of the fracture were measured by 3D laser scanning and fluid flow experiment, respectively. The sorption and desorption breakthrough experiments of Sr in the single fracture were conducted at different flow rates and initial concentrates of Sr, and the important transport parameters were derived by fitting the BTCs and DPCs. The results suggested that the sorption of Sr onto the fracture surface was a linear and reversible ion-exchange process, unaffected by the variation of flow rate and initial concentrate of Sr.


Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.
In human metabolism, pyruvate dehydrogenase complex (PDC) is one of the most intricate and large multimeric protein systems representing a central hub for cellular homeostasis. The worldwide used antiepileptic drug valproic acid (VPA) may potentially induce teratogenicity or a mild to severe hepatic toxicity, where the underlying mechanisms are not completely understood. This work aims to clarify the mechanisms that intersect VPA-related iatrogenic effects to PDC-associated dihydrolipoamide dehydrogenase (DLD; E3) activity. DLD is also a key enzyme of α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, α-ketoadipate dehydrogenase, and the glycine decarboxylase complexes. The molecular effects of VPA will be reviewed underlining the data that sustain a potential interaction with DLD. The drug-associated effects on lipoic acid-related complexes activity may induce alterations on the flux of metabolites through tricarboxylic acid cycle, branched-chain amino acid oxidation, glycine metabolism and other cellular acetyl-CoA-connected reactions. The biotransformation of VPA involves its complete β-oxidation in mitochondria causing an imbalance on energy homeostasis. The drug consequences as histone deacetylase inhibitor and thus gene expression modulator have also been recognized. The mitochondrial localization of PDC is unequivocal, but its presence and function in the nucleus were also demonstrated, generating acetyl-CoA, crucial for histone acetylation. Bridging metabolism and epigenetics, this review gathers the evidence of VPA-induced interference with DLD or PDC functions, mainly in animal and cellular models, and highlights the uncharted in human. The consequences of this interaction may have significant impact either in mitochondrial or in nuclear acetyl-CoA-dependent processes.


Water quality monitoring of Lake Burullus (Egypt) using Landsat satellite imageries.
Lake Burullus is one of the most important coastal lakes in Egypt, as it participates with a considerable amount of fish yield in Egypt. Despite its importance, it is considered as a vulnerable lake, since it is subjected to significant environmental changes caused by various anthropogenic activities. Severe deterioration of its water quality status, as well as a decrease in its water area, has been noticed throughout the last four decades. The main objective of this study is to evaluate the ability of remote sensing for assessing the water quality status of the lake for the period from August 2010 to August 2013. Remote sensing technique was used to retrieve and predict the lake water quality parameter records through the assessment period (August 2010 to August 2013). Stepwise multi-linear regression technique was used to correlate between the field measurements of water quality parameters and the reflectance of remote sensing imageries, and then the derived models were validated. The results revealed the critical status of water quality conditions of the lake, particularly of its southern and southeastern parts. The results showed also that some water quality parameters (Chl-a, TSS, pH, Fe, Zn, Cr, and NH4) can be retrieved from remote sensing imageries with reasonable accuracy (R2 = 0.86, 0.67, 0.65, 0.63, 0.62, 0.61, and 0.6, respectively), while the water quality parameters, which can be predicted, based on calibrated and validated regression models are TSS and Chl-a, with acceptable accuracy (R2 = 0.6 and 0.43, respectively). Lake Burullus needs urgent plans and strategies to protect its water quality from the potential hazards of human activities. The study proved the ability of remote sensing as an effective technique to monitor the changes in water quality conditions of shallow coastal lagoons and to predict with some water quality parameters without field measurements; therefore, it is highly recommended to be used by decision makers.


Resound Trial: A phase 2 study of regorafenib in patients with thymoma (type B2-B3) and thymic carcinoma previously treated with chemotherapy.
Angiogenesis has an important role in thymic epithelial tumors (TETs). Regorafenib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor β (PDGFR-β), and fibroblast growth factor receptors (FGFRs). This study explored the activity of regorafenib as monotherapy in patients with advanced or recurrent B2-B3 thymoma (T) and thymic carcinoma (TC) previously treated with platinum-containing chemotherapy. A Fleming single-arm, single-stage, phase 2 trial to evaluate the activity of regorafenib (160 mg once a day by mouth for 3 weeks on/1 week off) was planned. The study was designed to reject the null hypothesis of an 8-week progression-free survival (PFS) rate ≤25% with a type I error of 0.10 and a statistical power of 80% at the alternative hypothesis of an 8-week PFS rate of ≥50% (≥8 of 19 evaluable patients progression-free at 2 months). From June 2016 to November 2017, 19 patients were enrolled (11T/8TC). We observed partial response (PR) in 1 patient (1T) (5.3%), stable disease (SD) in 14 patients (9T/5TC) (73.7%), and progressive disease in 2 patients (1T/1TC) (10.5%), with a disease control rate of 78.9%. According to Choi-criteria, 13 patients (68.4%) achieved PR, and 2 patients SD (10.5%). The median PFS was 9.6 months whereas median overall survival was 33.8 months. The 8-week PFS rate was 78.9% (15 of 19 patients). Grade 3-4 treatment-related adverse events were observed in 10 patients (52.6%). The primary end point of this study was reached. The high rate of PR (Choi-criteria) suggests antitumor activity of regorafenib in TETs. On the basis of survival outcomes, the efficacy of regorafenib should be further evaluated in larger studies.


Psychosexual adjustment of men who underwent hypospadias repair: a norm-related study.
Psychosexual adjustment, sexual functioning and genital appraisal were studied in adult hypospadias patients. A total of 73 hypospadias patients and 50 comparison subjects received a semi-structured interview. More hypospadias patients (32.8%) than comparison subjects (12.8%) had been inhibited in seeking sexual contacts. Hypospadias patients reported a more negative genital appraisal than comparison subjects but did not have a different sexual adjustment. The severity of hypospadias negatively affected genital appraisal. Patient age at final operation positively correlated with sociosexual development. Many patients (37%) desired functional or cosmetic penile improvement. The majority of hypospadias patients experienced a normal adult sex life. They were reluctant to seek advice for problems. We recommend followup of patients through adolescence.


Improvement in Palivizumab Administration Prior to Discharge for Hospitalized Infants with Hemodynamically Significant Congenital Heart Disease: A Quality Improvement Initiative.
In this quality improvement initiative, we aimed to increase provider adherence with palivizumab administration guidelines for hospitalized infants with hemodynamically significant congenital heart disease. We included 470 infants over four respiratory syncytial virus (RSV) seasons from 11/2017 to 03/2021 (baseline season: 11/2017-03/2018). Interventions included the following: education, including palivizumab in the sign-out template, identifying a pharmacy expert, and a text alert (seasons 1 and 2: 11/2018-03/2020) that was replaced by an electronic health record (EHR) best practice alert (BPA) in season 3 (11/2020-03/2021). The text alert and BPA prompted providers to add "Need for RSV immunoprophylaxis" to the EHR problem list. The outcome metric was the percentage of eligible patients administered palivizumab prior to discharge. The process metric was the percentage of eligible patients with "Need for RSV immunoprophylaxis" on the EHR problem list. The balancing metric was the percentage of palivizumab doses administered to ineligible patients. A statistical process control P-chart was used to analyze the outcome metric. The mean percentage of eligible patients who received palivizumab prior to hospital discharge increased significantly from 70.1% (82/117) to 90.0% (86/96) in season 1 and to 97.9% (140/143) in season 3. Palivizumab guideline adherence was as high or higher for those with "Need for RSV immunoprophylaxis" on the problem list than for those without it in most time periods. The percentage of inappropriate palivizumab doses decreased from 5.7% (n = 5) at baseline to 4.4% (n = 4) in season 1 and 0.0% (n = 0) in season 3. Through this initiative, we improved adherence with palivizumab administration guidelines for eligible infants prior to hospital discharge.


The transfer of petrol on to clothing and shoes while pouring petrol around a room.
This study was aimed at measuring the approximate amount of petrol transferred on to the clothing and shoes of a person during the action of pouring petrol around a room. Two different heights of pouring and two different types of floor surface (carpet and concrete) were investigated. Results show that for all the combinations examined petrol was always transferred to the shoes and often transferred to the upper and lower clothing. This information illustrates the necessity of analysing the clothing and particularly the shoes of any suspected arsonists for the presence of hydrocarbon fuels.


Fluorescent sensing of transition metal ions based on the encapsulation of dithranol in a polymeric core shell architecture.
The encapsulation behaviour and the resulting transition metal ion sensing capabilities of a 5-arm star-shaped polymer bearing terpyridine ligands on its periphery are described.


The Challenges of Analyzing Behavioral Response Study Data: An Overview of the MOCHA (Multi-study OCean Acoustics Human Effects Analysis) Project.
This paper describes the MOCHA project which aims to develop novel approaches for the analysis of data collected during Behavioral Response Studies (BRSs). BRSs are experiments aimed at directly quantifying the effects of controlled dosages of natural or anthropogenic stimuli (typically sound) on marine mammal behavior. These experiments typically result in low sample size, relative to variability, and so we are looking at a number of studies in combination to maximize the gain from each one. We describe a suite of analytical tools applied to BRS data on beaked whales, including a simulation study aimed at informing future experimental design.


Dinosaur morphological diversity and the end-Cretaceous extinction.
The extinction of non-avian dinosaurs 65 million years ago is a perpetual topic of fascination, and lasting debate has focused on whether dinosaur biodiversity was in decline before end-Cretaceous volcanism and bolide impact. Here we calculate the morphological disparity (anatomical variability) exhibited by seven major dinosaur subgroups during the latest Cretaceous, at both global and regional scales. Our results demonstrate both geographic and clade-specific heterogeneity. Large-bodied bulk-feeding herbivores (ceratopsids and hadrosauroids) and some North American taxa declined in disparity during the final two stages of the Cretaceous, whereas carnivorous dinosaurs, mid-sized herbivores, and some Asian taxa did not. Late Cretaceous dinosaur evolution, therefore, was complex: there was no universal biodiversity trend and the intensively studied North American record may reveal primarily local patterns. At least some dinosaur groups, however, did endure long-term declines in morphological variability before their extinction.


Detectability of Anatomical Changes With Prompt-Gamma Imaging: First Systematic Evaluation of Clinical Application During Prostate-Cancer Proton Therapy.
The development of online-adaptive proton therapy (PT) is essential to overcome limitations encountered by day-to-day variations of the patient's anatomy. Range verification could play an essential role in an online feedback loop for the detection of treatment deviations such as anatomical changes. Here, we present the results of the first systematic patient study regarding the detectability of anatomical changes by a prompt-gamma imaging (PGI) slit-camera system. For 15 patients with prostate cancer, PGI measurements were performed during 105 fractions (201 fields) with in-room control computed tomography (CT)acquisitions. Field-wise doses on control CT scans were manually classified as whether showing relevant or non-relevant anatomical changes. This manual classification of the treatment fields was then used to establish an automatic field-wise ground truth based on spot-wise dosimetric range shifts, which were retrieved from integrated depth-dose (IDD) profiles. To determine the detection capability of anatomical changes with PGI, spot-wise PGI-based range shifts were initially compared with corresponding dosimetric IDD range shifts. As final endpoint, the agreement of a developed field-wise PGI classification model with the field-wise ground truth was determined. Therefore, the PGI model was optimized and tested for a subcohort of 131 and 70 treatment fields, respectively. The correlation between PGI and IDD range shifts was high, ρpearson = 0.67 (p < 0.01). Field-wise binary PGI classification resulted in an area under the curve of 0.72 and 0.80 for training and test cohorts, respectively. The model detected relevant anatomical changes in the independent test cohort, with a sensitivity and specificity of 74% and 79%, respectively. For the first time, evidence of the detection capability of anatomical changes in prostate-cancer PT from clinically acquired PGI data is shown. This emphasizes the benefit of PGI-based range verification and demonstrates its potential for online-adaptive PT.


The china patient-centered evaluative assessment of cardiac events (PEACE) prospective study of percutaneous coronary intervention: Study design.
The number of percutaneous coronary interventions (PCI) in China has increased more than 20-fold over the last decade. Consequently, there is a need for national-level information to characterize PCI indications and long-term patient outcomes, including health status, to understand and improve evolving practice patterns. This nationwide prospective study of patients receiving PCI is to: (1) measure long-term clinical outcomes (including death, acute myocardial infarction [AMI], and/or revascularization), patient-reported outcomes (PROs), cardiovascular risk factor control and adherence to medications for secondary prevention; (2) determine patient- and hospital-level factors associated with care process and outcomes; and (3) assess the appropriateness of PCI procedures. The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE) Prospective Study of PCI has enrolled 5,000 consecutive patients during 2012-2014 from 34 diverse hospitals across China undergoing PCI for any indication. We abstracted details of patient's medical history, treatments, and in-hospital outcomes from medical charts, and conducted baseline, 1-, 6-, and 12-month interviews to characterize patient demographics, risk factors, clinical presentation, healthcare utilization, and health status using validated PRO measures. The primary outcome, a composite measure of death, AMI and/or revascularization, as well as PROs, medication adherence and cardiovascular risk factor control, was assessed throughout the 12-month follow-up. Blood and urine samples were collected at baseline and 12 months and stored for future analyses. To validate reports of coronary anatomy, 2,000 angiograms are randomly selected and read by two independent core laboratories. Hospital characteristics regarding their facilities, processes and organizational characteristics are assessed by site surveys. China PEACE Prospective Study of PCI will be the first study to generate novel, high-quality, comprehensive national data on patients' socio-demographic, clinical, treatment, and metabolic/genetic factors, and importantly, their long-term outcomes following PCI, including health status. This will build the foundation for PCI performance improvement efforts in China. © 2016 The Authors. Catheterization and Cardiovascular Interventions. Published by Wiley Periodicals, Inc.


Prevention of restenosis by a herpes simplex virus mutant capable of controlled long-term expression in vascular tissue in vivo.
Neointimal hyperplasia resulting from vascular smooth muscle cell (SMC) proliferation and luminal migration is the major cause of autologous vein graft failure following vascular coronary or peripheral bypass surgery. Strategies to attenuate SMC proliferation by the delivery of oligonucleotides or genes controlling cell division rely on the use of high concentrations of vectors, and require pre-emptive disruption of the endothelial cell layer. We report a genetically engineered herpes simplex virus (HSV-1) mutant that, in an in vivo rabbit model system, infects all vascular layers without prior injury to the endothelium; expresses a reporter gene driven by a viral promoter with high efficiency for at least 4 weeks; exhibits no systemic toxicity; can be eliminated at will by administration of the antiviral drug acyclovir; and significantly reduces SMC proliferation and restenosis in vein grafts in immunocompetent hosts.


Left lateral imaging position in routine myocardial perfusion practice.
Left lateral position in myocardial perfusion imaging has been described in the literature to reduce the incidence of diaphragmatic attenuation artifact, therefore improving the specificity of the test.


Intramolecular Direct C-H Arylation via a Metallocenic Radical Pathway: Stereospecific Approach to Planar-Chiral Ferrocenes.
Transition metal-free synthesis of planar-chiral 1,2-fused ferrocenes via intramolecular direct C-H bond arylation was achieved. The C-H arylation reactions promoted by a catalytic amount of 1,10-phenanthroline highlighted a unique planar-chiral metallocenic radical intermediate, generated from iodoferrocenes via a single-electron transfer process.


Deletion of the GluRδ2 Receptor in the Hotfoot Mouse Mutant Causes Granule Cell Loss, Delayed Purkinje Cell Death, and Reductions in Purkinje Cell Dendritic Tree Area.
Recent studies have found that in the cerebellum, the δ2 glutamate receptor (GluRδ2) plays a key role in regulating the differentiation of parallel fiber-Purkinje synapses and mediating key physiological functions in the granule cell-Purkinje cell circuit. In the hotfoot mutant or GluRδ2 knockout mice, the absence of GluRδ2 expression results in impaired motor-related tasks, ataxia, and disruption of long-term depression at parallel fiber-Purkinje cell synapses. The goal of this study was to determine the long-term consequences of deletion of GluRδ2 expression in the hotfoot mutant (GluRδ2 ho/ho ) on Purkinje and granule cell survival and Purkinje cell dendritic differentiation. Quantitative estimates of Purkinje and granule cell numbers in 3-, 12-, and 20-month-old hotfoot mutants and wild-type controls showed that Purkinje cell numbers are within control values at 3 and 12 months in the hotfoot mutant but reduced by 20 % at 20 months compared with controls. In contrast, the number of granule cells is significantly reduced from 3 months onwards in GluRδ2 ho/ho mutant mice compared to wild-type controls. Although the overall structure of Purkinje cell dendrites does not appear to be altered, there is a significant 27 % reduction in the cross-sectional area of Purkinje cell dendritic trees in the 20-month-old GluRδ2 ho/ho mutants. The interpretation of the results is that the GluRδ2 receptor plays an important role in the long-term organization of the granule-Purkinje cell circuit through its involvement in the regulation of parallel fiber-Purkinje cell synaptogenesis and in the normal functioning of this critical cerebellar circuit.


Protein recovery and identification from the gulf killifish, Fundulus grandis: comparing snap-frozen and RNAlater® preserved tissues.
Reliable proteomic analysis of biological tissues requires sampling approaches that preserve proteins as close to their in vivo state as possible. In the current study, the patterns of protein abundance in one-dimensional (1-D) gels were assessed for five tissues of the gulf killifish, Fundulus grandis, following snap-freezing tissues in liquid nitrogen or immersion of fresh tissues in RNAlater(®). In liver and heart, the protein profiles in 1-D gels were better preserved by snap-freezing, while in gill, the 1-D protein profile was better preserved by immersion in RNAlater(®). In skeletal muscle and brain, the two approaches yielded similar patterns of protein abundance. LC-MS/MS analyses and database searching resulted in the identification of 17 proteins in liver and 12 proteins in gill. Identified proteins include enzymes of energy metabolism, structural proteins, and proteins serving other biological functions. These protein identifications for a species without a sequenced genome demonstrate the utility of F. grandis as a model organism for environmental proteomic studies in vertebrates.


Diabetes mellitus, hypertension and frailty: A population-based, cross-sectional study of Mexican older adults.
Chronic diseases are frequent in older adults, particularly hypertension and diabetes. The relationship between frailty and these two conditions is still unclear. The aim of the present analyses was to explore the association between frailty with diabetes and hypertension in Mexican older adults. Analyses of the Mexican Health and Nutrition Survey, a cross-sectional survey, are presented. Data on diabetes and hypertension were acquired along with associated conditions (time since diagnosis, pharmacological treatment, among others). A 36-item frailty index was constructed and rescaled to z-values (individual scores minus population mean divided by one standard deviation). Multiple linear regression models were carried out, adjusted for age and sex. From 7164 older adults, 54.8% were women, and their mean age was 70.6 years with a mean frailty index score of 0.175. The prevalence of diabetes was of 22.2%, and 37.3% for hypertension. An independent association between diabetes, hypertension or both conditions (coefficients 0.28, 0.4 and 0.63, respectively, P < 0.001) with frailty was found. Having any diabetic complication was significantly associated with frailty with a coefficient of 0.55 (95% CI 0.45-0.65, P < 0.001) in the adjusted model. The number of years since diagnosis was also associated with frailty for both conditions. Diabetes and hypertension are associated with frailty. In addition, an incremental association was found when both conditions were present or with worse associated features (any complication, more time since diagnosis). Frailty should be of particular concern in populations with a high prevalence of these conditions. Geriatr Gerontol Int 2017; 17: 925-930.


Cholesterol regulates high-density lipoprotein interaction with isolated epithelial cells of human small intestine.
The effect of cholesterol on the interaction of high-density lipoprotein (HDL) with isolated human small intestine epithelial cells (enterocytes) was studied. 125I-labeled HDL3 binding by these cells was enhanced in response to cholesterol loading of the cells in a time- and dose- dependent manner. Preincubation of the cells with cholesterol led to the enhancement both of the number of binding sites and the binding affinity. The enhancement of binding correlated with the cellular cholesterol content. Cycloheximide (0.5 mM) inhibited uptake of cholesterol by enterocytes and blocked its effect on 125I-labeled HDL3 binding. The effect of cholesterol on 125I-labeled HDL3 degradation had a double-phase character. At concentrations 10-20 micrograms/ml, the degradation rate was rapidly elevated, but further increase in cholesterol concentration led to a fall in the degradation rate. Incubation of enterocytes with HDL3 resulted in the efflux of cholesterol from cells and its incorporation into HDL3. The results obtained make it possible to assume that binding and degradation of 125I-labeled HDL3 by human enterocytes are independently regulated by the cell total cholesterol content. Binding of HDL by enterocytes may result both in the degradation of HDL and cholesterol efflux from cells.


Protective effect of obesity on survival in cancers treated with immunotherapy vanishes when controlling for type of cancer, weight loss and reduced skeletal muscle.
Association of high body mass index (BMI) with longer survival has been reported in patients on immune checkpoint inhibitors (ICIs), but results are inconsistent. This 'obesity paradox' is potentially confounded by the effects of BMI change over time and of skeletal muscle depletion. We conducted a secondary analysis of a prospective cohort, including consecutive patients receiving ICI treatment for melanoma (n = 411) and non-small cell lung cancer (NSCLC) (n = 389) in routine care. In the univariable analysis of the entire population, overweight/obesity (BMI ≥ 25 kg/m2) was associated with longer survival (p < 0.01); however, this effect was limited to NSCLC (p < 0.01) and was absent in melanoma. Weight loss (WL) and reduced skeletal muscle mass were observed in patients within all BMI categories. WL was associated with shorter survival in multivariable analysis in both tumour sites (p < 0.01), and for NSCLC, BMI lost significance when WL was included (p = 0.13). In models further adjusted for CT-defined skeletal muscle mass, WL retained significance for both tumour types (p < 0.01), and reduced skeletal muscle only for NSCLC (p = 0.02) was associated with shorter survival. WL retained significance when biomarkers (lactate dehydrogenase enzyme, albumin and derived neutrophil to lymphocyte ratio) were added to the multivariable model. The so-called 'obesity paradox', counterintuitive association between high BMI and longer survival, vanished when controlling for confounders, such as type of cancer, and manifestations of depletion (WL and reduced skeletal muscle mass).


Improved sensitivity of MRI in multiple sclerosis by use of extensive standardized procedures.
The relative value of two different MRI procedures for the assessment of infratentorial extension in multiple sclerosis (MS) was studied. Multislice spin-echo techniques were used overall. Procedure A consisted of parasagittal T1-weighted images (500/30) and axial T2-weighted images (2500/30, 2500/120). Procedure B consisted of parasagittal T2-weighted images (1600/35, 1600/90). In the parasagittal T2-weighted images clear visualization of MS lesions is achieved because signal intensities of CSF and normal nervous tissue are nearly identical. All images were performed with a 0.5 Tesla MR system. Data were obtained in 98 patients with definite (N = 30) or probable MS (N = 68). Areas with abnormal signal intensity in the infratentorial regions (brainstem, cerebellum, and/or cervical spinal cord) were identified in 44% of the patients with procedure A and in 64% with procedure B. The standard application of the combination of both procedures improves the sensitivity of the MR examination for the diagnosis of MS, the delineation of infratentorial lesions and the correlation between clinical and MR data without excessively increasing imaging time.


County-Level Variation in Utilization of Surgical Resection for Early-Stage Hepatopancreatic Cancer Among Medicare Beneficiaries in the USA.
Geographic variations in access to care exist in the USA. We sought to characterize county-level disparities relative to access to surgery among patients with early-stage hepatopancreatic (HP) cancer. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database from 2004 to 2015 to identify patients undergoing surgery for early-stage HP cancer . County-level information was acquired from the Area Health Resources Files (AHRF). Multivariable logistic regression analysis was performed to assess factors associated with utilization of HP surgery on the county level. Among 13,639 patients who met inclusion criteria, 66.9% (n = 9125) were diagnosed with pancreatic cancer and 33.1% (n = 4514) of patients had liver cancer. Among patients diagnosed with early-stage liver and pancreas malignancy, two-thirds (n = 8878, 65%) underwent surgery. Marked county-level variation in the utilization of surgery was noted among patients with early-stage HP cancer ranging from 57.1% to more than 83.3% depending on which county a patient resided. After controlling for patient and tumor-related characteristics, counties with the highest quartile of patients living below the poverty level had 35% lower odds of receiving surgery for early stage HP cancer compared patients who lived in a county with the lowest proportion of patients below the poverty line (OR 0.65, 95% CI 0.55-0.77). In addition, patients residing in counties with the highest surgeon-to-population ratio (OR 2.01, 95% CI 1.52-2.65), as well as the highest hospital bed-to-population ratio (OR 1.29, 95% CI 1.07-1.54), were more likely to undergo surgical treatment for an early-stage HP malignancy. Area-level variations among patients undergoing surgery for early-stage HP cancer were mainly due to differences in structural measures and county-level factors. Policies targeting high-poverty counties and improvement in structural measures may reduce variations in utilization of surgery among patients diagnosed with early-stage HP cancer.


Unexpected newcastle disease virus in day old commercial chicks and breeder hen.
Newcastle disease virus (NDV) specific antigen in the gut contents and NDV specific antibody in blood circulation were seen in day old chicks belonging to nine different commercial hatcheries of Tamil Nadu, India. Antigen disappeared by 4th week and antibody by 6th week of age. Fourteen NDV isolates obtained from the gut contents of day old chicks of different commercial hatcheries, one NDV isolate from dead in shell eggs and one NDV isolate from breeder hen were characterized and grouped under velogenic, mesogenic and lentogenic pathotypes. Four isolates were grouped under F and another four isolates were grouped under E based on reaction with monoclonal antibodies (Mabs) but found to be velogenic based on pathogenicity tests. In one particular flock velogenie NDV was isolated from breeder hen, dead in shell embryos and day old chicks and they all belong to Mabs group E. Vertical transmission of velogenic, mesogenic and lentogenic NDVs and role of NDVs in the gut contents have been discussed.


Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk.
This study assessed the choline status in newborns, infants, children, breast-feeding women, breast milk, infant formula, breast-fed and formula-fed infants. The serum free choline level was 35.1+/-1.1 micromol/L at birth and decreased to 24.2+/-1.6, 18.1+/-0.8, 16.3+/-0.9, 14.3+/-0.8, 12.9+/-0.6 or 10.9+/-0.6 micromol/L at 22-28, 151-180, 331-365, 571-730, 731-1095 or 4016-4380 days after birth, respectively. The serum phospholipid-bound choline level was 1997+/-75 micromol/L at birth and increased gradually to 2315+/-190 or 2572 +/-100 micromol/L at 571-730 or 4016-4380 days after birth, respectively. In breast-feeding women, serum free and phospholipid-bound choline levels were doubled at 12-28 days after birth, they decreased toward the control values with time. Free choline, phosphocholine and glycerophosphocholine were major choline compounds in breast milk. Their concentrations in mature milk were much greater than in colostrum and serum. Choline contents of breast milk varied greatly between mothers, and milk free choline levels were correlated with serum free choline (r=.541; P<.001), phospholipid-bound choline (r=.527; P<.001) and glycerophosphocholine (r=.299; P<.01) concentrations and lactating days (r=.520; P<.001). In breast-fed infants, serum free choline concentrations were correlated with free choline (r=.47; P<.001), phosphocholine (r=.345; P<.002), glycerophosphocholine (r=.311; P<.01) and total choline (r=.306; P<.01) contents of breast milk. Serum free choline concentration in formula-fed infants was lower than breast-fed infants. These data show that (a) circulating choline status is elevated during infancy and lactation, (b) choline contents of breast milk vary between mothers and milk free choline contents are influenced by maternal circulating choline status, and (c) the choline contents of breast milk can influence infants' circulating choline status.


Serial isometric contractions under imposed myotatic stretch conditions in high-strength and low-strength men.
The immediate effects of an imposed myotatic stretch on knee extensor force were studied in 12 high-strength and 12 low-strength men. Under nonfatigued pre-exercise conditions, significant tension increases of 6.5% for the high-strength group and 11.0% for low-strength subjects were observed as a result of the imposed stretch. An exercise treatment involving 28 serial isometic contractions, each of 5 s duration, with an intertrial rest period of 10 s was administered. This fatiguing exercise resulted in significant decrements in strength on the order of 28.0% and 18.5% for the high-strength and low-strength groups, respectively. A Similar treatment which included a 1 s imposed myotatic stretch during each trial resulted in a greater strength decrement for the low-strength group (26.4%) than for the high-strength subjects (15.0%). A neural factor involving the stretch reflex is tentatively suggested as a plausible explanation accounting for the observation that high-strength subjects fatigue faster than low-strength subjects under conditions of isometric exercise, while low-strength subjects fatigue faster than high-strength individuals in isometric exercise which is performed with an imposed stretch.


Feasibility and acceptability of inserts promoting virtual overdose monitoring services (VOMS) in naloxone kits: a qualitative study.
In response to the ongoing opioid epidemic, there have been efforts to develop novel harm reduction strategies alongside scaling of currently implemented programs. Virtual overdose monitoring services (VOMS) are a novel intervention which aims to reduce substance-related mortality through technology for those who are out of reach of current supervised consumption sites. Scaling of naloxone programs presents a unique opportunity to promote VOMS to people at risk of substance-related mortality. This study aims to explore the feasibility and acceptability of naloxone kit inserts in promoting awareness of VOMS. We used purposive and snowball sampling to recruit 52 key informants, including people who use drugs (PWUD) with experience using VOMS (n = 16), PWUD with no prior experience using VOMS (n = 9), family members of PWUD (n = 5), healthcare and emergency services professionals (n = 10), community-based harm reduction organizations (n = 6), and VOMS administrators/peer support workers (n = 6). Two evaluators completed semi-structured interviews. Interview transcripts were analyzed using thematic analysis informed to identify key themes. Four key interrelated themes emerged, including the acceptability of naloxone kit inserts to promote VOMS, best practices for implementation, key messaging to include within promotional materials and facilitators to dissemination of harm reduction material. Participants highlighted that messaging should be promoted both inside and outside the kits, should be concise, provide basic information about VOMS and can be facilitated through current distribution streams. Messaging could further be used to draw attention to local harm reduction services and could be promoted on other supplies, including lighters and safer consumption supplies. Findings demonstrate that it is acceptable to promote VOMS within naloxone kits and highlight interviewees preferred ways to do so. Key themes that emerged from interviewees can be used to inform the dissemination of harm reduction information, including VOMS and bolster current strategies for reducing illicit drug overdose.


Segregation of cerebrorubral and cerebellorubral synaptic inputs on rubrospinal neurons of fetal cats as demonstrated by intracellular recording.
Cerebrorubral and cerebellorubral inputs are localized to distal dendrites and somata of red nucleus neurons in adult cats, respectively. To examine if this segregation is established early in development, we performed intracellular recording from rubrospinal neurons of fetal cats aged from embryonic day 58 to 65. Stimulation of the contralateral cerebellar nuclei evoked excitatory postsynaptic potentials (EPSPs). EPSPs were also induced by stimulation of the ipsilateral pericruciate cortext but they were much slower in time course and smaller in amplitude compared to cerebellar ones. We suggest that cerebrorubral and cerebellorubral synapses are segregated on soma-dendritic membrane of rubrospinal neurons early in development.


Arrhythmias after repair of secundum atrial septal defect: the influence of surgical modification.
A retrospective study performed in our institution showed a significant correlation between venous cannulation and the incidence of arrhythmias after atrial septal defect (ASD) repair. We now report the results of a prospective study in 50 children operated on for ASD with selective cannulation of the superior vena cava. ECGs and Holter recordings were made before and after surgery, with a mean follow-up of 2.6 years. We found a significant decrease in postoperative arrhythmias (p less than 0.05) after changing the cannulation technique. Severe arrhythmias, present in 10% of the children in the retrospective group, were not found in the prospective study. Six children had asymptomatic arrhythmias on the Holter recording 1 year after surgery. Three of them, however, already had arrhythmias before the operation. We conclude that the incidence and severity of arrhythmias after ASD repair can be reduced significantly by surgical modifications, at least for the follow-up period of this study. The long-term significance has to be awaited.


A xeroderma pigmentosum complementation group A related gene: confirmation using monoclonal antibodies against the cyclobutane dimer and (6-4) photoproduct.
Xeroderma pigmentosum complementation group A was partially complemented by a cosmid genomic clone containing a 42-kb human DNA insert selected with a cDNA clone that we obtained through cDNA competition between the repair-proficient and repair-deficient cell line. The relationship between these two clones was confirmed using PCR amplifications. The enhancement in DNA-repair capacity of the transformants was assessed with the monoclonal antibodies specific for cyclobutane dimers and (6-4) photoproducts and partially correct the xeroderma pigmentosum complementation group A defect. Furthermore, the level of the photoproduct-repair capacity is in agreement with the survival enhancement calculated from the D37 values. This gene was mapped to chromosome 8, suggesting that this may represent one of the defective gene(s) in xeroderma pigmentosum complementation group A.


SAT: a late NS protein of porcine parvovirus.
The genomes of all members of the Parvovirus genus were found to contain a small open reading frame (ORF), designated SAT, with a start codon four or seven nucleotides downstream of the VP2 initiation codon. Green fluorescent protein or FLAG fusion constructs of SAT demonstrated that these ORFs were expressed. Although the SAT proteins of the different parvoviruses are not particularly conserved, they were all predicted to contain a membrane-spanning helix, and mutations in this hydrophobic stretch affected the localization of the SAT protein. SAT colocalized with calreticulin in the membranes of the endoplasmic reticulum and the nucleus. A knockout mutant (SAT(-)), with an unmodified VP sequence, showed a "slow-spreading" phenotype. These knockout mutants could be complemented with VP2(-) SAT(+) mutant. The SAT protein is a late nonstructural (NS) protein, in contrast to previously identified NS proteins, since it is expressed from the same mRNA as VP2.


Tyrosine phosphorylation in the postnatal rat brain: a developmental, immunohistochemical study.
We have used antibodies against phosphotyrosine to probe 50-microns cerebellar sections from rats of various ages as well as sections of adult brainstem, cerebrum, and olfactory bulb to investigate the developmental appearance of this phosphorylation system as revealed by light microscopy. While the overall intensity of staining in the cerebellum was highest at 7 days, the pattern of staining in the adult is quite disparate from that seen in younger animals. From 10 to 21 days postnatal, staining is associated primarily with the white matter and/or the lower premigratory zone of the external granular layer and adjacent formative molecular layer. While the temporal and spatial appearance of phosphotyrosine immunoreactivity corresponds well to the established patterns of axonal growth in these areas, we cannot at the light level ascertain whether the immunoreactivity is intrinsic or extrinsic to the growing fibers. In animals 28 days and older, however, staining is restricted to a subpopulation of multipolar cells distributed throughout the cerebellum, as well as the olfactory bulb, cerebrum, and brainstem. The phosphotyrosine-positive cells in the adult cerebellum are not comparable to glial-fibrillary-acidic-protein-immunoreactive elements with regard to morphology or distribution, and they fail to colocalize with neuronal somata stained with anti-microtubule-protein-2 antibodies. While it appears that the radial fibers of the Bergmann glia in the external granular layer stain at 7 days, there is no staining detected in the mitotically active neuroblasts of this layer at any age. We conclude that in the immature cerebellum, the majority of tyrosine phosphorylation detectable by this method may be involved in the formation and growth of axonal processes.(ABSTRACT TRUNCATED AT 250 WORDS)


The quaternary structure of the plasma membrane b-type cytochrome of human granulocytes.
Hydrodynamic, crosslinking and immunoprecipitation studies were performed on detergent solubilized cytochrome b to demonstrate that the two copurifying polypeptides of molecular weight 91,000 (glycosylated) and 22,000 [1,2] formed a molecular complex. The hydrodynamic studies indicated that the cytochrome b/detergent complex had a sedimentation coefficient, partial specific volume and Stokes radius of 5.25 S, 0.82 cm3/g and 6.2 nm in Triton X-100 and 6.05 S, 0.80 cm3/g and 5.6 nm in octylglucoside, respectively. These studies also indicated that the detergent-protein complex has a molecular mass of 202 and 188 kDa in Triton X-100 and octylglucoside, respectively, is asymmetric in shape with a frictional coefficient of 1.3-1.4 and binds significant amounts of detergent. The molecular mass of the protein portion of the detergent-cytochrome complex was estimated to be between 100 and 127 kDa. Crosslinking studies with disuccinimidyl suberate and alkaline cleavable bis[2-(succinimidooxy-carbonyloxy)ethyl]sulfone revealed that the Mr = 91,000 and Mr = 22,000 components of purified cytochrome b are closely associated and can be covalently bound to form a polypeptide which, by SDS-polyacrylamide gel electrophoresis, has Mr values of 110,000-120,000 and 120,000-135,000 on 8% and 11% (w/v) SDS-polyacrylamide gels, respectively. Cleavage of the crosslinked species resulted in the reappearance of the Mr = 91,000 and Mr = 22,000 species. Sedimentation profiles of crosslinked cytochrome b in linear sucrose density gradients made up in H2O were identical to those of non-crosslinked controls. A close association of the two protein species was further confirmed by the ability of antibody specific for the smaller subunit to immunoprecipitate the larger one also. Experiments aimed at identifying the heme-carrying subunit(s) were inconclusive, since dissociation of the complex resulted in loss of cytochrome b spectrum. These results, in combination with our SDS-polyacrylamide gel electrophoresis molecular-weight estimates, provide strong evidence for the cytochrome b being an alpha-beta-type heterodimer composed of a glycosylated Mr = 91,000 and non-glycosylated Mr = 22,000 polypeptide.


Prediction of pork color attributes using computer vision system.
Color image processing and regression methods were utilized to evaluate color score of pork center cut loin samples. One hundred loin samples of subjective color scores 1 to 5 (NPB, 2011; n=20 for each color score) were selected to determine correlation values between Minolta colorimeter measurements and image processing features. Eighteen image color features were extracted from three different RGB (red, green, blue) model, HSI (hue, saturation, intensity) and L*a*b* color spaces. When comparing Minolta colorimeter values with those obtained from image processing, correlations were significant (P<0.0001) for L* (0.91), a* (0.80), and b* (0.66). Two comparable regression models (linear and stepwise) were used to evaluate prediction results of pork color attributes. The proposed linear regression model had a coefficient of determination (R(2)) of 0.83 compared to the stepwise regression results (R(2)=0.70). These results indicate that computer vision methods have potential to be used as a tool in predicting pork color attributes.


Evaluation of some mechanical properties of a new silicone elastomer for maxillofacial prostheses after addition of intrinsic pigments.
The approximate life span of a silicone maxillofacial prosthesis is as short as 1.5-2 years of clinical service, then a new prosthesis should be fabricated. The most common reason for re-making the prosthesis is silicone mechanical properties degradation. The aim of this study was to assess some mechanical properties of VST-30 silicone for maxillofacial prostheses after addition of intrinsic pigments. Two types of intrinsic pigments (rayon flocking and burnt sienna); each of them was incorporated into silicone. One hundred and twenty samples were prepared and split into 4 groups according to the conducted tests (tear strength, hardness, surface roughness, and tensile strength and elongation percentage) with 30 samples for each test. Each group was equally split into three subgroups. Group (A) was without pigment (control group), group (B) was with rayon flocking and group (C) was with burnt sienna. Samples with rayon flocking showed a highly significant decrease in hardness and there was a significant increase in tear strength, while there were non-significant differences in surface roughness, tensile strength and elongation percentage. Samples with burnt sienna showed a highly significant increase in tear strength and a highly significant decrease in hardness, but surface roughness, tensile strength and elongation percentage showed non-significant differences. However, there were non-significant differences between experimental groups in all tests. The addition of each of rayon flocking and burnt sienna changed the mechanical properties of the VST-30 silicone, while no superior pigment-silicone combination was revealed in all the conducted tests.


Aurophilic Molecules on Surfaces. Part I. (NapNC)AuCl on Au(110).
Aurophilicity is a well-known phenomenon in structural gold chemistry and is found in many crystals of Au(I) complexes. However, these attractive dispersion forces between and within complexes containing Au(I) moieties have not been well studied in ultrathin films. In this paper, we elucidate the interaction of chlorido(2-naphthyl isonitrile)gold(I) on and with Au(110) surfaces. Already during physical vapor deposition, the condensation of ultrathin films is monitored by photoelectron emission microscopy (PEEM) and by incremental and spectrally resolved changes in the optical reflectance (DDRS). Additional structural data obtained by STM and LEED reveal that the "crossed swords" packing motif known from the bulk is also present in thin films. The molecular arrangement changes several times during thin-film deposition.


Identification of the major proteoglycans from human myometrium.
During pregnancy and parturition a remodeling within the extracellular matrix of the cervix and the corpus uteri occurs, which is of fundamental importance to a normal labor. The aim of this study is to identify the major proteoglycans in corpus uteri of non-pregnant subjects. From human uterine tissue proteoglycans were extracted and purified using CsCl-density gradient centrifugation, gel and ion-exchange chromatography. The proteoglycans were quantified and identified by Alcian Blue before and after ABC-digestion and by Western blotting. The results showed that the corpus uteri contains a substantial amount of proteoglycans, 1.825 microg/mg wet weight. Decorin is dominating, constituting 63% of the total amount of proteoglycans. Heparan sulphate proteoglycans accounted for 20% and biglycan for 16%. Less than 1% consisted of the large proteoglycan versican. Further investigations must be performed to provide more information of the biological role of the proteoglycans in the uterus, especially during labor, by the presence of heparan sulphate proteoglycans and the minute presence of versican which indicate that the proteoglycan composition and organization is different to that of the cervix.


Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States.
Juvenile systemic sclerosis is a very rare orphan disease. To date, only one publication has estimated the prevalence of juvenile systemic sclerosis using a survey of specialized physicians. We conducted a study of administrative claims data in the United States using the International Classification of Diseases, Ninth Revision diagnosis codes and found a prevalence of approximately 3 per 1,000,000 children. This estimate will inform the planning of prospective studies.


Influence of stem geometry on mechanics of cemented femoral hip components with a proximal bond.
Nonlinear, three-dimensional, finite element models of cemented femoral hip components with a proximal stem-cement bond were developed with use of a Charnley stem geometry and a modified Charnley stem geometry that had a cylindrical cross section over the distal two-thirds of the stem (Distal-Round). Peak tensile stresses in the proximal cement mantle increased 63 and 74% for the Charnley and Distal-Round stems, respectively, when the proximal stem-cement interface was debonded. The shear stresses over the stem-cement interface with a proximal bond were 29% larger for the Distal-Round stem than for the Charnley stem. After the proximal stem-cement interface was debonded, the peak tensile stresses in the cement mantle were 15% larger for the Distal-Round stem than for the Charnley stem. The results illustrate that stresses within the proximal cement mantle could be substantially reduced for both Charnley and Distal-Round stems through use of a proximal stem-cement bond. However, the risk of debonding may be higher for the Distal-Round stem because of increased shear stresses, and once debonded the risk of further loosening due to failure of the cement mantle would also be higher for the Distal-Round stem.


Interventions in the commercial sex industry during the rise in syphilis rates among men who have sex with men (MSM).
Describe sexually transmitted disease/human immunodeficiency virus prevention interventions targeting men who have sex with men (MSM) in commercial sex venues (CSV). Compilation of descriptive and evaluation data from the CDC 8-city MSM Syphilis Response on interventions conducted in bathhouses/sex clubs, circuit parties, the Internet, male sex workers, and the adult film industry. Interventions in the commercial sex industry (CSI) often involved multiple collaborative efforts between public health departments (PHD), community-based organizations (CBO), and CSV owners and managers. Education and condoms were provided at multiple venues, including circuit parties, bathhouses, and sex clubs. CBO staff reported one-on-one street and CSV outreach to engage MSM at risk. Evaluation data demonstrate that MSM exposed to media campaigns were more aware of syphilis and more likely to have been tested for syphilis than MSM who did not see the campaigns. PHD and CBO are using multiple means of reaching MSM in the CSI. Evaluations are needed to determine which of these efforts decreases syphilis transmission.


Evaluation of the In Vivo Anti-Atherosclerotic Activity of Quercetin Isolated from the Hairy Roots of Hedysarum neglectum Ledeb.
This study aimed to investigate the anti-atherosclerotic properties of quercetin isolated from the extract of Hedysarum neglectum Ledeb hairy roots. During the study, the hormonal composition of the nutrient medium for cultivation of H. neglectum hairy root biomass was selected: Gamborg's medium enriched with the cytokine 6-benzylaminopurine (1.5 mg/1 dm3). It was found that the extraction of hairy root biomass with a 50% water-ethanol solution (40:1 1 h at 60 ± 2 °C) yielded an extract that contained the highest amount of quercetin (an average of 2.1 times higher than in extracts obtained at other parameters). It was determined that 100 µM quercetin solution showed the greatest bioactivity on Caenorhabditis elegans: on day 61, the percentage of surviving nematodes was 2.06 times higher compared to other samples and 6 times higher compared to control, resulting in a 12.5-fold increase in SOD-3 expression compared to control (without biologically active substance (BAS) addition). Meanwhile, the 10 µM quercetin solution exhibited the best ability to inhibit the accumulation of lipid fractions; the accumulation was 1.06 times less compared to the control. The results of this study show that quercetin, which was isolated from the biomass of H. neglectum hairy roots, can be used as a component of anti-atherosclerotic dietary supplements.


Correlation of intraabdominal fat accumulation and left ventricular performance in obesity.
The correlation of intraabdominal visceral fat accumulation and left ventricular performance was investigated in 37 obese patients who had 154 +/- 23% of ideal body weight. The left ventricle was studied noninvasively by means of echocardiography, whereas the distribution of body fat was determined by computed tomography. The end-diastolic left ventricular dimension and stroke volume were greater in obese patients than in non-obese control subjects. Not only the absolute values of these parameters, but also the diastolic left ventricular dimension index (calculated as end-diastolic dimension/cube root of body surface area) and stroke index were greater in obese patients. When the obese patients were divided into 2 groups according to the intraabdominal visceral fat area to subcutaneous fat area ratio (V/S) determined by computed tomography, the diastolic dimension index and the stroke index were significantly greater in visceral-type obesity (V/S greater than or equal to 0.4) than in subcutaneous-type obesity (V/S less than 0.4) (43.2 +/- 2.9 vs 40.3 +/- 3.1 mm/m2/3, p less than 0.01 and 49.3 +/- 6.1 vs 40.3 +/- 5.6 ml/m2, respectively). Multiple regression analysis with independent variables of age, body weight, duration of obesity and V/S ratio showed that diastolic dimension index and stroke index significantly correlated with the V/S ratio. Thus, the alteration of cardiac function in obese patients is attributable not only to excess body weight and duration of obesity but also to intraabdominal fat accumulation.


Massive bronchogenic cyst mimicking ischaemic chest pain.
The presentation of the bronchogenic cyst is variable making preoperative diagnosis difficult. The majority are either asymptomatic or discovered incidentally. The most common presenting symptoms are cough, fever and dyspnoea. We discuss the case of a large bronchogenic cyst in the posterior mediastinum mimicking ischaemic cardiac pain in a patient with known heart disease. This case demonstrates the need for detailed investigations prior to the treatment of an assumed acute coronary syndrome as a bronchogenic cyst may be the rare cause of such symptoms.


Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study.
As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.


Multifunctional composite nanoparticles based on hyaluronic acid-paclitaxel conjugates for enhanced cancer therapy.
The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase. mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro. More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo, with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.


Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria.
Malaria has provided a major selective pressure and has modulated the genetic diversity of the human genome. The variants of the Duffy Antigen/Receptor for Chemokines (DARC) gene have probably been selected by malaria parasites, particularly the FY*O allele, which is fixed in sub-Saharan Africa and confers resistance to Plasmodium vivax infection. Here, we showed the influence of genomic ancestry on the distribution of DARC genotypes in a highly admixed Brazilian population and confirmed the decreased susceptibility of the FY*A/FY*O genotype to clinical P. vivax malaria. FY*B/FY*O individuals were associated with a greater risk of developing clinical malaria. A remarkable difference among DARC variants concerning the susceptibility to clinical malaria was more evident for individuals who were less exposed to malaria, as measured by the time of residence in the endemic area. Additionally, we found that DARC-negative and FY*A/FY*O individuals had a greater chance of acquiring high levels of antibodies against the 19-kDa C-terminal region of the P. vivax merozoite surface protein-1. Altogether, our results provide evidence that DARC polymorphisms modulate the susceptibility to clinical P. vivax malaria and influence the naturally-acquired humoral immune response to malaria blood antigens, which may interfere with the efficacy of a future vaccine against malaria.


Maternal and congenital syphilis in Indigenous Peoples: a scoping review of the worldwide literature.
Syphilis is among the most common sexually transmitted infections worldwide. When it occurs during pregnancy, it can seriously affect the fetus and newborn`s health. The scarcity of studies on maternal and congenital syphilis in Indigenous Peoples remains an obstacle to its control in these populations. This study aimed to explore the breadth of the literature, map updated evidence, and identify knowledge gaps on maternal and congenital syphilis in Indigenous Peoples worldwide. We conducted a Scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews. In March 2021, we collected data through a priority search on PubMed, Web of Science, Embase, and SciELO. The strategy yielded 24 studies for analysis. Data in the articles were collected from 1989 to 2020, half from 2015 onwards. Studies were in Oceania and the Americas, mainly in South America (66.7%), particularly in Brazil (50.0%). The topics assessed were Data quality related to maternal and congenital syphilis (20.8%); Diagnosis, provision, access, and use of health services (62.5%); Disease frequency and health inequities (54.2%); Determinants of maternal syphilis and congenital syphilis (20.8%); and Outcomes of maternal and congenital syphilis in the fetus (20.8%). The results show that the available literature on maternal and congenital syphilis is sparse and concentrated in some geographic areas; the frequency of these diseases in Indigenous Peoples varies but is generally higher than in the non-indigenous counterparts; the quality of surveillance data and health information systems is poor; multiple healthcare barriers exist; and the diversity of terms to identify Indigenous Peoples is a challenge to mapping scientific outputs on Indigenous Peoples' health. Maternal and congenital syphilis in Indigenous Peoples is a double-neglected condition and research in this area should be given the priority and encouragement it deserves globally. Reliable data and improving access to health care are needed to reduce the burden of syphilis and correctly inform policies and health services response to mitigate ethnic-racial inequalities in maternal and congenital syphilis.


Characterization, in vitro digestibility, antioxidant activity and intestinal peristalsis in zebrafish of Dioscorea opposita polysaccharides.
The soluble crude polysaccharides from Dioscorea opposita (DOP1 and DOP2) were prepared and characterized. DOP1 and DOP2 obtained carbohydrate (65.71% and 70.18%, respectively), uronic acid (63.71% and 24.84%, respectively) and protein (8.09% and 9.51%, respectively) with molecular weight of 49.24 kDa and 21.62 kDa, respectively. DOP samples were mainly composed of mannose, glucose, galacturonic acid, galactose, and glucuronic acid. The digestibility in vitro, antioxidant activity and intestinal peristalsis effect were then investigated. DOP1 and DOP2 were degraded with decreased molecular weights (39.58 kDa and 18.56 kDa respectively), increased reducing sugar contents (from 16.95% to 19.27%; 12.45% to 15.50% respectively) and free monosaccharides (from 0.89% to 1.42%; 0.90% to 1.14% respectively) after gastric digestion. Both DOP1 and DOP2 were resistant to intestinal digestion, suggesting that DOP samples can be considered as a dietary fiber. Additionally, DOP1 and DOP2 exhibited antioxidant activities positively correlated with the concentration and remained the activities after gastrointestinal digestion in vitro. Furthermore, DOP reduced the fluorescence intensity significantly, indicating DOP can promote the intestinal peristalsis of zebrafish larvae (5 pdf) at 500 μg/mL. Therefore, DOP1 and DOP2 have a better functionality as dietary fibers, including antioxidant activity and intestinal peristalsis promotion, which can be developed as functional foods.


Distributed Gaussian Valence Bond Surface Derived from Ab Initio Calculations.
The experimental and computational results for the tautomerization reaction of 2-pyridone are reviewed. G3, G4, CBS-APNO, and W1 model chemistries are used to generate state-of-the-art reaction energetics for the tautomerization reaction with and without catalytic water molecules in both the gas and aqueous phases. Reactive, electronic potential energy surface surfaces for use in molecular dynamics simulations were generated for these reactions following a recently improved empirical valence bond formulation. The form of molecular mechanics potentials needed for a satisfactory fit is also discussed.


A 'weekend effect' in operative emergency general surgery.
Evidence of a "weekend effect" is limited in emergency general surgery (EGS). We hypothesized that there are increased rates of complications, death, and failure-to-rescue (FTR) in patients undergoing weekend EGS operations. National Inpatient Sample (NIS) data, January 2014-September 2015 were used. Operative EGS patients were identified by ICD-9 procedure code and timing to operation. Complications were defined by ICD-9 code. We performed survey-weighted multivariable regression analyses. Of 438,110 EGS patients, 103,450 underwent weekend operation. There was no association between weekend operation and FTR (OR 1.17; 95%CI 0.95-1.45) or complications (OR 1.04; 95%CI 0.97-1.13). There was a weekend effect on mortality (OR 1.22; 95%CI 1.02-1.46) and an interactive effect between weekend operation and teaching status on complications (teaching OR 1.22; 95%CI 1.15-1.29; interaction OR 1.13; 95%CI 1.03-1.25). There is evidence for a "weekend effect" on mortality, but not complications or FTR, in this cohort.


Amino acid sequence of human myelin basic protein peptide 45-89 as determined by mass spectrometry.
In order to resolve the uncertainties about the primary structure of human myelin basic protein at residues 45-89, the sequence of this peptide and its tryptic fragments were reinvestigated by fast atom bombardment mass spectrometry. The sequence at positions 77-78 was found to be His-Gly and the sequence at positions 83-84 was shown to be Glu-Asn. The Ser at position 56 was not phosphorylated, whereas the residue at position 46 or 47 showed a heterogeneity of Gly and Ser in this peptide fragment in one of two protein preparations from different patients. These results demonstrate the usefulness of fast atom bombardment mass spectrometry for primary structure information. The corrected sequence of human basic protein peptide 45-89 will permit a more detailed immunochemical analysis of this peptide and its in vivo degradation products.