Health belief model factors in mammography screening: testing for interactions among subpopulations of Caribbean women.
To explore the implementation of health belief models in breast cancer screening and elucidate its potential to offer avenues for intervention among variables that may be easily amenable to change. The relations between three major cognitive factors-cancer knowledge, perceived personal risk, and beliefs about treatment efficacy-and mammography utilization were examined by using analysis of variance (ANOVA) and regression analyses. A large sample of women (N=1364) between 50 and 70 years of age. The women were of six ethnicities: US-born European Americans, US-born African Americans, Dominicans, Haitians, English-speaking Caribbeans, and Eastern Europeans. All three variables were significantly associated with screening behavior in zero-order correlations. However, only perceived risk and treatment efficacy remained significant in multiple regressions controlling for background variables. Perhaps most importantly, while there were mean-level differences in the cognitive variables across the six groups, only one of the 15 interaction terms was significant, attesting to the generalizable effect of these health belief variables upon screening behavior in understudied groups of minority women. The results are discussed in the context of health belief models and implications for interventions tailored to the health belief profiles characterizing women from each group are presented.


A comparison between bilateral and unilateral thyroid eye disease.
To compare characteristics of unilateral vs. bilateral thyroid eye disease (TED). This retrospective analytical cross-sectional study was conducted on patients with TED who were evaluated at an academic referral center over a 6-year period. We compared demographics, activity (clinical activity score) and severity (EUGOGO classification) of TED, thyroid disease duration, TED duration, the time interval between thyroid and eye involvement, thyroid function status, and clinical signs between bilateral and unilateral TED. Three hundred eighty-three patients including 213 females (55.6%), who had a mean age of 40.23 ± 13.72 years, were enrolled. Active TED was seen in 8.8% of bilateral and none of unilateral cases (P = 0.04). Bilateral TED patients had more severe disease (P = 0.001). The distribution of hyperthyroidism, hypothyroidism, and euthyroidism was significantly different between unilateral and bilateral groups (P = 0.001). Abnormal ocular motility was present in 26.3% versus 2.3% of bilateral and unilateral ones, respectively (P = 0.001). Proptosis was more prevalent in bilateral than unilateral cases (P = 0.001). We did not observe any statistically significant difference between the two groups in others variables. Bilateral TED patients present with more severity, activity, movement abnormality, proptosis, and hyperthyroidism.


Using self-management procedures to improve the productivity of adults with developmental disabilities in a competitive employment setting.
This study describes the use of self-management procedures, similar to those proposed by Lagomarcino, Hughes, and Rusch (1989), to improve the productivity of 2 women with mild mental retardation who worked in restaurants. Substantial improvements were observed as a function of treatment, and the procedures were deemed acceptable by the participants, their coworkers, and their supervisors.


Correction to: Switching from natalizumab to fingolimod treatment in multiple sclerosis: real life data from the Austrian MS Treatment Registry.
The original version of this article unfortunately contained a mistake. First and last names of the authors were interchanged. The correct author names are given below.


Compromised hippocampus-striatum pathway as a potential imaging biomarker of mild-traumatic brain injury and posttraumatic stress disorder.
Military service members risk acquiring posttraumatic stress disorder (PTSD) and mild-traumatic brain injury (mTBI), with high comorbidity. Owing to overlapping symptomatology in chronic mTBI or postconcussion syndrome (PCS) and PTSD, it is difficult to assess the etiology of a patient's condition without objective measures. Using resting-state functional MRI in a novel framework, we tested the hypothesis that their neural signatures are characterized by functionally hyperconnected brain regions which are less variable over time. Additionally, we predicted that such connectivities possessed the highest ability in predicting the diagnostic membership of a novel subject (top-predictors) in addition to being statistically significant. U.S. Army Soldiers (N = 87) with PTSD and comorbid PCS + PTSD were recruited along with combat controls. Static and dynamic functional connectivities were evaluated. Group differences were obtained in accordance with our hypothesis. Machine learning classification (MLC) was employed to determine top predictors. From whole-brain connectivity, we identified the hippocampus-striatum connectivity to be significantly altered in accordance with our hypothesis. Diffusion tractography revealed compromised white-matter integrity between aforementioned regions only in the PCS + PTSD group, suggesting a structural etiology for the PCS + PTSD group rather than being an extreme subset of PTSD. Employing MLC, connectivities provided worst-case accuracy of 84% (9% more than psychological measures). Additionally, the hippocampus-striatum connectivities were found to be top predictors and thus a potential biomarker of PTSD/mTBI. PTSD/mTBI are associated with hippocampal-striatal hyperconnectivity from which it is difficult to disengage, leading to a habit-like response toward episodic traumatic memories, which fits well with behavioral manifestations of combat-related PTSD/mTBI. Hum Brain Mapp 38:2843-2864, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.


The association of vitamin D deficiency with hemogram-derived inflammatory biomarkers in children.
One of the extraosseous effects of vitamin D is that it is a potent modulator of inflammatory processes. Many studies have demonstrated the inverse association between vitamin D and inflammation. Therefore, we hypothesize that vitamin D deficiency may affect the inflammatory markers derived from hemogram parameters [neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), platelet distribution width (PDW), red blood cell distribution width (RDW)] in healthy children. We conducted a retrospective study on healthy children. From 2015 to 2020, 16,321 children with simultaneous vitamin D and hemogram measurements were identified from electronic records. Participants were divided into 2 groups according to whether they had vitamin D deficiency or not. The relationship between vitamin D status and the levels of inflammatory markers was analyzed. All inflammatory markers showed statistically significant differences between vitamin D status (p < 0.001 for all). Vitamin D levels were significantly negatively correlated with NLR (r = -0.285), PLR (r = -0.257), PDW (r = -0.181), and positively correlated with LMR (r = 0.218), and RDW (r = 0.057). In logistic regression analysis, age (OR = 1.15, 95% CI: 1.14-1.16), gender (OR = 1.66, 95% CI: 1.54-1.78), LMR (OR = 0.96, 95% CI: 0.95-0.98), PLR (OR = 1.003, 95% CI: 1.001-1.004), and RDW (OR = 1.10, 95%CI: 1.07-1.13) were found to be independent predictors for vitamin D deficiency. Statistically significant differences were detected between vitamin D status and inflammatory parameters. However, the difference between the median values of vitamin D groups was very small and the degree of correlation was very weak. Therefore, the clinical significance of the difference should be questioned.


Neuroradiological findings in a child with primary leptomeningeal melanoma.
A case of primary leptomeningeal melanoma in a child is presented. The patient was studied with multiple neuroradiological methods, however computed tomography (CT) provided the most important information. The CT findings with leptomeningeal tumor, although not completely specific, do suggest the diagnosis, thus providing important information to explain the acute onset of symptoms in a previously healthy child. This case also differs from previously reported cases in terms of the type of hydrocephalus associated with the tumor.


Adsorption of anionic and cationic dyes on ferromagnetic ordered mesoporous carbon from aqueous solution: equilibrium, thermodynamic and kinetics.
Ordered mesoporous carbon (Fe-CMK-3) with iron magnetic nanoparticles was prepared by a casting process via SBA-15 silica as template and anthracene as carbon source, was used as a magnetic adsorbent for the removal of anionic dye Orange II (O II) and cationic dye methylene blue (MB) from aqueous solution. TEM and magnetometer images showed that the iron magnetic nanoparticles were successfully embedded in the interior of the mesoporous carbon. The effect of various process parameters such as temperature (25-45°C), initial concentration (100-500 mg L(-1)) and pH (2-12) were performed. Equilibrium adsorption isotherms and kinetics were also studied. The equilibrium experimental data were analyzed by the Langmuir, Freundlich, Temkin and Redlich-Peterson model. The equilibrium data for two dyes adsorption was fitted to the Langmuir, and the maximum monolayer adsorption capacity for O II and MB dyes were 269 and 316 mg g(-1), respectively. Pseudo-first-order and pseudo-second-order kinetic and intraparticle diffusion model were used to evaluate the adsorption kinetic data. The kinetic data of two dyes could be better described by the pseudo second-order model. Thermodynamic data of the adsorption process were also obtained. It was found that the adsorption process of the two dyes were spontaneous and exothermic.


From Yeast to Humans: Leveraging New Approaches in Yeast to Accelerate Discovery of Therapeutic Targets for Synucleinopathies.
Neurodegenerative diseases (ND) represent a growing, global health crisis, one that lacks any disease-modifying therapeutic strategy. This critical need for new therapies must be met with an exhaustive approach to exploit all tools available. A yeast (Saccharomyces cerevisiae) model of α-synuclein toxicity-the protein causally linked to Parkinson's disease and other synucleinopathies-offers a powerful approach that takes advantage of the unique offerings of this system: tractable genetics, robust high-throughput screening strategies, unparalleled data repositories, powerful computational tools, and extensive evolutionary conservation of fundamental biological pathways. These attributes have enabled genetic and small molecule screens that have revealed toxic phenotypes and drug targets that translate directly to patient-derived iPSC neurons. Extending these insights, recent advances in genetic network analyses have generated the first "humanized" α-synuclein network, which has identified druggable proteins and led to validation of the toxic phenotypes in patient-derived cells. Unbiased phenotypic small molecule screens can identify compounds targeting critical proteins within α-synuclein networks. While identification of direct drug targets for phenotypic screen hits represents a bottleneck, high-throughput chemical genetic methods provide a means to uncover cellular targets and pathways for large numbers of compounds in parallel. Taken together, the yeast α-synuclein model and associated tools can reveal insights into underlying cellular pathologies, lead molecules and their cognate targets, and strategies to translate mechanisms of toxicity and cytoprotection into complex neuronal systems.


Self-organized criticality and dynamic instability of microtubule growth.
We have shown that the distribution of lengths of site nucleated microtubules obey an algebraic power law relationship D(s) = A s(-tau), where D(s) is relative number of microtubules with length s, A and tau are constants. This relationship indicates the possibility of a self-organized criticality in the dynamic instability of microtubule growth.


Handling High-Throughput Omics Data for Systems Genetics Analysis.
Omics data are being generated and collected at unprecedented scale. During the last decade, single omics, such as genomics, transcriptomics, proteomics, and metabolomics, have already highlighted pathophysiological pathways underpinning a variety of conditions across all the fields of medicine.In fact, high-throughput data generated by the comprehensive and unbiased analysis of an entire segment of the flow of genetic information (i.e., genetic variants in the case of genomics, or gene expression in transcriptomics) certainly provide a plethora of information and a precious support to dissect the mechanisms involved in complex diseases.Yet the most effective approach, set to fully exploit the potential of such big data, lies in the possibility to integrate various omics to unveil previously unappreciated pathways. This approach is the foundation of Systems Biology and allows to overcome the limitations inherent to single omics and traditional biology analyses.A robust and powerful strategy has been developed to integrate genetics and gene expression data in the framework of Systems Genetics. With this technique the first two layers of the flow of genetic information are integrated and specifically it is possible to pinpoint which genetic variants are associated with gene co-expression networks.Here we present a versatile bioinformatic protocol that can be used to study the Systems Genetics of CTLs, in order to identify genes (also known as master regulators) that influence the activation of biological pathways in these cells in a particular state or condition.


The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma.
Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Here, we found that phosphorylation of AMP-dependent kinase (AMPK) was elevated in BAP1-altered (or mutant) compared to BAP1-unaltered (or wild-type [WT]) UM tumors. As a readout of AMPK pathway activation, phosphorylation of an AMPK downstream effector, acetyl-CoA-carboxylase (ACC), was also elevated. BAP1 re-expression in BAP1-null UM cell lines decreased phospho-AMPK (pAMPK) and phospho-ACC (pACC) levels. AMPK phosphorylation is mediated by calcium/calmodulin dependent protein kinase kinase 2 (CaMKK2) and potentially liver kinase B1 (LKB1) in BAP1 mutant UM cells. Knockdown of AMPKα1/2 reduced the viability of BAP1 mutant UM cells, indicating a survival function of AMPK in BAP1 mutant UM. Our data suggest that the AMPK pathway is an important mechanism mediating the survival of BAP1 mutant UM. Targeting the AMPK pathway may be a novel therapeutic strategy for metastatic UM.


Albumin is an Independent Predictor of up to 9-Year Mortality for Intracapsular Femoral Neck Fractures Aiding in Decision-Making for Total Hip Arthroplasty or Hemiarthroplasty.
Intracapsular femoral neck fractures in the geriatric population are usually treated with hemiarthroplasty or total hip arthroplasty. The patients' medium-term to long-term mortality is a consideration to help decide which procedure to perform. The aim of this study is to examine whether easily identifiable serum investigations and patient identifiable factors on admission are associated with medium-term and long-term mortality. A consecutive series of 331 patients who sustained intracapsular femoral neck fractures and were over the age of 55 years were identified and retrospectively reviewed. American Society of Anesthesiologists (ASA) grade, cognitive function, gender, age, mobility status, and admission serum investigations were considered. Low albumin levels, advanced age, men, and a combination of high ASA with lower mobility status were independent predictors of mean 5-year mortality. Similarly, low albumin levels and a combination of high ASA with lower mobility status were found to be independent predictors of longer term mortality (7-9 years). The optimal albumin cut-off to identify patient survival was >42 g/L with an area under the curve of 0.71. We suggest that serum albumin on admission can be utilized as a factor to identify patients who are likely to survive at up to 9-year mean follow-up, to guide decision for total hip arthroplasty over hemiarthroplasty.


Value chain analysis of wheat in Duna district, Hadiya zone, Southern Ethiopia.
Wheat is a source of food and income for Ethiopian farmers in general, and the Duna district in particular. Despite the district's high wheat production potential, a number of constraints impede the wheat sector's and value chain's development. This study, thus, analyzed the wheat value chain in Duna district, Hadiya zone, Southern Ethiopia. Descriptive statistics, marketing margin, and a multiple linear regression model were used to analyze data from 149 respondents. The result showed that the actors in the wheat value chain have a shaky relationship. According to the findings, flour wholesalers had the highest market margin (18.36%), followed by flour processors (17.70%). The estimated multiple linear regression result revealed that wheat supply is influenced by the quantity of wheat produced, household education level, farming experience, frequency of extension contact, and lagged market price. Furthermore, wheat producers identified climate variability and low wheat prices as the top two problems in wheat production and wheat marketing, respectively. Hence, the government and other concerned bodies should focus on productivity increasing technologies in the study area in order to boost productivity and thus increase wheat market supply. In addition, to solve the marketing problem, the promotion of value-added practices and the formation of wheat cooperatives are suggested.


The Outcome of Acute Lymphoblastic Leukemia in 109 Adult Iraqi Patients.
While many studies addressed the outcome of adult ALL in developed Western countries, there is paucity of such prospective studies from developing Mediterranean ones. This is a prospective cohort study conducted at Hiwa Cancer Hospital in Sulaimani city and Nanakali Hospital in Erbil city-Kurdistan Iraq from March 2012 to August 2017. The main characteristics of adult ALL patients, type of therapy and risk factors were analyzed to assess their impact on treatment outcome and survival status. A total of 109 adult ALL patients were included with a median age of 24 years and male to female ratio of 1.7:1. B-ALL accounted for 76.1% of the cases, while the rest were T-ALL. BCR-ABL rearrangement was encountered in 12% of B-ALL. Complete remission (CR) rate was 81.7%, the overall 5 year survival (OS) was 38%, Relapse Free 5 year Survival (RFS) was 49%. Younger adults (< 35 years) had significantly higher CR rates and OS compared to the older group (P < 0.001 each). On the other hand, gender, high leucocyte count ≥ 50×109/L, immunophenotype (including B and T ALL subtypes), and clinical risk status did not predict a poor outcome. Multivariate analysis revealed that only age < 35 years and BCR-ABL rearrangement were significantly associated with better OS. Despite some limitations, the outcomes of Iraqi adult ALL is comparable to those reported in Western developed countries, with particularly favorable outcomes in younger patients. The need to improve outcome in adult ALL remains an important priority in our country as it is throughout the world.


Hepatitis B Vaccination Uptake Rate and Predictors in Healthcare Professionals of Ethiopia.
Healthcare professionals continue to be at risk of acquiring occupation-related hepatitis B virus infection because of noncompliance for the 3-dose primary series of hepatitis B vaccine recommended. The objective of the study was to determine the rate of and to identify the predictors of hepatitis B vaccination uptake in healthcare professionals in Ethiopia. A multicenter cross-sectional survey was conducted between May 19 2018 and June 15 2018. A stratified with systematic random sampling technique was used to select 260 healthcare professionals. A structured questionnaire was used to collect all the necessary primary data from samples. This survey analyzed hepatitis B vaccination uptake as the binary outcome variable ("noncomplete" vs "complete") with regard to the 30 potential predictor variables. Both descriptive and inferential statistical analysis techniques have been used to address the study objective. The rate of complete vs noncomplete hepatitis B vaccination uptake was 37.7% vs 62.3%. The significantly independent predictors of hepatitis B vaccination uptake were professional qualification (P=0.004), professional experience (P=0.013), household income (P=0.006), workload status (P=0.015), routine infant immunization program existence at the workplace (P=0.014), perceived susceptibility to infection (P=0.005), perceived safety of vaccine (P=0.001), prior occupational exposure to blood (P=0.006), training on universal precautions (P=0.015), and colleagues' suggestion (P=0.002). The rate of hepatitis B vaccination uptake found was currently low. The significantly independent predictors of hepatitis B vaccination uptake included perceived safety, colleagues' suggestion, professional qualification, perceived susceptibility, household income, prior occupational exposure to blood, professional experience, existence of routine infant immunization program at the workplace facility, workload status, and universal precautions training.


Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus.
Aspergillus flavus is a pathogenic fungus that produces carcinogenic aflatoxins, posing a great threat to crops, animals and humans. Lysine acetylation is one of the most important reversible post-translational modifications and plays a vital regulatory role in various cellular processes. However, current information on the extent and function of lysine acetylation and aflatoxin biosynthesis in A. flavus is limited. Here, a global acetylome analysis of A. flavus was performed by peptide pre-fractionation, pan-acetylation antibody enrichment and liquid chromatography-mass spectrometry. A total of 1313 high-confidence acetylation sites in 727 acetylated proteins were identified in A. flavus. These acetylation proteins are widely involved in glycolysis/gluconeogenesis, pentose phosphate pathway, citric acid cycle and aflatoxin biosynthesis. AflO (O-methyltransferase), a key enzyme in aflatoxin biosynthesis, was found to be acetylated at K241 and K384. Deletion of aflO not only impaired conidial and sclerotial developments, but also dramatically suppressed aflatoxin production and pathogenicity of A. flavus. Further site-specific mutations showed that lysine acetylation of AflO could also result in defects in development, aflatoxin production and pathogenicity, suggesting that acetylation plays a vital role in the regulation of the enzymatic activity of AflO in A. flavus. Our findings provide evidence for the involvement of lysine acetylation in various biological processes in A. flavus and facilitating in the elucidation of metabolic networks.


Successful resection of schwannoma from an intercostal nerve causing bloody pleural effusion: report of a case.
We report a case of schwannoma arising from the 9th intercostal nerve, which caused a bloodstained pleural effusion. The patient, a 37-year-old woman, presented with left-sided back pain. A chest X-ray showed left pleural effusion, which was subsequently found to be bloodstained but without malignant cells. Chest magnetic resonance imaging showed a 76-mm tumor arising from the 9th intercostal nerve. The tumor and intercostal nerve were successfully resected. Histological examination revealed that the tumor comprised spindle cells with both Antoni types A and B patterns. There were necrotic changes and cystic degeneration, but no atypical or mitotic cells. Based on these findings, benign schwannoma was diagnosed. Schwannoma is rarely accompanied by bloody pleural effusion, which we assume was caused by partial tumor rupture. Magnetic resonance imaging proved very useful in localizing and characterizing the tumor in this case.


A retropancreatic celio-mesenteric paraganglioma.
Paragangliomas are extra-adrenal pheochromocytomas that arise from chromaffin cells in the sympathetic or parasympathetic neural paraganglia. Surgery remains the only curative treatment, although prominent vascularity can make excision difficult. We have recently encountered a patient with a retropancreatic celio-mesenteric paraganglioma unusually located between celiac trunk (CT) and superior mesenteric artery.


IRFinder: assessing the impact of intron retention on mammalian gene expression.
Intron retention (IR) occurs when an intron is transcribed into pre-mRNA and remains in the final mRNA. We have developed a program and database called IRFinder to accurately detect IR from mRNA sequencing data. Analysis of 2573 samples showed that IR occurs in all tissues analyzed, affects over 80% of all coding genes and is associated with cell differentiation and the cell cycle. Frequently retained introns are enriched for specific RNA binding protein sites and are often retained in clusters in the same gene. IR is associated with lower protein levels and intron-retaining transcripts that escape nonsense-mediated decay are not actively translated.


A Case of Severe, Nilotinib-Induced Liver Injury.
Idiosyncratic hepatotoxicity is a leading reason for the discontinuation or dose modification of Food and Drug Administration (FDA)-approved medications in the United States. We report the case of a 53-year-old woman with chronic myeloid leukemia who developed acute cholestatic hepatitis in response to the tyrosine kinase inhibitor nilotinib. Nilotinib was discontinued, and the patient's liver function tests normalized over the next 3 months. We conclude that nilotinib may cause life-threatening hepatotoxicity and recommend that patients on the medication undergo regular monitoring of their liver tests.


Granzyme A produces bioactive IL-1β through a nonapoptotic inflammasome-independent pathway.
Bacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1? (IL-1?), a pleiotropic cytokine and one of the most important mediators of inflammation, through the protease caspase-1. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, given that disturbed control of IL-1? release can cause severe autoinflammatory diseases or contribute to cancer development. We show that the bacterial Pasteurella multocida toxin (PMT) triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-?? activation. Furthermore, PMT mediates signal transducer and activator of transcription (STAT) protein-controlled granzyme A (a serine protease) expression in macrophages. The exocytosed granzyme A enters target cells and mediates IL-1? maturation independently of caspase-1 and without inducing cytotoxicity. These findings show that macrophages can induce an IL-1?-initiated immune response independently of inflammasome activity.


Structure of the extra-membranous domain of the beta-subunit of (Na,K)-ATPase revealed by the sequences of its tryptic peptides.
Membrane bound dog kidney (Na,K)-ATPase was digested with trypsin. The peptides that were recovered in the supernatant were purified and sequenced. By comparing these results with the sequence of alpha- and human beta-subunits, the location of each of the peptides could be allotted. Both accessibility to trypsin and the facility of release into the water phase indicated that these peptides were derived from the exposed surface of the intact enzyme. The sequence, GXGXXG, reported in the Torpedo californica beta-subunit [(1986) FEBS Lett. 196, 315-319] was likely a mere coincidence with the sequence of the dinucleotide-binding site, since the last glycine was replaced by proline in the sequence of the dog beta-subunit. A disulfide bridge was found within a peptide derived from the beta-subunit. A possible model for the beta-subunit structure is proposed.


Retrospective evaluation of the relationship between admission variables and brain herniation in dogs (2010-2019): 54 cases.
To document the admission systolic blood pressure (SBP), heart rate (HR), and modified Glasgow coma scale (MGCS) score in dogs with and without brain herniation and to determine their relationship with brain herniation. Retrospective study between 2010 and 2019. University veterinary teaching hospital. Fifty-four client-owned dogs with brain herniation and 40 client-owned dogs as a control group, as determined on magnetic resonance imaging. None. SBP, HR, MGCS score, and outcome were extracted from medical records. MGCS score was retrospectively calculated based on initial neurological examination in dogs with adequate available information. Dogs with brain herniation had a significantly higher SBP (P = 0.0078), greater SBP-HR difference (P = 0.0006), and lower MGCS score (P < 0.0001) compared to control dogs. A cutoff value of an SBP ≥ 178 mm Hg, SBP-HR ≥ 60, and MGCS score ≤ 14 each provides a specificity of 90%-98%. A combination of an SBP > 140 mm Hg and HR < 80/min provided 24% sensitivity and 100% specificity to diagnose dogs with brain herniation (P < 0.0001). A high SBP, a greater difference between SBP and HR, a combination of higher SBP and lower HR, and a low MGCS score were associated with brain herniation in dogs presenting with neurological signs upon admission. Early recognition of these abnormalities may help veterinarians to suspect brain herniation and determine timely treatment.


Larvicidal activity of Tagetes erecta against Aedes aegypti.
The aim of this study was to evaluate the activity of essential oil from Tagetes erecta against 3rd instars of Aedes aegypti and to determine the amounts of larvicidal thiophenes in all plant tissues. The oil obtained by steam distillation and analyzed by gas chromatography/mass spectrometry showed 14 compounds. The main compounds were piperitone (45.72%), D-limonene (9.67%), and piperitenone (5.89%). The essential oil was active against larvae of Ae. aegypti, with LC50 of 79.78 microg/ml and LC90 of 100.84 microg/ml. The larvicidal thiophene contents were higher in the roots and flowers as demonstrated by high-performance liquid chromatography analysis. Thus, T. erecta constitutes a good source of varied compounds showing larvicidal activity against Ae. aegypti.


Understanding Epidermal Necrolysis after the Initial Hospitalization.
In-hospital mortality for epidermal necrolysis (EN) has been well-characterized, but less is known about the long-term complications. Marxer et al. (2020) report mortality rates of 7.4% during the initial hospitalization, 4.8% within 90 days, and 7.6% after 91 days. Compared with that of matched controls, long-term mortality was not increased, highlighting the importance of understanding the long-term sequelae of EN survivors.


Characteristics of venous-venous extracorporeal membrane oxygenation related bloodstream infections.
Infectious complications have been shown to increase the morbidity of venous-venous extracorporeal membrane oxygenation (VV-ECMO) population, including the use of right ventricular assist devices. We aimed to evaluate our VV-ECMO population for ECMO related bloodstream infections (E-BSI) and characteristics that affect risk and overall outcomes. A retrospective chart review of adult patients (>18 years of age)supported with VV ECMO was conducted. Demographic data as well as antimicrobial use and presecence of bacteremia was collected. We report a low infection rate of 2.7%. We postulate our low BSI rate may be due to our use of perioperative antimicrobials as well as a majority of our cannulations occurring in the operating room. We do not routinely utilize prophylactic antimicrobials on ECMO. Further investigation into trends, risks, and outcomes related to E-BSI is needed.


Evaluation of a biodegradable polyurethane patch for repair of diaphragmatic hernia in a rat model: A pilot study.
Congenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch. The biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials. There were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides. The biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo. Level II, Prospective Comparative Study.


[The use of moexipril in postmenopausal women with hypertension and associated changes of bone mineral density].
Moexipril was given to 35 postmenopausal women with mild and moderate hypertension, menopausal syndrome and decreased bone mineral density. Blood pressure (BP) was measured before and in 1, 3, 6, and 12 months, while ultrasonic bone densitometry was carried out before and in 12 months of moexipril use. Significant lowering of systolic and diastolic BP, reduction of severity of climacteric syndrome occurred after 1, 3 and 6 months of moexipril use, respectively. After 12 months parameters of bone densitometry in moexipril treated women became better than in control group (p<0.01). Treatment was also associated with significant improvement of quality of life, diminished reactive anxiety and depression.


Impact of Tobacco Smoke in HIV Progression: a Major Risk Factor for the Development of NeuroAIDS and Associated of CNS Disorders.
With the advent of highly active and combination antiretroviral therapy have substantially increased the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this has brought into sharp contrast the incidence of several 'Non-acquired immunodeficiency syndrome (AIDS) diseases such as NeuroAIDS which identifies a group of neurological disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems. Given the patients depleted immune condition, the use and abuse of drug and addictive substances such as tobacco smoking can further deteriorates their overall health and accelerate the progression and severity of the disease. In this review we detail the pathogenesis, progression and characteristics of HIV and the impact of tobacco smoking as a risk factor for the progression of the disease to NeuroAIDS. This is a poorly understood aspect of HIV-related complications that needs to be addressed. Review of theoretical approaches and knowledge synthesis. Tobacco smoking is highly prevalent in HIV patients when compared to the general population. The oxidative damage and inflammatory stress caused by chronic smoking on the cerebrovascular system have been well established. Considering that HIV patients have an impaired immune system and smokers per se are more susceptible to viral and bacterial inflammatory neuropathologies than non-smokers, it is conceivable that tobacco smoking as a risk factor for the progression of HIV into NeuroAIDS and related neurological impairments. Tobacco smoke (TS) may bring about a synergistic effect in the context of persistent inflammatory state and cerebrovascular damage which facilitate HIV infection and progression to NeuroAIDS when compared to non-smokers.


Efficacy and Safety of Biosimilar and Originator Etanercept in Rheumatoid Arthritis Patients: Real-Life Data.
There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound. To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals. The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment. Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1. The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings.


Effect of the adsorbate kinetic diameter on the accuracy of the Dubinin-Radushkevich equation for modeling adsorption of organic vapors on activated carbon.
This paper investigates the effect of the kinetic diameter (KD) of the reference adsorbate on the accuracy of the Dubinin-Radushkevich (D-R) equation for predicting the adsorption isotherms of organic vapors on microporous activated carbon. Adsorption isotherms for 13 organic compounds on microporous beaded activated carbon were experimentally measured, and predicted using the D-R model and affinity coefficients. The affinity coefficients calculated based on molar volumes, molecular polarizabilities, and molecular parachors were used to predict the isotherms based on four reference compounds (4.3≤KD≤6.8 Å). The results show that the affinity coefficients are independent of the calculation method if the reference and test adsorbates are from the same organic group. Choosing a reference adsorbate with a KD similar to that of the test adsorbate results in better prediction of the adsorption isotherm. The relative error between the predicted and the measured adsorption isotherms increases as the absolute difference in the kinetic diameters of the reference and test adsorbates increases. Finally, the proposed hypothesis was used to explain reports of inconsistent findings among published articles. The results from this study are important because they allow a more accurate prediction of adsorption capacities of adsorbents which allow for better design of adsorption systems.


A dual-catalysis approach to the kinetic resolution of 1,2-diaryl-1,2-diaminoethanes.
The kinetic resolution of racemic C(2)-symmetric 1,2-diaryl-1,2-diaminoethanes was accomplished for the first time through application of a dual-catalysis approach.


Multiple brain tumor nodule resections under direct visualization of a neuronavigated endoscope.
With neuronavigation-assistance, endoscopic neurosurgery has a variety of advantages for brain tumor resection. However, intraoperative neuronavigation has to be operated by frequently alternating a neuronavigation wand and moving the microscope back-and-forth on the surgical field while the microscope is being used for surgery, except when using stereo overlays in the operating microscope aligned to the operative scene. In our practice, our surgical endoscope was used as a sole optical device and was also calibrated as a virtual wand targeting to tumor nodules while the operation was being performed under its simultaneous visualization. This paper gives a brief description and technical report of applications of image-guided endoscopy in two cases with multiple tumor nodules. A 0-degree, 4-mm rigid endoscopes (DCI; Storz and Co., Tuttlingen, Germany) and Voyager SX navigation system by Z-KAT (Marconi, USA) were used for both cases, a 32-year-old woman with multiple hemangioblastomas and a 46-year-old man with two recurrent astrocytomas. The endoscope has a digital video output, which was registered with reference calibration for rendered image-guided stereoscopic views. The neuronavigation screen was formatted to provide axial, coronal, and sagittal magnetic resonance (MR) images demonstrating the location and trajectory of the endoscope's tip. Endoscope angles of 0 degrees and 30 degrees were used interchangeably during surgery. For both posterior fossa tumors, an entry point on the skull was identified using "virtual endoscopy" to visualize the intracranial anatomy and lesions. A 3-cm linear skin incision for both cases was made at the entry point guided by the endoscope's video output and a 3-dimensional (3-D) rendered image on the navigation system. Three tumor nodules in the first patient, and two nodules in the second, were removed directly under navigated-endoscopic visualization on one monitor with 3D imaging-guidance images on the other side-by-side. The neuronavigated endoscope coordinates of the tip of endoscope, and the trajectory of targets, provide both 3D orientation and direct endoscopic visualization simultaneously, and present with the unique feature for solely endoscopic minimally invasive procedures, especially for multiple intracranial lesions.


[A series of cases of sinonasal cancer among shoemakers and tannery workers].
A series of cases of sinunasal cancer has been observed among shoe-makers (11 cases) and tannery workers (8 cases) in the leather production area in Tuscany in the period 1990-2002. We stress the possible etiologic role of tannins both in leather and in wood industry.


At the dawn of a new era in treating angina pectoris, or just another antianginal drug? Some considerations about ranolazine.
Ranolazine is a new compound that has been approved by the FDA for use in patients who have chronic stable angina refractory to conventional antianginal medications. Ranolazine proved to be effective also as monotherapy in patients with stable angina and as part of a combination regimen. This review is inspired by the presentation that legendary figures in contemporary cardiology, such as Braunwald, Komajda and Camm made recently at the Congress of the European Society of Cardiology held in Stockholm, Sweden, last September.


Choledochal cyst: a case report and review of literature.
We present our first experience in managing a case of choledochal cyst in a two and half year old girl highlighting the difficulties in the management together with a review of literature. A two and half year old girl presented to the University of Maiduguri Teaching Hospital. A pertinent clinical evaluation with abdominal ultrasound allowed accurate pre-operative diagnosis. A young girl with a right hypochondrial mass confirmed as choledochal cyst by ultrasound scans. Haematological parameters were normal but deranged clotting profiles were corrected with vitamin-K injection before surgical drainage. High index of suspicion with abdominal ultrasound scan allowed accurate pre-operative diagnosis of choledochal cyst that was successfully managed by surgical drainage, when attempted dissection of cyst wall for excision failed.


Simultaneous mass spectrometry analysis of cisplatin with oligonucleotide-peptide mixtures: implications for the mechanism of action.
Although genomic DNA is the primary target of anticancer platinum-based drugs, interactions with proteins also play a significant role in their overall activity. In this study, competitive binding of cisplatin with an oligonucleotide and two peptides corresponding to segments of H2A and H2B histone proteins was investigated by mass spectrometry. Following the determination of the cisplatin binding sites on the oligonucleotide and peptides by tandem mass spectrometry, competitive binding was studied and transfer of platinum fragments from the platinated peptides to the oligonucleotide explored. In conjunction with previous studies on the nucleosome, the results suggest that all four of the abundant histone proteins serve as a platinum drug reservoir in the cell nucleus, providing an adduct pool that can be ultimately transferred to the DNA.


Cerebral infarction secondary to unsuspected intracranial fibromuscular dysplasia following bypass of aortic coarctation.
Fibromuscular dysplasia (FMD) is an uncommon finding in the cerebral circulation. We present a case of unsuspected intracranial FMD in a patient dying from a large cerebral infarct following a bypass operation for coarctation of the aorta. The need for recognizing the possible co-existence of these two lesions is emphasized.


Effects of potassium and magnesium in the enhanced biological phosphorus removal process using a membrane bioreactor.
This study assessed the role of potassium (K+), magnesium (Mg2+), and calcium (Ca2+) ions in the enhanced biological phosphorus removal (EBPR) from wastewaters using a membrane bioreactor (MBR). A linear relationship in the anaerobic and aerobic/ anoxic phases for P(uptake) versus P(release) was obtained using the known equation deltaP(uptake) = a x deltaP(release)+ b, where the constants "a" and "b" were found to be 0.44 and 8.40, respectively. Both potassium and magnesium were soluble with phosphate in the anaerobic phase, but they accumulated again during the successive aerobic/anoxic phase. The linear correlation coefficients (R2) of K+/PO4-P and Mg2/PO4-P were calculated as 0.6682 and 0.8884, respectively. The molar ratio of C(K/P) during anaerobic phosphorus release was observed to be 0.20 mol/mol, whereas C(Mg/P) was 0.21 mol/mol. Furthermore, unlike potassium and magnesium, calcium was not co-transported with phosphorus during the release and uptake processes.


NHS failing to meet basic standards of care for older people.
John Tingle discusses a recent report by the Health Service Ombudsman on ten investigations into NHS care of older people.


Determining the diagnostic value of three clinical criteria Wells', YEARS and modified Geneva in pregnant women with suspected pulmonary thromboembolism.
Diagnosis of pulmonary thromboembolism (PTE) during pregnancy is a challenging medical issue due to complications of X-ray-based imaging studies such as Ct-angiography for neonates and pregnant women. Here we aimed to assess the predictive values of three clinical criteria for diagnosing PTE during pregnancy. This is a retrospective cohort study performed in 2018-2020 on 166 pregnant women suspected of PTE. We reviewed the documents of all patients referred to our medical center with suspected symptoms of PTE. The demographic characteristics of the patients, signs and clinical findings upon the arrival of patients as well as their laboratory tests including D-dimer with a history of abortion or delivery and leg symptoms were entered into the data collection form. Then, according to the information extracted from the patient's files, each patient was evaluated by all clinical PTE criteria, including Wells, YEARS and modified Geneva. For each patient according to clinical criteria and all three algorithms, clinical suspicion for PTE and treatment or non-treatment was determined were compared to the final MDCT result of patients. The Well's criteria had 100% sensitivity, 6.47% specificity, a positive predictive value of 7.8% and a negative predictive value of 100%. In patients with Well's score of more than four, the sensitivity and specificity of PTE diagnosis were 100% and 6% respectively. The modified Geneva criteria had 100% sensitivity, 8.89% specificity, a positive predictive value of 8.21% and a negative predictive value of 100%. The modified Geneva criteria had 100% sensitivity, 7.74% specificity, positive predictive value of 8.44% and a negative predictive value of 100%. Wells, YEARS and modified Geneva criteria could significantly rule out PTE in pregnancy with 100% sensitivity.


Long-term treatment with oral nifedipine plus theophylline in the management of chronic bronchial asthma.
The effect on bronchial smooth muscle of slow release theophylline plus placebo and theophylline plus slow release nifedipine administered for a prolonged period to 12 asthmatic and hypertensive patients has been studied. Both combinations led to a significant improvement in respiratory function parameters when compared to baseline values. No additional improvement in pulmonary function was found on long term treatment with theophylline plus nifedipine. A reduction in the number of asthmatic attacks, in the use of inhaled beta 2-agonists and better control of arterial blood pressure resulted from use of theophylline plus nifedipine. That drug combination is safe and valuable in patients with chronic bronchial obstruction and cardiovascular disease.


Forward to a methodological proposal to support cancer patients: the dialogics' contribution for the precision care.
In scientific context, the first step for scientific theoretical and methodological production is the epistemological analysis. What are assumptions for interaction between oncology and psychology? What are the conditions for psycho-oncological contribution in treating cancer? Furthermore, what are epistemological observations about the current developments in cancer field? And what are implications for sciences treating patients with neoplasms? Due to advances in oncology and in sciences supporting oncology, epistemological questions focus on the object of study of the integration between oncology and psychology. Therefore, the purpose of this study is to describe a proposal of theoretical and methodological frame suitable for current clinical and research needs in cancer patients asking for psychological support. Epistemological analysis lets the health professionals and researchers observe there are sciences using formal languages and sciences using ordinary language. Currently, personalized approach is pursued by oncology, identifying specific patients' characteristics to define the proper treatment process: not only tumor characteristics but also behavioral and psychological features. Cancer patients features can be found in patients' narrations about neoplasms: narration represents the core of clinical and research in psychoncology. Therefore when formalized, language provides the connection between oncology and psychology. Language used by patients and all the roles involved in the care of cancer patients can become a measure of these patients' features. Dialogics science measuring the ordinary language allows the ordinary language formalization, pursuing a personalized medicine.


Non-steroidal anti-inflammatory drugs and risk of lower gastrointestinal adverse events: a nationwide study in Taiwan.
Only limited studies have evaluated the risk of non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and coxibs for lower gastrointestinal (GI) adverse outcomes. The objective of this study was to evaluate risks of lower GI adverse events associated with use of celecoxib, oral and parenteral nsNSAIDs. Retrospective case-crossover study. Records of all patients aged ≥20 years hospitalised for lower GI adverse events (bleeding from small or large intestine, perforation, and complicated diverticular disease) in 2006 were retrieved using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance database. Case periods were defined for each patient as 1-30 days prior to hospital admission date and control period as 91-120 days prior to hospital admission date. The pharmacy prescription database was searched for NSAID use during case and control periods. We calculated adjusted self-matched ORs and 95% CIs with a conditional logistic regression model to determine the associations between NSAID use and lower GI adverse outcomes. A total of 1297 patients hospitalised for lower GI adverse events were included. Celecoxib was associated with an adjusted OR of 2.33 (95% CI 0.97 to 5.59); the association became statistically significant (OR: 3.26, 95% CI 1.07 to 9.91) when a different control period (31-60 days) was applied. Both oral and parenteral nsNSAIDs significantly increased risk for lower GI adverse events (OR: 2.26, 95% CI 1.78 to 2.85 and OR: 5.64, 95% CI 3.24 to 9.82, respectively). Oral and parenteral NSAIDs were associated with significantly increased risk for lower GI adverse events. Celecoxib also increased risk to a comparable extent, despite risk estimates being affected slightly by the control period chosen for comparison. The association of NSAIDs with specific lower GI adverse events and long-term complications requires further investigation.


Epidemiology and source of infection in patients with febrile neutropenia: A ten-year longitudinal study.
No recent studies are available from Saudi Arabia on the etiology of febrile neutropenia. The objective of this study was to describe the characteristics of patients with febrile neutropenia and to calculate the rate of occurrence of bacteremia in these patients. This is a hospital-based study of patients admitted with febrile neutropenia from 2006 to 2015. A total of 372 distinct episodes of febrile neutropenia representing 231 patients were included. Hematologic malignancies constituted 56.6% of the episodes. Positive blood cultures were reported in 13.5% with equal frequency of Gram-negative bacilli and gram positive cocci. The most commonly suspected sites of infection were blood 10.8% and pulmonary 9.2%, and the majority (72.5%) was thought to have no identifiable source of infection. Of all the episode, 32% had central venous catheters. The most frequently used single antimicrobial agents were imipenem (38%) and ceftazidime (7.5%). The mortality rate was 11.2% and it was significantly associated with the presence of bacteremia 24.4% versus 12.4% (P=0.016). Mortality was not significantly association with age, type of malignancy, presence of central venous catheter, or the severity of neutropenia. Compared to patients with hematological malignancy, patients with solid organ malignancy were more likely to be female 62% versus 14.9% (P<0.001) and were less likely to have bacteremia 8.7% versus 17.1%, P=0.042, respectively. We had shown that febrile neutropenia in this study has a low rate of bacteremia and that about 45% received the recommended initial empiric therapy.


Older Adults' Expectations about Mortality, Driving Life and Years Left without Driving.
People are living and driving longer than ever before, with little preparation for transitioning to being non-drivers. We investigated driving expectations among drivers age 65 and older, including sociodemographic and driving context predictors. Cross-sectional data from 349 older drivers were explored to determine variation in how many years they expected to continue driving. General linear models examined predictors of both expectations. In this predominantly Black/African American sample, 76% of older drivers (mean age = 73 ± 5.7 years) expected a non-driving future, forecasting living an average of 5.75 ± 7.29 years after driving cessation. Regression models on years left of driving life and years left to live post-driving cessation predicted nearly half of the variance in older drivers' expectations with five significant predictors: income, current age, age expected to live to, self-limiting driving to nearby places and difficulty, visualizing being a non-driver. Many older drivers expect to stop driving before end of life.


The effect of cyclic hydrostatic pressure on the functional development of cartilaginous tissues engineered using bone marrow derived mesenchymal stem cells.
Mechanical signals can play a key role in regulating the chondrogenic differentiation of mesenchymal stem cells (MSCs). The objective of this study was to determine if the long-term application of cyclic hydrostatic pressure could be used to improve the functional properties of cartilaginous tissues engineered using bone marrow derived MSCs. MSCs were isolated from the femora of two porcine donors, expanded separately under identical conditions, and then suspended in cylindrical agarose hydrogels. Constructs from both donors were maintained in a chemically defined media supplemented with TGF-β3 for 42 days. TGF-β3 was removed from a subset of constructs from day 21 to 42. Loaded groups were subjected to 10 MPa of cyclic hydrostatic pressurisation at 1 Hz for one hour/day, five days/week. Loading consisted either of continuous hydrostatic pressure (CHP) initiated at day 0, or delayed hydrostatic pressure (DHP) initiated at day 21. Free swelling (FS) constructs were cultured in parallel as controls. Constructs were assessed at days 0, 21 and 42. MSCs isolated from both donors were morphologically similar, demonstrated comparable colony forming unit-fibroblast (CFU-F) numbers, and accumulated near identical levels of collagen and GAG following 42 days of free swelling culture. Somewhat unexpectedly the two donors displayed a differential response to hydrostatic pressure. For one donor the application of CHP resulted in increased collagen and GAG accumulation by day 42, resulting in an increased dynamic modulus compared to FS controls. In contrast, CHP had no effect on matrix accumulation for the other donor. The application of DHP had no effect on either matrix accumulation or construct mechanical properties for both donors. Variability in the response to hydrostatic pressure was also observed for three further donors. In conclusion, this study demonstrates that the application of long-term hydrostatic pressure can be used to improve the functional properties of cartilaginous tissues engineered using bone marrow derived MSCs by enhancing collagen and GAG accumulation. The response to such loading however is donor dependent, which has implications for the clinical utilisation of such a stimulus when engineering cartilaginous grafts using autologous MSCs.


Unravelling crystal growth of nanoparticles.
Crystal growth from nanoscale constituents is a ubiquitous phenomenon in biology, geology and materials science. Numerous studies have focused on understanding the onset of nucleation and on producing high-quality crystals by empirically sampling constituents with different attributes and varying the growth conditions. However, the kinetics of post-nucleation growth processes, an important determinant of crystal morphology and properties, have remained underexplored due to experimental challenges associated with real-space imaging at the nanoscale. Here we report the imaging of the crystal growth of nanoparticles of different shapes using liquid-phase transmission electron microscopy, resolving both lateral and perpendicular growth of crystal layers by tracking individual nanoparticles. We observe that these nanoscale systems exhibit layer-by-layer growth, typical of atomic crystallization, as well as rough growth prevalent in colloidal systems. Surprisingly, the lateral and perpendicular growth modes can be independently controlled, resulting in two mixed crystallization modes that, until now, have received only scant attention. Combining analytical considerations with molecular dynamics and kinetic Monte Carlo simulations, we develop a comprehensive framework for our observations, which are fundamentally determined by the size and shape of the building blocks. These insights unify the understanding of crystal growth across four orders of magnitude in particle size and suggest novel pathways to crystal engineering.


Mitochondrial network remodeling: an important feature of myogenesis and skeletal muscle regeneration.
The remodeling of the mitochondrial network is a critical process in maintaining cellular homeostasis and is intimately related to mitochondrial function. The interplay between the formation of new mitochondria (biogenesis) and the removal of damaged mitochondria (mitophagy) provide a means for the repopulation of the mitochondrial network. Additionally, mitochondrial fission and fusion serve as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been characterised in multiple tissue- and cell-types, and under various conditions. In skeletal muscle, the robust remodeling of the mitochondrial network is observed, particularly after injury where large portions of the tissue/cell structures are damaged. The significance of mitochondrial remodeling in regulating skeletal muscle regeneration has been widely studied, with alterations in mitochondrial remodeling processes leading to incomplete regeneration and impaired skeletal muscle function. Needless to say, important questions related to mitochondrial remodeling and skeletal muscle regeneration still remain unanswered and require further investigation. Therefore, this review will discuss the known molecular mechanisms of mitochondrial network remodeling, as well as integrate these mechanisms and discuss their relevance in myogenesis and regenerating skeletal muscle.


Using humor to teach postpartum topics.
I have found that these two hands-on activities--demonstration and return demonstration, and roleplaying of a postpartum woman--help promote learning in a relaxed environment.


Characterization and genomic analysis of novel bacteriophage NK20 to revert colistin resistance and combat pandrug-resistant Klebsiella pneumoniae in a rat respiratory infection model.
We investigated the therapeutic capacity of the isolated Klebsiella bacteriophage NK20 against pandrug-resistant strains. Moreover, we assessed the impact of resistance development on the overall therapeutic outcome both in vitro and in vivo. The pandrug-resistant K. pneumoniae Kp20 is used as a host strain for the isolation of bacteriophages using sewage samples. Spot assay was then used to compare the spectra of the isolated phages, while kinetic and genomic analysis of the phage with the broadest spectrum was assessed. Antibacterial potential of the phage was assessed using turbidimetric assay and MIC with and without colistin. Finally, the therapeutic efficacy was evaluated in vivo using a rat respiratory infection model. The isolated lytic bacteriophage (NK20) showed a relatively broad spectrum and an acceptable genomic profile. In vitro antibacterial assay revealed bacterial resistance development after 12 h. Colistin inhibited bacterial regrowth and reduced pandrug-resistant strains' colistin MICs. Despite the isolation of resistant clones, intranasal administration of NK20 significantly (p < 0.05) reduced the bacterial load in both the pulmonary and blood compartments and rescued 100 % of challenged rats. Histological and immunological analysis of treated animals' lung tissue revealed less inflammation and lower TNF-α and caspase-3 expression. NK20 is a promising candidate that rescued rats from untreatable, pan-drug-resistant K. pneumoniae Kp20. Moreover, it steers the evolution of resistant mutants with higher sensitivity to colistin and less virulence, opening the door for using phages as sensitizing and anti-virulence entities rather than direct killer.


In vitro study of the antioxidative properties of the glucose derivatives against oxidation of plasma components.
Oxidative stress has been implicated in the pathogenesis of variety of diseases. Since the endogenous antioxidant defense may be not adequate to counteract the enhanced generation of oxidants, a growing interest in research for exogenous nutrients has been observed. The present study was designed to assess in vitro the antioxidative properties of the glucose derivatives: calcium D-glucarate, D-gluconic acid lactone, and sodium D-gluconate (0.5-3 mM) in the protection of plasma proteins and lipids, against the damage caused by 0.1 mM peroxynitrite (ONOO⁻). Exposure of plasma to ONOO⁻ resulted in carbonyl groups increase, 3-nitrotyrosine (3-NT) formation, reduction in thiol groups, and enhanced lipid peroxidation. D-gluconic acid lactone and sodium D-gluconate effectively decreased 3-NT formation; the antinitrative action of calcium D-glucarate was less effective. In plasma samples incubated with ONOO⁻ and tested compounds, the level of carbonyl groups was decreased in comparison to plasma samples treated only with ONOO⁻. The level of protein -SH groups and glutathione was significantly higher in the presence of glucose derivatives than in plasma samples treated with ONOO⁻ only. All the tested compounds had the inhibitory effect on the peroxynitrite-induced plasma lipids peroxidation. The results obtained from our work indicate that calcium D-glucarate, D-gluconic acid lactone, and sodium D-gluconate may partly protect plasma proteins and lipids against peroxynitrite-induced damages.


Abnormal tissue distribution of lead in amyotrophic lateral sclerosis.
The lead content of cerebrospinal fluid (CSF) was found to be significantly elevated in 12 patients with amyotrophic lateral sclerosis, when compared to 28 control subjects having non-degenerative neurological disorders. The difference could not be explained as being merely secondary to blood-CSF barrier damage. A hypothetical model of the pathogenesis of the disease is advanced and the results are discussed in relation to this model.


Plastid genome evolution in Amazonian açaí palm (Euterpe oleracea Mart.) and Atlantic forest açaí palm (Euterpe edulis Mart.).
The plastomes of E. edulis and E. oleracea revealed several molecular markers useful for genetic studies in natural populations and indicate specific evolutionary features determined by vicariant speciation. Arecaceae is a large and diverse family occurring in tropical and subtropical ecosystems worldwide. E. oleracea is a hyperdominant species of the Amazon forest, while E. edulis is a keystone species of the Atlantic forest. It has reported that E. edulis arose from vicariant speciation after the emergence of the belt barrier of dry environment (Cerrado and Caatinga biomes) between Amazon and Atlantic forests, isolating the E. edulis in the Atlantic forest. We sequenced the complete plastomes of E. edulis and E. oleracea and compared them concerning plastome structure, SSRs, tandem repeats, SNPs, indels, hotspots of nucleotide polymorphism, codon Ka/Ks ratios and RNA editing sites aiming to investigate evolutionary traits possibly affected by distinct environments. Our analyses revealed 303 SNPs, 91 indels, and 82 polymorphic SSRs among both species. Curiously, the narrow correlation among localization of repetitive sequences and indels strongly suggests that replication slippage is involved in plastid DNA mutations in Euterpe. Moreover, most non-synonymous substitutions represent amino acid variants in E. edulis that evolved specifically or in a convergent manner across the palm phylogeny. Amino acid variants observed in several plastid proteins in E. edulis were also identified as positive signatures across palm phylogeny. The higher incidence of specific amino acid changes in plastid genes of E. edulis in comparison with E. oleracea probably configures adaptive genetic variations determined by vicariant speciation. Our data indicate that the environment generates a selective pressure on the plastome making it more adapted to specific conditions.


Household material hardships impact emergency department reliance in pediatric patients with sickle cell disease.
In sickle cell disease (SCD), high emergency department (ED) utilization is associated with worse outcomes and increased costs. A metric called ED reliance (EDr), the percentage of healthcare visits that occur in the ED, attempts to identify ED overutilization. It is unknown if household material hardships (HMH)-housing, utility, or food insecurity-impact reliance on the ED. As these may represent modifiable risk factors for high ED utilization, we aimed to estimate the association between HMH and EDr in pediatric patients with SCD. We reviewed the electronic medical records of pediatric patients with SCD who received care in the Boston Medical Center network in Massachusetts, USA, to collect data on HMH and healthcare utilization. Using linear regression to control for potential confounders, we modeled the association between material hardships and EDr. Of 101 eligible patients, 60 (59%) reported one or more HMH. The mean EDr was 12% overall, with significant differences between those with and without HMH (15.9 vs 5.9, P = 0.0001). Each additional hardship experienced was associated with an increased average EDr of 7.7 percentage points (R2 = 0.34, P < 0.0001). Housing and utility hardships were each independently associated with increased EDr. HMH are associated with significantly increased EDr in children with SCD, independent of transportation hardship or insurance type. Through screening for HMH, providers and health systems could identify at-risk patients with modifiable risk factors for high EDr in order to provide them additional support.


Spatial-temporal differentiation and dynamic spatial convergence of inclusive low-carbon development: evidence from China.
Promoting green and low-carbon development has become a global consensus. However, few studies have explored the scientific connotation and influencing factors of inclusive low-carbon development (ILCD). Based on the perspective of inclusive growth and sustainable development, this paper constructs an economic growth-social inclusion-low carbon development (ESC) analytical framework and uses the improved entropy weight method to estimate the ILCD level of 30 provinces in China from 2006 to 2020. Kernel density estimation, Moran's I index, and Dagum Gini coefficient decomposition are used to characterize the spatial and temporal variation patterns, and the variation coefficient and the dynamic spatial Durbin model are used to explore the dynamic spatial convergence characteristics. The results show that (1) ILCD in China is increasing steadily overall, but there is a significant spatial non-equilibrium characteristic of high in the east and low in the west. (2) The overall difference in ILCD shows a trend of fluctuation and narrowing, and the imbalance between regions is the primary source of the overall difference. (3) ILCD has significant path dependence and dynamic spatial convergence characteristics in the whole country and the three regions, and the spatial spillover effect tends to be good neighborliness. The rate of convergence shows a trend of national (4.77%) > western (2.33%) > eastern (1.97%) > central (0.96%), and the spatial convergence of the club is gradually becoming prominent. (4) The factors including economic development, technological innovation, urbanization level and human capital significantly affect ILCD, which also has regional heterogeneous. Therefore, it is necessary to break down administrative and market barriers, strengthen cross-regional cooperation and resource interconnectivity, and bring into play policy synergy to provide decision-making reference for achieving inclusive low-carbon development.


Gate-Modulated Ultrasensitive Visible and Near-Infrared Photodetection of Oxygen Plasma-Treated WSe2 Lateral pn-Homojunctions.
We investigate the development of gate-modulated tungsten diselenide (WSe2)-based lateral pn-homojunctions for visible and near-infrared photodetector applications via an effective oxygen (O2) plasma treatment. O2 plasma acts to induce the p-type WSe2 for the otherwise n-type WSe2 by forming a tungsten oxide (WOx) layer upon O2 plasma treatment. The WSe2 lateral pn-homojunctions displayed an enhanced photoresponse and resulted in open-circuit voltage (VOC) and short-circuit current (ISC) originating from the pn-junction formed after O2 plasma treatment. We further notice that the amplitude of the photocurrent can be modulated by different gate biases. The fabricated WSe2 pn-homojunctions exhibit greater photoresponse with photoresponsivities (ratio of the photocurrent and incident laser power) of 250 and 2000 mA/W, high external quantum efficiency values (%, total number of charge carriers generated for the number of incident photons on photodetectors) of 97 and 420%, and superior detectivity values (magnitude of detector sensitivity) of 7.7 × 109 and 7.2 × 1010 Jones upon illumination with visible (520 nm) and near-infrared lasers (852 nm), respectively, at low bias (Vg = 0 V and Vd = 1 V) at room temperature, demonstrating very high-performance in the IR region superior to the contending two-dimensional material-based photonic devices. These superior optoelectronic properties are attributed to the junctions induced by O2 plasma doping, which facilitate the effective carrier generation and separation of photocarriers with applied external drain bias upon strong light absorption.


Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats.
Polyphenols from tea and other beverages such as red wine have been regarded with interest as possible chemopreventive agents against cancer. Here we report that red wine polyphenols (50 mg/kg) administered with the diet to F344 rats for 16 weeks inhibited colon carcinogenesis induced by azoxymethane (AOM, 7.4 mg/kg, total dose 74 mg/kg) or dimethylhydrazine (DMH, 30 mg/kg, total dose, 300 mg/kg). Polyphenol-treated animals had a consistently lower tumour yield compared to controls. In polyphenol-treated rats, the main bacterial strains in the faeces at sacrifice were Bacteroides, Lactobacillus and Bifidobacterium spp., whereas microorganisms predominantly identified in control-fed rats were Bacteroides, Clostridium and Propionibacterium spp. Wine polyphenols (57 mg/kg for 10 days, by gavage), administered to rats not treated with carcinogens, produced a significant decrease in the basal level of DNA oxidative damage of the colon mucosa as measured with the comet assay (average pyrimidine oxidation was reduced by 62% and purine oxidation by 57%, p<0.05). To further explore the molecular effects of wine polyphenols we used the microarray technology to study gene expression profiles: rats were treated with 50 mg/kg wine polyphenols for 14 days, mixed in the diet. Global expression analysis of 5707 genes revealed an extensive down-regulation of genes involved in a wide range of physiological functions, such as metabolism, transport, signal transduction and intercellular signalling. By analysing metabolic pathways with the GenMAPP software program we observed that two major regulatory pathways were down-regulated in the colon mucosa of polyphenols-treated rats: inflammatory response and steroid metabolism. We also found a down-regulation of many genes regulating cell surface antigens, metabolic enzymes and cellular response to oxidative stress. In conclusion, reduction of oxidative damage, modulation of colonic flora and variation in gene expression may all concur in the modulation of intestinal function and carcinogenesis by wine polyphenols.


Intraoral sonographic features of tongue cancer after radical radiotherapy.
The purpose was to illustrate the sonographic changes of tongue cancer after radical radiotherapy. In 24 patients with tongue cancer treated by interstitial brachytherapy (BRT) (uneventful recovery n = 16 , recurrence n = 5, severe soft tissue complication n = 3), follow-up examination were performed and both the margin and the vascular pattern were retrospectively assessed. We basically performed US examination at least once every 3 months after BRT within 1 year during follow-up period. In the healing process, intraoral sonography shows an unclear margin immediately after brachytherapy and a transient increase of the vascularity lasted within 6 months after BRT, followed by a decrease in the vascularity. The large difference in echogenicity between the primary site and the surrounding tissue and the increased difference suggested the possibility of either radiation ulceration or recurrence. Intraoral sonography could depict the sequence changes of the tongue after BRT, and it was thus useful to confirm the clinical findings of either radiation ulcers or recurrence.


[Ovarian hyperstimulation syndrome].
The ovarian hyperstimulation syndrome (OHSS) is a complication of controlled ovarian hyperstimulation (COH) protocols performed in women undergoing assisted reproductive technologies. This syndrome is characterized by multiple intra-ovarian corpus luteum and constitution of a third space that can lead to a life-threatening situation. Although the pathophysiology remains unclear, vascular endothelial growth factor (VEGF) and other cytokines, secreted under the influence of exogenous gonadotrophins administered for COH, are involved in increasing capillary permeability. The clinical course varies from increased size of the ovaries to anasarca with potentially fatal circulatory dysfunction. Mortality rate, though not accurately quantified, is significant (1/45 000 to 1/500 000) and mostly due to thromboembolic complications. The only effective treatment is prevention, by adapting ovarian stimulation protocols to OHSS risk factors. There are no specific treatments and therapy is mainly symptomatic until the condition resolves spontaneously.


Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance.
Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per-Arnt-Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK-/-) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK-/-), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A "lower" cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres, and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK-/- mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK-/- were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease.


Feasibility of using computerized tomography in diagnosing nasopharyngeal closure.
The feasibility of using computerized tomography for diagnosing nasopharyngeal anatomy and physiology was investigated. Ten adult subjects with normal communication were assessed with an Ohio-Nuclear Delta Scan 2020 Whole Body Computed Tomographic Scanner at two different levels of the nasopharynx during rest and production of /u/ and /s/. Lateral and anterior-posterior dimensions of the pharynx were simultaneously x-rayed and computed for each subject and condition. Computerized tomography appears to be useful in directly mapping the nasopharynx and in providing precise three-dimensional configurations without using a contrast medium.


Efficacy of Catheter Ablation for Nonparoxysmal Atrial Fibrillation.
Is catheter ablation better than antiarrhythmic drugs for the prevention of nonparoxysmal atrial fibrillation? Radiofrequency catheter ablation was found to be superior to antiarrhythmic drugs in preventing recurrences of nonparoxysmal atrial fibrillation and reducing hospital admissions.


Inhibitory effect of Salvia coccinea on inflammatory responses through NF-κB signaling pathways in THP-1 cells and acute rat diabetes mellitus.
Hyperglycemia-induced oxidative stress has been implicated in diabetes and its complications. Medicinal plants possessing antioxidant activity may decrease oxidative stress by scavenging radicals and reducing power activity and would be a promising strategy for the treatment of inflammatory disorders like diabetes. This study was designed to evaluate the antioxidant effect of Aqueous Extract of S.coccinea leaf (AESL) in HG treated THP-1 cells and streptozotocin (STZ)-induced diabetic Wistar rats. AESL and the standard antidiabetic drug glibenclamide were administered orally by intragastric tube for 14 days and pre-treated HG grown THP-1 cells. AESL treatment reduced HG induced increase in ROS production, NF-κB dependent proinflammatory gene expression by influencing NF-κB nuclear translocation in THP-1 cells. Oral administration of AESL inhibited STZ-induced increase in serum lipid peroxidation, aspartate transaminase, alanine transaminase, and Lactate dehydrogenase of diabetic rats. Significant increase in activity of superoxide dismutase, catalase and glutathione peroxidase, and a reduced level of glutathione, were observed in AESL treatment. The results demonstrate that AESL is useful in controlling blood glucose and also has antioxidant potential to influence the translocation of NF-κB, protect damage caused by hyperglycemia-induced inflammation.


Rundown of GH3 cell K+ conductance response to TRH following patch recording can be obviated with GH3 cell extract.
GH3/B6 pituitary cells release prolactin (PRL) in response to thyrotropin releasing hormone (TRH). Electrophysiological assays of individual GH3 cells with sharp high-resistance microelectrodes have revealed complex effects of TRH on membrane excitability consisting of a transient hyperpolarization (1), which is thought to result from activation of Ca-dependent K+ conductance (2), followed by a prolonged phase of spontaneous, Ca-dependent action potential activity (3). Using the whole-cell patch recording (WCR) technique (4), we have found that these TRH actions on GH3 excitability rapidly rundown following patch recording. When the supernatant from osmotically lysed GH3 cells was added to the WCR patch pipette, the K+ conductance response was not only promoted but well-maintained. The results indicate that diffusible factors mediate these TRH actions and further, that the WCR technique should be useful in identifying different second messengers and elucidating their roles in membrane excitability and PRL secretion.


Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes.
The effects of antifungal heptaene antibiotics candicidin and amphotericin B were investigated in isolated cerebral cortical nerve terminals (synaptosomes). The synaptosomes were incubated with candicidin or amphotericin B in the presence or absence of external Ca2+. Candicidin (0.4-0.8 I.U./mL) increased intrasynaptosomal free Ca2+ significantly. This increase was not significantly suppressed by 30 microM verapamil or 2 microM nifedipine. In the absence of extrasynaptosomal Ca2+ intrasynaptosomal free Ca2+ was not changed by candicidin. Amphotericin B increased intrasynaptosomal free Ca2+ as well. Candicidin (0.05-0.6 I.U./mL) increased the respiration rate up to 3.5-fold above the basal rate. This response was not affected by the absence of extracellular Ca2+. Ouabain completely blocked the increase of respiration caused by candicidin, whereas tetrodotoxin was ineffective. The plasma membrane depolarized in a dose-dependent manner after candicidin (0.2-0.8 I.U./mL). The mitochondrial membrane potential was little affected and only at the highest concentrations. The results indicate that heptaene polyenes increase synaptosomal ionic permeability, which is reflected in increased Ca2(+)-influx and accelerated respiration. The increment in synaptosomal free calcium takes place probably as a nonspecific leak via typical polyene-cholesterol channels. The respiration is accelerated by increased Na(+)-permeability through the plasma membrane which stimulates the function of Na+, K(+)-ATPase and thus increases the energy demand.


Predicting Weight Loss and Comorbidity Improvement 7 Years Following Laparoscopic Sleeve Gastrectomy: Does Early Weight Loss Matter?
Predicting the variables that affect the outcomes following laparoscopic sleeve gastrectomy (LSG) would allow focused resource allocation with a view to improving results. Whilst greater early post-operative weight loss following LSG is associated with greater short-term weight loss, the relationship between early results and long-term outcomes has not been described. A retrospective cohort analysis was performed on patients who underwent LSG 7 years before a follow-up telephone interview was performed. Multivariate regression analysis was used to explore the relationship between early weight loss at 4 weeks following surgery and weight loss at 7 years. A non-inferiority analysis assessed whether early weight loss was associated with either improvement or resolution of hypertension or type 2 diabetes mellitus (T2DM) at 7 years after surgery. Of the 156 patients identified between April and October 2012, 130 (83.3%) met the inclusion criteria and were included in the analysis. The average preoperative BMI was 42.5 kg/m2 (standard deviation 5.2). The change in BMI was 4.6 kg/m2 (4.0) at 4 weeks and 12.2 kg/m2 (5.4) at 7 years. There was improvement or resolution in 19/31 (61.3%) patients with T2DM and 14/26 (53.8%) patients with hypertension. Whilst younger age was associated with greater weight loss at 7 years follow-up, no such relationship was identified with early post-operative weight loss. Early post-operative weight loss was also not associated with long-term improvement or resolution in hypertension or T2DM. Early weight loss does not appear to be associated with greater weight loss nor comorbidity improvement 7 years following LSG. ClinicalTrials.gov (SZMC-95/19).


Effects of Laser Shock Peening on Microstructure and Properties of Ti-6Al-4V Titanium Alloy Fabricated via Selective Laser Melting.
Laser shock peening (LSP) is an innovative surface treatment process with the potential to change surface microstructure and improve mechanical properties of additively manufactured (AM) parts. In this paper, the influences of LSP on the microstructure and properties of Ti-6Al-4V (Ti64) titanium alloy fabricated via selective laser melting (SLM), as an attractive AM method, were investigated. The microstructural evolution, residual stress distribution and mechanical properties of SLM-built Ti64 samples were characterized before and after LSP. Results show that the SLM sample was composed of single hcp α' phase, which deviates from equilibrium microstructure at room temperature: α + β phases. The LSP significantly refines the grains of α' phase and produces compressive residual stress (CRS) of maximum magnitude up to -180 MPa with a depth of 250 μm. Grain refinement of α' phase is attributed to the complex interaction of dislocations and the intersection of deformation twinning subjected to LSP treatment. The main mechanism of strength and micro-hardness enhancement via LSP is ascribed to the effects of CRS and α' phase grain refinement.


Antimalarial therapy for lupus erythematosus: an apparent advantage of quinacrine.
A retrospective study of 26 quinacrine-treated lupus erythematosus patients failed to show evidence of drug-induced ocular changes. Although quinacrine commonly produces minor side effects, such as yellow discoloration of the skin, and may rarely produce very serious side effects, such as aplastic anemia, it appears to produce much less oculotoxicity than does chloroquine.


Epigenetic aging of the demographically non-aging naked mole-rat.
The naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age. We develop an epigenetic aging clock that accurately predicts the NMR age. We show that these animals age much slower than mice and much faster than humans, consistent with their known maximum lifespans. Interestingly, patterns of age-related changes of clock sites in Tert and Prpf19 differ between NMRs and mice, but there are also sites conserved between the two species. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.


Structural assessment of thalamus morphology in brain disorders: A review and recommendation of thalamic nucleus segmentation and shape analysis.
The thalamus is a central brain structure crucially involved in cognitive, emotional, sensory, and motor functions and is often reported to be involved in the pathophysiology of neurological and psychiatric disorders. The functional subdivision of the thalamus warrants morphological investigation on the level of individual subnuclei. In addition to volumetric measures, the investigation of other morphological features may give additional insights into thalamic morphology. For instance, shape features offer a higher spatial resolution by revealing small, regional differences that are left undetected in volumetric analyses. In this review, we discuss the benefits and limitations of recent advances in neuroimaging techniques to investigate thalamic morphology in vivo, leading to our proposed methodology. This methodology consists of available pipelines for volume and shape analysis, focussing on the morphological features of volume, thickness, and surface area. We demonstrate this combined approach in a Parkinson's disease cohort to illustrate their complementarity. Considering our findings, we recommend a combined methodology as it allows for more sensitive investigation of thalamic morphology in clinical populations.


The spectrum of multimodality imaging findings in hepatic alveolar echinococcosis and the potential role of diffusion-weighted imaging in its characterisation.
To study the spectrum of imaging findings in hepatic alveolar echinococcosis (HAE) and to evaluate the potential role of diffusion-weighted imaging (DWI) in its characterisation. Two radiologists with more than seven years of experience retrospectively studied ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) findings in 23 histopathologically proven cases of HAE with emphasis on the appearance and extent of disease. DWI characteristics of lesions were noted, and their apparent diffusion values (ADC) were calculated. Ultrasonography features of HAE included heterogeneous, hyperechoic hepatic mass with or without calcification (n = 20), or heterogeneous mass with solid-cystic appearance (n = 2). CT revealed heterogeneous density infiltrative hepatic mass with no contrast enhancement in 19 patients or thick-walled cystic mass (n = 4). Following Kodama classification one type 1, six type 2, two type 3, eight type 4, and two type 5 lesions were identified on T2-weighted MRI. No enhancement was seen on post-contrast T1-weighted images. Mean ADC values were 1.74 ± 0.48 × 10-3 mm2/s (range: 1.39 × 10-3 mm2/s to 2.3 × 10-3 mm2/s). HAE by virtue of its infiltrative growth pattern with a tendency to involve biliary, vascular, and extra hepatic structures can be easily misdiagnosed as malignant hepatic neoplasm. Knowledge of varied imaging appearances of HAE is essential to suspect the condition and to make an appropriate diagnosis. Diffusion-weighted imaging is a useful adjunct with relatively high diffusivity (high ADC values) suggesting diagnosis of alveolar hydatid.


Cardiovascular risk assessment by coronary artery calcium score in subjects with maturity-onset diabetes of the young caused by glucokinase mutations.
Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.


A novel approach to nodule feature optimization on thin section thoracic CT.
An analysis for the optimum selection of image features in feature domain to represent lung nodules was performed, with implementation into a classification module of a computer-aided diagnosis system. Forty-two regions of interest obtained from 38 cases with effective diameters of 3 to 8.5 mm were used. On the basis of image characteristics and dimensionality, 11 features were computed. Nonparametric correlation coefficients, multiple regression analysis, and principal-component analysis were used to map the relation between the represented features from four radiologists and the computed features. An artificial neural network was used for the classification of benign and malignant nodules to test the hypothesis obtained from the mapping analysis. Correlation coefficients ranging from 0.2693 to 0.5178 were obtained between the radiologists' annotations and the computed features. Of the 11 features used, three were found to be redundant when both nodule and non-nodule cases were used, and five were found redundant when nodule or non-nodule cases were used. Combination of analysis from correlation coefficients, regression analysis, principal-component analysis, and the artificial neural network resulted in the selection of optimum features to achieve F-test values of 0.821 and 0.643 for malignant and benign nodules, respectively. This study demonstrates that for the optimum selection of features, each feature should be analyzed individually and collectively to evaluate the impact on the computer-aided diagnosis system on the basis of its class representation. This methodology will ultimately aid in improving the generalization capability of a classification module for early lung cancer diagnosis.


The Optimization of Extraction Process, Antioxidant, Whitening and Antibacterial Effects of Fengdan Peony Flavonoids.
Flavonoids have important biological activities, such as anti-inflammatory, antibacterial, antioxidant and whitening, which is a potential functional food raw material. However, the biological activity of Fengdan peony flavonoid is not particularly clear. Therefore, in this study, the peony flavonoid was extracted from Fengdan peony seed meal, and the antioxidant, antibacterial and whitening activities of the peony flavonoid were explored. The optimal extraction conditions were methanol concentration of 90%, solid-to-liquid ratio of 1:35 g:mL, temperature of 55 °C and time of 80 min; under these conditions, the yield of Fengdan peony flavonoid could reach 1.205 ± 0.019% (the ratio of the dry mass of rutin to the dry mass of peony seed meal). The clearance of Fengdan peony total flavonoids to 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, hydroxyl radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical could reach 75%, 70% and 97%, respectively. Fengdan peony flavonoid could inhibit the growth of the Gram-positive bacteria. The minimal inhibitory concentrations (MICs) of Fengdan peony flavonoid on S. aureus, B. anthracis, B. subtilis and C. perfringens were 0.0293 mg/mL, 0.1172 mg/mL, 0.2344 mg/mL and 7.500 mg/mL, respectively. The inhibition rate of Fengdan peony flavonoid on tyrosinase was 8.53-81.08%. This study intensely illustrated that the antioxidant, whitening and antibacterial activity of Fengdan peony total flavonoids were significant. Fengdan peony total flavonoids have a great possibility of being used as functional food materials.