Bu-M-P-ing Iron: How BMP Signaling Regulates Muscle Growth and Regeneration.
The bone morphogenetic protein (BMP) pathway is best known for its role in promoting bone formation, however it has been shown to play important roles in both development and regeneration of many different tissues. Recent work has shown that the BMP proteins have a number of functions in skeletal muscle, from embryonic to postnatal development. Furthermore, complementary studies have recently demonstrated that specific components of the pathway are required for efficient muscle regeneration.


CD4+CD25+ and CD4+CD2+high regulatory T cells in disseminated and localized forms of allergic contact dermatitis: relation to specific cytokines.
The aim of this study was to evaluate regulatory T lymphocytes (Tregs) in the course of allergic contact dermatitis (ACD) and to elucidate the role of IL-10 and TGF-β in Tregs activity. Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) cells were determined by flow cytometry in patients with acute disseminated ACD ('ad', n = 36), acute localized ACD ('al', n = 26), and disseminated ACD during remission ('rd', n = 27) as well as in controls (n = 22). Serum levels of cytokines were measured using ELISA. The mean percentage of CD4(+)CD25(+) and CD4(+)CD25(high) cells in patients with ad ACD was significantly higher than in controls (p < 0.01) and the remaining patients (p < 0.05). Both cell populations were significantly elevated in persons with widespread skin lesions (p < 0.05). In ad patients the CD4(+)CD25(+) increased during three weeks of disease, although the significant increase of CD4(+)CD25(high) was noted only in the third week. Patients with ad ACD showed a significantly decreased serum level of TGF-β1 as compared with controls and the remaining ACD patients. IL-10 level did not differ between all groups. The elevated population of CD4(+)CD25(high) cells in ad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating the course of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. The development of lesions despite an increased population of Tregs suggests their functional defect. The role of TGF-β1 in the suppressive activity of Tregs cannot be excluded.


[Long-term response to rituximab in a patient with acquired hemophilia].
A 28 year-old female without history of previous disease. In the seventh month of her first pregnancy she developed hemorrhagic tendency that worsened in the early postpartum period. Activated partial thromboplastin time was 110 sec (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial therapy included methylprednisolone, prednisone, and cyclophosphamide. After two weeks of treatment, clinical conditions of the patient improved slightly and she was discharged. Outpatient therapy included azathioprine, and prednisone for a period of 22 months but in-hospital management was several times required. We initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased levels of factors VIII and XI were observed 10 weeks later and factor VIII inhibitor decreased to undetectable levels. After a 82-month follow-up period (since the first rituximab infusion), she is asymptomatic and factor VIII and factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is still undetectable. Rituximab seems an alternative for the treatment of acquired hemophilia refractory to standard treatment.


[The incidence of certain E. coli serotypes in urinary tract infections in childhood and their source].
E. coli strains isolated from urine and feces specimens of 100 children with urinary tract infection and, from feces specimens of 50 apparently healthy children, were typed by using antisera prepared against 01-02-04-06-07-09-011-018-039-075 serotypes which are commonly seen in urine. 67% of E. coli strains isolated from urine, 51% from feces of patients and 34% of control group were typed. Urinary type 075 was most commonly isolated strain of E. coli in our experiments. 29.4% of E. coli 0 serotypes were fitting as being isolated both from urine and feces of patients with urinary tract infection.


Assessment of total- and partial-body irradiation in a baboon model: preliminary results of a kinetic study including clinical, physical, and biological parameters.
This biodosimetry study used irradiated baboons to investigate the efficacy of a kinetic multiparameter (clinical, physical, and biological) approach for discriminating partial-body irradiation (PBI) and total-body irradiation (TBI). Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min) using either TBI or vertical left hemi-body irradiation (HBI), as follows: 2.5 Gy TBI (n = 2), 5 Gy TBI (n = 2), 5 Gy HBI (n = 2), and 10 Gy HBI (n = 2). Midline tissue doses were measured at the anterior iliac crest level with an ionization chamber, and body dosimetry was performed using thermoluminescent dosimeters. Blood samples were collected before exposure and from 1 h until 200 d after irradiation. Clinical status, complete blood cell count, biochemical parameters, and cytogenetic analysis were evaluated. The partial least square discriminant analysis chosen for statistical analysis showed that the four groups of irradiated baboons were clearly separated. However, the dicentric chromosome assay may not distinguish HBI from TBI in confounding situations where equivalent whole-body doses are similar and the time of exposure is sufficient for peripheral blood lymphocyte homogenization. Interestingly, as bone marrow shielding in HBI animals prevented aplasia from happening, hematologic parameters such as the platelet count and Flt-3 ligand level helped to distinguish HBI and TBI. Moreover, the ratio of neutrophil to lymphocyte counts, creatine kinase, and citrulline levels may be discriminating biomarkers of dose or injury. Both early and delayed clinical signs and bioindicators appear to be useful for assessment of heterogeneous irradiation.


An Ethical Framework for Presenting Scientific Results to Policy-Makers.
Scientists have the ability to influence policy in important ways through how they present their results. Surprisingly, existing codes of scientific ethics have little to say about such choices. I propose that we can arrive at a set of ethical guidelines to govern scientists' presentation of information to policymakers by looking to bioethics: roughly, just as a clinician should aim to promote informed decision-making by patients, a scientist should aim to promote informed decision-making by policymakers. Though this may sound like a natural proposal, I show it offers guidance that conflicts with standard scientific practices. I conclude by considering one cost of the proposal: that it would prevent scientists from acting as advocates in a way that is currently common in certain fields. I accept that the proposal would restrict scientists' political advocacy rights, but argue that the benefits of adopting it-promoting democratic governance-justify the restriction.


The Role of Proton Pump Inhibitors in the Management of Upper Gastrointestinal Disorders.
Proton pump inhibitors (PPIs) have been in use since the early 1990s and play a crucial role in the management of a number of conditions affecting the upper gastrointestinal tract, including gastroesophageal reflux disease, Barrett esophagus, eosinophilic esophagitis, and dyspepsia. PPIs also play an important role in the treatment of Helicobacter pylori infection and in the prevention of upper gastrointestinal tract ulcers and bleeding among patients taking antiplatelet therapy and/or nonsteroidal anti-inflammatory drugs. Despite recent concerns regarding the long-term safety of PPIs, their risk-benefit profiles strongly favor their appropriate use in patients who have genuine indications for them. As with all drugs, PPIs should be administered in the lowest effective dose and only for as long as clinically indicated. However, for at least some of their approved indications, PPIs are likely to be required indefinitely. This article outlines the current indications for PPIs for the management of upper gastrointestinal disorders and reviews safety concerns.


Kefir and Its Biological Activities.
Kefir is a fermented beverage with renowned probiotics that coexist in symbiotic association with other microorganisms in kefir grains. This beverage consumption is associated with a wide array of nutraceutical benefits, including anti-inflammatory, anti-oxidative, anti-cancer, anti-microbial, anti-diabetic, anti-hypertensive, and anti-hypercholesterolemic effects. Moreover, kefir can be adapted into different substrates which allow the production of new functional beverages to provide product diversification. Being safe and inexpensive, there is an immense global interest in kefir's nutritional potential. Due to their promising benefits, kefir and kefir-like products have a great prospect for commercialization. This manuscript reviews the therapeutic aspects of kefir to date, and potential applications of kefir products in the health and food industries, along with the limitations. The literature reviewed here demonstrates that there is a growing demand for kefir as a functional food owing to a number of health-promoting properties.


A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information.
The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.


RH-0345 restored partly the effects induced by KK-42 on reproductive events in mealworms.
In the mealworm, Tenebrio molitor L., KK-42, an imidazole derivative, was found to reduce ovarian ecdysteroid production, while RH-0345, a benzoylhydrazine analogue, has been reported to affect growth and development of mealworm ovaries in a manner similar to 20-hydroxyecdysone. In order to determine whether the reduction of reproduction events is dependent on inhibition of ecdysteroid production by ovaries, RH-0345 (10 micrograms/insect) was applied before or after topical application of KK-42 (10 micrograms/insect) on newly emerged adult females. KK-42 applied alone increased significantly the pre-oviposition period compared to controls. It also significantly delayed egg-laying compared to combined treatments using KK-42 before or after RH-0345. KK-42 applied alone or with and before RH-0345, was found to reduce significantly the duration of oviposition period. Moreover, there was a significant difference in the duration of oviposition period between the two combined treatments. The fecundity was significantly reduced in all treated series compared to controls. In addition, the fecundity recorded in treated series by RH-0345 alone or before KK-42 was significantly higher than in KK-42 treated series. Lastly, the viability of eggs laid was significantly reduced in all treated series compared to controls. Moreover, the combined treatment pronounced the reduction in egg viability. Free ecdysteroids (ecdysone and 20-hydroxyecdysone) in eggs of control and RH-0345 treated females were analyzed by an enzymo-immunoassay using two specific antibodies.


Configuration Design and Dynamic Characteristics Analysis of Spacecraft Membrane Sunshield.
To meet the needs of large space telescopes, such as light weight, high folding ratio, and low manufacturing cost, a flexible deployable regular hexagonal membrane sunshield is proposed in this paper. Firstly, the dynamic equation of the membrane plane is established by the micro-element method. Then, the response surface method is used to obtain the mathematical model of the fundamental frequency of the membrane sunshield. The factors influencing this model, such as the corner pulling force, the effective circle radius, and the edge arch height, are analyzed. By combining the formula of the fundamental frequency of the membrane sunshield and the effective area ratio of the sunshield, the multi-objective optimization function of the fundamental frequency of the membrane sunshield is obtained. A scaled-down experimental prototype of the membrane sunshield is built, and the modal test is performed on the thin membrane plane with a circular fixed boundary in the middle. Comparing the experimental results with the finite element simulation results, the mode shape and the fundamental frequency are highly consistent. This proves that the model can be used to solve the fundamental frequency of the membrane sunshield under the same boundary.


The Hamburg Spondylodiscitis Assessment Score (HSAS) for Immediate Evaluation of Mortality Risk on Hospital Admission.
(1) Background: Patients with spondylodiscitis often present with unspecific and heterogeneous symptoms that delay diagnosis and inevitable therapeutic steps leading to increased mortality rates of up to 27%. A rapid initial triage is essential to identify patients at risk for a complicative disease course. We therefore aimed to develop a risk assessment score using fast available parameters to predict in-hospital mortality of patients admitted with spondylodiscitis. (2) Methods: A retrospective data analysis of 307 patients with spondylodiscitis recruited from 2013 to 2020 was carried out. Patients were grouped according to all-cause mortality. Via logistic regression, individual patient and clinical characteristics predictive of mortality were identified. A weighted sum score to estimate a patient's risk of mortality was developed and validated in a randomly selected subgroup of spondylodiscitis patients. (3) Results: 14% of patients with spondylodiscitis died during their in-hospital stay at a tertiary center for spinal surgery. Univariate and logistic regression analyses of parameters recorded at hospital admission showed that age older than 72.5 years, rheumatoid arthritis, creatinine > 1.29 mg/dL and CRP > 140.5 mg/L increased the risk of mortality 3.9-fold, 9.4-fold, 4.3-fold and 4.1-fold, respectively. S. aureus detection increased the risk of mortality by 2.3-fold. (4) Conclusions: The novel Hamburg Spondylodiscitis Assessment Score (HSAS) shows a good fit identifying patients at low-, moderate-, high- and very high risk for in hospital mortality on admission (AUC: 0.795; p < 0.001). The implementation of the HSAS into clinical practice could ease identification of high-risk patients using readily available parameters alone, improving the patient's safety and outcome.


Increase of plasma IgE during treatment correlates with better outcome of patients with glioblastoma.
Previous studies have shown that glioma patients have lower blood IgE levels than controls. To evaluate its potential as a surrogate biomarker for glioma, we measured plasma IgE levels in glioma patients and healthy controls, and correlated them with clinicopathological factors and the patients' outcome. We used enzyme-linked immunosorbant assay (ELISA) to determine the plasma IgE levels of 25 normal subjects and 252 glioma patients (85 patients with grade II glioma, 46 patients with grade III glioma, and 121 patients with glioblastoma). We also collected longitudinal plasma samples from glioblastoma patients and compared the plasma IgE levels before operation, one week after operation, in the middle of radiotherapy, after two cycles of chemotherapy, and after recurrence. The correlations between plasma IgE levels and the outcomes of the patients were determined. Plasma IgE levels were significantly lower in glioma patients (P = 0.004); patients with low-grade glioma have lower IgE levels than patients with high-grade glioma do (P = 0.029). In 24 patients with both preoperative plasma and two-cycle chemotherapy plasma samples, IgE levels increased after successful removal of the tumor (P = 0.021), and the increase correlated with the patients' survival (increase > 100 ng/ml vs. ≤ 100 ng/ml, 127.5 weeks vs. 62.3 weeks. P = 0.012, log-rank). Plasma IgE level increase of > 100 ng/ml has a specificity of 80% and a sensitivity of 78% to predict the patients' long survival (> 18 months). Our results suggest that plasma IgE level correlates with clinical and pathological factors in glioma patients. It has the potential to be a biomarker for glioma patients.


Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin.
Bradykinin (BK) liberates nitric oxide, prostacyclin, and tissue plasminogen activator from endothelial cells. We hypothesized that BK B2 receptor knockout (KO) mice (BKB2R(-/-)) have increased thrombosis risk. Paradoxically, the BKB2R(-/-) mice have long bleeding times and delayed carotid artery thrombosis, 78 +/- 6.7 minutes, versus 31 +/- 2.7 minutes in controls. The mechanism(s) for thrombosis protection was sought. In BKB2R(-/-) plasma coagulation, fibrinolysis and anticoagulant proteins are normal except for an increased prekallikrein and decreased factor XI. BKB2R(-/-) mice have elevated BK 1-5 (160 +/- 75 fmol/mL, vs 44 +/- 29 fmol/mL in controls) and angiotensin II (182 +/- 41 pg/mL, vs 49 +/- 7 pg/mL in controls). Ramipril treatment shortens vessel occlusion time. BKB2R(-/-) mice have elevated plasma 6-keto-PGF1alpha (666 +/- 232 ng/mL, vs 23 +/- 5.3 ng/mL in controls) and serum nitrate (61 +/- 5.3 microM, vs 24 +/- 1.8 microM in controls). Treatment with L-NAME (NG-mono-methyl-L-arginine ester) or nimesulide shortens the thrombosis time. BKB2R(-/-) mice have increased angiotensin receptor 2 (AT2R) mRNA and protein expression. Treatment with an AT2R antagonist, PD123 319, normalizes the thrombosis time and nitrate and 6-keto-PGF1alpha. The long bleeding times in BKB2R(-/-) mice also correct with L-NAME and nimesulide therapy. In BKB2R(-/-) mice, angiotensin II binding to an overexpressed AT2R promotes thromboprotection by elevating nitric oxide and prostacyclin. These investigations indicate a pathway for thrombosis risk reduction via the plasma kallikrein/kinin and renin angiotensin systems.


Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery.
Intestinal organoids can be used as an ex vivo epithelial model to study different drug delivery effects on epithelial cells' luminal surface. In this study, the impact of surface charge on the delivery of 5-ASA loaded PLGA nanoparticles into the lumen of organoids was investigated. Alginate and chitosan were used to coat the nanoparticles and provide negative and positive charges on the particles, respectively. The organoid growth and viability were not affected by the presence of either alginate- or chitosan-coated nanoparticles. It was shown that nanoparticles could be transported from the serosal side of the organoids to the lumen as the dye gradually accumulated in the lumen by day 2-3 after adding the nanoparticles to the Matrigel. By day 5, the dye was eliminated from the lumen of the organoids. It was concluded that the positively charged nanoparticles were more readily transported across the epithelium into the lumen. It may be attributed to the affinity of epithelial cells to the positive charge. Thus, the organoid can be utilized as an appropriate model to mimic the functions of the intestinal epithelium and can be used as a model to evaluate the benefits of nanoparticle-based drug delivery.


Neuroimaging through Sonolucent Cranioplasty: A Systematic Scoping Review Protocol.
Cranioplasty is a neurosurgical procedure in which the skull bone is repaired after craniectomy. Recently, studies have suggested that sonolucent synthetic materials are safe and useful for cranioplasty. Sonolucent cranioplasty (SC) implants provide unprecedented opportunity in adult neurosurgery to monitor neuroanatomy, assess hemodynamics, view devices located within the implant, and conduct focused ultrasound treatments. Current research on SC includes proof-of-concept cadaveric studies, patient-related safety and feasibility studies, and case series demonstrating transcranioplasty ultrasonography (TCUS). The purpose of this protocol is to investigate the current literature on SC use and outcomes in TCUS. We will perform a systematic literature search following PRISMA-ScR guidelines. The search will be conducted using Ovid Embase, Ovid Medline, and Web of Science Core Collection databases. Titles, abstracts, and full texts will be screened. Joanna Briggs Institute critical appraisal tools will be utilized. Data extraction points will include subject characteristics, SC implant characteristics, ultrasound characteristics, and sonographic findings. These findings will provide a comprehensive review of the literature on sonolucent cranioplasty and directions for future research.


Natural products targeting strategies involving molecular networking: different manners, one goal.
Covering: up to 2019Landmark advances in bioinformatics tools have recently enhanced the field of natural products research, putting today's natural product chemists in the enviable position of being able to perform the efficient targeting/discovery of previously undescribed molecules by expediting the prioritization of the isolation workflow. Among these advances, MS/MS molecular networking has appeared as a promising approach to dereplicate complex natural product mixtures, leading to a real revolution in the "art of natural product isolation" by accelerating the pace of research of this field. This review illustrates through selected cornerstone studies the new thinking in natural product isolation by drawing a parallel between the different underlying philosophies behind the use of molecular networking in targeting natural products.


The Effect of Humidity on the Dissolution Kinetics and Tablet Properties of Immediate-Release Tablet Formulation Containing Lamotrigine.
This study aims to find the effects of high (75%) and low (30%) humidity conditions and its correlation with formulation composition on dissolution kinetics of lamotrigine (LMT) from prepared immediate-release tablets during one- and four-week periods. Two types of fillers microcrystalline cellulose (MCC) or anhydrous lactose (LAC), disintegrant sodium starch glycolate (NaSG, 0.5% or 4%), and lubricant magnesium stearate (MgST, 0.25% or 5%) were used. A three-factor two-stage complete factorial design (23) was used to assess the influence of the composition of the tested formulations. The tablets were produced by direct compression and characterized using a disintegration test, a resistance to crushing test, and dissolution tests (pH 1.2 and pH 6.8). Using Design Expert software, it was concluded that in addition to the effect of fillers on pH 6.8, NaSG has a significant impact after exposure to high and low humidity, as well as its interaction with LAC and MCC. In the dissolution medium pH 1.2, under conditions of high humidity, the content of MgST and NaSG and their interaction show a significant influence. The release rate of LMT was affected by humidity as well as type of excipients and their interactions.


Effect of Central Line Bundle Compliance on Central Line-Associated Bloodstream Infections.
The present study aimed to evaluate the effect of central line (CL) bundle compliance on central line-associated bloodstream infections (CLABSIs) in different departments of the same hospital, including the intensive care unit (ICU) and other departments. The four components of the CL bundle were hand hygiene, use of maximal sterile barrier precautions, chlorhexidine use, and selection of an appropriate site for venous access. Compliance of the CL bundle and CLABSIs were measured for every department [emergency room (ER), ICU, general ward (GW), and operating room (OR)]. A total of 1672 patients were included over 3 years (August 2013 through July 2016). A total of 29 CLABSI episodes (1.73%) were identified, and only 53.7% of the patients completed CL bundles. The performance rates of all components of the CL bundle were 22.3%, 28.5%, 36.5%, and 84.6% for the ER, ICU, GW, and OR, respectively. The highest CLABSI rate was observed in patients of the ICU, for whom all components were not performed perfectly. Conversely, the lowest CLABSI rate was observed for patients of GWs, for whom all components were performed. Among individual components, femoral insertion site [relative risk (RR), 2.26; 95% confidence interval (CI), 1.09-4.68], not using a full body drape (RR, 3.55; 95% CI, 1.44-8.71), and not performing all CL bundle components (RR, 2.79; 95% CI, 1.19-6.54) were significant variables associated with CLABSIs. This study provides direct evidence that completing all CL bundle components perfectly is essential for preventing CLABSIs. Customized education should be provided, according to specific weaknesses of bundle performance.


Alpha-adrenergic stimulation of sarcolemmal protein phosphorylation and slow responses in intact myocardium.
The effects of alpha- and beta-adrenergic stimulation on sarcolemmal protein phosphorylation and contractile slow responses were studied in intact myocardium. Isolated rat ventricles were perfused via the coronary arteries with 32Pi after which membrane vesicles partially enriched in sarcolemma were isolated from individual hearts. Alterations in the sarcolemmal slow inward Ca2+ current were assessed in the 32P-perfused hearts using a contractile slow response model. In this model, Na+ channels were first inactivated by partial depolarization of the hearts in 25 mM K+ after which alterations in Ca2+ channel activity produced by either alpha- or beta-adrenergic agonists could be assessed as restoration of contractions. alpha-Adrenergic stimulation (phenylephrine + propranolol) of the perfused hearts resulted in increased 32P incorporation into a 15-kDa sarcolemmal protein. This protein co-migrated with the 15-kDa sarcolemmal protein phosphorylated in hearts exposed to beta-adrenergic stimulation produced by isoproterenol. beta-Adrenergic stimulation, but not alpha-adrenergic stimulation, also resulted in phosphorylation of the sarcoplasmic reticulum protein, phospholamban. Phosphorylation of the 15-kDa protein in perfused hearts in response to either alpha- or beta-adrenergic stimulation was associated with restoration of contractions, indicative of increases in the slow inward Ca2+ current. Increases in 32P incorporation into the 15-kDa protein preceded restoration of contractions by phenylephrine. Nifedipine abolished the contractile responses to alpha-adrenergic stimulation while having no effect on increases in 15-kDa protein phosphorylation. The effects of alpha-adrenergic stimulation occurred in the absence of increases in cAMP levels. These results suggest that phosphorylation of the 15-kDa protein may be involved in increases in the slow inward current produced by stimulation of either alpha- or beta-adrenergic receptors.


Exploring relationships between personality and anatomy performance.
There is increasing recognition in medicine of the importance of noncognitive factors, including personality, for performance, and for good medical practice. The personality domain of conscientiousness is a well-established predictor of performance in workplace and academic settings. This study investigates the relationships between the "Big Five" personality domains, the facets of conscientiousness and performance in a practical anatomy examination. First- and second-year undergraduate medical students (n = 85) completed a paper-based questionnaire, which included a 50-item measure of the Big Five personality domains (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and a 60-item measure of the six conscientiousness facets (orderliness, dutifulness, achievement-striving, self-discipline, self-efficacy, and cautiousness) from the International Personality Item Pool (IPIP). In addition, routinely-collected academic performance scores from the end of semester anatomy practical examinations (spotters) were obtained. Anatomy examination performance correlated moderately with conscientiousness (r = 0.24, P = 0.03). Of the six facets of conscientiousness, a positive relationship was observed between anatomy examination performance and achievement striving (r = 0.22, P = 0.05). In conclusion, this study found that performance in an anatomy examination was related to higher levels of conscientiousness and, more specifically, to higher levels of achievement striving. The results have implications for selection and assessment in medicine.


Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment.
A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This 'metabolic bacteremia' is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.


The rate of checking urine microalbumin and aspirin primary prevention in type 2 DM.
The American Diabetic Association recommends type 2 Diabetes Mellitus (DM) to take aspirin therapy as a primary preventive way. It should be implemented in cases that are aged over 40 with at least one additional risk such as hypertension, obesity, dyslipidemia. Urine microalbumin now also ranks as a major risk factor for atherosclerosis. The authors aimed to evaluate the rate of urine microalbumin determination and the use of such preventative aspirin therapy at Srinagarind Hospital. The authors randomly selected the charts of type 2 diabetics treated for at least one year at the hospital a outpatient department by a block of four techniques. The inclusion criteria were aged more than 40 years old and never had any atherosclerotic events. Cases were excluded if they had a history of aspirin allergy or active upper gastrointestinal bleeding. By the end of July, 2004, 109 patients were enrolled (44 males). The mean age and duration of diagnosed diabetes mellitus was 60.8 and 7.4 years, respectively. Forty-four cases (40.4%) were checked for urine microalbumin. Eight cases had microalbuminuria and four cases had macroalbuminuria. Every case was treated with aspirin because they had at least one additional atherosclerotic risk factor, mostly more than two. But aspirin therapy was used in only 35 cases (32.1%) with the appropriate dose in only six cases (17.1%). Physicians should consider more about checking urine microalbumin and aspirin as primary prevention in type 2 DM.


Heat-related deaths among construction workers in the United States.
Heat is a severe hazard for construction workers and may be worsening with global warming. This study sought to explore heat-related deaths among U.S. construction workers and a possible association with climate change. Heat-related deaths in the Census of Fatal Occupational Injuries from 1992 to 2016 were analyzed. Denominators estimated from the Current Population Survey were matched with demographic and occupational categories in rate calculations. Statistical tests were used to examine heat-related deaths in relation to time, geographic region, and temperature. Construction workers, comprising 6% of the total workforce, accounted for 36% (n = 285) of all occupational heat-related deaths from 1992 to 2016 in the U.S. Mean temperatures from June to August increased gradually over the study period. Increasing summer temperatures from 1997 to 2016 were associated with higher heat-related death rates (r = 0.649; 95% confidence interval: 0.290, 0.848). Compared to all construction workers (risk index = 1), statistically significant elevated risk of heat-related death was found among Hispanics (1.21), in particular workers born in Mexico (1.91). Occupations with a high risk index included cement masons (10.80), roofers (6.93), helpers (6.87), brick masons (3.33), construction laborers (1.93) and heating, air conditioning, and refrigeration mechanics (1.60). U.S. construction workers are at a high risk of heat-related death, and this risk has increased with climate change over time. Effective workplace interventions, enhanced surveillance, and improved regulations and enforcement should accompany broader efforts to combat global warming. The construction industry can help reduce global warming through increased implementation of green building principles.


Simple Universal Strategy for Quantification of Carboxyl Groups on Carbon Nanomaterials: Carbon Dioxide Vapor Generation Coupled to Microplasma for Optical Emission Spectrometric Detection.
The physicochemical properties and applications of carbon nanomaterials are remarkably dependent on the amount of carboxyl group on their surfaces. Unfortunately, it is challenging to determine the carboxyl group on carbon nanomaterials at an ultralow density not only due to the low sensitivities of conventional techniques, but also because there are no matrix-matched certified reference materials available. In this work, a novel strategy comprising coupling carbon dioxide vapor generation to a microplasma optical emission spectrometer was developed for the sensitive and accurate quantification of surface carboxyl groups on carbon nanomaterials. The carboxyl group on multiwall carbon nanotubes (MWCNTs), graphene (G), or its oxide (GO) was converted to carboxylic acid using concentrated hydrochloric acid prior to quantification. The generated carboxylic acid was purified and then reacted with sodium bicarbonate to generate CO2, which was swept into a miniaturized point discharge optical emission spectrometer (μPD-OES) for the detection of carbon atomic emission lines. Potassium hydrogen phthalate (KHP) served as a calibration standard for quantification of the carboxyl group on G/GO/MWCNTs, thus, overcoming the lack of CRMs. Owing to the high sensitivity of μPD-OES for the detection of CO2, a limit of detection of 0.1 μmol g-1 (1 nmol) was obtained for the carboxyl group based on a sample mass of 10 mg G/GO/MWCNTs, superior to that obtained using conventional methods. Moreover, the proposed method not only retains several unique advantages of good accuracy and elimination of the use of complicated, expensive, and high power-consumption instruments, but was also applicable to the quantification of the carboxyl group on other nanomaterials such as carboxylated magnetic microspheres.


Fear and pain: investigating the interaction between aversive states.
Pain and fear often co-occur and appear to interact, although the nature and direction of their relation is not clearly delineated. The present study investigates how exposure to the experience of one of these states subsequently affects responding to the other. Pressure stimulation and carbon dioxide-enriched air (CO2) were used to induce pain and fear, respectively, in 48 healthy individuals. The order in which the stimuli were introduced was manipulated, as was the CO2 level. Measures of overt behavior, physiological responding, and self-report were obtained; analyses of stimuli effects generally supported their ability to produce pain or fear. Results indicate that the stimulus rated as the most aversive, the higher level of CO2, led to the highest levels of distressed responding across dependent measures. This pattern was replicated for the stimuli found to be less aversive (i.e., pressure stimulation and low-level CO2, respectively). The authors conclude that fear and pain, in and of themselves, do not dictate the nature of their interaction; the most important factor is how aversive they are perceived to be in relation to one another.


Role of microbiological factors in predicting early childhood caries.
Microbiological methods that accurately identify caries-susceptible children may enhance caries control and assist treatment planning. This study's purpose was to evaluate the usefulness of two microbiological indicators (mutans streptococci [MS] and lactobacilli [LB] levels), singly and in combination, for predicting early childhood caries (ECC) and their contributions in multifactorial modeling. A total of 1,782 randomly selected three- to five-year-olds were recruited and underwent oral examination and microbiological tests using commercially available diagnostic kits. A questionnaire was completed by their parents. After 12 months, the caries increment in 1,576 (∼88 percent) children was assessed. Caries risk increased with the MS and LB levels but plateaued above the LB level of 10(5) CFU/ml saliva. MS, LB, and combined MS+LB models predicted one-year caries increment (Δdmft>0) with a sensitivity/specificity of 79 percent/67 percent, 51 percent/89 percent, and 66 percent/85 percent, respectively. Sensitivity/specificity reached 80 percent/80 percent when baseline caries experience ("past caries") was added to the MS+LB model and up to 85 percent/80 percent and 81 percent/85 percent when psychosociobehavioral factors and oral hygiene status were added to the MS+LB model, without and with "past caries," respectively. The combined "mutans streptococci+lactobacilli+past caries" model is useful for identifying at-risk children. Incorporating MS and LB into a biopsychosociobehavioral model slightly improved the prediction, even without "past caries".


Trabeculectomy versus trabeculotomy in congenital glaucoma.
Congenital glaucoma is one of the main causes of blindness in children and is more common in Saudi Arabia than in Western countries, perhaps owing to the prevalence of consanguinity with families. Trabeculotomy has given poorer in Saudi Arabia than elsewhere. This study compared the results of trabeculotomy (67% success rate) with trabeculectomy (54% success rate), and reports fewer complications following trabeculotomy.


Intraparticle concentration gradients for substrate and acidic product in immobilized cephalosporin C amidase and their dependencies on carrier characteristics and reaction parameters.
Cephalosporin C amidase was covalently attached using a protein loading of 7.0-200 mg protein/g dry carrier on four epoxy-activated Sepabeads differing in particle size and pore diameter. Initial-rate kinetic analysis showed that for Sepabeads with small pore diameters (30-40 nm), the apparent K(M) of the amidase for hydrolysis of cephalosporin C at 37 degrees C and pH 8.0 increased approximately 3-fold in response to increased particle size (approximately 120-400 microm) and increased amount of immobilized enzyme (7.0-70 mg protein/g dry carrier) while maximum specific activity (3.2 U/mg protein; 25% of free amidase) was affected only by particle size. In contrast, for Sepabeads with wide pores (150-250 nm), the K(M) was independent of the enzyme loading. Internal effectiveness factors calculated from observable Thiele modulus reflected the dependence of K(M) on geometrical parameters of the particles. A new method for determination of the overall intraparticle pH was developed based on luminescence lifetime measurements in the frequency domain. Sepabeads were doubly labeled using a lipophilic variant of the pH-sensitive dye fluorescein, and Ru(II) tris(4,7-diphenyl-1,10-phenantroline) whose phosphorescence properties are independent of pH. Luminescent lifetime measurements of doubly labeled particle suspensions showed superior signal-to-noise ratio compared to fluorescence intensity-based measurements using singly labeled particles. The difference at apparent steady state (DeltapH) between bulk (external pH) and intraparticle pH (internal pH) was as large as approximately 0.6 units. The DeltapH was dependent on substrate concentration, particle size, and pore diameter. Therefore, these results characterize the role of carrier characteristics and reaction parameters in the formation of concentration gradients for substrate and acidic product during hydrolysis of cephalosporin C by immobilized amidase. The strong pH dependence of the immobilized amidase underscores the importance of considering intraparticle pH gradients in the design of an efficient carrier-bound biocatalyst.


Persistence and biodegradation of carbaryl in soils.
The persistence of the methylcarbamate pesticide carbaryl was studied in four soils under flooded conditions. A substantial portion of the pesticide was recovered from all soils even after 15 days of its application, with the recovery ranging from 37% in an alluvial soil to 73% in an acid sulfate soil. The degradation of carbaryl was more rapid under flooded conditions than under nonflooded conditions. A bacterium, Pseudomonas cepacia, isolated from a flooded soil amended with a related methylcarbamate pesticide carbofuran, degraded carbaryl in a mineral medium supplemented with yeast extract.


[Acute pancreatitis after bilateral laparoscopic adrenalectomy in patients with ectopic ACTH syndrome].
Two cases of acute necrotizing pancreatitis after bilateral laparoscopic adrenalectomy were observed in patients with an ectopic ACTH syndrome. Two reasons may be suspected: the difficulty of dissection in such patients and the specific morbidity in relation to hypercorticism.


Long non-coding RNA FEZF1-AS1 is up-regulated and associated with poor prognosis in patients with cervical cancer.
Long noncoding RNA FEZF1-AS1 (FEZF1-AS1) has been showed to involve in a variety of cancers. However, its function and clinical significance in cervical cancer (CC) have not been investigated. The aim of this study was to explore the prognostic value of FEZF1-AS1 in CC patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of FEZF1-AS1 in CC specimens and adjacent normal cervical tissues. Association between FEZF1-AS1 expression and clinicopathological characteristics was analyzed x2-test. The Kaplan-Meier method was used to estimate survival curves, and the log-rank statistic was used to test the role of FEZF1-AS1 expression. The possibility of FEZF1-AS1 as a prognostic biomarker for CC was examined by Cox proportional hazard regression model. We found that FEZF1-AS1 expression levels were significantly higher in CC tissues compared with adjacent non-cancerous tissues (p < 0.01). High expressions of FEZF1-AS1 were significantly association with poorer histological grade (p = 0.004), positive distant metastasis (p = 0.002) and advanced FIGO stage (p = 0.001). Furthermore, patients with low FEZF1-AS1 expression lived shorter than those with high FEZF1-AS1 expression (Log-rank test, p < 0.0034). Cox regression analysis demonstrated that FEZF1-AS1 expression level was an independent prognostic factor for CC overall survival rates (p = 0.008). We firstly provided clinical evidence that FEZF1-AS1 may be a possible biomarker of poor prognosis in CC.


Neolignans from Schisandra wilsoniana and their anti-human immunodeficiency virus-1 activities.
Four new neolignans, marphenols G-J (1-4), together with two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1-4 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. New compounds 1-4 were tested for their anti-human immunodeficiency virus (HIV)-1 activities and they showed weak bioactivities.


Psychotherapy Combined with Western Medicine in the Treatment of Children with Tic Disorder: Systematic Review and Meta-Analysis.
To evaluate the efficacy of psychotherapy in children with tic disorder and to provide basis for the application of psychotherapy in the treatment of children with tic disorder. A detailed search was conducted based on PubMed, Cochrane library database, CNKI, Wanfang Data, and VIP database to determine the randomized controlled trial (RCT) of psychotherapy combined with drugs and oral drugs in the treatment of tic disorder. The search time was from the establishment of the database to August 20, 2021. All kinds of extracted data are meta analyzed, and the statistical software used is Review Manager 5.3 software. According to the inclusion and exclusion criteria, 14 clinical trials were finally included, including 513 TD children, including 267 in the psychological intervention group and 246 in the control group. All trials were conducted in China and published from 2013 to 2021. In terms of clinical efficacy, compared with the control group, the psychotherapy combined with drugs group had more advantages in improving the effective rate (RR = 3.25, 95% CI: 2.17~4.85, Z = 5.74, P < 0.00001) and improving the clinical symptoms of children with TD (WM = -5.36, 95% CI: -6.41 ~ -4.30, Z = 9.97, P < 0.00000 1). Psychotherapy as an adjuvant therapy for clinical treatment of TD can improve the clinical efficacy, but due to the low methodological quality of the existing trials, the research may have potential bias. In the future, large sample, multicenter, and double-blind randomized controlled trials need to be carried out to provide further support.


Does a history of population co-occurrence predict plant performance, community productivity, or invasion resistance?
A history of species co-occurrence in plant communities is hypothesized to lead to greater niche differentiation, more efficient resource partitioning, and more productive, resistant communities as a result of evolution in response to biotic interactions. A similar question can be asked of co-occurring populations: do individual species or community responses differ when communities are founded with plants sharing a history of population co-occurrence (sympatric) or originating from different locations (allopatric)? Using shrub, grass, and forb species from six locations in the western Great Basin, North America, we compared establishment, productivity, reproduction, phenology, and resistance to invaders for experimental communities with either sympatric or allopatric population associations. Each community type was planted with six taxa in outdoor mesocosms, measured over three growing seasons, and invaded with the annual grass Bromus tectorum in the final season. For most populations, the allopatric or sympatric status of neighbors was not important. However, in some cases, it was beneficial for some species from some locations to be planted with allopatric neighbors, while others benefited from sympatric neighbors, and some of these responses had large effects. For instance, the Elymus population that benefited the most from allopatry grew 50% larger with allopatric neighbors than in single origin mesocosms. This response affected invasion resistance, as B. tectorum biomass was strongly affected by productivity and phenology of Elymus spp., as well as Poa secunda. Our results demonstrate that, while community composition can affect plant performance in semi-arid plant communities, assembling communities from sympatric populations is not sufficient to ensure high productivity and invasion resistance. Instead, we observed an idiosyncratic interaction between sampling effects and evolutionary history, with the potential for seed source of individual populations to have community-level effects.


Maternal phenylketonuria: experiences from the United Kingdom.
Charles Dent was one of the first physicians to recognize the teratogenic effects of maternal phenylalanine (Phe) on the fetus in 1956. This article describes the clinical experiences of women with phenylketonuria (PKU) within the unit that was established by Dent in the United Kingdom. Between 1977 and 2002, 79 infants were born to women with PKU. Of the 79, 18 (23%) were conceived while the women were on a normal diet with high blood Phe levels. The mean birth weight was 2.89 kg, and head circumference was 32.8 cm. At 1 year, the mean developmental quotient was 105.5 and at 4 years was 82.3. Four of these infants had congenital heart disease (2 of whom died as a result). In the remaining 61 infants, Phe-restricted diet started before conception. None of them had congenital heart disease. The mean birth weight was 3.23 kg, and head circumference was 34.0 cm. At 1 year, mean developmental quotient was 108.0 and at 4 years was 90.9. They continue to be followed up with additional neuropsychometric assessments at 8 and 14 years of age. This cohort is a proportion of infants who were born to mothers with PKU in the United Kingdom. Between 1978 and 1997, 255 live births were reported. Of these, 56% were conceived on unrestricted diet with subsequently poor outcome. This relatively high rate of conception off PKU diet is likely to reflect the scarcity of medical services for adults with metabolic disorders. We conclude that many features of the maternal PKU syndrome can be prevented but still occur because of the lack of appropriate resources to care for at-risk women. The precise targets for blood Phe and other nutrients during pregnancy are not entirely clear, neither are the reasons that some offspring are spared the harmful effects of Phe. The impact of the postnatal environment in which these infants find themselves requires additional assessment, too.


[Treatment of thoracolumbar burst fracture with lateral anterior decompression, internal fixation with Ventrofix and bone graft with titanic mesh].
To discuss the efficacy of lateral anterior decompression, internal fixation with Ventrofix and bone graft with titanic mesh in the treatment of severe thoracolumbar burst fracture. From January 2008 to January 2010, 21 patients with severe thoracolumbar burst fracture were treated with lateral anterior decompression, internal fixation with Ventrofix, bone graft with titanic mesh. There were 15 males and 6 females, ranging in age from 21 to 46 years with an average of 32.2 years. Segment of fracture: 3 cases were in T11, 6 cases in T12, 7 cases in L1, 5 cases in L2. The mean kyphosis angle was 20.1 degrees and loading of fracture was 7.8 scores. Twenty-one cases accompany with incomplete paralysis. Nerves functions were observed according to Frankel grade; correction and maintain of kyphosis angle were observed by X-rays and CT. All the patients were followed up from 12 to 34 months with an average of 18.5 years. Postoperative complication including injury of pleura in 1 case, dynamic ileus in 2 cases, ilioinguinal nerve injury in 1 case, faulty union of wound in 1 case. All the above complications got recovery after symptomatic treatment. The mean kyphosis angle in fusional segment were 4.2 degrees and the rate of correction was 79%. Nerves functions of all patients got improvement and no internal fixation fail, kyphosis angle obviously lost, titanium mesh shifting, loosening and breakage of screw were found at final follow-up. Lateral anterior decompression, bone graft with titanic mesh, internal fixation with Ventrofix is an idea technique for severe thoracolumber burst fracture, but the method can not be used for patient with severity osteoporosis.


Osteochondritis dissecans of the talar dome in a collegiate swimmer: a case report.
To present the case of an intercollegiate swimmer with a stage IV lateral talar dome injury and associated bony fragments. Lack of distinct diagnostic symptoms, low index of clinical suspicion, and the difficulty of visualizing the early stages of this injury on standard x-rays cause frequent misdiagnosis of talar dome lesions. Ganglion cyst, with inflammatory synovitis secondary to rupture of cyst; loose bodies from previous occult fracture; osteochondral fracture. Initial treatment with nonsteroidal antiinflammatory drugs and a posterior splint for comfort, followed by arthroscopic excision of loose bodies with abrasion and drilling arthroplasty. Patient presented to the team physician for care of acute left medial ankle pain after the athletic trainer had attempted to rupture a ganglion cyst on the anterolateral aspect of the patient's ankle. Increased clinical suspicion is necessary to correctly diagnose osteochondral lesions, particularly in the early stages. Aggressive treatment of talar dome lesions has a good success rate and may be an attractive option for competitive athletes.


Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway.
Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME) has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL) and then treated with LPS (1 μg/mL). The results showed that CME (10, 20, and 50 μg/mL) inhibited the LPS- (1 μg/mL) induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL). Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway.


Enhanced delivery of rapamycin by V156K-apoA-I high-density lipoprotein inhibits cellular proatherogenic effects and senescence and promotes tissue regeneration.
Although rapamycin (rapa) is a fungicide, it is now believed to possess the capacity to extend mammalian life span. Because rapamycin is insoluble in water, its study in the aqueous phase has been limited. We therefore solubilized rapamycin in isotonic buffer using reconstituted high-density lipoprotein containing V156K-apolipoprotein A-I (V156K-rHDL). Rapamycin (final concentration, 0.1 mg/mL) was solubilized in rHDL containing either wild-type (WT) or V156K-apoA-I (1 mg/mL of protein) prepared using the sodium cholate dialysis method. V156K-rHDL containing rapamycin (V156K-rapa-rHDL) had a slightly larger particle size than rapamycin-loaded WT-rHDL (WT-rapa-rHDL). V156K-rapa-rHDL exhibited enhanced antioxidant ability, cholesteryl ester transfer protein inhibitory activity, and anti-atherosclerotic activity. Treatment with V156K-rapa-rHDL resulted in attenuation of senescence in human cells with increased cell survival and enhancement of tissue regenerative activities in zebrafish model compared with WT-rapa-rHDL or rHDL alone.


Models and Tools for Studying Enteroendocrine Cells.
Gut hormones produced by gastrointestinal enteroendocrine cells modulate key physiological processes including glucose homeostasis and food intake, making them potential therapeutic candidates to treat obesity and diabetes. Understanding the function of enteroendocrine cells and the molecular mechanisms driving hormone production is a key step toward mobilizing endogenous hormone reserves in the gut as a therapeutic strategy. In this review, we will discuss the variety of ex vivo and in vitro model systems driving this research and their contributions to our current understanding of nutrient-sensing mechanisms in enteroendocrine cells.


Discrimination and Leukocyte Telomere Length by Depressive Symptomatology: The Jackson Heart Study.
Psychosocial stressors, such as perceived discrimination and depressive symptoms, may shorten telomeres and exacerbate aging-related illnesses. Participants from the Jackson Heart Study at visit 1 (2000-2004) with LTL data and Center for Epidemiological Studies-Depression (CES-D) scores (n = 580 men, n = 910 women) were utilized. The dimensions of discrimination scores (everyday, lifetime, burden of lifetime, and stress from lifetime discrimination) were standardized and categorized as low, moderate, and high. Coping responses to everyday and lifetime discrimination were categorized as passive and active coping. Multivariable linear regression analyses were performed to estimate the mean difference (standard errors-SEs) in LTL by dimensions of discrimination and coping responses stratified by CES-D scores < 16 (low) and ≥ 16 (high) and sex. Covariates were age, education, waist circumference, smoking and CVD status. Neither everyday nor lifetime discrimination was associated with mean differences in LTL for men or women by levels of depressive symptoms. Burden of lifetime discrimination was marginally associated with LTL among women who reported low depressive symptoms after full adjustment (b = 0.11, SE = 0.06, p = 0.08). Passive coping with lifetime discrimination was associated with longer LTL among men who reported low depressive symptoms after full adjustment (b = 0.18, SE = 0.09, p < 0.05); and active coping with lifetime discrimination was associated with longer LTL among men who reported high depressive symptoms after full adjustment (b = 1.18, SE = 0.35, p < 0.05). The intersection of perceived discrimination and depressive symptomatology may be related to LTL, and the effects may vary by sex.


[Developing process of guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019)].
Pharmacoepidemiology refers to the use of epidemiological research methods in studying the application and use of drugs in large populations to evaluate the safety and efficacy of medical products. Therefore, standardized pharmacoepidemiology research is the basis of the above work. Based on systematic reviews of national and international pharmacoepidemiological methodological standards and guidelines, and in combination with Chinese medical and health practice and experts' opinions, the Professional Committee of Pharmacoepidemiology of Chinese Pharmaceutical Association developed the group standard, guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019), to better guide the work of pharmacoepidemiology. The guideline was designed to provide advice and reference for pharmacoepidemiology research by government, regulatory agencies, research institutions, and pharmaceutical manufacturers in China.


Flexible and rigid dicarboxylic acids enable the assembly of achiral and chiral 3D Co(ii) metal-organic frameworks.
Two novel 3D Co(ii) metal-organic frameworks induced by flexible and rigid dicarboxylic acids [Co3(μ3-OH)(1,4-ttb)3(sa)]·3H2O (1) and Co2(μ3-OH)(1,4-ttb)(4,4'-bpdc) (2) (1,4-ttb = 1-(tetrazo-5-yl)-4-(triazo-1-yl)benzene, sa = succinic acid and 4,4'-bpdc = biphenyl-4,4'-dicarboxylic acid) have been successfully synthesized and characterized via X-ray single-crystal diffraction, powder X-ray diffraction (PXRD), FT-IR spectroscopy and TG analyses. In the structures of the compounds 1 and 2, the main ligand 1,4-ttb coordinates with Co(ii) ions to form 3D host frameworks with different cavities, and the auxiliary ligands sa and 4,4'-bpdc fill the 3D cavities. More strikingly, compound 2 is a chiral 3D metal-organic framework, in which 4,4'-bpdc acts as a rigid achiral ligand. Additionally, the electrochemical properties and magnetic properties of compounds 1 and 2 have been investigated.


Cotransplantation With Adipose Tissue-derived Stem Cells Improves Engraftment of Transplanted Hepatocytes.
Hepatocyte transplantation is expected to be an alternative therapy to liver transplantation; however, poor engraftment is a severe obstacle to be overcome. The adipose tissue-derived stem cells (ADSCs) are known to improve engraftment of transplanted pancreatic islets, which have many similarities to the hepatocytes. Therefore, we examined the effects and underlying mechanisms of ADSC cotransplantation on hepatocyte engraftment. Hepatocytes and ADSCs were cotransplanted into the renal subcapsular space and livers of syngeneic analbuminemic rats, and the serum albumin level was quantified to evaluate engraftment. Immunohistochemical staining and fluorescent staining to trace transplanted cells in the liver were also performed. To investigate the mechanisms, cocultured supernatants were analyzed by a multiplex assay and inhibition test using neutralizing antibodies for target factors. Hepatocyte engraftment at both transplant sites was significantly improved by ADSC cotransplantation ( P < 0.001, P < 0.001). In the renal subcapsular model, close proximity between hepatocytes and ADSCs was necessary to exert this effect. Unexpectedly, ≈50% of transplanted hepatocytes were attached by ADSCs in the liver. In an in vitro study, the hepatocyte function was significantly improved by ADSC coculture supernatant ( P < 0.001). The multiplex assay and inhibition test demonstrated that hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6 may be key factors for the abovementioned effects of ADSCs. The present study revealed that ADSC cotransplantation can improve the engraftment of transplanted hepatocytes. This effect may be based on crucial factors, such as hepatocyte growth factor, vascular endothelial growth factor, and interleukin-6, which are secreted by ADSCs.


Optimization of gene transfer into intestinal epithelial cells using a retroviral vector.
Somatic gene therapy has been proposed as a method of treating various metabolic diseases and conditions associated with a deficiency in secretory proteins. The intestine, because of its accessibility, large size, rapid rate of cell turnover, and known location of stem cells, is an attractive site for retroviral gene therapy. Stem cells in the intestine are known to reside in the crypts of Lieberkühn. In this study the IEC-6 cell line, derived from rat intestinal crypt cells, was used as an in vitro model to study the feasibility and dynamics of retroviral gene transfer in intestinal cells. Using a replication-deficient retrovirus, we delivered a reporter gene, bacterial beta-galactosidase (beta-gal) into NIH-3T3 fibroblasts and IEC-6 cells. Successful transduction was measured by X-gal histochemistry. Viral titers on IEC-6 cells were lower than on NIH-3T3 cells but were within the same order of magnitude. Gene transfer increased linearly with retroviral concentration up to a 1:5 dilution of retroviral supernatant. With undiluted viral medium, gene transfer was inhibited and this effect was more pronounced with the IEC-6 cells. The negative effect of the undiluted retroviral supernatant was minimized by decreasing the harvest time from the packaging cell line. An optimal plating density 12 h prior to infection was found to be approximately 10(5) cells/6-cm dish in both cell lines. The infection rate was proportionally enhanced by the use of multiple infections. In conclusion, under ideal conditions, the IEC-6 cells were infected at similar levels of efficacy as NIH-3T3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Enteral nutrition supplemented with L-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection.
To evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. Thirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. There were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0-47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. The EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters.


Brain Radiation Necrosis: Current Management With a Focus on Non-small Cell Lung Cancer Patients.
As the prognosis of metastatic non-small cell lung cancer (NSCLC) patients is constantly improving with advances in systemic therapies (immune checkpoint blockers and new generation of targeted molecular compounds), more attention should be paid to the diagnosis and management of treatments-related long-term secondary effects. Brain metastases (BM) occur frequently in the natural history of NSCLC and stereotactic radiation therapy (SRT) is one of the main efficient local non-invasive therapeutic methods. However, SRT may have some disabling side effects. Brain radiation necrosis (RN) represents one of the main limiting toxicities, generally occurring from 6 months to several years after treatment. The diagnosis of RN itself may be quite challenging, as conventional imaging is frequently not able to differentiate RN from BM recurrence. Retrospective studies have suggested increased incidence rates of RN in NSCLC patients with oncogenic driver mutations [epidermal growth factor receptor (EGFR) mutated or anaplastic lymphoma kinase (ALK) positive] or receiving tyrosine kinase inhibitors. The risk of immune checkpoint inhibitors in contributing to RN remains controversial. Treatment modalities for RN have not been prospectively compared. Those include surveillance, corticosteroids, bevacizumab and local interventions (minimally invasive laser interstitial thermal ablation or surgery). The aim of this review is to describe and discuss possible RN management options in the light of the newly available literature, with a particular focus on NSCLC patients.


Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations?
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.


Thyroid disease in the elderly: sex-related differences in clinical expression.
Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women >60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects >70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.


Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor.
The renal collecting duct is a site of insulin-like growth factor I (IGF I) synthesis. Epidermal growth factor (EGF) is also synthesized within the kidney in the thick ascending limb of Henle's loop and the distal tubule. EGF has been shown to regulate IGF I expression in nonrenal tissues. To shed light upon a role of EGF in intrarenal regulation of IGF I gene expression, plasma membranes prepared from collecting ducts isolated from rat kidney and collecting ducts themselves were incubated in the presence and absence of recombinant human EGF (hEGF). hEGF enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for EGF signal transduction at this site. Inclusion of hEGF in suspensions of collecting ducts increased production of immunoreactive IGF I in a concentration-dependent manner. Production was stimulated significantly by addition of 10(-8) or 10(-6) M hEGF to suspensions for 2 h. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M hEGF in vitro. Our findings demonstrate a direct action of hEGF to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect an effect of EGF to stimulate IGF I production in the collecting duct of the intact kidney. Since EGF is produced in kidney, our findings are consistent with intrarenal paracrine regulation of IGF I gene expression by EGF.


"Moving Fourth": Introduction of a practical toolkit for shared decision-making to facilitate healthy living beyond HIV viral suppression.
An extension of the UNAIDS 90-90-90 target proposes >90% of people living with HIV (PLHIV) should have good health-related quality of life (HrQoL); however, limited guidance exists. The "Health Goals for Me" framework, an individualized approach to HIV care, provides a framework to assess HrQoL. We analyzed several patient-reported outcome measures (PROMs) to develop a practical toolkit to facilitate shared physician-patient decision-making. HrQoL subdomains, actionable in the clinical setting and measurable as PROMs, were selected. PROMs were collated through systematic literature searches, scored by the authors on usability, validation, and availability, after which practical recommendations were made. Nine subdomains were selected across physical, psychological, social, and environmental domains; 46 validated PROMs were identified. After pre-screening, from 39 evaluated PROMs, we recommended PROMs in the following subdomains: fatigue/energy loss, frailty/resilience, sleep disturbance, substance use, anxiety/depression, cognition, sexual function and desire, and stigma. Using this toolkit, healthcare professionals and PLHIV can collaborate and mutually agree on individual care objectives. Following the "Health Goals for Me" framework, appropriate care interventions can be implemented and reviewed in a continuous cycle. We discussed how eHealth interventions, which will have increasing importance in the post-COVID era, can facilitate improved HrQoL for PLHIV by utilizing toolkits such as the one described here. Implementation of this practical framework and the PROMs toolkit could provide a useful approach to assessing HrQoL in PLHIV and could enhance the physician's ability to gain valuable insights into the patient's daily life across a broad range of HrQoL issues.


Pro-environmental behavior: rational choice meets moral motivation.
The determinants of individual behaviors that provide shared environmental benefits are a longstanding theme in social science research. Alternative behavioral models yield markedly different predictions and policy recommendations. This paper reviews and compares the literatures from two disciplines that appear to be moving toward a degree of convergence. In social psychology, moral theories of pro-environmental behavior have focused on the influence of personal moral norms while recognizing that external factors, such as costs and incentives, ultimately limit the strength of the norm-behavior relationship. Rational choice models, such as the theory of planned behavior in social psychology and the theories of voluntary provision of public goods in economics, have sought to incorporate the effects of personal norms and to measure their importance in explaining behaviors, such as recycling and the demand for green products. This paper explores the relationship between these approaches and their implications for the theory and practice of ecological economics.


Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7 Human Breast Cancer Cells.
cRNA microarray and real-time PCR (qPCR) studies identified a number of Estrogen Signaling Pathway (ESP) genes (GTF2H2, NCOR1, TAF9, NRAS, NRIP1, POLR2A, DDX5, NCOA3) and Cell Cycle Pathway genes (CCNA2, PCNA, CDKN1A, CCND1, PLK1) in MCF-7 breast cancer cells that are regulated by the bioflavonoid luteolin. Chromatin immunoprecipitation (ChIP) studies revealed that luteolin modified histone H4 acetylation at the PLK-1 promoter suggesting that this bioflavonoid controls gene transcription via an epigenetic mechanism involving histone H4 acetylation. These findings are consistent with the anti-estrogenic and anti-proliferative properties of luteolin in normal and malignant cells.


Brief Report: Development and Validation of the Autism Spectrum Knowledge Scale General Population Version: Preliminary Analyses.
Despite the dramatic rise in Autism Spectrum Disorder (ASD) prevalence, limited information is known about ASD knowledge of the general population. The Autism Spectrum Knowledge Scale, General Population version (ASKSG) was collaboratively constructed to create a measure of ASD knowledge specifically for the general population. The ASKSG is a 31-item measure that assesses one's knowledge and understanding of ASD. Adults in the general population participated in the current study (N = 318). Findings indicate that the ASKSG is a valid and reliable measure and can adequately measure ASD knowledge in this population. A greater understanding of general population knowledge pertaining to ASD can be used to better inform identification, intervention, and advocacy, thus improving the outcomes for individuals with ASD.


Ca2+-calmodulin-dependent regulation of F-actin-myelin basic protein interaction.
Myelin basic proteins (MBP) interacts with F-actin resulting in the precipitation of a complex of both proteins. Electron microscope observations of this complex reveal the presence of ordered bundles of F-actin filaments similar to those obtained from F-actin and troponin I. In addition to the bundles, there also appear short fragments of F-actin filaments. In the presence of Ca2+ calmodulin causes a release of MBP from its complex with F-actin, accompanied by dissociation of F-actin bundles into separate filaments. Parallel to the binding of MBP to F-actin the ATPase activity of actomyosin is progressively reduced. This inhibition is reversed by calmodulin but only in the presence of Ca2+. Studies of the binding of S-1 to F-actin and to the F-actin-MBP complex indicate that the interaction sites for MBP and S-1 on the actin molecule are different.


NGS-Based Diagnosis of Treatable Neurogenetic Disorders in Adults: Opportunities and Challenges.
The identification of neurological disorders by next-generation sequencing (NGS)-based gene panels has helped clinicians understand the underlying physiopathology, resulting in personalized treatment for some rare diseases. While the phenotype of distinct neurogenetic disorders is generally well-known in childhood, in adulthood, the phenotype can be unspecific and make the standard diagnostic approach more complex. Here we present three unrelated adults with various neurological manifestations who were successfully diagnosed using NGS, allowing for the initiation of potentially life-changing treatments. A 63-year-old woman with progressive cognitive decline, pyramidal signs, and bilateral cataract was treated by chenodeoxycholic acid following the diagnosis of cerebrotendinous xanthomatosis due to a homozygous variant in CYP27A1. A 32-year-old man with adult-onset spastic paraplegia, in whom a variant in ABCD1 confirmed an X-linked adrenoleukodystrophy, was treated with corticoids for adrenal insufficiency. The third patient, a 28-year-old woman with early-onset developmental delay, epilepsy, and movement disorders was treated with a ketogenic diet following the identification of a variant in SLC2A1, confirming a glucose transporter type 1 deficiency syndrome. This case study illustrates the challenges in the timely diagnosis of medically actionable neurogenetic conditions, but also the considerable potential for improving patient health through modern sequencing technologies.


Dust Sources in the Salton Sea Basin: A Clear Case of an Anthropogenically Impacted Dust Budget.
The Salton Sea Basin in California suffers from poor air quality, and an expanding dry lakebed (playa) presents a new potential dust source. In 2017-18, depositing dust was collected approximately monthly at five sites in the Salton Sea Basin and analyzed for total elemental and soluble anion content. These data were analyzed with Positive Matrix Factorization (PMF). The PMF method resolved seven dust sources with distinct compositional markers: Playa (Mg, SO42-, Na, Ca, Sr), Colorado Alluvium (U, Ca), Local Alluvium (Al, Fe, Ti), Agricultural Burning (K, PO43-), Sea Spray (Na, Cl-, Se), Anthropogenic Trace Metals (Sb, As, Zn, Cd, Pb, Na), and Anthropogenic Copper (Cu). All sources except Local Alluvium are influenced or caused by current or historic anthropogenic activities. PMF attributed 55 to 80% of the measured dust flux to these six sources. The dust fluxes at the site where the playa source was dominant (89 g m-2 yr-1) were less than, but approaching the scale of, those observed at Owens Lake playas in the late 20th century. Playa emissions in the Salton Sea region were most intense during the late spring to early summer and contain high concentrations of evaporite mineral tracers, particularly Mg, Ca, and SO42-.


[Urinary tract infections caused by hospital infections (nosocomial infections). A long-term study].
A computerized analysis of hospital acquired urinary tract infections from 1973-1976 as well as 1981-1982 was done at our institution. A change in the classic picture of "gramnegative infections" was observed. Grampositive germs such as enterococci and staphylococci increased in their significance. The incidence of bacteremia and sepsis was lowered. This success is due to strict antiseptic measures as well as to the more frequent use of the suprapubic puncture catheter instead of the transurethral catheter.


Degeneration of mouse oocytes in response to polycyclic aromatic hydrocarbons.
Destruction of mouse oocytes in primordial and small primary follicles in response to treatment with 3-methylcholanthrene (MC) was studied at the ultrastructural level. Four-week old C57Bl/6N (B6) strain mice received a single injection of 80 mg/Kg MC in corn oil intraperitoneally. Controls received only corn oil. Ovaries from animals were prepared for light and electron microscopic examination at specified intervals after treatment. The number of primordial follicles remained constant in control animals. In contrast, their number decreased significantly (P less than 0.01) by three days, and they were depleted by seven days after MC treatment. Subtle degenerative modifications were noted in the ooplasm of primordial follicles two days after treatment. These changes consisted of vesiculation of mitochondrial cristae, increased electron density of the mitochondrial matrix, myelin structures in lipid droplets and in mitochondria. More advanced stages of degeneration of primordial follicles were characterized by further vesiculation or disappearance of mitochondrial cristae, chromatin clumping, and increased density of the ooplasm. Small primary follicles had undergone similar initial degeneration as primordial follicles. In more advanced stages of degeneration nuclear and cytoplasmic contents condensed, endoplasmic reticulum, Golgi complex and mitochondria swelled, small vesicles and multivesicular bodies appeared. In the most advanced stages of degeneration of small primary follicles it appeared that small portions of the oocyte were engulfed by the surrounding follicular cells. It is concluded that exposure of B6 mice to a single dose of MC results in atresia of oocytes in primordial and small primary follicles. Ultrastructurally, these degenerating oocytes of treated mice looked much like the spontaneously atretic oocytes in untreated animals.


[A case of fibrous hamartoma of infancy and a review of the Japanese literature].
A case of fibrous hamartoma of infancy in the left axilla of an 18-month-old boy, is reported with some discussion (citations of references). The tumor was situated in the subcutaneous fatty tissue, and its border was unclear. It was removed easily and found to measure 2.5 X 1.5 X 1.5 cm. Histologically, in addition to the three main components, i.e., trabeculae of fibrous tissue, immature mesenchymal cells with a mucoid matrix and interspersed mature fat, a capillary vasoformative proliferation, peripheral nerve fibers and lymph follicle-like structures mingling with and transforming into one another were noted throughout the tumor. On the basis of these findings, immature mesenchymal cells were considered as having very important roles with regard to the histogenesis of fibrous hamartoma of infancy.


Interfacial kinetics of a model epoxy-amine addition reaction.
The kinetics of the addition reaction at a solid interface for a model epoxy-amine system composed of monofunctionalized phenyl glycidyl ether and hexylamine was examined. The chemical character for the reaction of this system at the interface was the same as that in the bulk, while the physical nature was significantly different. Slowing down of the diffusion for the reactants in close proximity to the solid interface was also addressed by interfacial selective spectroscopy.


Medical devices; exception from general requirements for informed consent. Final rule.
The Food and Drug Administration (FDA) is issuing a final regulation to confirm, with one change, the interim final rule (IFR) entitled "Medical Devices; Exception From General Requirements for Informed Consent." This final rule confirms the IFR's establishment of a new exception from the general requirements for informed consent to permit the use of investigational in vitro diagnostic devices to identify chemical, biological, radiological, or nuclear agents without informed consent in certain circumstances. FDA has created this exception to help ensure that individuals who may have been exposed to a chemical, biological, radiological, or nuclear agent are able to benefit from the timely use of the most appropriate diagnostic devices, including those that are investigational. This final rule adds a requirement that the investigator submit the required documentation to FDA, in addition to submitting it to the reviewing Institutional Review Board (IRB).


Pan-Genomic and Polymorphic Driven Prediction of Antibiotic Resistance in Elizabethkingia.
The Elizabethkingia are a genetically diverse genus of emerging pathogens that exhibit multidrug resistance to a range of common antibiotics. Two representative species, Elizabethkingia bruuniana and E. meningoseptica, were phenotypically tested to determine minimum inhibitory concentrations (MICs) for five antibiotics. Ultra-long read sequencing with Oxford Nanopore Technologies (ONT) and subsequent de novo assembly produced complete, gapless circular genomes for each strain. Alignment based annotation with Prokka identified 5,480 features in E. bruuniana and 5,203 features in E. meningoseptica, where none of these identified genes or gene combinations corresponded to observed phenotypic resistance values. Pan-genomic analysis, performed with an additional 19 Elizabethkingia strains, identified a core-genome size of 2,658,537 bp, 32 uniquely identifiable intrinsic chromosomal antibiotic resistance core-genes and 77 antibiotic resistance pan-genes. Using core-SNPs and pan-genes in combination with six machine learning (ML) algorithms, binary classification of clindamycin and vancomycin resistance achieved f1 scores of 0.94 and 0.84, respectively. Performance on the more challenging multiclass problem for fusidic acid, rifampin and ciprofloxacin resulted in f1 scores of 0.70, 0.75, and 0.54, respectively. By producing two sets of quality biological predictors, pan-genome genes and core-genome SNPs, from long-read sequence data and applying an ensemble of ML techniques, our results demonstrated that accurate phenotypic inference, at multiple AMR resolutions, can be achieved.


Maxillofacial oncology at the University of Minnesota: treating the epidemic of oral cancer.
Oral cancer may present with a variety of signs and symptoms including pain, dysphagia, non-healing ulcers, red and white lesions, and indurated masses. Historically, oral cancer has been associated with the male population, particularly those who use tobacco and alcohol. Recently, there has been a dramatic increase in oral cancer rates seen in the population aged 40 years and younger. This increase has not been associated with the traditional risk factors for oral cancer and is likely linked to etiologic factors that remain still undefined. The proliferation of oral cancer is also mirrored by an increase in oropharyngeal malignancies such as base of tongue and tonsil cancer, although the increase in this subset of patients appears to be clearly associated with Human Papillomavirus (HPV). We present a summary of all oral malignancies treated at the University of Minnesota Oral and Maxillofacial Surgery Division from 2008 through early 2011. Since July of 2008, the Oral and Maxillofacial Surgery Department at the University of Minnesota has been referred a total of 69 cases of head and neck malignant tumors, of which 58 were primarily managed with surgery. A broad range of head and neck cancers were seen, with the most common being oral squamous cell carcinoma (OSCC), which accounted for 81% of patients treated by oncologic tumor resection. The tongue was the most common site of occurrence of OSCC with 33% of cases. There was an even distribution between genders. Traditional treatment modalities included surgical resection of primary tumors including neck dissection, when indicated, with postoperative adjuvant therapies being reserved for advanced stage tumors or high-risk pathologic features for recurrence. At the conclusion of the study period in January, 2011, 83% of patients treated surgically for OSCC were living disease free, 4% had recurrent tumors not amenable to resection, 6% of patients had died from other causes, and 6% had succumbed to OSCC, resulting in a disease-specific survival rate of 93% with an overall survival rate of 87%. Oral cancer continues to be diagnosed with advanced stage disease in 50% of patients. Dental practitioners play a significant role in the early detection and diagnosis of oral cavity cancer. It is incumbent upon dental practitioners to be aware of the early signs and symptoms of oral cancer and to make prompt referral to head and neck cancer specialists when indicated. Diligent and frequent examination, particularly in patients with risk factors, will greatly improve survival rates and minimize the complexity and morbidity of oncologic treatment when patients are diagnosed with earlier stage disease.


Statistics for real-time deformability cytometry: Clustering, dimensionality reduction, and significance testing.
Real-time deformability (RT-DC) is a method for high-throughput mechanical and morphological phenotyping of cells in suspension. While analysis rates exceeding 1000 cells per second allow for a label-free characterization of complex biological samples, e.g., whole blood, data evaluation has so far been limited to a few geometrical and material parameters such as cell size, deformation, and elastic Young's modulus. But as a microscopy-based technology, RT-DC actually generates and yields multidimensional datasets that require automated and unbiased tools to obtain morphological and rheological cell information. Here, we present a statistical framework to shed light on this complex parameter space and to extract quantitative results under various experimental conditions. As model systems, we apply cell lines as well as primary cells and highlight more than 11 parameters that can be obtained from RT-DC data. These parameters are used to identify sub-populations in heterogeneous samples using Gaussian mixture models, to perform a dimensionality reduction using principal component analysis, and to quantify the statistical significance applying linear mixed models to datasets of multiple replicates.


Is there detrimental gender bias in preoperative cardiac management of patients undergoing vascular surgery?
To investigate the possibility of gender bias in the cardiac management of patients who undergo peripheral vascular surgery, we examined the hospital data and outcomes for 350 adult men and 128 women who underwent vascular surgery from September 1987 to December 1991. There were no significant differences between the two groups in age at operation, incidence of standard risk factors for myocardial infarction, or incidence or duration of episodes of perioperative silent ischemia. Nevertheless, a significantly lower percentage of women than men had undergone prior coronary bypass procedures (6.3% and 17.1%, respectively; P < .01), an apparent example of gender bias. However, there was no significant difference in the incidence of perioperative myocardial infarction in women (3.9%) compared with men (4.0%). Furthermore, actuarial analysis showed that at 24 months after operation a significantly higher percentage of women (77.9%) had escaped late cardiac death and cardiac complications than men (71.9%; P < .05). These findings indicate that apparent gender bias in the preoperative cardiac management of this group of women who underwent vascular surgery may have had no detrimental effect on short- and long-term incidence of cardiac death and complications, and may represent sound clinical judgment rather than true bias. However, the possibility that female patients might have had even better short- and long-term cardiac results if they had undergone more preoperative cardiac revascularization cannot be discounted.


Mechanisms of dexamethasone-induced insulin resistance in healthy humans.
Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.