Enhanced recovery after elective surgery. A revolution that reduces post-operative morbidity and mortality.
Enhanced recovery (ER) after elective surgery has been a real revolution in peri-operative care. This concept, initially called "fast-track surgery", has evolved into "enhanced recovery or rehabilitation" (ER), which highlights the improvement of post-operative procedures rather than the simple shortening of hospital stay. The main benefit of ER is the reduction of the impact of surgical trauma with an attendant reduction of post-operative complications. This result has been demonstrated based on a good level of evidence for multiple surgical specialties. Mild complications are the most impacted by this program. The reduction in the duration of stay is thus the result of the improvement in post-operative care. This update illustrates the benefits of ER by taking three examples of elective surgery in three major surgical specialties: colorectal surgery, orthopedics and gynecological surgery. The post-operative complications impacted by ER programs and the mechanisms of this effect are also discussed.


Radiological features of the visceral and skeletal involvement of hemochromatosis.
Hemochromatosis is a multisystem disorder produced by the excessive accumulation of iron in visceral organs and the musculoskeletal system. Clinically the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in an increased attenuation at unenhanced CT and an decreased signal intensity at MR imaging. Hemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.


Regeneration and endocrinology in the polychaetePlatynereis dumerilii : An experimental and structural study.
1. In the polychaetePlatynereis dumerilii, the hormone-elaborating portion of the prostomium was determined by means of prostomium transection and implantation experiments. The area in question lies between the two pairs of eyes, extending longitudinally from the posterior border of the anterior eyes to about the posterior border of the posterior eyes. This corresponds approximately with the brain area delimited by the anterior and posterior dorsoventral connective tissue tubes and which is covered ventrally by the infracerebral gland epithelium. 2. The infracerebral gland-complex and neurosecretory neurons within the brain were envisaged as possible sites of hormone synthesis. 3. The infracerebral gland-complex inPl. dumerilii was investigated with light-and electron-microscopical techniques. A leaf-shaped area (measuring 120 by 95 μm at the most) of the pericapsular epithelium at the ventral side of the brain, adjacent to the main blood vessel and to its efferent branches, consists of specialized columnar epithelial cells. Numerousa-cells and scarceb-cells can be distinguished. Fibre tracts with glia fibres and axons (some being neurosecretory axons) descend from the neuropile and in part terminate with prominent end-structures at the inner face of the brain capsule in the gland region. Probably some axons penetrate the capsule and make contact with the gland cells. Neither structural nor experimental findings prove that the infracerebral gland synthesizes the brain hormone. Accessory functions are discussed. 4. Investigations in secretory brain cells ofPl. dumerilii are reported. In agreement with Müller (1973), a lack of correlation between the number of stainable neurosecretory neurons and the hormonal activity of the brain was found: in immature worms (to which high hormonal titers are ascribed) only few or even no neurosecretory brain cells at all were detectable. Prostomium transection and implantation experiments show further that not all regions of the brain which enclose neurosecretory neurons produce brain hormone. The results are discussed with reference to the hypotheses of Müller (1973) which suggest that the appearance of stainable neurosecretory brain cells indicates inactivation of neurons possibly previously involved with hormone synthesis.


Lack of in vivo cross-resistance with 4'-thio-ara-C against drug-resistant murine P388 and L1210 leukemias.
4'-Thio-β-D-arabinofuranosylcytosine (4'-thio-ara-C), which has shown a broad spectrum of antitumor activity against human tumor systems in mice and is undergoing clinical trials, was evaluated for cross-resistance to seven clinical agents in order to identify potentially useful guides for patient selection for further clinical trials of 4'-thio-ara-C and possible noncross-resistant drug combinations with 4'-thio-ara-C. A drug resistance profile for 4'-thio-ara-C, which was administered intraperitoneally daily for nine consecutive days, was obtained using seven drug-resistant P388 and L1210 leukemias that were implanted intraperitoneally in mice. Multidrug-resistant P388 leukemias (leukemias resistant to doxorubicin, etoposide, or paclitaxel) exhibited no cross-resistance to 4'-thio-ara-C. Leukemias resistant to camptothecin, cisplatin, and 5-fluorouracil were also not cross-resistant to 4'-thio-ara-C. Only the leukemia resistant to 1-β-D-arabinofuranosylcytosine was cross-resistant to 4'-thio-ara-C. The data suggest that (1) it may be important to exclude or to monitor with extra care patients who have previously been treated with 1-β-D-arabinofuranosylcytosine and (2) the lack of cross-resistance seen with 4'-thio-ara-C may contribute to therapeutic synergism when 4'-thio-ara-C is combined with other agents.


Real-time virtual infection prevention and control assessments in skilled nursing homes, New York, March 2020-A pilot project.
To describe a pilot project infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal 2-week period when the region became the nation's epicenter for coronavirus disease 2019 (COVID-19). A telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity. SNFs in 14 New York counties, including New York City. A 3-component remote IPC assessment: (1) screening tool; (2) telephone IPC checklist; and (3) COVID-19 video IPC assessment (ie, "COVIDeo"). In total, 92 SNFs completed the IPC screening tool and checklist: 52 (57%) were conducted as part COVID-19 investigations, and 40 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26 (28%) of 92 assessments and provided observations that other tools would have missed: personal protective equipment (PPE) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took ∼1 hour each and reached an estimated 4 times as many SNFs as on-site visits in a similar time frame. Remote IPC assessments by telephone and video were timely and feasible methods of assessing the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across New York State and in various healthcare facility types. Similar methods have been adapted nationally by the Centers for Disease Control and Prevention.


Odor perception between heterosexual partners: its association with depression, anxiety, and genetic variation in odorant receptor OR7D4.
We performed a study on a sample of 856 individuals to answer whether the pleasantness/unpleasantness of the odor perception of their partners (rating of partner odor) is associated with depression and anxiety. To evaluate the influence of common genetic variation of the odorant receptor OR7D4 on the rating of partner odor, the variant rs8109935 was genotyped in the whole sample. The rating of partner odor was significantly associated with scores of anxiety and depression. Depression (OR: 0.75, 95% CI: 0.56-0.98, p = 0.039) and anxiety (Robust Coef ± SE: -13 ± 0.6, p = 0.044) were inversely associated with pleasantness rating of partner odor. Ordered probit regression analysis shows that the rating of partner odor was significantly associated with the rs8109935 genotypes (Coef ± robust SE: 0.19 ± 0.09, p = 0.028). These findings suggest that odor perception between heterosexual partners may have an impact on the development of depression and anxiety, and that it might be influenced by genetic variation in OR7D4.


Herpesnephropathy.
Two cases of acute renal insufficiency occurred in association with episodes of severe encephalitis due to herpes simplex type I. The possibility was considered that the renal failure was due to viral infection of the kidneys, and animal experiments were carried out in an attempt to confirm this. Young New Zealand albino rabbits were infected i. v. with HSV type I; the virus antigen was detected in the kidney of 8 of 10 animals, and IgG was found on the GBM in 9 of 19 animals. Viruria was observed in 12 of the 29 infected animals, and electronmicroscopic examination confirmed the presence of immune complexes in the glomeruli.


Identification of New Shikonin Derivatives as Antitumor Agents Targeting STAT3 SH2 Domain.
Signal transducer and activator of transcription 3 (STAT3) is hyper-activated in diversiform human tumors and has been validated as an attractive therapeutic target. Current research showed that a natural product, shikonin, along with its synthetic analogues, is able to inhibit the activity of STAT3 potently. The potential space of shikonin in developing novel anti-cancer agents encouraged us to carry out the investigation of the probable binding mode with STAT3. From this foundation, we have designed new types of STAT3 SH2 inhibitors. Combined simulations were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Among the entities, PMM-172 exhibited the best anti-proliferative activity against MDA-MB-231 cells with IC50 value 1.98 ± 0.49 μM. Besides, it was identified to decrease luciferase activity, induce cell apoptosis and reduce mitochondrial transmembrane potential in MDA-MB-231 cells. Also, PMM-172 inhibited constitutive/inducible STAT3 activation without affecting STAT1 and STAT5 in MDA-MB-231 cells, and had no effect in non-tumorigenic MCF-10A cells. Moreover, PMM-172 suppressed STAT3 nuclear localization and STAT3 downstream target genes expression. Overall, these results indicate that the antitumor activity of PMM-172 is at least partially due to inhibition of STAT3 in breast cancer cells.


The relationship between chronic obstructive pulmonary disease and comorbidities: a cross-sectional study using data from KNHANES 2010-2012.
Multiple comorbidities related to chronic obstructive pulmonary disease (COPD) make it a difficult disease to treat. The relationship between these comorbidities and COPD has not been fully investigated. We aimed to determine whether COPD was independently associated with various comorbidities. This was a cross-sectional study, which used data from the Korean National Health and Nutrition Examination Survey (KNHANES) V conducted between 2010 and 2012. Survey design analysis was employed to determine the association between COPD and 15 comorbidities. A COPD patient was defined as a smoker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 and comorbidities were defined based on objective laboratory findings and questionnaires. Of a total of 9488 patient who underwent spirometry, 744 (7.84%) COPD cases and 3313 non-COPD controls were included in the analyses. Although the prevalence rates of the majority of the comorbidities were high among the COPD patients, only hypertension (adjusted odds ratio [aOR], 1.63; 95% CI, 1.13-2.33 in Stage 1 COPD group; aOR, 1.92; 95% CI, 1.36-2.72 in Stage 2-4 COPD group) and a history of pulmonary tuberculosis (aOR, 3.38; 95% CI, 1.90-5.99 in Stage 2-4 COPD group) were independently associated with COPD after adjustment for age, smoking status, and confounders. Only hypertension and a history of pulmonary tuberculosis were independently associated with COPD after adjustment for confounders among 15 comorbidities. The results suggest that majority of COPD patients might have similar risk factors with its comorbidities, including age and smoking status.


Functional analysis of 1440 Escherichia coli genes using the combination of knock-out library and phenotype microarrays.
Escherichia coli is one of the best elucidated organisms. However, about 40% of E. coli genes have not been assigned to their function yet. We analyzed 1440 single gene knock-out mutants using the GN2-MicroPlate, which permits assay of 95 carbon-source utilizations simultaneously. In the knock-out library there are 1044 of so called y-genes with no apparent function. The raw dataset was analyzed and genes were interrelated by the clustering method of the GeneSpring software. In the resulted dendrogram of genes, a group of genes with known and related function tended to be assembled into a cluster. Our clustering method would be useful for functional assignment of so called y-genes with no apparent function, since the resulted dendrogram could connect y-genes to phenotype and function of well-studied genes.


[Rheumathism and pneumology].
Due to the broad range of diagnostic and therapeutic aspects with an increased risk of mortality, lung manifestations of rheumatic diseases are an exciting and important field in the clinical routine of pulmonologists and rheumatologists. Discussion of different presentations in the lung, diagnostics and management of lung manifestation associated with rheumatic diseases. Analysis and presentation of current literature on the subject. The manuscript presents forms of lung involvement associated with rheumatic diseases, in particular the connective tissue disease-associated interstitial lung disease. Considering the negative impact on survival, rapid and adequate diagnosis is of great importance. In the case of a known underlying rheumatic disease, histological confirmation of interstitial changes is not always necessary. In addition to the patient's history, pulmonary function testing and diagnostic imaging with high-resolution CT-scan (HR-CT) are cornerstones of the diagnostic process. The final diagnosis and therapeutic approach should be determined by a multidisciplinary discussion process. The basis of the treatment is immunosuppressants, however the use antifibrotic drugs is currently under investigation in clinical trials. In the case of advanced lung disease, lung transplantation should be evaluated promptly. In the case of pulmonary involvement with rheumatic disease, the teamwork of pulmonologists, rheumatologists and radiologists is of particular importance.


Vitamin D endocrine system and the immune response in rheumatic diseases.
Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders.


Intervention to Reduce Anxiety Pre- and Post-Eye Surgery in Pediatric Patients in South Korea: A Preliminary Quasi-Experimental Study.
In this study, we aimed to identify the effect of preoperative information on postoperative anxiety among children undergoing one-day eye surgery. We utilized a nonequivalent control group and a pretest-posttest quasi-experimental design. The participants were 15 children in the experimental group and 15 children in the control group. Preoperative information was provided to the experimental group in the waiting room. Anxiety level was measured using the Children's Emotional Manifestation Scale and pulse rate. For pulse rate, there were no statistically significant differences between the groups. In the behavioral anxiety response, there were statistically significant differences between the experimental and control groups (Z = -4.15, p < 0.001). The results suggest that the provision of preoperative information can be an effective intervention for reducing postoperative anxiety and improving the health of children undergoing surgery.


Comparison of structurally different allosteric modulators of muscarinic receptors by self-organizing neural networks.
Similarities in the molecular structure and surface properties of the allosteric modulators of muscarinic receptors, alcuronium, gallamine, tubocurarine, and the hexamethonium compound W84, a well-known pharmacological tool, are explored. The analysis of the molecular electrostatic potential (MEP) as well as of the shape of the molecular surface is performed by self-organizing neural networks. A distorted sandwich conformation of W84 is suggested to be the active form. The importance of the MEP for binding of these compounds could be established.


Subclinical semitendinosus and obturator externus involvement defines an autosomal dominant myopathy with early respiratory failure.
We recently described a dominant limb myopathy characterised by early respiratory failure whilst affected individuals were still ambulant (autosomal dominant myopathy with early respiratory failure). Early diagnosis and exclusion of this disorder is difficult because of the insidious onset in late adult life and the highly selective muscle involvement, both clinically and pathologically. We performed muscle magnetic resonance imaging on seven cases of autosomal dominant myopathy with early respiratory failure (age range 37-66 years, 4 male) and show selective early involvement of semitendinosus and obturator externus on magnetic resonance imaging that cannot be detected clinically, with different rates of progression in closely related muscles. These findings are specific to autosomal dominant myopathy with early respiratory failure and enable early non-invasive diagnosis for individuals at risk.


Association between dietary phytochemical index and breast cancer: a case-control study.
Dietary intake of isoflavones has been positively associated with risk of breast cancer (BC) in some earlier studies. In addition, most studies on diet-disease associations came from western countries and limited data are available in the Middle-East. This case-control study was performed on 350 women with BC aged over 30 years who were recruited from hospitals or private clinics in Isfahan, Iran. All patients were diagnosed with BC during the maximum of the last 6 months using physical examination and mammography findings. Using cluster method sampling, 700 apparently healthy age- and socioeconomic status-matched controls were randomly selected from healthy women who had no relationship with BC patients and had no familial history of BC. Data on dietary intakes were collected using a validated food-frequency questionnaire. The DPI was calculated based on dietary energy derived from foods rich in phytochemicals (kcal) divided by total daily energy intake (kcal) of each participant. Mean ± SD age and BMI in the study participants were 62.4 ± 10.8 years and 24.3 ± 5.2 kg/m2, respectively. In the crude model, participants in the highest quartile of DPI had 63% lower odds of breast cancer compared to those in the lowest quartile (95% CI 0.26, 0.54; P-trend < 0.001). After adjustment for potential confounders, this inverse association became strengthened (95% CI 0.22, 0.49; P-trend < 0.001). Further adjustment for BMI did not change the association (OR for the highest quartile vs. the lowest quartile = 0.40, 95% CI 0.26, 0.60; P-trend < 0.001). In conclusion, a protective association was observed between DPI and BC in this case-control study. Therefore, high consumption of foods rich in phytochemicals such as fruits, vegetables, and whole grains might help reducing the odds of BC among women.


Experimental gynogenesis provides evidence of hybridogenetic reproduction in the Rana esculenta complex.
The gynogenetic offspring of the hybrid frog Rana esculenta (R. ridibunda X R. lessonae) are exclusively of the ridibunda type. This is due to the premeiotic exclusion of the lessonae genome from the hybrid's germ cells.


Activation of the prefrontal cortex is associated with exertional dyspnea in chronic obstructive pulmonary disease.
Exertional dyspnea is the primary symptom that limits exercise in patients with chronic obstructive pulmonary disease (COPD). It is unknown which activated brain area is associated with this symptom in COPD patients. To investigate the activation of cortical areas associated with dyspnea during exercise in COPD patients. COPD patients (n = 10) and age-matched controls (n = 10) performed mild-intensity constant work rate cycle exercise (40% of their symptom-limited peak work rates) for 10 min, while cerebral hemodynamics and oxygenation were measured by near-infrared spectroscopy (NIRS). Ventilatory responses (breathing pattern and pulmonary gas exchange) and Borg scale ratings of dyspnea and leg fatigue were measured during exercise. Three NIRS probes were placed over the prefrontal and temporoparietal cortical regions of the subjects' heads. Changes in cortical oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total Hb) concentrations from baseline recordings were measured. Increased oxy-Hb (oxygenation) was assumed to reflect cortical activation. Oxy-Hb concentration was significantly increased in the prefrontal region during exercise in both groups but not in the temporoparietal regions. The change in prefrontal oxy-Hb concentration of COPD patients was not different from that of controls. Dyspnea scores were positively correlated with changes in oxy-Hb concentrations of the prefrontal regions in both groups. Multivariate analysis showed that oxy-Hb concentration in the prefrontal region was the best predictor of dyspnea in both groups. Exertional dyspnea was related to activation (oxygenation) of the prefrontal cortex in COPD patients and control subjects.


Association of severity of coexisting patellofemoral disease with increased impairments and functional limitations in patients with knee osteoarthritis.
To evaluate the association between severity of coexisting patellofemoral (PF) disease with lower extremity impairments and functional limitations in patients with tibiofemoral (TF) osteoarthritis (OA). Radiographic views of the TF and PF compartments, knee extension strength, and knee range of motion were obtained for 167 patients with knee OA. Additionally, knee-specific symptoms and functional limitations were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Activities of Daily Living Scale (ADLS). Moderate/severe PFOA was associated with lower knee extension strength (mean ± SD 1.4 ± 0.5 Nm/body weight [BW]) compared to no PFOA (mean ± SD 1.8 ± 0.5 Nm/BW). Additionally, total knee range of motion was significantly lower for patients with moderate/severe PFOA (mean ± SD 120.8° ± 14.4°) compared to no PFOA (mean ± SD 133.5° ± 10.7°) and mild PFOA (mean ± SD 125.8° ± 13.0°). Moderate/severe PFOA and mild PFOA were also associated with less pain while standing (odds ratio [OR] 0.2, 95% confidence interval [95% CI] 0.1-0.7 and OR 0.2, 95% CI 0.1-0.6, respectively) on the WOMAC, and moderate/severe PFOA was associated with greater difficulty with going downstairs (OR 2.9, 95% CI 1.0-8.1) on the ADLS. It appears that knees with more severe coexisting PF disease demonstrate features distinct from those observed in TFOA in isolation or in combination with mild PF disease. Treatment strategies targeting the PF joint may be warranted to mitigate the specific lower extremity impairments and functional problems present in this patient population.


Bladder dysfunction in boys with posterior urethral valves before and after puberty.
We characterized bladder dysfunction in boys with posterior urethral valves during childhood and adolescence. A total of 12 prepubertal boys with posterior urethral valves presenting before age 1 year was followed from ages 4 to 14 years and compared to 6 postpubertal boys with posterior urethral valves. Urodynamic evaluations and renal function studies were performed repeatedly. Patients had a changing urodynamic pattern with instability decreasing with time, increasing bladder capacity and commonly an unsustained voiding contraction causing emptying difficulties. Postpubertal boys had high capacity bladders with low contractility. We suggest that previously described urodynamic patterns of the valve bladder (unstable, poorly compliant and over distended bladders) are variations of the same basic pattern that changes with time toward decompensation.


Efficient nitrogen removal in a total floc sludge system from domestic wastewater with low C/N: High anammox nitrogen removal contribution driven by endogenous partial denitrification.
Since unsustainable partial nitrification prone to unstable nitrogen removal rates, cultivation and enrichment of AnAOB, further improve autotrophic nitrogen removal contribution have been challenges in the mainstream anammox process. This study proposed a new strategy to enrich AnAOB motivated by endogenous partial denitrification (EPD) in total floc sludge system through the AOA process with sustainable nitrification. The results showed that in the presence of NH4+ and NO3- at the anoxic stage of N-EPDA, Ca. Brocadia was enriched (0.005%→0.92%) in floc sludge via internal carbon source metabolism of EPD. The C/N and temperature of N-EPDA were also optimized to achieve higher activities of EPD and anammox. The N-EPDA was operated at low C/N ratio (3.1) with anammox nitrogen removal contribution of 78% during the anoxic stage, Eff.TIN of 8.3 mg/L and NRE of 83.5% during phase III, achieved efficient autotrophic nitrogen removal and AnAOB enrichment in the absence of partial nitrification.


Effect of regional versus general anesthesia on thirty-day outcomes following carotid endarterectomy: a cohort study.
The effect of regional versus general anesthesia on carotid endarterectomy outcomes is debated. This study assesses the effect of anesthetic technique on major morbidity and mortality and additional secondary endpoints following carotid endarterectomy. This was a retrospective propensity-matched-cohort analysis investigating elective carotid endarterectomy patients in the 2015-2019 American College of Surgeons National Surgical Quality Improvement Program ( n =37 204). The primary endpoint was 30-day mortality and major morbidity, defined as stroke, myocardial infarction, or death. Secondary endpoints included minor morbidity, bleeding events, healthcare resource utilization, and length of hospital stay. Univariate, multivariable, and survival analyses were applied. The 1 : 1 propensity-matched-cohort included 8304 patients (4152 in each group). Regional anesthesia was associated with similar incidences of major morbidity and mortality [odds ratio (OR), 0.81 (95% CI, 0.61-1.09); P = 0.162] and unplanned resource utilization [OR, 0.93 (95% CI, 0.78-1.11); P = 0.443], but lower incidences of minor morbidity [OR, 0.60 (95% CI, 0.44-0.81); P < 0.001] and bleeding events [OR, 0.49 (95% CI, 0.30-0.78); P = 0.002], and a shorter length of hospital stay [1.4 vs. 1.6 days; mean difference, -0.16 days (95% CI, -0.25 to -0.07); P < 0.001]. On multivariable analysis, regional anesthesia remained independently predictive of minor morbidity [adjusted odds ratio (AOR), 0.58 (95% CI, 0.42-0.79); P = 0.001] and bleeding events [AOR, 0.49 (95% CI, 0.30-0.77); P = 0.003]. Significance was maintained on survival analysis for these two endpoints. A mortality benefit was observed on univariate [OR, 0.50 (95% CI, 0.25-1.00); P = 0.045], multivariable [AOR, 0.49 (95% CI, 0.24-0.96); P = 0.043], and survival analysis ( P = 0.045). Carotid endarterectomy patients receiving regional anesthesia experience favorable outcomes compared to propensity-matched general anesthesia controls.


Predictors of coronary arterial remodeling patterns in patients with myocardial ischemia.
Preangioplasty intravascular ultrasound in 81 patients showed that adaptive remodeling occurred in 35% and constrictive remodeling in 34%. Multivariate analysis showed that smoking and fibrocalcific plaques were associated with constrictive remodeling, whereas small vessel size and hypercholesterolemia were associated with adaptive remodeling.


Erratum: The expression of Wnt-1 inducible signaling pathway protein-2 in astrocytoma: Correlation between pathological grade and clinical outcome.
[This corrects the article DOI: 10.3892/ol.2014.2663.].


Technical considerations of multi-parametric tissue outcome prediction methods in acute ischemic stroke patients.
Decisions regarding acute stroke treatment rely heavily on imaging, but interpretation can be difficult for physicians. Machine learning methods can assist clinicians by providing tissue outcome predictions for different treatment approaches based on acute multi-parametric imaging. To produce such clinically viable machine learning models, factors such as classifier choice, data normalization, and data balancing must be considered. This study gives comprehensive consideration to these factors by comparing the agreement of voxel-based tissue outcome predictions using acute imaging and clinical parameters with manual lesion segmentations derived from follow-up imaging. This study considers random decision forest, generalized linear model, and k-nearest-neighbor machine learning classifiers in conjunction with three data normalization approaches (non-normalized, relative to contralateral hemisphere, and relative to contralateral VOI), and two data balancing strategies (full dataset and stratified subsampling). These classifier settings were evaluated based on 90 MRI datasets from acute ischemic stroke patients. Distinction was made between patients recanalized using intraarterial and intravenous methods, as well as those without successful recanalization. For primary quantitative comparison, the Dice metric was computed for each voxel-based tissue outcome prediction and its corresponding follow-up lesion segmentation. It was found that the random forest classifier outperformed the generalized linear model and the k-nearest-neighbor classifier, that normalization did not improve the Dice score of the lesion outcome predictions, and that the models generated lesion outcome predictions with higher Dice scores when trained with balanced datasets. No significant difference was found between the treatment groups (intraarterial vs intravenous) regarding the Dice score of the tissue outcome predictions.


Prognostic significance of poorly differentiated histology and impact of adjuvant chemotherapy in early squamous cell carcinoma of cervix uteri.
This study is to determine whether the addition of cisplatin-based chemotherapy after radical hysterectomy will improve the survival of low-risk squamous cervical carcinoma with poor differentiation. Patients with low-risk squamous cervical cancer (FIGO IA2-IIA, absent high- and intermediate-risk factors after pathological evaluation) were eligible for this study. As first, the prognostic relevance of G3 versus G1/G2 among patients with low-risk squamous cervical cancer was analyzed, then, the oncological results of postoperative chemotherapy among low-risk squamous cervical cancer with poor differentiation was explored. Totally, there were 367 low-risk squamous cervical cancer patients, of whom 161 were poor-differentiated (47 in the chemotherapy group and 114 in the nonchemotherapy group), with a median follow-up time of 56 months. Patients with G3 displayed a significantly worse overall survival (p = 0.035), and a higher recurrence rate (p = 0.014) than patients with G1/G2. Compared with the nonchemotherapy group, the hazard ratios (95%CI) for recurrence-free survival in the chemotherapy group was 0.24 (0.06-0.93), (p = 0.038). No difference in overall survival was observed between the chemotherapy group and the nonchemotherapy group. The addition of cisplatin-based chemotherapy following surgery significantly improved recurrence-free survival for low-risk, poor differentiation, and early stage squamous cervical cancer patients.


A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19.
Gastrodin is an extract from the dried tuber of the Chinese herb Gastrodia elata (Tian ma), with anti-inflammatory, antioxidant, and antiviral properties. Recent studies have shown that, compared to commonly used diabetes drugs, gastrodin has antidiabetic effects in multiple ways, with characteristics of low cost, high safety, less side effects, protection of β-cell function, relieving insulin resistance and alleviating multiple complications. In addition, it is confirmed that gastrodin can protect the function of lung and other organs, enhance antiviral activity via upregulating the type I interferon (IFN-I), and inhibit angiotensin II (AngII), a key factor in "cytokine storm" caused by COVID-19. Therefore, we reviewed the effect and mechanism of gastrodin on type 2 diabetes mellitus (T2DM), and speculated other potential mechanisms of gastrodin in alleviating insulin resistance from insulin signal pathway, inflammation, mitochondrial and endoplasmic reticulum and its potential in the prevention and treatment of COVID-19. We hope to provide new direction and treatment strategy for basic research and clinical work: gastrodin is considered as a drug for the prevention and treatment of diabetes and COVID-19.


Prostaglandin removal and metabolism by isolated perfused rat lung.
We have investigated the mechanism(s) involved in the removal of prostaglandins (PG) from the pulmonary circulation by the lung. Unidirectional fluxes of PG from the circulation into the lung are measured in an isolated perfused rat lung preparation. Evidence is presented which suggests that a transport system for PG exists in lung tissue. This transport system is responsible for the removal of some PG from the circulation by the lung. PGE1 and PGF2alpha are substrates for this system, whereas PGB1, PGA1, and 15-keto-PGF2alpha are not. Since PGA1 is a substrate for the intracellular PG dehydrogenase, the selectivity of the lung's metabolism system for circulating PG is probably due to the selectivity of the transport system for PG. It is shown that the percentage of the pulmonary arterial concentration (CA) of PGE1 or PGF2alpha that is metabolized on passage through the pulmonary circulation decreases rapidly as CA increases. When the lungs were perfused with PGE1(PGF2alpha), the metabolites detected in the venous effluent were 15-keto-PGE1 (PGF2alpha) and 15-keto-13, 14-dihydro-PGE1 (PGF2alpha). The time course pattern of the appearance of metabolites in the venous effluent after the initiation of a constant CA, and the relative concentrations of the metabolites in the venous effluent, were examined as a function of CA.


Optimum gradient material for a functionally graded dental implant using metaheuristic algorithms.
Despite dental implantation being a great success, one of the key issues facing it is a mismatch of mechanical properties between engineered and native biomaterials, which makes osseointegration and bone remodeling problematical. Functionally graded material (FGM) has been proposed as a potential upgrade to some conventional implant materials such as titanium for selection in prosthetic dentistry. The idea of an FGM dental implant is that the property would vary in a certain pattern to match the biomechanical characteristics required at different regions in the hosting bone. However, matching the properties does not necessarily guarantee the best osseointegration and bone remodeling. Little existing research has been reported on developing an optimal design of an FGM dental implant for promoting long-term success. Based upon remodeling results, metaheuristic algorithms such as the genetic algorithms (GAs) and simulated annealing (SA) have been adopted to develop a multi-objective optimal design for FGM implantation design. The results are compared with those in literature.


Tricuspid valve replacement with a melody stented bovine jugular vein conduit.
Atrioventricular valve replacement options are limited in infants and small children. The Melody stented bovine jugular vein conduit is being used with increasing frequency for percutaneous pulmonary valve replacement. The Melody valve can be serially dilated over time to accommodate the somatic growth of pediatric patients. We report the initial experience of using the Melody valve as a surgical tricuspid valve replacement in an infant.


Organisation and molecular analysis of repeated DNA sequences in the rice blast fungus Magnaporthe grisea.
The distribution of a previously described repeated DNA sequence present as a 1.3-kb PstI fragment in the genome of the rice blast fungus Magnaporthe grisea was analysed by carrying out DNA fingerprint analysis of 36 isolates including rice, non-rice and laboratory strains. The analysis of various higher-molecular-weight PstI fragments with homology to the 1.3-kb repeat revealed that these may arise predominantly from transposon insertions or point mutations. Analysis of a 5.1-kb derivative revealed both a point mutation at a PstI site and an insertion of a putative transposable element which caused an increase in molecular weight from 1.3 to 5.1 kb. Another repeat element of 1.4 kb was identified and found to exist in association with the 1.3-kb repeat. Both 1.3- and 1.4-kb elements were found to be parts of MGR583 (Hamer et al. 1989), a LINE-like element. These elements were present in a high copy number in all the rice and a majority of non-rice pathogens indicating that MGR583 is not a host-specific sequence as reported earlier. Our results suggest that repeated DNA elements in M. grisea have amplified independently of one another and further indicate that different isolates of M. grisea may have evolved from several distinct lines of origin.


Mitotic spindle misorientation in cancer--out of alignment and into the fire.
Mitotic spindle orientation can influence tissue organization and vice versa. Cells orient their spindles by rotating them parallel or perpendicular to the cell--and hence the tissue--axis. Spindle orientation in turn controls the placement of daughter cells within a tissue, influencing tissue morphology. Recent findings implicating tumor suppressor proteins in spindle orientation bring to the forefront a connection between spindle misorientation and cancer. In this Commentary, we focus on the role of three major human tumor suppressors--adenomatous polyposis coli (APC), E-cadherin and von Hippel-Lindau (VHL)--in spindle orientation. We discuss how, in addition to their better-known functions, these proteins affect microtubule stability and cell polarity, and how their loss of function causes spindles to become misoriented. We also consider how other cancer-associated features, such as oncogene mutations, centrosome amplification and the tumor microenvironment, might influence spindle orientation. Finally, we speculate on the role of spindle misorientation in cancer development and progression. We conclude that spindle misorientation alone is unlikely to be tumorigenic, but it has the potential to synergize with cancer-associated changes to facilitate genomic instability, tissue disorganization, metastasis and expansion of cancer stem cell compartments.


The minimum spanning tree: an unbiased method for brain network analysis.
The brain is increasingly studied with graph theoretical approaches, which can be used to characterize network topology. However, studies on brain networks have reported contradictory findings, and do not easily converge to a clear concept of the structural and functional network organization of the brain. It has recently been suggested that the minimum spanning tree (MST) may help to increase comparability between studies. The MST is an acyclic sub-network that connects all nodes and may solve several methodological limitations of previous work, such as sensitivity to alterations in connection strength (for weighted networks) or link density (for unweighted networks), which may occur concomitantly with alterations in network topology under empirical conditions. If analysis of MSTs avoids these methodological limitations, understanding the relationship between MST characteristics and conventional network measures is crucial for interpreting MST brain network studies. Here, we firstly demonstrated that the MST is insensitive to alterations in connection strength or link density. We then explored the behavior of MST and conventional network-characteristics for simulated regular and scale-free networks that were gradually rewired to random networks. Surprisingly, although most connections are discarded during construction of the MST, MST characteristics were equally sensitive to alterations in network topology as the conventional graph theoretical measures. The MST characteristics diameter and leaf fraction were very strongly related to changes in the characteristic path length when the network changed from a regular to a random configuration. Similarly, MST degree, diameter, and leaf fraction were very strongly related to the degree of scale-free networks that were rewired to random networks. Analysis of the MST is especially suitable for the comparison of brain networks, as it avoids methodological biases. Even though the MST does not utilize all the connections in the network, it still provides a, mathematically defined and unbiased, sub-network with characteristics that can provide similar information about network topology as conventional graph measures.


Comparison of perioperative outcomes of robotic vs. laparoscopic partial nephrectomy for renal tumors with a RENAL nephrometry score ≥7: A meta-analysis.
To compare the perioperative outcomes of robotic partial nephrectomy (RPN) vs. laparoscopic partial nephrectomy (LPN) for complex renal tumors with a RENAL nephrometry score ≥7. We searched PubMed, EMBASE and the Cochrane Central Register for studies from 2000 to 2020 to evaluate the perioperative outcomes of RPN and LPN in patients with a RENAL nephrometry score ≥7. We used RevMan 5.2 to pool the data. Seven studies were acquired in our study. No significant differences were found in the estimated blood loss (WMD: 34.49; 95% CI: -75.16-144.14; p = 0.54), hospital stay (WMD: -0.59; 95% CI: -1.24-0.06; p = 0.07), positive surgical margin (OR: 0.85; 95% CI: 0.65-1.11; p = 0.23), major postoperative complications (OR: 0.90; 95% CI: 0.52-1.54; p = 0.69) and transfusion (OR: 0.72; 95% CI: 0.48-1.08; p = 0.11) between the groups. RPN showed better outcomes in the operating time (WMD: -22.45; 95% CI: -35.06 to -9.85; p = 0.0005), postoperative renal function (WMD: 3.32; 95% CI: 0.73-5.91; p = 0.01), warm ischemia time (WMD: -6.96; 95% CI: -7.30--6.62; p < 0.0001), conversion rate to radical nephrectomy (OR: 0.34; 95% CI: 0.17 to 0.66; p = 0.002) and intraoperative complications (OR: 0.52; 95% CI: 0.28-0.97; p = 0.04). RPN is a safe and effective alternative to LPNs for or the treatment of complex renal tumors with a RENAL nephrometry score ≥7 with a shorter warm ischemic time and better postoperative renal function.


Intensity of the hydrogen peroxide upsilon(6)(b) band around 1266 cm(-1).
Laboratory spectra of the upsilon(6)(b) band of H(2)O(2) at 1266 cm(-1) have been obtained at a resolution of 0.06 cm(-1) and at temperatures ranging from 278 to 294 K. A total band intensity of 375 +/- 17 cm(-2) amagat(-1) is determined from the spectra. Special techniques to handle the H(2)O(2) samples in a way that minimizes abundance determination errors are discussed.


Remote assessment of dental records by using intraoral scan-based digital three-dimensional models in an elderly patient population - an exploratory study.
To assess the agreement rates of dental records derived from intraoral scan-based digital three-dimensional models (3DM) and 3DM + panoramic radiographs (3DM+PAN-X) compared to clinical findings. Based on the 3DM/3DM+PAN-X of 50 patients undergoing supportive periodontal therapy (SPT), ten remote raters (inexperienced in using IOS or 3DM) assessed for each site of the dental scheme (32 sites) whether a tooth was missing (M), filled (F), restoration- and caries-free (H), replaced by an implant (I) or decayed (D). Remote records were compared to the clinical reference record of each patient at tooth-level. The clinical records were assessed by an experienced dentist who supplemented the clinical findings with information from available radiographs and the patient records to define the clinical reference record. The agreement-rates for 3DM/3DM+PAN-X at tooth-level are: M: 93%/94%, F: 84%/88%, H: 92%/92%, I: 65%/96%, D: 29%/29%. The overall agreement-rate is 88% for the 3DM-based dental records (14093 of 16000 entries true) and 91% for 3DM+PAN-X (14499 of 16000 entries true). Using 3DM for dental record assessment, posterior teeth had higher odds of correct findings compared to anterior teeth (upper jaw OR=2.34, lower jaw OR=1.27). The remote detection of healthy, missing and filled teeth and implants by raters inexperienced in using IOS or 3DM shows a high agreement-rate with the clinical findings. The additional evaluation of PAN-X increased the agreement-rate significantly for implants. Thus, the remote assessment of dental records using 3DM+PAN-X has a high accuracy when applied in SPT-patients with low caries activity.


[Revascularization of a necrotic bone by transfer of a arteriovenous pedicle flap. Experimental study in rats].
An experiment in adult rats with histologic study of isolated bone segment revascularization is reported vascular bundle is inserted into the humeral head that has been transferred under abdominal skin. It induces an active proliferation of new blood vessels with formation of new bone/invading the necrotized bone.


Separation and properties of EA-rosette-forming lymphocytes in humans.
Human peripheral blood lymphocytes were separated into subpopulations enriched or depleted with respect to B lymphocytes (Ig-bearing cells), T lymphocytes, (cell forming rosettes with sheep erythrocytes: E-RFC) and Fc receptor-bearing lymphocytes (EA-RFC). From the distributions and recoveries of the various cell types it could be concluded that there was very little overlap between Ig-bearing lymphocytes and EA-RFC. The latter cells partly belonged to "null" (non-T, non-B) cells; it was however demonstrated that 30 % of the EA-RFC were T cells (E-RFC). The lytic capacity in antibody-dependent lymphocytotoxicity (ADL) was shown to correspond with the proportions of EA-RFC in the various fractions. Non-T cells showed enhanced ADL activity when compared to the unseparated cells. Purified T cells populations also displayed ADL activity. Since the latter could not be due to contaminating non-T cells, this activity was ascribed to Fc receptor-bearing T lymphocytes.


Focusing of X-rays by Total External Reflection from a Paraboloidally Tapered Glass Capillary.
The first observation of a true geometrical focus of X-rays well beyond the exit of a paraboloidally tapered glass monocapillary is reported. An intensity gain of 250 +/- 20 into a 6 x 9 mum pinhole for 8 keV X-rays and transmission efficiencies of more than 90% below 20 keV were observed.


Surfactant dependent toxicity of lipid nanocapsules in HaCaT cells.
Lipid nanocapsules (LNC) have been suggested for a variety of pharmaceutical applications. Among them approaches for drug delivery to the skin appear particularly interesting. The current standard composition has been modified to better understand their properties by selecting a variety of different surfactants. LNC have been prepared using different non-ionic surfactants (Solutol(®) HS15: Polyoxyl 15 Hydroxystearate; Cremophor(®) EL: Polyoxyl 35 Castor Oil; Simulsol(®) 4000: Polyoxyl 40 Hydrogenated Castor Oil; Vitamin E TPGS(®): alpha-tocopheryl poly(ethylene glycol) succinate; Polysorbate 20 and 80) and analysed for their size, stability, drug release and toxicity on keratinocytes in cell culture. The feasibility of LNC using different surfactant was surprisingly easy and led to a variety of stable formulations that were selected for further investigations. Surfactants led to a variability of the release kinetics (t50% release varied from Polysorbate 20: 2.5h to Simulsol(®) 4000: 5.0h), however different formulations from the same surfactant did not differ significantly. In vitro toxicity of LNC was surfactant type dependent and a correlation between LNC and the pure respective surfactant was found. This toxicity was found to be mainly independent from the surface active properties. The surfactant type in LNC is easily interchangeable from formulation point of view. LNC appear to be appropriate as carrier for cutaneous delivery however toxicity can vary distinctly depending on the surfactant used for the preparation.


Visualization of hypoxia-induced glutamate release in gerbil hippocampal slice.
Microfluorometry was used to investigate distribution of hypoxia-induced release of glutamate. Mongolian gerbil hippocampal slice was perfused in a medium containing glutamate dehydrogenase and NAD+. Release of glutamate into extracellular space caused an increase in fluorescence due to the formation of NADH. The hypoxia-induced release of glutamate was gradually increased throughout the slice: no significant difference was detected among CA1 region, CA3 region and the dentate gyrus.


Age-related changes in immune function of rats and the effect of long-term hypophysectomy.
The effect of age on the ability of rats to raise antibodies to sheep erythrocytes and on the number of IgM plaque-forming cells in the spleen was investigated. An age-related decline in both parameters was observed. Additionally, the possibility that long-term hypophysectomy coupled with minimal replacement therapy might result in a delay and/or reversal of the age-related decline in immune function was studied. It was observed that long-term hypophysectomized rats responded better to immunization with sheep erythrocytes than did their age-matched unoperated littermates. The possible relationship of this to aging is discussed.


The actions of caerulein on gastric secretion of the dog and the rat.
1. Caerulein, as expected from its amino-acid composition and sequence, has a potent stimulant action on gastric secretion in the dog, the rat and the frog.2. In the denervated fundic pouch of the dog, caerulein increases the rate of flow of gastric juice and the outputs of acid and pepsin. Acid concentration and pepsin concentration in caerulein-produced juice are generally greater than in control juice. The threshold subcutaneous dose of caerulein is 0.15-0.5 mug/kg and the threshold rate of intravenous infusion 0.25-0.5 mug/kg per hr. Rapid intravenous injection is ineffective. On a molar basis, caerulein is approximately twice as active as human gastrin I on volume and acid output of the gastric pouch and 4 times as active on pepsin output.3. Sustained acid secretion of the fundic pouch produced by histamine infusion is inhibited by caerulein, administered either intravenously or subcutaneously. In turn, acid secretion elicited by caerulein is inhibited by atropine.4. In the rat, the activity ratio of caerulein to human gastrin I is 7-30, calculated on a molar basis, and is thus considerably greater than in the dog. Further, caerulein is 3 times more active than cholecystokinin-pancreozymin. Tested on the perfused stomach preparation of the rat, the threshold dose of caerulein by rapid intravenous injection is 25 ng/kg, by intravenous infusion 0.25 mug/kg per hr, and by subcutaneous injection 0.25 to 0.5 mug/kg.5. The activity of caerulein is sharply reduced by pretreatment of the rats with the histamine liberator 48/80 and potentiated by pretreatment with the diamine oxidase inhibitor aminoguanidine. When caerulein is given by rapid intravenous injection during a priming infusion of histamine its effect is enhanced and considerably prolonged.6. The isolated mucosa of the frog stomach is extremely sensitive to caerulein which, in a concentration of a few pg/ml., stimulates active transport of chloride.7. Qualitative and quantitative differences in the action of gastrin and caerulein are pointed out, and particular emphasis is laid on the importance of esterification of the tyrosyl residue for the biological activity of caerulein.


Inflammatory carcinoma of the bladder and interstitial cystitis.
Two patients were treated for interstitial cystitis after having had bladder biopsies that did not reveal tumor. However, in both cases an aggressive carcinoma of the bladder later proved to be present when simple cystectomy for the "benign" disease was done. The masquerade of carcinoma of the bladder as interstitial cystitis and the pitfalls inherent in making the correct diagnosis are emphasized. The possibility of underlying bladder carcinoma should be excluded in any patient who presents with symptoms of chronic cystitis. Urinary cytology is most helpful but repeated bladder biopsy with careful serial sectioning may be necessary to establish the diagnosis of malignancy. It is not known whether the carcinomas were primary or secondary developments in our cases. The term inflammatory carcinoma of the bladder is proposed to call the attention of clinicians and pathologists to this lethal imitator.


Near real-time, on-site, quantitative analysis of PAHs in the aqueous environment using an antibody-based biosensor.
Rapid, on-site, quantitative assessments of dissolved polycyclic aromatic hydrocarbons (PAHs) were demonstrated for two field applications. The platform, a KinExA Inline Sensor (Sapidyne Instruments), employed the monoclonal anti-PAH antibody, 7B2.3, which has specificity for 3- to 5-ring PAHs. A spatial study was conducted near a dredging site where contaminated sediments were being removed, and a temporal study was performed during a rainfall event. Most importantly, the generation of near real-time data guided management decisions in the field and determined proper sampling protocols for conventional analyses. The method was able to determine PAH concentrations as low as 0.3 µg/L, within 10 min of sample acquisition, and to assess 80+ samples (not including standards and blanks) in less than 3 d. These results were compared with a laboratory-based gas chromatography-mass spectrometry method in which a wide array of PAHs, including alkylated homologs, were examined. This system shows great promise as a field instrument for the rapid monitoring of PAH pollution.


Searches for B0 decays to combinations of two charmless isoscalar mesons.
We search for B meson decays into two-body combinations of eta, eta', omega, and phi mesons from 89 x 10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e+e- collider at SLAC. We find the branching fraction B(B0-->etaomega)=(4.0(+1.3)(-1.2)+/-0.4)x10(-6) with a significance of 4.3 sigma. For the other decay modes we set the following 90% confidence level upper limits on the branching fractions, in units of 10(-6): B(B0-->etaeta)<2.8, B(B0-->etaeta')<4.6, B(B0-->eta'eta')<10, B(B0-->eta'omega)<2.8, B(B0-->etaphi)<1.0, B(B0-->eta'phi)<4.5, and B(B0-->phiphi)<1.5.


A retinal snap shot may indicate individual risk for cardiovascular disease - the MIPH Eye&Health Study.
Examination of retinal vasculature can be used to non-invasively quantify changes within the microvasculature of the human body and might be a predictor of cardiovascular disease. This study evaluates associations of the structure of the retinal vasculature with established risk factors for cardiovascular disease. A cross-sectional study was performed in a working age population. Several systemic cardiovascular parameters were analyzed and PROCAM- and SCORE-risk estimates were calculated. A quantitative ophthalmological examination including digital fundus imaging has taken place. Central retinal arterial/venous equivalents (CRAE/CRVE) and arterio-venous ratio (AVR) were analyzed using validated software. Associations of retinal vessel parameters and systemic cardiovascular and ocular parameters were calculated by multivariate analysis using SPSS software. A p-value of <0.05 with Bonferroni correction was accepted as significant. 338 probands were included. A smaller CRAE was independently associated with increased mean arterial blood pressure, higher age and higher body-mass index. Regarding CRVE age was inversely associated. Other cardiovascular risk parameters were not associated to the examined retinal vessel equivalents. AVR showed a significant association to mean arterial blood pressure and body-mass-index. PROCAM- and SCORE-risk estimates were negatively associated with CRAE and AVR, but not associated to CRVE. Arterial retinal vessel analysis and AV-ratio showed associations to established cardiovascular parameters in the study population. PROCAM- and SCORE-risk estimates as indicators of cardiovascular risk were associated with the CRAE and the AV-ratio. This suggests that a single snap shot of the retinal vessels may indicate the individual relative risk for cardiovascular events.


Simultaneous separation of inorganic anions and cations by using anion-exchange and cation-exchange columns connected in tandem in ion chromatography.
Inorganic anions and cations in environmental waters were determined by ion chromatography. Stationary and mobile phases were examined for the simultaneous separation of both anions and cations. Cations detection by UV detection requires a mobile phase with a UV absorbing additive, which indirectly visualizes cations as negative peaks. Simultaneous separation of anions and cations were achieved when using an eluent that consists of inorganic acid with weak basic amino acid as additives. It was convenient to separate both anions and cations by coupling anion-exchange and cation-exchange columns in tandem. The order of the separation columns connected affected the elution profiles. When the eluent comprises of multiple anions and a single cation, the anion-exchange column should be connected in the upper stream, whereas when the eluent comprises multiple cations and a single anion, the cation-exchange column should be connected in the upper stream. Use of switching valves also allowed simultaneous separation of anions and cations in a single chromatographic run. In the present work, operating conditions were optimized for the simultaneous separation of anions and cations.


A 66-Year-Old Woman With Progressive Dyspnea and Obstructive Pneumonia.
A 66-year-old woman with a history of diabetes presented with an intermittent low-grade fever, cough, shortness of breath, and decreased activity tolerance over a 3-month period. She is a farmer, and denied a history of chronic pulmonary disease. Her only medical history was type 2 diabetes managed without medication. She denied smoking or tobacco use. She did not report any recent travel and denied having birds at home. Imaging at a local hospital showed left lower lobe atelectasis with a small pleural effusion. An infection with mucormycosis was diagnosed through transbronchial biopsy. The patient was given nebulized amphotericin B along with concurrent IV liposomal amphotericin B for a total of 15 days. She experienced no significant improvement in symptoms during therapy and, in fact, developed worsening, progressive dyspnea.


Complications of excimer laser photorefractive keratectomy for myopia.
To evaluate the safety and complication rates of excimer laser photorefractive keratectomy (PRK). Assutah Laser Center, Tel-Aviv, Israel. This retrospective study evaluated the complication rate after PRK in 825 consecutive patients who had PRK for myopia and had a follow-up of at least 12 months. At 12 months postoperatively, 4.0% of patients suffered from overcorrection and 8.6% from undercorrection. Induced astigmatism developed in 1.4% of all operated eyes. Three percent of the patients had haze, and 3.6% reported glare or halos. Twenty-three eyes (2.7%) lost one line or more of best corrected visual acuity (BCVA). Ptosis developed in 0.4% of the eyes, and 3.5% had a significant increase in intraocular pressure resulting from corticosteroid treatment. There were no complications in 678 eyes (82.5%). Eighty-two percent of eyes having PRK did not develop complications. In 18.0% one or more complication, mainly undercorrection, overcorrection, or loss of BCVA, occurred.


The clinical and radiologic features of paediatric rhabdomyosarcoma.
Rhabdomyosarcoma is the most common soft-tissue sarcoma in children. The most common sites are head and neck, genitourinary tract and extremities. In this review we outline the clinical and radiologic features of paediatric rhabdomyosarcoma, as well as imaging considerations and imaging of relapse.


Pharmacogenetics in diffuse large B-cell lymphoma treated with R-CHOP: Still an unmet challenge.
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma representing approximately one third of all non-Hodgkin lymphomas and about 40% of patients do not benefit of the standard first-line immune-chemotherapeutic treatment (i.e., R-CHOP - rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) that is administered as upfront therapy to substantially all patients independently from the stage of disease and other prognostic parameters. The administration of other pharmacological treatments is in fact limited to selected patients, unfitting for R-CHOP. Although clinical prognostic scores, i.e. International Prognostic Index (IPI), and molecular classifiers based on the cell of origin are available, at present no biomarkers predictive of R-CHOP response has been identified and validated. Constitutional polymorphisms of genes involved in the mechanism of action of drugs included in R-CHOP have been suggested by many authors to play a role in the efficacy and in some case in the toxicity of this treatment. Thus, it is conceivable that in the future, after proper validation, some polymorphisms can be used as pharmacogenetic biomarkers of therapeutic outcome in this disease setting. This review discusses the status of the art on molecular biomarkers predictive of DLBCL prognosis and deals with the relevant issue of the variability in response to DLBCL drug treatment. Overall, this review focuses on single nucleotide polymorphisms (SNPs) that, based on a candidate gene approach or on a genome-wide association study (GWAS) analysis, have been suggested to play a role in response to R-CHOP. In particular, SNPs discovered by a candidate gene approach are related to genes involved in drug transport (i.e., ATP-binding cassette transporters), drug metabolism, drug detoxification enzymes, oxidative stress, apoptosis, DNA repair, immunity and angiogenesis. Data from a GWAS analysis performed in DLBCL patients treated with R-CHOP, identified two SNPs associated with clinical outcomes related to genes involved in pivotal cellular processes and in transcriptional regulation and cell cycle progression, respectively. Ongoing prospective pharmacogenetic clinical trials, including a GWAS study we performed, have also been discussed.


Systemic immunosuppressive therapy for progressive bilateral Mooren's ulcer.
Nine patients with progressive bilateral Mooren's ulcer unresponsive to conventional ocular and systemic therapy were treated with methotrexate or with cyclophosphamide. The progressively destructive inflammatory process was arrested, and ocular anatomy and function were preserved, in eight patients who were adequately treated with immunosuppressive doses of the cytotoxic drugs for 6 to 24 months. The inflammatory process eventually destroyed both eyes of one patient who received inadequate therapy and follow-up care. Used properly, cytotoxic immunosuppressive therapy may offer a reasonable option in the care of patients with bilateral progressive Mooren's ulcer.


Emerging tools and strategies in cyanobacterial omics.
Cyanobacteria are emerging as a popular system in both basic and applied microbial research. However, the incomplete understanding of their molecular biology hinders their practical applications in the industrial, agricultural, and environmental sectors. We present the potential of recently developed omics approaches to obtain deeper insights into cyanobacterial molecular physiology.


Analgesia and patient comfort after enhanced recovery after surgery in uvulopalatopharyngoplasty: a randomised controlled pilot study.
Uvulopalatopharyngoplasty(UPPP) is the most prevalent surgical treatment of obstructive sleep apnea, but postoperative pharyngeal pain may affect patient comfort. The enhanced recovery after surgery pathway has been proved beneficial to many types of surgery but not to UPPP yet. The aim of this pilot study was to preliminarily standrize an enhanced recovery after surgery protocol for UPPP, to assess whether it has positive effects on reducing postoperative pharyngeal pain and improving patient comfort, and to test its feasibility for an international multicentre study. This randomised controlled study analysed 116 patients with obstructive sleep apnoea (OSA) who were undergoing UPPP in a single tertiary care hospital. They were randomly divided according to treatment: the ERAS group (those who received ERAS treatment) and the control group (those who received traditional treatment). Ninety-five patients completed the assessment (ERAS group, 59 patients; control group, 36 patients). Pharyngeal pain and patient comfort were evaluated using a visual analogue scale (VAS) at 30 min and at 6, 12, 24 and 48 h after UPPP. Complications, hospitalisation duration, and hospital cost were recorded. The VAS scores for resting pain and swallowing pain were significantly lower in the ERAS group than those in the control group at 30 min and at 6, 12, 24 and 48 h after surgery. Patient comfort was improved in the ERAS group. The hospitalisation duration and cost were comparable between the groups. The incidence of complications showed an increasing trend in the ERAS group. The ERAS protocol significantly relieved pharyngeal pain after UPPP and improved comfort in patients with OSA, which showed the prospect for an larger study. Meanwhile a potential increase of post-operative complications in the ERAS group should be noticed. Chinese Clinical Trial Registry (23/09/2018, ChiCTR1800018537 ).


Allostery in the LacI/GalR family: variations on a theme.
The lactose repressor protein (LacI) was among the very first genetic regulatory proteins discovered, and more than 1000 members of the bacterial LacI/GalR family are now identified. LacI has been the prototype for understanding how transcription is controlled using small metabolites to modulate protein association with specific DNA sites. This understanding has been greatly expanded by the study of other LacI/GalR homologues. A general picture emerges in which the conserved fold provides a scaffold for multiple types of interactions - including oligomerization, small molecule binding, and protein-protein binding - that in turn influence target DNA binding and thereby regulate mRNA production. Although many different functions have evolved from this basic scaffold, each homologue retains functional flexibility: For the same protein, different small molecules can have disparate impact on DNA binding and hence transcriptional outcome. In turn, binding to alternative DNA sequences may impact the degree of allosteric response. Thus, this family exhibits a symphony of variations by which transcriptional control is achieved.


The journal impact factor: judging a book by its cover.
Journal impact factors have been used to evaluate the quality of the work of an individual author and as a guide to the quality of a given study. Despite a rough correlation between the quality of an article and the impact factor of the journal it is published in, the reader cannot be sure of the value of an individual article without a careful appraisal of its content.


Computed tomographic assessment of vertebral bone mineral in childhood.
Quantitative computed tomography (QCT) was used to assess trabecular bone mineral concentration in the vertebrae of 132 children, 45 with suspected disorder of bone mineralisation, 54 with thalassaemia and 37 controls. The range for bone mineral concentration in controls, expressed as equivalent K2HPO4 concentrations, was 90-190 mg cm-3. Abnormally low values were seen in all untreated children with idiopathic juvenile osteoporosis, 3/9 steroid recipients, and three patients with osteogenesis imperfecta. Abnormally high values were seen in 10/14 chronic renal failure patients. Comparison of the single and dual-energy methods showed that the single energy method, which has a lower radiation dose and is less prone to error from movement artifact, is satisfactory in most paediatric applications.


Analyzing the relationship between managers' working pressure and creative behavior from the social network perspective.
With the social environment requirements for innovation and creativity, requirements for enterprises' innovation and creativity are also higher. However, research on the working pressure and innovation behavior of enterprise managers is rare. To explore the relationship between the working pressure of managers and creative organizational behavior, provide a reference for the development of corporate innovation activities, thereby improving corporate organizational creativity. Managers in enterprises under social networks' background are selected as research objects to study the relationship between their working pressure and creative organizational behavior. First, the theory of pressure cognition activation is elaborated. The challenge pressure, hindrance pressure, and organizational creativity are selected as the basis, and the reliability and validity of the corresponding scale tools are analyzed and tested. Second, based on the relationship among challenging working pressure, hindrance working pressure, and organizational, creative behavior activities, two hypotheses are proposed, which are expressed as Hypothesis 1 and Hypothesis 2, respectively. Finally, according to the managerial working pressure in organizational, creative behavioral activities, two kinds of hypotheses are proposed, which are represented by Hypothesis 3 and Hypothesis 4, respectively. The results show: The selected scale tools have good reliability and validity. The Cronbach's Alpha reliability coefficients corresponding to challenge pressure, hindrance pressure, and organizational, creative behavior activities are all above 0.85. The challenge pressure has a significantly positive impact on organizational creativity (P < 0.01), while the hindrance pressure has a significantly negative impact on organizational creativity (P < 0.01); therefore, Hypothesis 1 and Hypothesis 2 are verified. The organizational support for creative behavior activities has a dual adjustment impact. In addition to negatively regulating the positive path of managers' working pressure on work engagement, organizational support also positively regulates the positive path of managers' work engagement on organizational creativity. Therefore, Hypothesis 3 and Hypothesis 4 are verified. The above results provide a theoretical reference for a profound understanding of the relationship between working pressure and creative behavior and the improvement of the creative ability of enterprises.


Quartz crystal microbalance study of endothelial cell number dependent differences in initial adhesion and steady-state behavior: evidence for cell-cell cooperativity in initial adhesion and spreading.
The quartz crystal microbalance (QCM) technique has been applied to the real time monitoring of endothelial cell (EC) adhesion and spreading on the QCM gold surface. We previously showed that the measured QCM Deltaf and DeltaR shifts were due to cells adhering to the gold crystal surface, requiring proteolytic enzyme treatment to be removed from the surface, in order for the Deltaf and DeltaR shifts to return to zero. In the present report, we demonstrate the quantitative dependence and saturation of the measured Deltaf and DeltaR shifts on the number of firmly attached ECs as measured by electronic counting of the cells. We demonstrate through a light microscope simulation experiment that the different Deltaf and DeltaR regions of the QCM temporal response curve correspond to the incident ECs contacting the surface, followed by their adhesion and spreading, which reflect cellular mass distribution and cytoskeletal viscoelasticity changes. Also, we demonstrate that the dose response curve of Deltaf and DeltaR values versus attached EC number is more sensitive and possesses less scatter for the hydrophilically treated surface compared to the native gold surface of the QCM. For both surfaces, a Deltaf and DeltaR versus trypsinized, attached EC number plot 1 h post-seeding exhibits a sigmoid curve shape whereas a similar plot 24 h post-seeding exhibits a hyperbolic curve shape. This number dependence suggests cell-cell cooperativity in the initial cell adhesion and spreading processes. These QCM data and our interpretation are corroborated by differences in cell appearance and spreading behavior we observed for ECs in a light microscope fluorescence simulation experiment of the cell density effect. For a stably attached EC monolayer at 24 h post-addition, steady-state Deltaf and DeltaR values are higher and exhibit saturation behavior for both the hydrophilically treated gold surface as compared to the untreated surface. The steady-state 24 h Deltaf and DeltaR values of stably attached ECs are shifted from the 1 h attached ECs. The 24 h values are characteristic of a more energy-dissipative structure. This is consistent with the time-dependent elaboration of surface contacts in anchorage-dependent ECs via the attachment of intregrins to underlying extracellular matrix. It is also in agreement with the known energy dissipation function of the ECs that cover the interior of blood vessels and are exposed to continuous pulsatile blood flow.


Developing a risk prediction model for survival to discharge in cardiac arrest patients who undergo extracorporeal membrane oxygenation.
Limited data are available on a risk model for survival to discharge after extracorporeal membrane oxygenation (ECMO)-assisted cardiopulmonary resuscitation (ECPR). We aimed to develop a risk prediction model for survival to discharge in cardiac arrest patients who undergo ECMO. Between January 2004 and December 2012, 505 patients supported by ECMO were enrolled in a retrospective, observational registry. Among those, we studied 152 adult patients with in-hospital cardiac arrest. The primary outcome was survival to discharge. A new predictive scoring system, named the ECPR score, was developed to monitor survival to discharge using the β coefficients of prognostic factors from the logistic model, which were internally validated. In-hospital death occurred in 104 patients (68.4%). In multivariate logistic regression, age ≤ 66, shockable arrest rhythm, CPR to ECMO pump-on time ≤ 38 min, post-ECMO arterial pulse pressure > 24 mmHg, and post-ECMO Sequential Organ Failure Assessment score ≤ 14 were independent predictors for survival to discharge. Survival to discharge was predicted by the ECPR score with a c-statistics of 0.8595 (95% confidence interval [CI], 0.80-0.92; p<0.001) which was similar to the c-statistics obtained from internal validation (training vs. test set; c-statistics, 0.86 vs. 0.86005; 95% CI, 0.80-0.92 vs. 0.77-0.94). The sensitivity and specificity for prediction of survival to discharge were 89.6% and 75.0%, respectively, when the ECPR score was >10. The new risk prediction model might be helpful for decisions about ECPR management and could provide better information regarding early prognosis.


History of immunotherapy: the first 100 years.
Allergen-specific immunotherapy (SIT) defines and distinguishes the modern practice of clinical allergy and immunology as the 100th anniversary of this pioneering technique is celebrated. Despite the tremendous advancements made in therapeutics, pharmacology, and the basic science of allergy, SIT remains the only treatment modality that offers a potential cure for atopic diseases rather than simply an amelioration of symptoms. A historical perspective not only offers an opportunity to tell some of the fascinating stories that led to the conception of SIT but also gives an occasion to recognize, remember, and honor those individuals who have contributed to its development.


New mammography screening performance metrics based on the entire screening episode.
Established mammography screening performance metrics use the initial screening mammography assessment because they were developed for radiologist performance auditing, yet these metrics are frequently used to inform health policy and screening decision making. The authors have developed new performance metrics based on the final assessment that consider the entire screening episode, including diagnostic workup. The authors used data from 2,512,577 screening episodes during 2005-2017 at 146 facilities in the United States participating in the Breast Cancer Surveillance Consortium. Screening performance metrics based on the final assessment of the screening episode were compared with conventional metrics defined with the initial assessment. Results were also stratified by breast density and breast cancer risk. The cancer detection rates were similar for the final assessment (4.1 per 1000; 95% confidence interval [CI], 3.8-4.3 per 1000) and the initial assessment (4.1 per 1000; 95% CI, 3.9-4.3 per 1000). The interval cancer rate was 12% higher when it was based on the final assessment (0.77 per 1000; 95% CI, 0.71-0.83 per 1000) versus the initial assessment (0.69 per 1000; 95% CI, 0.64-0.74 per 1000), and this resulted in a modest difference in sensitivity (84.1% [95% CI, 83.0%-85.1%] vs 85.7% [95% CI, 84.8%-86.6%], respectively). Absolute differences in the interval cancer rate between final and initial assessments increased with breast density and breast cancer risk (eg, a difference of 0.29 per 1000 for women with extremely dense breasts and a 5-year risk >2.49%). Established screening performance metrics underestimate the interval cancer rate of a mammography screening episode, particularly for women with dense breasts or an elevated breast cancer risk. Women, clinicians, policymakers, and researchers should use final-assessment performance metrics to support informed screening decisions.


Clinical factors associated with discontinuation of ts/bDMARDs in rheumatic patients from the BIOBADASER III registry.
Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug's overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan-Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan-Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99-1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54-0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00-1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15-1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05-1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00-1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12-1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases.


Drug survival of anti-TNF agents compared with vedolizumab as a second-line biological treatment in inflammatory bowel disease: results from nationwide Swedish registers.
Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse. To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD). A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N = 1363) were included. The primary outcome was drug survival at 12 months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure. After 1:1 propensity score matching, 400 patients (Crohn's disease, N = 198; ulcerative colitis, N = 202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference: 1 percentage point; 95% confidence interval [CI]:-11-13; P = 0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference: -7 percentage points; 95% CI: -20 to 6; P = 0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P = 0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different. Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.


Spanish-Dementia Knowledge Assessment Scale (DKAS-S): Ecuadorian validation and comparison among Spanish health students.
Alzheimer's disease (AD) is the most frequent cause of cognitive impairment. Improving knowledge of dementia management through health education for health professionals can improve clinical and community care in home and specialist settings. It is important to guarantee good dementia knowledge in health students, and it is necessary to evaluate it with a good standardized tool. The aim of the current study was to assess the psychometric properties of the DKAS-S with cohorts of Ecuadorian health students, to compare these results with a former validation in Spanish health students and to analyse the level of knowledge according to different variables. We performed a cross-sectional study to assess the validity, reliability and feasibility of the DKAS-S by comparing two different cohorts of health students (nursing and psychologists). A total of 659 students from Spain (n = 233) and Ecuador (n = 426) completed the DKAS-S (mean age 24.02 (6.35) years old), and 52.80% were nursing students. The DKAS-S showed good internal consistency in the Ecuadorian cohort (Cronbach's α = 0.76). No significant difference was found between Spanish and Ecuadorian students (p = 0.767) in the global scale score, but there were differences in some subscales. Psychologist students scored significantly higher on the global scale than nursing students (32.08 (9.51) vs. 27.49 (7.15); p < 0.001)). Students with a family history of cognitive impairment scored higher on the global scale, and those who had contact with people with dementia obtained better results on the global scale. We confirmed that the DKAS-S is an adequate and useful instrument to measure levels of knowledge about dementia among health students in Spanish-speaking communities. It is a reliable and valid measure with good psychometric properties. Understanding health students' knowledge about dementia will allow better adaptation of academic plans to train better health professionals.


Subcutaneous nephrovesical bypass in a patient with advanced prostate cancer.
In the presence of hydronephrosis, as a result of ureteral malignant invasion, advanced pelvic tumor or retroperitoneal fibrosis, we most often perform a double J stent or percutaneous nephrostomy. In the search for a better quality of life for our patients in recent years in urological practice is increasingly becoming the use of subcutaneous nephrovesical bypass due to its proven safety, effectiveness and minimal invasiveness.


Practice effect and test-retest reliability of the Mini-Mental State Examination-2 in people with dementia.
The Mini-Mental State Examination-Second Edition (MMSE-2) consists of three visions: a brief version (MMSE-2:BV), a standard version (MMSE-2:SV), and an expanded version (MMSE-2: EV). Each version was equipped with alternate forms (blue and red). There was a lack of evidence on the practice effect and test-retest reliability of the three versions of the MMSE-2, limiting its utility in both clinical and research settings. The purpose of this study was to examine the practice effect and test-retest reliability of the MMSE-2 in people with dementia. One hundred and twenty participants were enrolled, of which 60 were administered with the blue form twice (i.e., the same-form group, [SF group]) and 60 were administered with the blue form first and then the red form (alternate-form group, [AF group]). The practice effect was evaluated using a paired t-test and Cohen's d. The test-retest reliability was examined using the intraclass correlation coefficient (ICC). For the practice effects, in the SF group, no statistically significant differences were found for the MMSE-2:BV and MMSE-2: EV total scores and eight subtests (p = 0.061-1.000), except for the MMSE-2:SV total score (p = 0.029). In the AF group, no statistically significant differences were found for all three versions of the total scores and subtests (p = 0.106-1.000), except for the visual-constructional ability subtest (p = 0.010). Cohen's d of all three versions' total scores and subtests were 0.00-0.20 and 0.00-0.26 for SF group and AF group, respectively. For the test-retest reliability, ICC values for all three versions and eight subtests in SF and AF groups were 0.60-0.93 and 0.56-0.93, respectively. Our results demonstrated that the practice effect could be minimized when alternate forms of the MMSE-2 were used. The MMSE-2 had good to excellent test-retest reliability, except for three subtests (i.e., visual-constructional ability, registration, and recall). Caution should be taken when interpreting the results of visual-constructional ability, registration, and recall subtests of the MMSE-2.


MRCQuant- an accurate LC-MS relative isotopic quantification algorithm on TOF instruments.
Relative isotope abundance quantification, which can be used for peptide identification and differential peptide quantification, plays an important role in liquid chromatography-mass spectrometry (LC-MS)-based proteomics. However, several major issues exist in the relative isotopic quantification of peptides on time-of-flight (TOF) instruments: LC peak boundary detection, thermal noise suppression, interference removal and mass drift correction. We propose to use the Maximum Ratio Combining (MRC) method to extract MS signal templates for interference detection/removal and LC peak boundary detection. In our method, MRCQuant, MS templates are extracted directly from experimental values, and the mass drift in each LC-MS run is automatically captured and compensated. We compared the quantification accuracy of MRCQuant to that of another representative LC-MS quantification algorithm (msInspect) using datasets downloaded from a public data repository. MRCQuant showed significant improvement in the number of accurately quantified peptides. MRCQuant effectively addresses major issues in the relative quantification of LC-MS-based proteomics data, and it provides improved performance in the quantification of low abundance peptides.


Cortical alpha-synuclein preformed fibrils do not affect interval timing in mice.
One hallmark feature of Parkinson's disease (PD) is Lewy body pathology associated with misfolded alpha-synuclein. Previous studies have shown that striatal injection of alpha-synuclein preformed fibrils (PFF) can induce misfolding and aggregation of native alpha-synuclein in a prion-like manner, leading to cell death and motor dysfunction in mouse models. Here, we tested whether alpha-synuclein PFFs injected into the medial prefrontal cortex results in deficits in interval timing, a cognitive task which is disrupted in human PD patients and in rodent models of PD. We injected PFF or monomers of human alpha-synuclein into the medial prefrontal cortex of mice pre-injected with adeno-associated virus (AAV) coding for overexpression of human alpha-synuclein or control protein. Despite notable medial prefrontal cortical synucleinopathy, we did not observe consistent deficits in fixed-interval timing. These results suggest that cortical alpha-synuclein does not reliably disrupt fixed-interval timing.


A review of the medical hyperspectral imaging systems and unmixing algorithms' in biological tissues.
Hyperspectral fluorescence imaging (HFI) is a well-known technique in the medical research field and is considered a non-invasive tool for tissue diagnosis. This review article gives a brief introduction to acquisition methods, including the image preprocessing methods, feature selection and extraction methods, data classification techniques and medical image analysis along with recent relevant references. The process of fusion of unsupervised unmixing techniques with other classification methods, like the combination of support vector machine with an artificial neural network, the latest snapshot Hyperspectral imaging (HSI) and vortex analysis techniques are also outlined. Finally, the recent applications of hyperspectral images in cellular differentiation of various types of cancer are discussed.


Antitumor effect and mechanisms of arsenic trioxide on subcutaneously implanted human gastric cancer in nude mice.
We sought to investigate the efficacy of arsenic trioxide (As(2)O(3)) against a human gastric cell line implanted in nude mice in vivo, as well as the mechanism involved. The solid tumor model was created in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into animals in two arsenic-treated groups (2.5 mg/kg and 5 mg/kg), and the same volume of saline solution was injected into the control group. The inhibitory effect was observed in every group. Apoptotic cells and apoptotic bodies were observed by transmission electron microscope; the fraction of apoptotic cells was detected by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) under laser confocal technology. The expression of Fas and FasL was detected by immunohistochemical staining. In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3), approximately 50% and 30% tumor growth inhibition were observed, respectively (P < 0.05 for both treatment groups). Increase in apoptotic cells and apoptotic bodies appeared in As(2)O(3)-treated tumors compared with the control group. The fluorescence intensity levels of apoptotic cells in tumor were significantly higher in the arsenic-treated groups (P < 0.05 for both treatment groups). The fluorescence intensity level of apoptotic cells in the 5-mg/kg group was higher than that in the 2.5-mg/kg group (P < 0.05). The expression of Fas protein increased in dose- and time-dependent manner after the treatment with As(2)O(3), but that of FasL protein showed no significant difference between control and treated groups. As(2)O(3) did not induce hepatic and renal system injury in the nude mice. As(2)O(3) can inhibit the growth of human gastric cell implanted tumor. We ascribe this to upregulation of Fas, which can induce apoptosis of gastric cells.


Epithelial senescence in idiopathic pulmonary fibrosis is propagated by small extracellular vesicles.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that affects 3 million people worldwide. Senescence and small extracellular vesicles (sEVs) have been implicated in the pathogenesis of IPF, although how sEVs promote disease remains unclear. Here, we profile sEVs from bronchial epithelial cells and determine small RNA (smRNA) content. Conditioned media was collected and sEVs were isolated from normal human bronchial epithelial cells (NHBEs) and IPF-diseased human bronchial epithelial cells (DHBEs). Increased sEV release from DHBEs compared to NHBEs (n = 4; p < 0.05) was detected by nanoparticle tracking analysis. NHBEs co-cultured with DHBE-derived sEVs for 72 h expressed higher levels of SA-β-Gal and γH2AX protein, p16 and p21 RNA and increased secretion of IL6 and IL8 proteins (all n = 6-8; p < 0.05). sEVs were also co-cultured with healthy air-liquid interface (ALI) cultures and similar results were observed, with increases in p21 and p16 gene expression and IL6 and IL8 (basal and apical) secretion (n = 6; p < 0.05). Transepithelial electrical resistance (TEER) measurements, a reflection of epithelial barrier integrity, were decreased upon the addition of DHBE-derived sEVs (n = 6; p < 0.05). smRNA-sequencing identified nineteen significantly differentially expressed miRNA in DHBE-derived sEVs compared to NHBE-derived sEVs, with candidate miRNAs validated by qPCR (all n = 5; p < 0.05). Four of these miRNAs were upregulated in NHBEs co-cultured with DHBE-derived sEVs and three in healthy ALI cultures co-cultured with DHBE-derived sEVs (n = 3-4; p < 0.05). This data demonstrates that DHBE-derived sEVs transfer senescence to neighbouring healthy cells, promoting the disease state in IPF.


β-arrestins negatively control human adrenomedullin type 1-receptor internalization.
Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β2-adrenergic receptor (β2-AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [125I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β2-AR. Thus, both β-arrs negatively control AM1 receptor internalization, which depends on the C-tail of CLR.