Moderate-to-severe blood pressure elevation at ED entry: hypertension or normotension?
It is controversial whether arterial hypertension (AHT) can be diagnosed in the emergency department (ED). We sought to prospectively investigate the natural time course of blood pressure (BP) to define an optimal period for AHT screening in ED patients with an elevated initial BP. Patients with a BP greater than 160/100 mm Hg upon ED admission underwent repeated BP measurements every 5 minutes for 2 hours using an automated device. Arterial hypertension was confirmed using 12-hour ambulatory BP measurement or repeated office BP measurement according to the Joint National Committee VII guidelines by the primary care physician after discharge from the hospital. Systolic BP decreased significantly during the first 10 to 20 minutes of ED stay in hypertensive and normotensive patients without further significant changes thereafter. Diastolic BP remained stable in both hypertensive and normotensive patients. Discrimination between hypertensive and normotensive patients was best between minutes 60 and 80 after ED admission. An average BP of 165/105 mm Hg or higher during this period strongly suggests AHT whereas a BP of less than 130/80 mm Hg excludes AHT with high sensitivity. Screening for AHT in the ED is possible with high specificity and sensitivity. Blood pressure measurements between minutes 60 and 80 after entry into the ED yield the highest diagnostic value.


Quality of life in a real-world cohort of advanced breast cancer patients: a study of the SONABRE Registry.
We aimed to evaluate quality of life (QoL) using the European Quality of Life Five-Dimensions questionnaire (EQ-5D-3L) in a real-world cohort of Dutch advanced breast cancer (ABC) patients. Secondary, we reported differences in QoL between subgroups of patients based on age, comorbidity, tumor-, and treatment characteristics, and assessed the association of duration of metastatic disease and time to death with QoL. ABC patients who attended the outpatient clinic between October 2010 and May 2011 were asked to fill out the EQ-5D-3L questionnaire. Patient-, disease-, and treatment characteristics were obtained from the medical files. Health-utility scores were calculated. Subgroups were described and compared for utility scores by parametric and non-parametric methods. A total of 92 patients were included with a median utility score of 0.691 (Interquartile range [IQR] 0.244). Patients ≥ 65 years had significantly worse median utility scores than younger patients; 0.638 versus 0.743, respectively (p = 0.017). Moreover, scores were significantly worse for patients with versus those without comorbidity (medians 0.620 versus 0.725, p = 0.005). Utility scores did not significantly differ between subgroups of tumor type, type of systemic treatment, number of previous palliative treatment(s), or number or location of metastatic site(s). The remaining survival was correlated with utility scores (correlation coefficient (r) = 0.260, p = 0.0252), especially in the subgroup < 65 years (r = 0.340, p = 0.0169), whereas there was no significant correlation with time since metastatic diagnosis (r = - 0.106, p = 0.3136). Within this real-world cross-sectional study, QoL was significantly associated with age, comorbidity, and remaining survival duration. The observation of a lower QoL in ABC patients, possibly indicating the last period of life, may assist clinical decision-making on timing of cessation of systemic antitumor therapy.


Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.
Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.


Effect of high compost temperature on enzymatic activity and species diversity of culturable bacteria in cattle manure compost.
To clarify the characteristics of thermophilic bacteria in cattle manure compost, enzymatic activity and species diversity of cultivated bacteria were investigated at 54, 60, 63, 66 and 70 degrees C, which were dependent on composting temperature. The highest level of thermophilic bacterial activity was observed at 54 degrees C. Following an increase in temperature to 63 degrees C, a reduction in bacterial diversity was observed. At 66 degrees C, bacterial diversity increased again, and diverse bacteria including Thermus spp. and thermophilic Bacillus spp. appeared to adapt to the higher temperature. At 70 degrees C, bacterial activity measured as superoxide dismutase and catalase activity was significantly higher than at 66 degrees C. However, the decomposition rate of protein in the compost was lower than the rate at 66 degrees C due to the higher compost temperature.


[Dental concerns and oral health in population of Greece--future perspectives].
With a profusion of statistical data the authors describe the dental service in Greece, pointing out in particular the difference between the facilities available in the cities and in the country. This is followed by details of the dental insurance system, epidemiological data on the oral health of the population, and examples of prophylactic dentistry. The article concludes with some thoughts on the outlook for the future.


Unusual variant of left superior vena cava.
The first computed tomography-documented case of a persistent left superior vena cava that drains directly into the right superior vena cava is presented. The venous embryology is reviewed and the differential diagnosis of other pertinent venous anomalies is discussed. The patient also had an incidental finding of a congenitally absent left lobe of the thyroid gland.


Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological and immunohistochemical study of five cases.
Five cases of an unusual variant of thymic carcinoma are described, which represent the counterpart of the so-called micronodular thymoma with lymphoid hyperplasia. The patients were three men and two women aged 42-78 years (mean 64 years). Three patients were asymptomatic and the tumors were found incidentally on chest radiographs performed for unrelated reasons. Two patients complained of dyspnea, chest pain and shortness of breath prompting further investigations. The tumors ranged in size from 3.2 to 10.0 cm and were described as infiltrative masses often invading adjacent structures. Prominent cystic changes were not identified. Histologically, the neoplasms were composed of epithelial tumor cells arranged in a micronodular growth pattern set in a stroma showing florid lymphoid hyperplasia. Contrary to micronodular thymoma, the epithelial cell component of the present cases showed unequivocal signs of malignancy characterized by cytological atypia and increased mitotic activity. Immunohistochemical studies showed the lymphoid component to be of mixed B- and T-cell lineage. None of the patients had a history of myasthenia gravis or other autoimmune disorder. Follow-up revealed that 4 patients were alive and well 3-26 months after diagnosis while 1 patient was dead of disease 21 months after diagnosis. The tumors in this series represent a distinct subtype of thymic carcinoma histologically strongly resembling micronodular thymoma with lymphoid hyperplasia. Awareness of this type of thymic carcinoma is important in order not to dismiss this tumor for a neoplasm of lower-grade malignancy.


The impact of expanded brucellosis surveillance in beef cattle on human brucellosis in Korea: an interrupted time-series analysis.
Korean surveillance program for bovine brucellosis was improved by extending it to beef slaughterhouses and by pre-movement testing of bulls on May 2005 (Intervention 1). The bovine brucellosis surveillance program was further extended to beef cattle farms with more than 10 heads of cattle on June 2006 (Intervention 2). To quantify the temporal relationship between bovine and human brucellosis, a time-series analysis was conducted using Korean national notification data reported between January 2004 and December 2014. Our findings indicate that while during the pre-intervention phase (January 2004 to March 2005) there was no significant temporal relationship between the incidences of bovine and human brucellosis, significant temporal relationships were observed after Intervention 1 (June 2005 to June 2006, no lag, β = 0.57, p = 0.04), and Intervention 2 (July 2006 to June 2007, 1-month lag, β = 0.65, p = 0.03). Furthermore, significant changes in incidence in human were observed after Intervention 1 (β = - 0.17 per 10 million-people, p = 0.03) and Intervention 2 (β = - 0.19 per 10 million-people, p = 0.04). These findings indicated the changes of a nationwide comprehensive surveillance programme targeting all cattle is required for effective reduction in the human population.


Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments.
Cell wall hydrolases (CWH) are enzymes that build, remodel and degrade peptidoglycan within bacterial cell walls and serve essential roles in cell-wall metabolism, bacteriophage adsorption and bacteriolysis, environmental niche expansion, as well as eukaryotic innate immune defense against bacterial infection. Some CWHs, when tested as recombinant purified proteins, have been shown to have bactericidal activities both as single agents and in combinations with other antimicrobials, displaying synergies in vitro and potent activities in animal models of infection greater than the single agents alone. We summarize in vitro, in vivo, and mechanistic studies that illustrate ACWH synergy with antibiotics, antimicrobial peptides, and other ACWHs, underscoring the overall synergistic potential of the ACWH class.


Chronic pain and comorbid depression.
For patients with chronic pain, the experience of pain is intimately linked with psychologic distress. Epidemiologic studies indicate that depression is a common comorbidity accompanying chronic pain states. Longitudinal studies also suggest that depression can predict the emergence of chronic pain in selected populations. Emerging evidence suggests numerous pathophysiologic mechanisms that underlie the coexistence of depression and chronic pain states. Comorbid depression can complicate the presentation, clinical course, and response to treatment of patients with chronic pain. The literature reviewed herein focuses on treatment approaches applicable to chronic, nonmalignant pain states predominantly. Although antidepressants offer advantages in simultaneously producing pain relief and mitigating depression, not all antidepressants share equal efficacy; those with noradrenergic and serotonergic influences seem to fare better than agents with single neurotransmitter influences. Treatment of depression may be essential to fully enlist the patient with chronic pain in comprehensive pain management and rehabilitative approaches. Management plans of patients with chronic pain can be designed with specific individual patient needs in mind, and may involve concurrent use of antidepressants, analgesics, and psychotherapeutic approaches.


Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice.
Momordica charantia Linn. (Cucurbitaceae) fruit is commonly known as bitter melon. C57BL/6J mice were firstly divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% high-fat (HF) diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and still on HF diet and was given orally M. charantia extract (MCE) or rosiglitazone (Rosi) or not for 4 weeks. M. charantia decreased the weights of visceral fat and caused glucose lowering. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. MCE significantly increases the hepatic protein contents of AMPK phosphorylation by 126.2-297.3% and reduces expression of phosphenolpyruvate carboxykinase (PEPCK) and glucose production. Most importantly, MCE decreased expression of hepatic 11beta hydroxysteroid dehydroxygenase (11beta-HSD1) gene, which contributed in attenuating diabetic state. Furthermore, MCE lowered serum triglycerides (TGs) by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein 1c and fatty acid synthase mRNA leading to reduction in TGs synthesis. This study demonstrates M. charantia ameliorates diabetic and hyperlipidemic state in HF-fed mice occurred by regulation of hepatic PEPCK, 11beta-HSD1 and AMPK phosphorylation.


Screening of enzymatic activities for the depolymerisation of the marine bacterial exopolysaccharide HE800.
The exopolysaccharide (EPS) HE800 is a marine-derived polysaccharide (from 8 × 10(5) to 1.5 × 10(6) g mol(-1)) produced by Vibrio diabolicus and displaying original structural features close to those of glycosaminoglycans. In order to confer new biological activities to the EPS HE800 or to improve them, structural modifications need to be performed. In particular, depolymerisation is required to generate low-molecular-weight derivatives. To circumvent the use of chemical methods that lack specificity and reproducibility, enzymes able to perform such reaction are sought. This study reports the screening for enzymes capable of depolymerising the EPS HE800. A large diversity of enzyme sources has been studied: commercially available glycoside hydrolases with broad substrate specificity, lyases, and proteases as well as growing microorganisms. Interestingly, we found that the genus Enterococcus and, more particularly, the strain Enterococcus faecalis were able to depolymerise the EPS HE800. Partial characterization of the enzymatic activity gives evidence for a random and incomplete depolymerisation pattern that yields low-molecular-weight products of 40,000 g mol(-1). Genomic analysis and activity assays allowed the identification of a relevant open reading frame (ORF) which encodes an endo-N-acetyl-galactosaminidase. This study establishes the foundation for the development of an enzymatic depolymerisation process.


Reorganization of sleep patterns in severe OSAS under prolonged CPAP treatment.
To evaluate the immediate and long-term recovery processes of sleep and daytime vigilance in patients with sleep apnea syndrome (OSAS) after continuous CPAP treatment. Five consecutive polysomnographic (PSG) studies were carried out on 10 male patients with severe OSAS. The first recording (baseline) was accomplished without ventilatory support (N0). The other 4 recordings were carried out during the CPAP titration night (N1), during the second night of treatment (N2), during the third night of treatment (N3), and after 30 days of regular CPAP use (N30). Ten age-balanced healthy male subjects were selected from the Parma Sleep Center database as controls. Respiratory variables, conventional PSG variables, arousals, CAP (cyclic alternating pattern) variables, and daytime function (including MSLT) were quantified. ANOVA followed by post-hoc tests explored the differences between controls and OSAS patients in the different recording conditions (N0, N1, N2, N3, N30). The PSG measures that showed significant ANOVA values were correlated with the MSLT scores. Values of control subjects were recovered by REM sleep, REM latency, subtypes A3 and arousal index during N1, by CAP rate and total arousals during N2, by deep sleep (stages 3 + 4) during N3, by light sleep (stages 1 + 2) during N30. The only measures which remained below control values even after 1 month of sustained treatment were the amount of CAP cycles and A1 subtypes. MSLT scores correlated significantly with CAP rate, deep sleep and arousals. The changes induced by CPAP treatment do not restore immediately a normal sleep structure, which is re-established with different time scales The modifications of sleep patterns and the different adjustments of phase A subtypes allow us to monitor the reorganization of sleep in OSAS patients treated with CPAP and the hierarchy of the mechanisms involved in sleep regulation.


Erratum: Language outcomes from the UK-CDI Project: can risk factors, vocabulary skills and gesture scores in infancy predict later language disorders or concern for language development?
[This corrects the article DOI: 10.3389/fpsyg.2023.1167810.].


Single-atom site catalysts for environmental remediation: Recent advances.
Single-atom site catalysts (SACs) can maximize the utilization of active metal species and provide an attractive way to regulate the activity and selectivity of catalytic reactions. The adjustable coordination configuration and atomic structure of SACs enable them to be an ideal candidate for revealing reaction mechanisms in various catalytic processes. The minimum use of metals and relatively tight anchoring of the metal atoms significantly reduce leaching and environmental risks. Additionally, the unique physicochemical properties of single atom sites endow SACs with superior activity in various catalytic processes for environmental remediation (ER). Generally, SACs are burgeoning and promising materials in the application of ER. However, a systematic and critical review on the mechanism and broad application of SACs-based ER is lacking. Herein, we review emerging studies applying SACs for different ERs, such as eliminating organic pollutants in water, removing volatile organic compounds, purifying automobile exhaust, and others (hydrodefluorination and disinfection). We have summarized the synthesis, characterization, reaction mechanism and structural-function relationship of SACs in ER. In addition, the perspectives and challenges of SACs for ER are also analyzed. We expect that this review can provide constructive inspiration for discoveries and applications of SACs in environmental catalysis in the future.


Interventions to Change Movement Behaviors After Stroke: A Systematic Review and Meta-analysis.
This systematic review aimed to determine which interventions increase physical activity (PA) and decrease sedentary behavior (SB) based on objective measures of movement behavior in individuals with stroke. The PubMed (Medline), EMBASE, Scopus, CINAHL (EBSCO), and Web of Science databases were searched for articles published up to January 3, 2023. The StArt 3.0.3 BETA software was used to screen titles, abstracts, and full texts for studies with randomized controlled trial designs; individuals with stroke (≥18 years of age); interventions aimed at increasing PA or decreasing SB; and objective measurement instruments. Data extraction was standardized, considering participants and assessments of interest. The risk of bias and quality of evidence of the included studies were assessed. Twenty-eight studies involving 1855 patients were included. Meta-analyses revealed that in the post-stroke acute/subacute phase, exercise interventions combined with behavior change techniques (BCTs) increased both daily steps (standardized mean difference [SMD]=0.65, P=.0002) and time spent on moderate-to-vigorous intensity physical activities (MVPAs) duration of PA (SMD=0.68, P=.0004) with moderate-quality evidence. In addition, interventions based only on BCTs increased PA levels with very low-quality evidence (SMD (low-intensity physical activity)=0.36, P=.02; SMD (MVPA)=0.56, P=.0004) and decreased SB with low-quality evidence (SMD=0.48, P=.03). In the post-stroke chronic phase, there is statistical significance in favor of exercise-only interventions in PA frequency (steps/day) with moderate-quality evidence (SMD=0.68, P=.002). In general, the risk of bias in the included studies was low. In the acute/subacute phase after stroke, the use of BCTs combined with exercise can increase the number of daily steps and time spent on MVPA. In contrast, in the post-stroke chronic phase, exercise-only interventions resulted in a significant increase in daily steps.


Quantification of serum levels of precursors to vitelline envelope proteins (choriogenins) and vitellogenin in estrogen treated masu salmon, Oncorhynchus masou.
Previously two precursors to vitelline envelope proteins, choriogenin H (Chg H) and choriogenin L (Chg L), were identified in masu salmon, Oncorhynchus masou, and specific antisera against these two proteins were generated in rabbits. In this study, two methods of immunoassay have been developed using these specific antibodies: single radial immunodiffusion (SRID) and enzyme-linked immunosorbent assay (ELISA). Non-competitive sandwich ELISAs for Chg H and Chg L were designed using digoxigenin-labeled antibodies and purified Chgs as assay components. The working range of the ELISAs was 1-128 and 2-256 ng/ml for Chg H and Chg L, respectively. Using these immunoassays and a chemiluminescent immunoassay for vitellogenin (Vg), the changes in these three estrogen-responsive proteins were measured in the serum of masu salmon after treatment with various doses of estradiol-17beta (E2). The changes in serum levels of Chgs and Vg in male fish differed according to the E2 dose. When fish were given a 5 mg/kg body weight (BW) of E2, Vg was induced to a greater extent than Chgs. By contrast, Chg levels were higher than that of Vg after a 10 microg/kg BW of E2 injection. A similar trend was seen in the response time to exogenous E2. Serum Chgs were induced from 8h after E2 injection and reached a peak of about 5 microg/ml at 24h. Although Vg was not detected until 8h after E2 injection, its levels remained considerably low at around 0.03 microg/ml, even after 24 h. Chg H was more sensitive than was Chg L to 1 microg/kg BW of estrogen: the long-term exposure of fish to E2 showed that Chg H could be induced from a lower dose of E2 than could Chg L. Taken together, these results suggest that the serum levels of Chg H, Chg L, and Vg in masu salmon are regulated by circulating levels of E2.


In Vivo Knee Kinematics: How Important Are the Roles of Femoral Geometry and the Cruciate Ligaments?
While posterior cruciate-retaining (PCR) implants are a more common total knee arthroplasty (TKA) design, newer bicruciate-retaining (BCR) TKAs are now being considered as an option for many patients, especially those that are younger. While PCR TKAs remove the ACL, the BCR TKA designs keep both cruciate ligaments intact, as it is believed that the resection of the ACL greatly affects the overall kinematic patterns of TKA designs. The objectives of this study are to assess the in vivo kinematics for subjects implanted with either a PCR or BCR TKA and to compare the in vivo kinematic patterns to the normal knee during flexion. These objectives were achieved with an emphasis on understanding the roles of the cruciate ligaments, as well as the role of changes in femoral geometry of nonimplanted anatomical femurs vs implanted subjects having a metal femoral component. Tibiofemoral kinematics of 50 subjects having a PCR (40 subjects) or BCR (10 subjects) TKA were analyzed using fluoroscopy while performing a deep knee bend activity. The kinematics were compared to previously published normal knee data (10 subjects). Kinematics were determined during specific intervals of flexion where the ACL or PCL was most dominant. In early flexion, subjects having a BCR TKA experienced more normal-like kinematic patterns, possibly attributed to the ACL. In mid-flexion, both TKA groups exhibited variable kinematic patterns, which could be due to the transitional cruciate ligament function period. In deeper flexion, both TKA functioned more similar to the normal knee, leading to the assumption that the PCL was properly balanced and functioning in the TKA groups. Interestingly, during late flexion (after 90°), the kinematic patterns for all three groups appeared to be statistically similar. Subjects having a PCR TKA experienced greater weight-bearing flexion than the BCR TKA group. Subjects having a BCR TKA exhibited a more normal-like kinematic pattern in early and late flexion. The normal knee subjects achieved greater lateral condyle rollback and axial rotation compared to the TKA groups.


Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity.
We reviewed single-institution experience using brachytherapy alone for primary high-grade soft tissue sarcoma of the extremity. Between July 1982 and September 1997, 202 adult patients with primary high-grade soft tissue sarcoma of the extremity were treated with limb-sparing surgery and adjuvant brachytherapy. All patients underwent complete gross resection, but the margin of resection was microscopically positive in 18% of patients. The median dose of brachytherapy was 45 Gy delivered over 5 days. Tumors located in the shoulder or groin were defined as central location. Complications were assessed in terms of wound complications, bone fracture, and peripheral nerve damage. With a median follow-up of 61 months, the 5-year local control, distant relapse-free survival, and overall survival rates were 84%, 63%, and 70%, respectively. On multivariate analysis, poor local control correlated with shoulder location, positive microscopic margins of resection, and nonshoulder upper extremity site. The 5-year actuarial rates of wound complications requiring reoperation, bone fracture, and grade > or = 3 nerve damage were 12%, 3%, and 5%, respectively. Adjuvant brachytherapy provides adequate local control and acceptable morbidity that compares favorably with data reported for external beam radiation. Shoulder tumor location was identified as an independent prognostic factor for poor local control, mandating further improvement in the local management of these tumors.


Demonstration of the polysaccharides in the cell wall of Candida albicans blastospores, using silver methenamine staining and a sequence of extraction procedures.
Blastospores of Candida albicans were subjected to a series of extractions of increasing severity to remove polysaccharides from the wall. The procedure was observed by electron microscopy, using silver methenamine staining to localize the polysaccharides.


Single-breath-hold T2WI MRI with artificial intelligence-assisted technique in liver imaging: As compared with conventional respiratory-triggered T2WI.
To investigate the clinical feasibility of single-breath-hold T2-weighted (SBH-T2WI) liver MRI using Artificial Intelligence-assisted Compressed Sensing (ACS) technique in liver imaging as compared with conventional respiratory-triggered T2WI (RT-T2WI). From January 2021 to October 2021, 81 patients suspected of liver lesions were enrolled in this prospective study. The liver MRI was performed, including both RT-T2WI and ACS SBH-T2WI. Two experienced radiologists reviewed all images of each studied sequence, and recorded the lesion location and the largest diameter of the lesions. The image quality was quantitatively and qualitatively analyzed regarding signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contrast ratio (CR), motion artifact, lesion conspicuity, liver boundary sharpness, and overall image quality. The lesion detection and image quality were compared between two sequences using the Chi-square test or Wilcoxon signed-rank test. For lesion detection, 64 lesions were identified in 53 enrolled patients as the reference standard. The average size was 12.09 ± 7.4 mm for the benign lesions and 45.89 ± 22.01 mm for the malignant lesions. Of 64 liver lesions, ACS SBH-T2WI detected 60 lesions (93.8%), and RT-T2WI detected 58 lesions (90.6%). For image quality analysis, the motion artifact of ACS SBH-T2WI sequence was significantly reduced compared with the conventional RT-T2WI sequence (p < 0.05). The SNR, liver boundary sharpness, and overall image quality showed no statistical differences between the two sequences. While the CNR, CR, and lesion conspicuity of ACS SBH-T2WI were significantly better than RT-T2WI (all p < 0.05). The SBH-T2WI with ACS technique showed promising performance as it provided significantly better image quality and lesion detectability with a considerable decrease in scanning time as compared with the conventional RT-T2WI.


Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.
The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). Spanish colorectal cancer screening program. 3213 persons with a positive fecal immunochemical test. Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Medtronic.


Liraglutide reduces plasma dihydroceramide levels in patients with type 2 diabetes.
Emerging evidence supports that dihydroceramides (DhCer) and ceramides (Cer) contribute to the pathophysiology of insulin resistance and liver steatosis, and that their circulating concentrations are independently associated with cardiovascular outcomes. Circulating DhCer levels are increased in patients with type 2 diabetes (T2D). On the other hand, the GLP-1 receptor agonist liraglutide reduces major adverse cardiac events, insulin resistance and liver steatosis in T2D patients. The main purpose of the present study was therefore to investigate whether liraglutide decreases circulating levels of DhCer and Cer in T2D patients, which could be a mechanism involved in its cardiometabolic benefits. The secondary purpose was to assess the relationship between liraglutide-induced changes in DhCer/Cer levels and insulin resistance and liver steatosis. Plasma concentrations of 11 DhCer and 15 Cer species were measured by a highly-sensitive mass spectrometry system in 35 controls and 86 T2D patients before and after 6 months of liraglutide (1.2 mg/day). Insulin resistance was estimated by the triglyceride-glucose (TyG) index. Liver fat content (LFC) was assessed in 53 patients by proton magnetic resonance spectroscopy. Plasma levels of total DhCer, 7 DhCer and 7 Cer species were increased in T2D patients compared to controls. Liraglutide decreased total DhCer by 15.1% (p = 0.005), affecting 16:0 (p = 0.037), 18:0 (p < 0.0001), 18:1 (p = 0.0005), 20:0 (p = 0.0003), 23:0 (p = 0.005) and 24:1 (p = 0.04) species. Total plasma Cer did not significantly change after liraglutide (p = 0.18), but 5 Cer species decreased significantly, i.e. 18:0 and 18:1 (both p < 0.0001), 19:0 and 24:1 (both p < 0.01) and 26:1 (p = 0.04). In multivariate analysis, the reduction in DhCer after liraglutide was independently associated with the reduction in LFC (p = 0.0005) and in TyG index (p = 0.05). Liraglutide reduces plasma levels of numerous DhCer and Cer species in T2D patients, which may contribute to the cardiovascular benefit observed in the LEADER trial. The independent association between the decrease in plasma DhCer level with the reduction in LFC and TyG index adds new insights regarding the relationship between DhCer, liver steatosis and insulin resistance. Trial registration ClinicalTrials.gov identifier: NCT02721888.


Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5.
We studied a recessive, progressive neurodegenerative disease occurring in Golden Retriever siblings with an onset of signs at 15 months of age. As the disease progressed these signs included ataxia, anxiety, pacing and circling, tremors, aggression, visual impairment and localized and generalized seizures. A whole genome sequence, generated with DNA from one affected dog, contained a plausibly causal homozygous mutation: CLN5:c.934_935delAG. This mutation was predicted to produce a frameshift and premature termination codon and encode a protein variant, CLN5:p.E312Vfs*6, which would lack 39 C-terminal amino acids. Eighteen DNA samples from the Golden Retriever family members were genotyped at CLN5:c.934_935delAG. Three clinically affected dogs were homozygous for the deletion allele; whereas, the clinically normal family members were either heterozygotes (n = 11) or homozygous for the reference allele (n = 4). Among archived Golden Retrievers DNA samples with incomplete clinical records that were also genotyped at the CLN5:c.934_935delAG variant, 1053 of 1062 were homozygous for the reference allele, 8 were heterozygotes and one was a deletion-allele homozygote. When contacted, the owner of this homozygote indicated that their dog had been euthanized because of a neurologic disease that progressed similarly to that of the affected Golden Retriever siblings. We have collected and stored semen from a heterozygous Golden Retriever, thereby preserving an opportunity for us or others to establish a colony of CLN5-deficient dogs.


Anti-murine antibody response to mouse monoclonal antibodies: clinical findings and implications.
Many patients given murine monoclonal antibody become immune to these proteins. Important factors in the development of immunity are (1) the patient's ability to become immune and (2) whether whole immunoglobulin or Fab fragment was used. Circulating anti-murine antibodies increase the murine antibody plasma clearance and the liver or spleen uptake while reducing tumor targeting. Clearance rates and radioassay measured levels of anti-murine antibodies are related to serum murine/anti-murine antibody complexes. Unlabeled murine antibody displaces radiolabeled antibody from these complexes.


Opposed locomotor asymmetries following lesions of the medial and lateral substantia nigra pars compacta or pars reticulata in the rat.
In animals with lesions in the medial or lateral portions of the substantia nigra pars compacta (SNC) amphetamine produces circling in opposite directions. The present study examined the relationships between lesion site and the direction of circling using glyoxylic acid histofluorescence to visualize DA cells. Lesions were produced by 6-hydroxydopamine (2-6 micrograms) or 0.05% ascorbate injected into the SN. After lesions in the medial SNC, amphetamine caused rats to circle ipsiversive to the lesion while after lateral SNC lesions rats circled contraversively. When the lesion extended to the middle of the SNC, or deeper into the SN pars reticulata (SNR), the direction of circling was unpredictable. When the damage produced by the cannula track and ascorbate injection was in the lateral SNR animals circled ipsiversively while medial SNR damage led to contraversive circling. Thus the medial and lateral SN, and the pars compacta and pars reticulata, are functionally antagonistic. This four way division of the SN is consistent with the topographic mapping of SNC to striatum and striatum to SNR.


Advancement and application of novel cell-penetrating peptide in cancer management.
Cell-penetrating peptides (CPPs) are small amino acid sequences with the potential to enter cell membranes. Along with nucleic acids, large proteins, and other chemical compounds, they can deliver several bioactive cargos inside cells. Numerous CPPs have been extracted from natural or synthetic materials since the discovery of the first CPP. In the past few decades, a significant variety of studies have shown the potential of CPPs to cure different diseases. The low toxicity in peptide compared to other drug delivery carriers is a significant benefit of CPP-based therapy, in addition to the high efficacy brought about by swift and effective delivery. A significant tendency for intracellular DNA delivery may also be observed when nanoparticles and the cell penetration peptide are combined. CPPs are frequently used to increase intracellular absorption of nucleic acid, and other therapeutic agents inside the cell. Due to long-term side effects and possible toxicity, its implementation is restricted. The use of cell-permeating peptides is a commonly used technique to increase their intracellular absorption. Additionally, CPPs have lately been sought for application in vivo, following their success in cellular studies. This review will go through the numerous CPPs, the chemical modifications that improve their cellular uptake, the various means for getting them across cell membranes, and the biological activity they acquire after being conjugate with specific chemicals.


Increased risk for postoperative periprosthetic fracture in hip fracture patients with the Exeter stem than the anatomic SP2 Lubinus stem.
The purpose of this study was to compare the cumulative incidence of postoperative periprosthetic fracture (PPF) in a cohort of femoral neck fracture (FNF) patients treated with two commonly used cemented stems: either a collarless, polished, tapered Exeter stem or the anatomic Lubinus SP2 stem. In this retrospective multicenter cohort study of a consecutive series of patients, we included 2528 patients of age 60 years and above with an FNF who were treated with either hemiarthroplasty or total hip arthroplasty using either a polished tapered Exeter stem or an anatomic Lubinus SP2 stem. The incidence of PPF was assessed at a minimum of 2 years postoperatively. The incidence of PPF was assessed at a median follow-up of 47 months postoperatively. Thirty nine patients (1.5%) sustained a PPF at a median of 27 months (range 0-96 months) postoperatively. Two of the operatively treated fractures were Vancouver A (5%), 7 were Vancouver B1 (18%), 10 were Vancouver B2 (26%), 7 were Vancouver B3 (18%), and 13 were Vancouver C (32%). The cumulative incidence of PPF was 2.3% in the Exeter group compared with 0.7% in the SP2 group (p < 0.001). The HR was 5.4 (95% CI 2.4-12.5, p < 0.001), using the SP2 group as the denominator. The Exeter stem was associated with a higher risk for PPF than the Lubinus SP2 stem. We suggest that the tapered Exeter stem should be used with caution in the treatment of FNF. The study was registered at clinicaltrials.gov (identifier: NCT03326271).


Establishing an oncocardiology service.
Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.


Long non-coding RNA H19X promotes tumorigenesis and metastasis of colorectal cancer through regulating the miR-503-5p/KANK1 axis.
It has been well established that the long non-coding RNAs (lncRNAs) plays a critical role in tumor progression. However, the function of these transcripts and mechanisms responsible for their deregulation in colorectal cancer (CRC) remain to be investigated. To explore the potential effect and regulation mechanism of lncRNA H19X in colorectal cancer. We predicted and validated long non-coding RNA H19X from microarray data of colorectal cancer tissues. In addition, the biological behaviors of H19X and miR-503-5p on CRC were examined in vitro and in vivo, including MTT, colony formation assay, Hoechst33342 and transwell assay. The mRNA and protein levels of KN Motif and Ankyrin Repeat Domains 1 (KANK1) were analyzed by Quantitative real-time PCR (qRT-PCR), western blotting (WB) assay. Moreover, bioinformatics tools and dual-luciferase reporter assay were applied to demonstrate the relationship between KANK1 and miR-503-5p. H19X was remarkably up-regulated in CRC tissues. Its expression related to tumor size (p = 0.041), lymph node metastasis (p = 0.037), distal metastasis (p = 0.028), advanced TNM stage (p = 0.034) and poor survival in CRC. H19X acted as an oncogenic lncRNA that induced CRC cell proliferation, invasion and metastasis. Through a number of functional studies, we found that H19X silencing inhibited the malignance phenotype of cancer cells through loss of miR-503-5p. Further studies demonstrated that miR-503-5p was involved in the progression of CRC by directly regulating the downstream target KANK1. Collectively, the findings of the present study indicate H19X/miR-503-5p/KANK1 axis has critical role in the progression of colorectal cancer, providing an effective prognostic indicator and promising target in treatment of colorectal cancer.


Protein activation of a ribozyme: the role of bacterial RNase P protein.
Bacterial ribonuclease P (RNase P) belongs to a class of enzymes that utilize both RNAs and proteins to perform essential cellular functions. The bacterial RNase P protein is required to activate bacterial RNase P RNA in vivo, but previous studies have yielded contradictory conclusions regarding its specific functions. Here, we use biochemical and biophysical techniques to examine all of the proposed functions of the protein in both Escherichia coli and Bacillus subtilis RNase P. We demonstrate that the E. coli protein, but not the B. subtilis protein, stabilizes the global structure of RNase P RNA, although both proteins influence holoenzyme dimer formation and precursor tRNA recognition to different extents. By comparing each protein in complex with its cognate and noncognate RNA, we show that differences between the two types of holoenzymes reside primarily in the RNA and not the protein components of each. Our results reconcile previous contradictory conclusions regarding the role of the protein and support a model where the protein activates local RNA structures that manifest multiple holoenzyme properties.


[Growth rate can be manipulated. Estrogen production in pubertal boys can be blocked by an aromatase inhibitor].
A review of a twelve month clinical trial [1] using a new, effective aromatase inhibitor treatment in boys with delayed puberty shows that the pubertal increase in estrogen levels can be blocked, with concomitant preserved pubertal growth rate. Circulating testosterone levels are greatly enhanced during treatment due to increased gonadotrophin secretion. Despite this, bone age maturation is slow leading to an increased final height prognosis (mean 5.1 cm) for the boys treated with aromatase inhibitor.


Experiences of African American Mothers Following the Death of Their Infants.
To explore the lived experiences of African American mothers after the death of their infants. Qualitative, interpretive phenomenologic study. Northeast Louisiana. Seven self-identified African American women whose infants died during the first year of life; the women's ages ranged from 18 to 38 years at the time of the infant's death. Heidegger's interpretive phenomenologic approach guided the data collection and analysis. The women were interviewed using in-depth questioning to determine the meaning of the infant loss experience and their subsequent efforts to cope. Six themes represented the experiences of loss for the mothers: Shattered Dreams, Questioning God, Dissociation, Paralyzing Fear, Left in the Dark, and Uniqueness of Grieving. Three themes affected the women's efforts to cope after their loss: Authentic Presence, Spiritual Empowerment, and Disconnectedness. African American women who experienced infant death described intense feelings of loss, guilt, and isolation. These negative emotions can potentially affect their physical and psychological health. These findings may help health care providers develop culturally sensitive understanding of African American mothers' experiences of loss and equip providers to provide holistic assessment, appropriate support, and treatment for these vulnerable women.


Crystal Chemistry, Optic and Magnetic Characterizations of a New Copper Based Material Templated by Hexahydrodiazepine.
Crystals of the new organic-inorganic material (DAP-H2)[CuBr4] (1); (DAP = hexahydrodiazepine (C5H14N2)) were successfully synthesized by slow evaporation and characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermal analysis, UV-Vis-NIR diffuse reflectance spectroscopy, and magnetic measurements. X-ray investigation demonstrates that 1 crystallizes in the monoclinic space group C2/c. The supramolecular crystal structure of 1 is guided by several types of hydrogen bonding which connect anions and cations together into a three-dimensional network. The optical band gap was determined by diffuse reflectance spectroscopy to be 1.78 eV for a direct allowed transition, implying that it is suitable for light harvesting in solar cells. The vibrational properties of this compound were studied by infrared spectroscopy, while its thermal stability was established by simultaneous TGA-DTA from ambient temperature to 600 °C. The study of the photoresponse behavior of an optoelectronic device, based on (C5H14N2)[CuBr4], has shown a power conversion efficiency (PCE) of 0.0017%, with J sc = 0.0208 mA/cm2, V oc = 313.7 mV, and FF = 25.46. Temperature dependent magnetic susceptibility measurements in the temperature range 1.8-310 K reveal weak antiferromagnetic interactions via the two-halide superexchange pathway [2J/k B = -8.4(3) K].


Production of melanin pigment from Pseudomonas stutzeri isolated from red seaweed Hypnea musciformis.
Hypnea musciformis red seaweed is popularly known to produce carrageenan was collected from the Gulf of Mannar, India. Strain HMGM-7 [MTCC 11712] was isolated from the surface of this seaweed, which was capable of producing an extracellular black-coloured polymeric pigment. Based on phenotypic characterization and 16S rDNA sequencing, the strain HMGM-7 was identified as Pseudomonas stutzeri. Biophysical characterization by UV-visible, FT-IR, EPR and XRD spectroscopic studies confirmed the pigment as melanin. Further chemical characterization showed that it was acid-resistant, alkali-soluble and alkali-insoluble in most of the organic solvents and distilled water. To our knowledge, this is a first report on a marine Pseudomonas stutzeri strain producing significant amounts of melanin of about 6·7 g l(-1) without L-tyrosine supplementation in the sea-water production medium. This investigation reports a marine Pseudomonas stutzeri strain HMGM-7 [MTCC 11712] that produces significant quantities of melanin (6·7 g l(-1) ) in sea-water medium without the supplementation of L-tyrosine. The confirmation of the produced melanin was carried out by various chemical and physical characterization studies. The isolated melanin may find potential application for use in cosmetic and/or pharmaceutical industries.


The molecular and cellular biology of tau.
Tau protein was a well-studied molecule before it was discovered in the Alzheimer neurofibrillary tangles. As a microtubule-associated protein (MAP), it continues to be of interest to microtubule biologists who have provided a rather rich knowledge about this protein. Recent work suggests that tau, a neuronal MAP, is capable of generating some features of an axonal shape and an axon-like organization of the cytoskeleton. The importance of tau in pathology stems from its relationship to Alzheimer paired helical filaments and dystrophic neurites. Tau was first believed to be a component of paired helical filaments based upon immunocytochemical grounds (1-6) and then conclusively demonstrated by protein chemical techniques (7-9). Most recently it was shown that bacterially expressed tau fragments from the microtubule-binding domain can self-assemble into paired helical filaments that resemble those from the Alzheimer brain (10).


In vitro and in vivo effects of kelatorphan on enkephalin metabolism in rodent brain.
Biologically relevant assays were used to compare the potency of kelatorphan (N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine) as inhibitor of the peptidase-induced metabolism of enkephalins to that of bestatin, a non-specific inhibitor of aminopeptidase and thiorphan, a highly potent blocker of the neutral endopeptidase (EC 18.104.22.168) designated as enkephalinase. Kelatorphan almost completely inhibited the formation of the three metabolites [3H]Tyr, [3H]Tyr-Gly and [3H]Tyr-Gly-Gly produced by incubation of [3H][Tyr1,Met5]enkephalin with rat striatal slices. Co-administered with [Met5]enkephalin in mouse brain, kelatorphan was able to prevent by 80% the degradation of the exogenous peptide. Moreover, a mixture of thiorphan (1 microM) and bestatin (20 microM) or kelatorphan alone (20 microM) induced a 2.2 to 2.5-fold increase in endogenous [Met5]enkephalin overflow after evoked depolarization of superfused rat striatal slices. In this assay, kelatorphan was the only compound to increase by 63% the basal level of released [Met5]enkephalin. Kelatorphan was about 100 times less potent than bestatin to inhibit the total rat striatal aminopeptidases, but as efficient (IC50 = 4 X 10(-7) M) as bestatin to inhibit a minor aminopeptidase activity resembling aminopeptidase M. Therefore the reported enhanced analgesic potency of kelatorphan with regard to the association of bestatin and thiorphan is very likely related to its ability to almost completely inhibit enkephalin-degrading enzymes (including the Tyr-Gly releasing peptidase) and to its better selectivity for the biologically relevant aminopeptidase M. Kelatorphan would be a valuable probe, preferable to the association of bestatin and thiorphan, to investigate the physiological functions regulated by a phasic enkephalinergic activity.


Postnatal development of retinogeniculate, retinopretectal and retinotectal projections in the opossum.
The postnatal development of retinogeniculate, retinopretectal and retinotectal projections has been studied by the anterograde transport of proline-labeled proteins in 20 pouch young opossums aged from 10 to 60 days. Radioautographical findings suggest delayed development of uncrossed as compared to crossed projections. There is a phase of overlapping projections from both eyes in thalamic and tectal target sites. Partial segregation of projections to the dorsal lateral geniculate nucleus (GLD) is preceded by differential distribution of crossed and uncrossed terminal fields along its dorsoventral axis (at age 23 days). The quasilaminar pattern of projections in the dorsocaudal region of GLD pars alpha is incipient by 42 days and is fully established at 60 days of age, as eye opening starts. The mature pattern of projections to the ventral lateral geniculate nucleus (GLV) is established much earlier, at 23 days of age. The development of retinopretectal projections is assessed mostly from the analysis of the olivary pretectal nucleus (PO). Distribution of silver grains into discrete areas coextensive with PO is relatively delayed (by 23 days of age) as compared to the nuclei of the lateral geniculate body. Soon after, however, the mature pattern of projections to PO is established (at 33 days of age). The early development of retinotectal projections (from 10 to 23 days) is compatible with an initial tangential course of crossed optic fibers in the superior colliculus (CS) but other alternatives remain open, such as a sequential outside-in arrangement of terminal fields of deeply coursing fibers. Arborization of uncrossed fibers is delayed at extreme rostromedial and caudolateral portion of the territory of the main uncrossed retinotectal projection. Segregation of uncrossed projections at different depths of CS is nearly complete by 42 days. Differences in the development of terminal fields in different target nuclei or in regions of a given target site are discussed in relation to retinal and local factors.


Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study.
The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. 112 malignant melanomas were identified during follow-up through 2000. Use of clomiphene, gonadotrophins, hCG or GnRH did not affect risk of malignant melanoma significantly. When stratifying for parity, however, use of gonadotrophins (RR = 2.29; CI: 1.16-4.52) or GnRH (RR = 3.26; 95% CI: 1.50-7.09) among parous women was associated with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency). Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use of gonadotrophins or GnRH might increase risk in parous women. Longer follow-up is needed to confirm our findings.


A simple "signal off-on" fluorescence nanoplatform for the label-free quantification of exosome-derived microRNA-21 in lung cancer plasma.
A simple nanoplatform based on molybdenum disulfide (MoS2) nanosheets, a fluorescence quencher (signal off), and a hybridization chain reaction (HCR) signal amplification (signal on) used for the enzyme-free, label-free, and low-background signal quantification of microRNA-21 in plasma exosome is reported. According to the sequence of microRNA-21, carboxy-fluorescein (FAM)-labeled hybridization probe 1 (FAM-H1) and hybridization probes 2 (FAM-H2) were designed with excitation maxima at 488 nm and emission maxima at 518 nm. MoS2 nanosheets could adsorb FAM-H1 and FAM-H2 and quenched their fluorescence signals to reduce the background signal. However, HCR was triggered when microRNA-21 was present. Consequently, HCR products containing a large number of FAM fluorophores can emit a strong fluorescence at 518 nm and could realize the detection of microRNA-21 as low as 6 pmol/L and had a wide linear relation of 0.01-25 nmol/L. This assay has the ability of single-base mismatch recognition and could identify microRNA-21 with high specificity. Most importantly, this approach was successfully applied to the detection of plasma exosomal microRNA-21 in patients with lung cancer, and it is proposed that other targets can also be detected by changing the FAM-H1 and FAM-H2 corresponding to the target sequence. Thus, a novel, hands-on strategy for liquid biopsy was proposed and has a potential application value in the early diagnosis of lung cancer.


Kinetic rates of tryptic digestion of bovine cardiac myofibrils. An improved measurement of cross-bridge dissociation.
The rates of tryptic digestion of the 50/20-kDa junction in myosin in cardiac myofibrils were determined under various solvent conditions. This cleavage reaction is slow in the rigor solvent and proceeds at a fast rate in the presence of MgATP. When the reaction solvent contains 50% ethylene glycol, the digestion of myosin in the presence of MgATP occurs at the same rate as in myofibrils relaxed by Mg adenyl-5'-yl imidodiphosphate (AMP-PNP). It is shown that with the help of two reference rates of digestion, for attached and dissociated myosin heads, the initial cleavage rates of myosin in the presence of nucleotides accurately measure the dissociation of cross-bridges from actin in myofibrils. Under physiological salt conditions and at 24 degrees C, MgADP, MgPPi, and MgAMP-PNP cause only small cross-bridge detachment (less than or equal to 15%) in cardiac myofibrils. The dissociation of myosin from actin is greatly increased by lowering the solvent temperature to 4 degrees C. Lowering the salt concentration of the solvent from 0.1 to 0.01 M NaCl has the most pronounced effect on the rates of myosin digestion in the presence of MgATP. In the low salt medium a substantial fraction of myosin heads (at least 30%) appears to be attached to actin in the presence of 5 mM MgATP.


Water Extract of Senecio scandens Buch.-Ham Ameliorates Pruritus by Inhibiting MrgprB2 Receptor.
Senecio scandens Buch.-Ham (S. scandens) belongs to the Compositae family. As a Traditional Chinese medicine, S. scandens has been used in China to treat conjunctivitis, mastitis and vaginitis, it also has the function of antibacterial and relieving itching. Water extract of S. scandens (WSS) was prepared and its quality was controlled by HPLC. The antipruritic effects of WSS were evaluated by itch behavioral experiments. The oxazolone and compound 48/80 were induced to mice scratch behavior, scratch was recorded 30 min after sensitization. The relationship between the antipruritic mechanism and MrgprB2 on mast cell was studied by using mast cell-deficient Kit (W-sh) "Sash" mice and MrgprB2-/- mice. The mast cells were observed by toluidine blue staining. In vitro, the effects of WSS on MrgprB2 were studied by calcium imaging; The whole-cell patch clamp method recorded the MrgprB2 mediate voltage-dependent currents in mast cells. The content of rutin (0.012%) and hyperin (0.014%) in the WSS were determined. WSS could ameliorate the pruritus induced by Oxazolone (inhibition was 41.19%, p = 0.004) and compound 48/80 (inhibition was 50.29%, p = 0.001). Meanwhile, WSS could reduce the number of mast cells in mice skin tissue with allergic contact dermatitis (ACD) (p = 0.002) or compound 48/80 (p = 0.013). In addition, WSS could inhibit the calcium influx (1 mg/mL: p = 0.001, 3 mg/mL: p < 0.0001) and the voltage-dependent currents induced by activation of MrgprB2 on mast cell. WSS also attenuated the calcium influx induced by compound 48/80 in HEK293 cells overexpressing MrgprB2/X2. These results showed that WSS could ameliorate pruritus by inhibiting MrgprB2 receptor on mast cells.


The relationships between the chemosensitivity of human gastric cancer to paclitaxel and the expressions of class III β-tubulin, MAPT, and survivin.
Lack of effective biomarkers is one of the challenges in current chemotherapy to predict drug response and sensitivity. This study was carried out to investigate the relationships between the expressions of class III β-tubulin, microtubule-associated protein tau (MAPT), survivin, and the sensitivity of primary gastric cancer (GC) to paclitaxel treatment. Reverse transcription PCR and Western blot were used to evaluate the mRNA and protein expressions of class III β-tubulin, MAPT, and survivin in fifty-four GC tissues. Viable tumor cells from gastric carcinomas were tested for their sensitivity to paclitaxel using adenosine triphosphate-based tumor chemosensitivity assay in vitro. Out of 54 samples, 30 samples were sensitive to paclitaxel, while the other 24 samples were resistant. The overall efficacy of paclitaxel was 55.56% (30/54). The mRNA expressions of class III β-tubulin and survivin were significantly correlated with the histological grade (P = 0.029, 0.009, respectively). The sensitivity of GC patients to paclitaxel treatment was inversely correlated with the mRNA and protein expressions of class III β-tubulin (P < 0.01), MAPT (P < 0.05), and survivin (P < 0.05). A significant positive correlation was found between class III β-tubulin and MAPT expression at mRNA and protein levels (mRNA: P = 0.037; protein: P = 0.001). Our results indicate that the expression levels of class III β-tubulin, MAPT, and survivin are good biomarkers for predicting the sensitivity of GC to paclitaxel treatment.


Combined tachykinin receptor antagonist: synthesis and stereochemical structure-activity relationships of novel morpholine analogues.
We report herein the synthesis and stereochemical structure-activity relationships of novel morpholine analogues 12 and 13 with regards to NK1, NK2 and NK3 tachykinin receptor binding affinity. An essential requirement for more potent binding affinities was controlled by absolute configuration. (S,R)-12 and (S,R)-13 exhibited high binding affinities for NK1, NK2 and NK3 receptors.


Patient-related factors influence the risk of developing intestinal stoma complications in early post-operative period.
Few studies have investigated the risk factors associated with developing intestinal stoma complications using appropriate multivariable methods. We aimed to determine the prevalence of, and risk factors for, stomal complications. A retrospective, case-control methodology was used to investigate 12 explanatory variables and four outcome variables in 202 consecutive patients receiving stomas in a district general hospital in the United Kingdom between January 2013 and December 2014. Univariable and multivariable logistic regression were used to calculate odds ratios (ORs). There were 69 complications (69/202; 34.2%) in the early post-operative period (median 12 months) in total, the most common being retraction (30.4%). Performance status (World Health Organization score 1 or more; OR 2.67; 95% confidence intervals (CIs) 1.33-5.33; P = 0.006) and body mass index (>30 kg/m2 ; OR 3.30; 95% CIs 1.61-6.78; P = 0.001) were significantly associated with developing complications in multivariable analysis. Surgery-related risk factors, such as time of day or week of operation and grade of surgeon, were not associated with the development of stoma complications. Thirty-eight patients (18.8%) died over the follow-up period, but mortality was not related to the development of stoma complications (1.01; 0.48-2.13, P = 0.98). Patient-related risk factors influence the risk of developing a stoma complication more than surgery-related risk factors. Preoperative and post-operative interventions, planning, vigilance and management should be focussed to at-risk groups, particularly obese patients.


Thirty-six month follow-up of 25 patients treated with combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell-binding peptide (P-15) bone replacement grafts in human infrabony defects. I. Clinical findings.
Long-term evaluation of periodontal therapy is important for clinical decision making. A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived hydroxyapatite bone matrix (ABM) was evaluated as a bone replacement graft in human periodontal osseous defects. Following initial preparation and reevaluation, flap surgery was performed. A variety of 1-, 2-, 3-wall bony defects were curetted and root surfaces subjected to mechanical debridement only. The bone defects were grafted with ABM/P-15, and the host flaps replaced or slightly coronally positioned. Weekly, then monthly deplaquing was performed until surgical reentry at 6 to 7 months. Patients were then followed on approximate 3-month recalls for 3 years. Twenty-five of the original 31 patients qualified for long-term evaluation in that their ABM/P-15 treated sites did not receive any additional therapy at the time of reentry. Significant clinical changes for the overall group of bony defects included improvement in mean clinical attachment level from 5.4 mm at surgery to 4.5 mm at the 6-month reentry to 3.8 mm at 3 years. There was also a decrease in mean probing depth from 5.3 mm at surgery to 3.1 mm at the 6-month reentry to 2.9 mm at 3 years. The mean gingival recession changed from +0.1 mm at surgery to 1.4 mm at the 6-month reentry to 0.9 mm at 3 years. All of these differences were at least P <0.05 from surgery to the 6-month reentry, and surgery to 3 years, but were not significant from reentry to 3 years via repeated measures analysis of variance. These favorable 3-year results with ABM/P-15 suggest that it may have a beneficial effect in the long-term clinical management of infrabony defects. Further long-term randomized controlled studies are needed to better assess the role of ABM/P-15 in long-term healing of periodontal osseous defects.


Anal sphincter function and integrity after primary repair of third-degree tear: uncontrolled prospective analysis.
The purpose of the present paper was to determine the anatomical integrity and functional effect of a tear to the anal sphincter in women after vaginal delivery. A prospective review of third- and fourth-degree vaginal tears over a 3 year period at Lyell McEwin and Queen Elizabeth Hospitals, Adelaide. Obstetric details were obtained from the records. All were counselled by a continence advisor and offered consultation with a colorectal surgeon. The integrity of the anal sphincter was assessed by endoanal ultrasound. During the study period there were 6875 vaginal deliveries. There were 89 women (1.3%) who had a third- or fourth-degree tear. Fifty-one (57%) agreed to participate. Primiparity (67%), episiotomy (49%), forceps delivery (29%) and instrumental delivery were common in women sustaining a tear. Symptoms of anal incontinence (mild) or faecal urgency were described in 23 women (45%). Except for three women with an anovaginal fistula none required surgery for the management of faecal incontinence. A sphincter defect was seen in 27 women (53%) on endoanal ultrasound. The presence or absence of a sphincter defect was not significantly associated with symptoms but a trend was suggested (chi2=3.21; P=0.07). Third-degree tear after vaginal delivery was a significant intrapartum event, yet associated only with minimal symptoms (excluding patients with anovaginal fistula) even in the presence of a sphincter defect on anal ultrasound.


Development of a fast DNA extraction method for sea food and marine species identification.
The authentication of food components is one of the key issues in food safety. Similarly taxonomy, population and conservation genetics as well as food web structure analysis, also rely on genetic analyses including the DNA barcoding technology. In this scenario we developed a fast DNA extraction method without any purification step from fresh and processed seafood, suitable for any PCR analysis. The protocol allows the fast DNA amplification from any sample, including fresh, stored and processed seafood and from any waste of industrial fish processing, independently of the sample storage method. Therefore, this procedure is particularly suitable for the fast processing of samples and to carry out investigations for the authentication of seafood by means of DNA analysis.


Effect of steam explosion and enzymatic pre-treatments on pulping and bleaching of Hesperaloe funifera.
A non-wood raw material with high potential for pulp and paper applications (Hesperaloe funifera) was subjected to a steam explosion pre-treatment, and the subsequent effect of this pretreatment on biopulping and biobleaching was studied. An increase in the delignification rate, bigger than that reported for autohydrolysis and acid hydrolysis pre-treatments, and a reduction in chemical consumption were found during kraft pulping of the exploded samples. However, biopulping with the laccase-mediator system (LMS) did not lead to a reduction in the kappa number in either non-exploded or exploded unbleached pulps. On the other hand, the steam explosion pretreatment boosted the advantages of the LMS pre-treatment (decrease in kappa number and increase in brightness) favored biobleaching, with a 53.1% delignification rate and a final brightness of 67% ISO. Finally, the steam explosion pre-treatment also improved the color properties of the bleached pulp and reduced the hydrogen peroxide consumption by 24.6%.


The genetic diversity of culturable nitrogen-fixing bacteria in the rhizosphere of wheat.
A total of 17 culturable nitrogen-fixing bacterial strains associated with the roots of wheat growing in different regions of Greece were isolated and characterized for plant-growth-promoting traits such as auxin production and phosphate solubilization. The phylogenetic position of the isolates was first assessed by the analysis of the PCR-amplified 16S rRNA gene. The comparative sequence analysis and phylogenetic analysis based on 16S rRNA gene sequences show that the isolates recovered in this study are grouped with Azospirillum brasilense, Azospirillum zeae, and Pseudomonas stutzeri. The diazotrophic nature of all isolates was confirmed by amplification of partial nifH gene sequences. The phylogenetic tree based on nifH gene sequences is consistent with 16S rRNA gene phylogeny. The isolates belonging to Azospirillum species were further characterized by examining the partial dnaK gene phylogenetic tree. Furthermore, it was demonstrated that the ipdC gene was present in all Azospirillum isolates, suggesting that auxin is mainly synthesized via the indole-3-pyruvate pathway. Although members of P. stutzeri and A. zeae are known diazotrophic bacteria, to the best of our knowledge, this is the first report of isolation and characterization of strains belonging to these bacterial genera associated with wheat.


Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice.
In an attempt to identify the histological properties of the klotho-deficient (kl/kl) bone matrix, bone mineralization and the localization of Ca(2+)-binding bone matrix proteins - osteocalcin, dentin matrix protein-1 (DMP-1) and matrix Gla protein (MGP) - were examined in kl/kl tibiae. While a widespread osteocalcin staining could be verified in the wild-type bone matrix, localization of the same protein in the kl/kl tibiae seemed rather restricted to osteocytes with only a faint staining of the whole bone matrix. In wild-type mice, MGP immunoreactivity was present at the junction between the epiphyseal bone and cartilage, and at the insertion of the cruciate ligaments. In kl/kl mice, however, MGP was seen around the cartilaginous cores of the metaphyseal trabeculae and in the periphery of some cells of the bone surface. DMP-1 was identified in the osteocytic canalicular system of wild-type tibiae, but in the kl/kl tibiae this protein was mostly found in the osteocytic lacunae and in the periphery of some cells of the bone surface. Mineralization of the kl/kl bone seemed somewhat defective, with broad unmineralized areas within its matrix. In these areas, mineralized osteocytes along with their lacunae and osteocytic cytoplasmic processes were found to have intense osteocalcin and DMP-1 staining. Taken together, it might be that the excessive production of Ca(2+)-binding molecules such as osteocalcin and DMP-1 by osteocytes concentrates mineralization around such cells, disturbing the completeness of mineralization in the kl/kl bone matrix.


Congenital arteriovenous fistula of the maxillofacial region.
Long-term follow-up is essential to evaluate our present modalities of treatment of arteriovenous malformations of the maxillae. Embolization followed by surgical resection has produced long-term survival in our patient population.


Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma.
Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) (P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes (P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion (P=0.0057), lymph-node metastasis (P=0.0371) and tumor stages (P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant (P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR (P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-alpha treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma.


Antihyperglycaemic activity of the methanol extract from leaves of Eremophila maculata (Scrophulariaceae) in streptozotocin-induced diabetic rats.
This study was designed to evaluate the antihyperglycaemic activity of the methanol leaf extract of Eremophila maculata (EMM) both in vitro and in vivo. The antihyperglycaemic activity was assessed in vitro using differentiated 3T3-L1 adipocytes, whereas in-vivo effect was evaluated in streptozotocin-induced diabetic rats. Chemical profiling of EMM was done using LC-ESI-MS techniques. Molecular modelling experiments of the identified compounds were performed using C-Docker protocol. Eremophila maculata slightly enhanced cellular glucose uptake and utilization in vitro by 3.92% relative to the untreated control. A stronger in-vivo effect was observed for EMM and its dichloromethane fraction. A pronounced elevation in serum insulin by 88.89 and 66.67%, respectively, accompanied by an apparent decline in fasting blood glucose (FBG) level by 65.60 and 70.37% comparable to streptozotocin-induced diabetic rats was observed. This effect was stronger than that of the reference drug glibenclamide (GLB). Chemical profiling of EMM revealed that leucoseptoside A, verbascoside, syringaresinol-4-O-β-D-glucopyranoside, pinoresinol-4-O-β-D-glucopyranoside and pinoresinol-4-O-[6″-O-(E)-feruloyl]-β-D-glucopyranoside are the major compounds. Molecular modelling showed that martynoside, verbascoside and phillygenin exhibited the highest inhibition to human pancreatic α-amylase (HPA), maltase glucoamylase (MGAM) and aldose reductase (AR), respectively. Eremophila maculata offers an interesting relatively safer antihyperglycaemic candidate comparable to synthetic analogues.


Functional and Morphological Parameters with Tissue Characterization of Cardiovascular Magnetic Imaging in Clinically Verified "Infarct-like Myocarditis".
Cardiac magnetic resonance (CMR) has increasingly proved to be a valuable diagnostic tool for evaluating patients with suspected myocarditis. The objective of this study was to evaluate the diagnostic value of functional and morphological parameters including tissue characterization in patients with "infarct-like myocarditis". 43 patients with clinically verified cases of "infarct-like myocarditis" (median time to MRI scanning after admission for acute symptoms 3 days) and 35 control patients matched by age and sex were included in this retrospective case control study. In this study we used a 1.5 T MRI scanner conducting steady-state-free-precession sequences, T2-weighted imaging, T1-weighted imaging before and after contrast administration and late gadolinium enhancement sequences. According to the recommendations for CMR diagnosis of myocarditis (Lake Louise consensus criteria), a scan was positive for acute myocarditis if 2 of 3 CMR criteria were present. 30 % of the patients with "infarct-like myocarditis" had a reduced left ventricular ejection fraction, 11 % had an increased LV end-diastolic volume index and 35 % had an increased LV mass index. The sensitivity of wall motion abnormalities was 63 % with a regional distribution in 49 %. In 47 % of cases regional wall motion abnormalities were present in the lateral left ventricular segments. Pericardial effusions were discovered in 65 % of cases with a circular appearance in 21 % and focal manifestation in 44 %. The diagnostic sensitivity, specificity, and accuracy of CMR in patients with "infarct-like myocarditis" were 67 %, 100 % and 82 %, respectively. The LGE alone was the most sensitive test parameter with 86 %, providing a specificity of 100 % and accuracy of 92 %. Our study results can be applied to the subgroup of patients with "infarct-like myocarditis", where we found that LGE alone was the most sensitive test parameter. In addition to tissue characterization, the functional and morphological analysis of patients with acute myocarditis provides a useful further diagnostic tool. •Infarct-like myocarditis can be diagnosed by CMR with high validity and reliability. •LGE allone performed best with a sensitivity of 86 %. •Functional and morphological CMR parameters in addition to tissue characterization are useful tool in the diagnosis of acute myocarditis.


Short and Long-Term Trainability in Older Adults: Training and Detraining Following Two Years of Multicomponent Cognitive-Physical Exercise Training.
Despite the benefits of multicomponent physical-cognitive training programs (MCCogTPs), lower training intensities in the concurrent approach, and bigger heterogeneity with aging, suggest the need for long-term analyses, with special attention to training and detraining in older adults. The present study aims to examine these training/detraining effects in a two year MCCogTP, looking for specific dynamics in the trainability of their physical and cognitive capacities. The intervention was divided into four periods: T1, T2 (8 months of training each), and D1, D2 (3.5 months of detraining plus 0.5 of testing each). Twenty-five healthy seniors (70.82 ± 5.18 years) comprised the final sample and were assessed for cardiovascular fitness (6-minutes walking test), lower-limbs strength (30-seconds chair-stand test) and agility (8-feet timed up-and-go test). Inhibition (Stroop test) was considered for executive function. Physical and cognitive status improved significantly (p < 0.05) throughout the two years, with larger enhancements for physical function (mainly strength and agility). Strength and cardiovascular fitness were more sensitive to detraining, whilst agility proved to have larger training retentions. Inhibition followed an initial similar trend, but it was the only variable to improve along D2 (d = 0.52), and changes were not significant within periods. Notwithstanding aging, and the exercise cessation in D2, physical and cognitive status remained enhanced two years later compared to baseline, except for lower-limb strength. According to these results, basic physical capacities are very sensitive to training/detraining, deserving continuous attention (especially strength). Both reducing detraining periods and complementary resistance training should be considered. Additionally, physical enhancements following MCcogTPs may help cognition maintenance during detraining.


[Septic arthritis in neonates and infants--treatment of septic arthritis in the shoulder].
Results of treatment of 55 acute hematogenous arthritis of the shoulder in newborns and infants are presented. There were 14 good results, 15 fair and 26 poor ones. The authors consider arthrotomy as the most efficient mode of treatment.


Late-onset bipolar disorder.
Mania in old age is not as rare as it was once thought to be. It may constitute up to 5 per cent of admissions in the psychogeriatric department. The clinical picture, for the most part, seems to correspond with mania in younger patients, although some patients may have atypical presentations. Secondary mania should be excluded first, before a firm diagnosis of primary affective disorder is made. The prognosis and treatment of late onset mania do not seem to differ appreciably from those in younger patients.


Isolated intraorbital schwannoma arising from the abducens nerve.
A case of isolated schwannoma of the orbit, arising from the terminal branches of the abducens nerve to the lateral rectus muscle, is reported. The patient presented with a painless proptosis of the left eye. Preoperative diagnosis of benign intraorbital neoplasm was made by means of CT and MR scans; the mass was radically excised through a microsurgical lateral orbitotomy and the pathological examination revealed a schwannoma. Features of orbital schwannoma are described, together with some details concerning the surgical strategy and the history of the evolution of the lateral orbitotomy.


Variation in tube voltage for adult neck MDCT: effect on radiation dose and image quality.
The purpose of this study was to assess the effect of peak kilovoltage on radiation dose and image quality in adult neck MDCT. An anthropomorphic phantom with metal oxide semiconductor field effect transistor detectors was imaged with a 64-MDCT scanner. The reference CT protocol called for 120 kVp, and images obtained with that protocol were compared with CT images obtained with protocols entailing 80, 100, and 140 kVp. All imaging was performed with automatic tube current modulation. Organ dose and effective dose were determined for each protocol and compared with those obtained with the 120-kVp protocol. Image noise was evaluated objectively and subjectively for each protocol. The highest organ doses for all protocols were to the thyroid, ocular lens, skin, and mandible. The greatest reductions in organ dose were for the bone marrow of the cervical spine and mandible: 43% and 35% with the 100-kVp protocol and 63% and 53% with the 80-kVp protocol. Effective dose decreased as much as 9% with the 100-kVp protocol and 12% with the 80-kVp protocol. Use of the 140-kVp protocol was associated with an increase in organ dose as high as 64% for bone marrow in the cervical spine and a 19% increase in effective dose. Image noise increased with lower peak kilovoltage. The measured noise difference was greatest at 80 kVp, absolute increases were less than 2.5 HU. There was no difference in subjective image quality among protocols. Reducing the voltage from 120 to 80 kVp for neck CT can result in greater than 50% reduction in the absorbed organ dose to the bone marrow of the cervical spine and mandible without impairment in subjective image quality.


Effect of other drugs and chemicals on the degradation of aspirin in vitro: possible extrapolation to in vivo metabolism of aspirin.
To assess the possible influence of other drugs and chemicals on the metabolic degradation of aspirin in man, their effect on the serum aspirin esterase activity was determined in vitro. The activation or inhibition of the enzyme as observed with these compounds suggest the possibility that simultaneous ingestion of these drugs with aspirin may influence the pharmacology and toxicity of the analgesic.


Primary pulmonary lymphoma.
Primary pulmonary lymphoma is a rare disease. The clinical characteristics, methods of treatment, and outcomes are not well elucidated. A retrospective review of primary pulmonary lymphoma cases at a single institution from 1990 to 2002 was performed. Eighteen patients were included, with a mean follow-up of 2.9 years. Fourteen patients had mucosa-associated lymphoid tissue (MALT) lymphoma, 2 had large cell transformation of sheet cells in MALT lymphoma, and 1 each had Hodgkin's disease and follicular lymphoma. Computed tomography-guided biopsy was diagnostic in only two of eight attempts. Eleven patients had disease confined to the pulmonary parenchyma, and 7 had parenchymal disease as well as mediastinal lymphadenopathy. Treatment methods included observation only (n = 1), surgery only (n = 6), surgery plus chemotherapy (n = 8), surgery plus radiotherapy (n = 1), and surgery plus chemotherapy plus radiotherapy (n = 2). Kaplan-Meier estimate of median time to disease recurrence or death was 6 years. Only 1 patient died of disease-related causes. Patients who had bilateral disease were more likely to have recurrent disease or death (p = 0.03). A wide range of treatments were used for patients with generally MALT lymphoma, resulting in good outcomes, and recurrent disease was well controlled.


Chondromyxoid fibroma of calcaneus.
Chondromyxoid fibroma is a rare benign primary bone tumor composed of immature myxoid mesenchymal and cartilaginous tissue. Its occurrence in calcaneus is very rare and few cases of calcaneal involvement have been reported in literature. We report five cases of CMF in calcaneus. Five cases, with the final diagnosis of chondromyxoid fibroma of the calcaneal bone are included in this report. Preoperative tumor workup was performed for our patients. We reviewed and recorded demographic data and the sign and symptoms of patients at presentation to our center. Mode of treatments, postoperative complications and recurrence were also studied. Curettage, high speed burring and bone grafting was performed in 4 of our patients and in the remaining case we only carried out curettage and burring. Of the five patients, 3 were male and 2 were female. The mean age at presentation was 21. Two of our cases had previous surgery in other centers and had been referred to our clinic because of recurrence. The chief complaint in all of our patients was heel pain. The mean follow up period was 25.2 months. All of our patients had a delay in the diagnosis of tumor. We did not have any recurrence in our patients during follow up period. This case series shows that chondromyxoid fibroma is not necessarily as exceedingly rare as generally reported in the current literature. This tumor should be considered in the differential diagnosis in patients with ankle and heel pain.


The antibacterial activity of vancomycin towards Staphylococcus aureus under aerobic and anaerobic conditions.
To investigate the antibacterial efficacy of vancomycin towards Staphylococcus aureus under aerobic and anaerobic conditions, and to assess the influence of oxygen on the duration of the post-antibiotic effect (PAE) after exposure to vancomycin. Culture-based techniques and flow cytometric measurements of 5-cyano-2,3-ditolyl tetrazolium chloride (an indicator of redox activity) and the membrane potential-sensitive fluorophore Sytox Green, were used to test four staphylococcal strains. The MICs for all strains, and the duration of PAE, were similar whether tested with or without oxygen. However, a fivefold logarithmic reduction in cell counts was observed in 10-15 h aerobically, depending on strain, compared with longer than 60 h in an anaerobic environment. Flow cytometric data correlated well with counts of colony-forming units under both aerobic and anaerobic conditions. The death rate of Staph. aureus exposed to vancomycin was greater in the presence of oxygen, although MIC values and PAE durations were similar whether tested aerobically or anaerobically. Also, flow cytometry provided a rapid and sensitive alternative to plate counts for the assessment of antibiotics in oxygen-free conditions. This study underlines the need for further anaerobic testing using different strain/antibiotic combinations, the results of which will have clinical significance due to the anaerobic nature of some sites of infection.


High sleep quality can increase the performance of CrossFit® athletes in highly technical- and cognitive-demanding categories.
In current sports science, the important role of sleep quality for health and peak performance is well acknowledged. More precisely, it is evident that the negative combination of stressful factors, low resources, and bad sleep habits causes short-term performance losses as well as long-term health consequences. As the maximization of human performance consisting of multiple fixed workloads is the main motivation in CrossFit® (CF), the aim of the present study was to investigate the influence of high sleep quality on performance in CrossFit® athletes (CFA) and the different training categories that are addressed in CF. In total, 149 CFA (81 females, 68 males; 32.01 ± 7.49 years old, 2.56 ± 1.77 active years in CF) filled in the online survey comprising the Pittsburgh Sleep Quality Index (PSQI) and CF performance-specific questions. It was found that CFA with high sleep quality reported higher values in all performance-related outcomes. Especially in Hero-/Girl-Workouts (χ2 = (1, n = 83) = 9.92, p = .002, φ = 0.37) and Gymnastics (χ2 = (1, n = 129) = 8.74, p = .003, φ = 0.28), performance differed significantly between good and poor sleeping CFA. Since those CF categories are highly technical- and cognitive-demanding high sleep quality seems to play a fundamental role in complex motor skill learning and performance development. These results reveal for the first time the positive effects of high sleep quality for performance in CFA and could be used as basis for future studies. Future research should also develop and empirically test suitable interventions to foster high sleep quality in CFA. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of University of the Federal Armed Forces Munich, Germany (06/04/2018).


The value or arthrography in the management of internal derangements of the knee: the first 1000 are the worst.
The acceptance of arthrography of the knee as an accurate diagnostic procedure by both radiologists and orthopaedic surgeons in the United Kingdom has been slow compared to many other parts of the world. The value of arthrography in the diagnosis of meniscal lesions is discussed with reference to the first 1000 documented cases in the authors' series. It is considered that the results obtained from such early experience is more relevant to those about to start as an arthrographic service. Problems in clinical, arthrographic and arthroscopic diagnosis are discussed. Arthrography constitutes an accurate method of diagnosing such lesions and should be employed whenever clinical doubt about the diagnosis of an internal derangement of the knee is encountered. In a selected group of 137 patients, in whom both arthrography and arthroscopy was performed, the two investigations showed a comparable accuracy of 89.8 and 88.3% respectively.


Whole-body volume regulation and escape from antidiuresis.
Both individual cells and organs regulate their volume in response to sustained hypo-osmolality via solute and water losses. Similar processes occur in the whole body to regulate the volumes of extracellular fluid (ECF) and intravascular spaces toward normal levels. Body water losses occur via the phenomena "escape from antidiuresis"; solute losses occur through the secondary natriuresis induced by water retention. As a result of resistance to arginine vasopressin (AVP) signaling, escape from antidiuresis is caused by downregulation of kidney aquaporin-2 expression despite high AVP plasma levels. Recent data have implicated downregulation of vasopressin V2R as a potential mechanism of resistance, and suggest that this may be a result of decreased intrarenal angiotensin II signaling in combination with increased intrarenal nitric oxide and prostaglandin E2 signaling. The natriuresis that results in volume regulation of the ECF and vascular spaces is the result of intrarenal hemodynamic changes produced by volume expansion, but the degree to which these effects are modulated by aldosterone secretion and the activity of distal sodium cotransporters and channels remains to be elucidated. The clinical implication of these volume-regulatory processes is that the chronic hyponatremic state is one of water retention and solute losses from intracellular fluid and ECF compartments. The degree to which solute losses versus water retention contribute to hyponatremia will vary in association with many factors, including the etiology of the hyponatremia, the rapidity of development of the hyponatremia, the chronicity of the hyponatremia, the volume of daily water loading, and individual variability. Understanding these volume-regulatory processes allows a better understanding of many aspects of the conundrum of patients with "clinical euvolemia" and dilutional hyponatremia from AVP-induced water retention.


Exploring the efficacy of using hypertonic saline for nebulizing treatment in children with bronchiolitis: a meta-analysis of randomized controlled trials.
Inhaled hypertonic saline (HS) has shown benefit in decreasing airway edema in acute bronchiolitis which is the most common lower respiratory infection resulting in dyspnea among infants under 2 years old. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of HS in the implementation of treatment with nebulized HS among children with bronchiolitis. A systematic literature search was conducted using Cochrane Library, PubMed, EMBASE and Airiti Library (Chinese Database) for randomized controlled trials from inception to July 2019. We calculated pooled risk ratios (RR), mean difference (MD) and 95% CI using RevMan 5.3 for meta-analysis. There were 4186 children from 32 publications included. Compared to the control group, the HS group exhibited significant reduction of severity of respiratory distress, included studies used the Clinical Severity Score (n = 8; MD, - 0.71; 95% CI, - 1.15 to - 0.27; I2 = 73%) and full stop after Respiratory Distress Assessment Instrument (n = 5; MD, - 0.60; 95% CI, - 0.95 to - 0.26; I2 = 0%) for evaluation respectively. Further, the HS group decreased the length of hospital stay 0.54 days (n = 20; MD, - 0.54; 95% CI, - 0.86 to - 0.23; I2 = 81%). We conclude that nebulization with 3% saline solution is effective in decreasing the length of hospital stay and the severity of symptoms as compared with 0.9% saline solution among children with acute bronchiolitis. Further rigorous randomized controlled trials with large sample size are needed.


Identification and linkage relationships of three hexokinase genes in Aedes aegypti.
Four regions of hexokinase activity are detected by starch gel electrophoresis of adult Aedes aegypti. Three of the regions, Hk-2, Hk-3, and Hk-4, are produced by three tightly linked loci, located on the third chromosome 7.25 map units from the locus fuzzy. The three loci show developmental differences as well as differences in substrate specificity.


Antioxidant peptides derived from hydrolyzed milk proteins by Lactobacillus strains: A BIOPEP-UWM database-based analysis.
Milk-derived peptides have been identified as the essential ingredients in the food industry for the health-promoting properties. Some bioactive peptides in the milk product can be released by the specific protease system of lactic acid bacteria (LAB) during the fermentation processing. In this research, the bioactive peptides released from the casein and whey protein are investigated by the hydrolyzing ability of the Lactobacillus brevis CGMCC15954, Lactobacillus reuteri WQ-Y1 and Lactobacillus plantarum A3. Results found that the hydrolysates of casein/whey protein generated by L. reuteri WQ-Y1 have the potential antioxidant activity. Furthermore, milk-derived peptides identified by the liquid chromatography-mass spectrometry (LC-MS/MS) with the BIOPEP-UWM database showed the YLGYLEQLLR (αS1-casein), VKEAMAPK (β-casein), YIPIQYVLSR (κ-casein) fragment had the promising antioxidant activity, especially VKEAMAPK, which exhibited IC50 of 0.63 and 0.86 mg/mL in DPPH and ABTS free radical scavenging activity. The finding of this study sheds some light of obtaining milk-derived peptides by using the Lactobacillus strains and proves the potential bioactive function of the LAB fermented milk products.