Lung function, arterial pressure and growth in sheep during early postnatal life following single and repeated prenatal corticosteroid treatments.
Antenatal corticosteroid therapy is of great benefit to preterm infants, owing largely to effects on lung maturation. In sheep, repeated betamethasone injections given to the ewe improve lung function following preterm birth but also cause intrauterine growth restriction (IUGR). In humans and in animal models, IUGR is associated with impaired postnatal lung function. The effects on lung function of repeated prenatal betamethasone treatments and associated IUGR following term delivery are unknown. AIM AND STUDY DESIGN: To determine the effects of antenatal betamethasone treatments on postnatal arterial pressure, blood gases, ventilation, pulmonary gas volumes and compliance in serial studies of four groups of lambs until 4 weeks of age. Treatment groups were (1) maternal injections of saline at 104, 111 and 118 days of gestation, (2) a single maternal injection of betamethasone (0.5 mg/kg) at 104 days followed by saline at 111 and 118 days, (3) repeated betamethasone injections at 104, 111 and 118 days, or (4) no intervention (term is approximately 150 days). Repeated maternal betamethasone injections reduced birthweight and resulted in reduced postnatal body weights and arterial pressure throughout the first postnatal month. Lung function was not deleteriously affected by single or repeated maternal betamethasone treatments: blood gases, minute ventilation, lung volumes and compliance were not different between groups of lambs. The absence of alterations in postnatal blood gases contrasts with other models of IUGR in sheep and suggests that changes in lung structure caused by betamethasone may benefit IUGR neonates born at term.


Separation and determination of lipids by one-dimensional micro-thin-layer chromatography followed by densitometry.
A method is described for the rapid analysis of a mixture of phospholipids and neutral lipids, which was used for the analysis of extracts obtained from a nuclear fraction isolated from rat liver. The lipids are separated by one-dimensional thin-layer chromatography on microchromatoplates (48 X 24 mm), using three solvents for development. After spraying the plates with phosphoric acid and heating, the amount of carbon from the charred compounds is measured densitometrically. Only 2-10 microgram of lipid mixture are needed for the determination of the relative amounts of the separated compounds.


The regulatory effects of growth rate and cyclic AMP levels on carbon catabolism and respiration in Escherichia coli K-12.
Cyclic AMP levels in glucose and succinate-limited and ammonia-limited glucose-containing continuous cultures of Escherichia coli were measured at different bacterial growth rates. Intracellular cyclic AMP concentrations were fairly constant (about 5 micrometer) at all dilution rates used when glucose was limiting. In ammonia-limited glucose cultures the cyclic AMP content was much lower (about 0.3 micrometer). In succinate-limited cultures cyclic AMP levels fell from 2.7 to 0.8 micrometer as dilution rate increased from 0.05 to 0.4 h-1. The effects of cyclic AMP on respiratory and carbon catabolic enzyme levels were studied. There was no indication of a direct cyclic AMP involvement in the regulation of these cellular functions. It seems more likely that the variations in enzyme levels observed resulted from variation of the specific growth rate of cultures.


The Floating Clavicle: Surgical Technique for Management of an Ipsilateral Acromioclavicular and Sternoclavicular Joint Dislocation.
Bipolar "floating" clavicle injuries are infrequent upper-extremity injuries that occur secondary to a high-energy trauma, which can cause dislocation at the sternoclavicular (SC) and acromioclavicular joints. Given the rarity of this injury, there is not a consensus regarding clinical management. Although anterior dislocations can be managed nonoperatively, posterior dislocations may pose a threat to chest-wall structures and typically are managed surgically. Here, we present our preferred technique for concomitant management of a locked posterior SC joint dislocation with associated grade 3 acromioclavicular joint dislocation. Reconstruction of both ends of the clavicle was performed in this case, using a figure-of-8 gracilis allograft and nonabsorbable suture reconstruction for the SC joint, and an anatomic acromioclavicular joint and coracoclavicular ligament reconstruction with semitendinosus allograft and nonabsorbable suture.


Surface-projection-based transperineal cognitive fusion targeted biopsy of the prostate: an original technique with a good cancer detection rate.
To report a new standardized cognitive fusion technique on transperineal targeted biopsy (TB) of prostate, and to evaluate its efficacy for cancer detection combined with systematic biopsy (SB) . We present a retrospective review of consecutive patients undergoing multiparametric magnetic resonance (mpMRI) imaging of the prostate with subsequent transperineal prostate biopsy from January 2016 to December 2018. A free-hand 12-core SB was performed for each patient. PI-RADS 3-5 lesions were further targeted for biopsy with our TB technique. Firstly, a central point of suspicious lesion (B') was registered cognitively on a transverse section of transrectal ultrasound (TRUS). Then, biopsy gun punctured vertically through a fixed pioneer site (A) on skin of perineum, and deep into the TRUS section to get A'. Next, targeted site (B), the surface-projection of B', would be determined on skin of perineum by A and distance from B' to A'. Finally, puncture through B to reach B'. Pathological findings of SB and TB were analyzed. A total of 126 patients underwent transperineal prostate biopsy (47 SB only, 79 SB + TB). The age of the patients was 68.7 ± 9.2 years. The median preoperative PSA value was 11.8 ng/mL. Preoperative prostate volume was 60.5 ± 50.0 mL. The numbers of patients with PI-RADS scores of 1 through 5 were 4, 43, 27, 21 and 31, respectively. The overall detection rate of cancer was 61/126 (48.4%), and it was significantly higher in the combination cohort (56/79, 70.9%) compared with the SB only cohort (5/47, 10.6%, p<0.001). When focused on the combination cohort, TB detected a similar overall rate of PCa (53/79, 67.1% vs 52/79, 65.8%; p = 0.87) compared with SB. The clinically significant PCa (csPC) detection rate was 52/79 (65.8%), while for TB and SB the csPC/PC rate was 51/53 (96.2%) and 48/52 (92.3%), respectively(p = 0.44). TB demonstrated a better sampling performance (positive rate for each core) compared with SB (51.0% vs 31.3%, p < 0.001). Surface-projection-based transperineal cognitive fusion targeted biopsy of the prostate has a good efficacy in detecting PCa.


Gaps in transitional care to adulthood for patients with cerebral palsy: a systematic review.
The transition from pediatric to adult care can be complex and difficult to navigate for adolescents with cerebral palsy (CP). We aimed to assess the current state of transitional care for young persons with CP and delineate guidelines for best practice with opportunities for intervention. A systematic review was conducted using PRISMA guidelines to search PubMed, Embase, and Scopus databases. Articles were screened for relevance via title and abstract prior to full-text review. Of 3151 resultant articles, 27 observational studies were included. Fourteen (52%) studies assessed clinical outcomes of patients with CP during and post-transition. Transition-associated poor outcomes included housing instability, unemployment, difficulty forming relationships, increased hospital admission rates, and decreased use of rehabilitation services. Factors associated with improved outcomes included family participation, promotion of self-efficacy, and meeting the adult team before transition. Nine (33%) studies conducted interviews with transition-age persons with CP. Key themes were a lack of transition preparedness, difficulty navigating the adult system, gaps in seamless care, and limited accessibility to specialists and environments suitable for patients with complex care needs. Four (15%) studies examined features of current transition services. Perceived barriers included poor communication within health service teams, limited adult providers accepting CP patients, and the lack of financial resources for specialized care. There was no standardized transition tool or approach. These findings underscore the importance of a planned transition process in optimizing long-term medical and psychosocial outcomes for persons with CP. Further research, including translational, team-based, and community-engaged research, are needed.


Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study.
To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS). Propensity score-matched cohort study from the database of the Tampere ACS registry. A single academic hospital in Finland. 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias. The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up. Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, µmol/l: 114.9±70.7). They also showed the highest C reactive protein (7.3±9.5 mg/l) levels. Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity.


Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease.
Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia. This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia. In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE). UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE. In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).


Stimulation of sciatic nerve regeneration in the adult rat by low-intensity electric current.
Morphometric analysis was used to evaluate regeneration in transected sciatic nerves of adult rats constantly stimulated with low-intensity direct current. The ends of the cut nerve were separated by a distance of 5 mm and inserted into a Silastic tube. Histological and electron microscopy criteria were used to measure and evaluate the cross-sectional area and the structure of the bridge connecting the distal and proximal stumps. After 3 weeks of stimulation (10 microA DC with distal cathode) the stimulated animals showed a cross-sectional bridge area twice the size of nonstimulated controls. The number of myelinated and unmyelinated axons, and the vascular areas, were also larger in the experimental group. This is the first quantitative analysis of low-intensity direct current-enhanced peripheral nerve regeneration in adult mammals.


High-dose chemotherapy with BEAM or Busulphan/Melphalan and Thiotepa followed by hematopoietic cell transplantation in malignant lymphoma.
We analysed treatment results of two high-dose regimens: BEAM (carmustine, etoposide, cytarabine, melphalan) and BuMelTT (busulphan, melphalan, thiotepa) in autologous transplant patients with non-Hodgkin lymphoma. Patients received BEAM (n=48) or BuMelTT (n=59) from 1998 to 2005. BEAM group patients were older (mean 59.7 vs 50.1 years), more advanced (stage>or=III 88 vs 61%), had higher IPI/FLIPI scores (score>or=3, 65 vs 19%), and a higher comorbidity index (HCT-CI) (score>or=2, 40 vs 19%). Grade 3-4 complications occurred in 10 patients (17%), with six deaths in the BuMelTT group versus none in the BEAM group. CR was achieved in 20 of 36 (56%) BuMelTT versus 12 of 39 (31%) BEAM patients. After adjusting for IPI/FLIPI, HCT-CI, age and stage of disease, the hazards of death, relapse and treatment failure were similar in both groups. In this retrospective comparison, BEAM regimen appeared to be equally effective but less toxic than BuMelTT.


Inherited DNA repair gene mutations detected by tumor next generation sequencing in urinary tract cancers.
Interpretation of next-generation sequencing (NGS) of tumor tissue in patients with advanced Urinary Tract Cancer (UTC) is performed to guide treatment selection but may reveal pathogenic variants with germline implications. We identified three patients with UTC with unexpected germline DNA repair gene mutations. Specific testing for these was prompted by the detection of these mutations by tumor NGS. All three patients were nonsmokers with a strong family history of cancer. Two patients had upper tract UTC with age at diagnosis in the 40 s. One had a family history suggestive of hereditary breast/ovarian predisposition and a FANCA mutation detected on NGS was confirmed to be germline. The second patient had a family history suggestive of Lynch syndrome but was found to have a germline BRCA2 mutation that was suggested by NGS. The third patient had bladder cancer at an advanced age, a family history of late-onset gastrointestinal malignancies that did not meet criteria for clinical testing for a hereditary cancer predisposition syndrome. NGS identified an MUTYH mutation, and targeted testing confirmed a monoallelic germline MUTYH mutation. Detection of variants with germline implications by tumor NGS may be clinically relevant for patients and their families and warrant genetic counseling and germline genetic testing. The prevalence of germline DNA repair defects in the context of inherited predisposition to UTC merits further study.


Perceptual learning in parafoveal vision.
The present study tests the effects of practice on parafoveal vernier and resolution acuity. By measuring task specificity, transfer of training to other retinal locations in the trained eye and transfer of training to the untrained eye, we directly address whether improvement on these tasks is the result of changes in the underlying physiological processes or simply the development of new cognitive strategies. We found that: (1) significant learning can occur for both vernier and resolution acuity in many (but not all) individuals; (2) there were significant individual differences in the degree and time-course of learning: (3) learning transfers to the untrained task; and (4) learning transfers to the other eye particularly when the visual pathway leads to the trained hemisphere. These results suggest that both physiological and cognitive processes contribute to the improvement seen after repetitive practice on these visual tasks.


Event-related potential (ERP) markers of 22q11.2 deletion syndrome and associated psychosis.
22q11.2 deletion syndrome (22q11.2DS) is a multisystemic disorder characterized by a wide range of clinical features, ranging from life-threatening to less severe conditions. One-third of individuals with the deletion live with mild to moderate intellectual disability; approximately 60% meet criteria for at least one psychiatric condition.22q11.2DS has become an important model for several medical, developmental, and psychiatric disorders. We have been particularly interested in understanding the risk for psychosis in this population: Approximately 30% of the individuals with the deletion go on to develop schizophrenia. The characterization of cognitive and neural differences between those individuals who develop schizophrenia and those who do not, despite being at genetic risk, holds important promise in what pertains to the clarification of paths to disease and to the development of tools for early identification and intervention.Here, we review our previous event-related potential (ERP) findings as potential markers for 22q11.2DS and the associated risk for psychosis, while discussing others' work. We focus on auditory processing (auditory-evoked potentials, auditory adaptation, and auditory sensory memory), visual processing (visual-evoked potentials and visual adaptation), and inhibition and error monitoring.The findings discussed suggest basic mechanistic and disease process effects on neural processing in 22q11.2DS that are present in both early sensory and later cognitive processing, with possible implications for phenotype. In early sensory processes, both during auditory and visual processing, two mechanisms that impact neural responses in opposite ways seem to coexist-one related to the deletion, which increases brain responses; another linked to psychosis, decreasing neural activity. Later, higher-order cognitive processes may be equally relevant as markers for psychosis. More specifically, we argue that components related to error monitoring may hold particular promise in the study of risk for schizophrenia in the general population.


Binding of acyl-CoA to liver fatty acid binding protein: effect on acyl-CoA synthesis.
The ability of purified rat liver and heart fatty acid binding proteins to bind oleoyl-CoA and modulate acyl-CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart fatty acid binding protein was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver fatty acid binding protein has a single binding site acyl-CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl-CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver fatty acid binding protein stimulated acyl-CoA production, whereas that from heart did not stimulate production over control values. 14C-labeled fatty acid-fatty acid binding protein complexes were prepared, incubated with membranes, and acyl-CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl-CoA in the presence of liver fatty acid binding protein but in the presence of heart fatty acid binding protein, only 45% of the fatty acid was converted. Liver but not heart fatty acid binding protein bound the acyl-CoA formed and removed it from the membranes. The amount of product formed was not changed by additional membrane, enzyme cofactors, or incubation time. Additional liver fatty acid binding protein was the only factor found that stimulated product formation. Acyl-CoA hydrolase activity was also shown in the absence of ATP and CoA. These studies suggest that liver fatty acid binding protein can increase the amount of acyl-CoA by binding this ligand, thereby removing it from the membrane and possibly aiding transport within the cell.


Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma.
Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. However adverse effects of ICS on Hypothalamo Pituitary Adrenal (HPA) axis, growth and bone metabolism are a concern. Hence the primary objective of this study was to describe the effects of long term inhaled corticosteroid therapy (ICS) on adrenal function, growth and bone health in children with asthma in comparison to an age and sex matched group of children with asthma who were not on long term ICS. Describing the association between the dose of ICS and duration of therapy on the above parameters were secondary objectives. Seventy children with asthma on ICS and 70 controls were studied. Diagnosis of asthma in selected patients was reviewed according to the criteria laid down by GINA 2018 guidelines. The estimated adult heights were interpreted relative to their Mid Parental Height (MPH) range. Serum calcium, alkaline phosphatase and vitamin D levels were analyzed in both groups and cortisol value at 30 min following a low dose short synacthen test was obtained from the study group. The average daily dose of ICS (Beclamethasone) was categorized as low, medium and high (100-200, 200-400, > 400 μg /day) respectively according to published literature. Heights of all children were within the MPH range. There was no statistically significant difference in the bone profiles and vitamin D levels between the two groups (Ca: p = 0.554, vitamin D: p = 0.187) but vitamin D levels were insufficient (< 50 nmol/l) in 34% of cases and 41% of controls. Suppressed cortisol levels were seen in 24%. Doses of ICS were low, medium and high in 56, 32 and 12% of children respectively. The association between adrenal suppression with longer duration of therapy (p < 0.01) and with increasing dose of ICS (p < 0.001) were statistically significant. ICS had no impact on the growth and bone profiles but its dose and duration were significantly associated with adrenal suppression.


Vaccination or immunization? The impact of search terms on the internet.
With steadily rising use of the Internet as a source of health information, public health authorities have expressed concern about the increasing visibility of unscientific information promulgated on the Internet by opponents of childhood vaccination. Searches were made on the four most popular Internet search engines using different combinations of the terms, "vaccination," "immunization," "immunisation," "immunize," "immunise," "vaccine," and "shots." Thirty results were tabulated for each search engine. Searching with the keyword "vaccination" resulted in a significantly higher percentage of antivaccination websites as compared with searches with all other keywords. Of all child-related websites retrieved, the single keyword "vaccination" yielded 40% provaccination sites and 60% antivaccination sites. By contrast, the single keyword "immunization" yielded 98% provaccination sites and 2% antivaccination sites. Using a combination of the words "vaccination" and "immunization" produced results between these two extremes. Thus, any use of the term "vaccination" during an Internet search is likely to expose a parent to a significant amount of antivaccination information. Recommendations are discussed for future research and methods to reduce the impact of misinformation on health consumers using the Internet.


An examination of ecological risk assessment and management practices.
Ecological risk assessment has grown and evolved since the 1980s, as have new challenges (e.g. global climate change, loss of habitat and biodiversity and the effects of multiple anthropogenic chemicals on ecological systems) that need to be factored into the risk assessment processes. There is also an on-going shift from evaluating adverse health impacts on particular, often small scale, environments to undertaking more complex ecological assessments of whole populations and communities across ecologically meaningful landscapes. These trends are generating an increased demand for much more complex ecological assessments, making it increasingly clear that to achieve its potential as a management tool, methods must be developed to apply ecological risk assessment to larger and more complex scales. This paper reviews the development of the ecological risk assessment paradigm in the United States, identifies ways it is being applied and adapted in other countries, explores future research needs and practice improvements, and examines current issues that need to be considered in taking forward the scientific development of ecological risk assessment as a useful environmental management tool.


Research on predictability in cephalometry of the relationship of chin symphysis and nose-chin balance.
A sample of 120 untreated Caucasian adults was selected. All subjects were dental and skeletal Class I. The approach calls for the use of an original cephalometric method that is applied to the cutaneous profile by an esthetic curve extending from the nose to the chin. Statistical study of the sample confirms the existence of this cutaneous profile, regardless of facial type. This approach is proposed in combination with Sassouni's analysis to specify pogonion in the vertical and anteroposterior planes from which the vertical position of the chin (menton) may be deduced.


[Diagnostics and classification of non-unions].
Non-union is defined as an insufficiently consolidated fracture in which healing without a surgical intervention is no longer foreseeable. Several underlying predispositions and factors have to be taken into account in order to optimize the diagnostics, classification and surgical treatment of this complex and challenging pathology. As the patient-specific optimized treatment sometimes pursues different goals depending on the specific subtype of non-union, an agreement on the most important parameters within the framework of a standardized classification is of crucial importance. In addition to established diagnostic algorithms, this article also describes modern radiologic diagnostic methods. In addition to the clinical examination, the diagnostics of non-union are mainly based on radiological imaging using X‑ray or computed tomography. Complex fracture morphology or uncertainty, particularly regarding the infection status and perfusion of non-union, can be an indication for an extension of the diagnostics using contrast-enhanced ultrasound (CEUS) or dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A practicable and precise classification of the different types of non-union can only be successful based on a focussed diagnostic procedure using radiologic and functional diagnostic tools, which guide the surgeon in establishing the optimal treatment. This also includes modern functional imaging examinations, such as CEUS and DCE-MRI.


Lactose-binding lectin from Vatairea macrocarpa seeds induces in vivo angiogenesis via VEGF and TNF-ɑ expression and modulates in vitro doxorubicin-induced genotoxicity.
Lactose-binding lectin from Vatairea macrocarpa seeds (VML) has attracted great attention due to its interesting biological activities, such as pro-inflammatory effects and macrophage activation. This study evaluated the cytotoxicity and genotoxicity/antigenotoxicity of VML in human lymphocytes using the CometChip assay, and angiogenic activity by the chick embryo chorioallantoic membrane (CAM) assay. In genotoxicity, lymphocytes were treated with different concentrations of VML (0.5, 2 and 8 μM). In antigenotoxicity, lymphocytes were treated with the same concentrations of VML concomitant doxorubicin (90 μM DXR). To evaluate angiogenesis, all CAM were treated with different concentrations of VML (0.5, 2 and 8 μM) alone or co-treated with lactose (0.1 M). Furthermore, the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM were assessed by immunohistochemistry. The results showed that VML was cytotoxic to lymphocytes, genotoxic at the highest concentration (8 μM) and antigenotoxic at low concentrations (0.5, and 2 μM). Regarding the CAM assay and immunohistochemistry, VML was angiogenic and significantly increased VEGF and TNF-α levels. In contrast, co-treatment with lactose significantly reduced the angiogenic effect and VEGF levels. We propose that protein-carbohydrate interactions between VML and glycans in the cell membrane are probably the major events involved in these activities. It seems likely that VML elicits a pro-inflammatory response through VEGF and TNF-α expression, resulting in increased vascularization at the site of inflammation. Therefore, our results show novel information on the effects of VML on DNA, as well as provide data regarded the neovascularization process involving this lectin.


Land use impacts on trace metal concentrations of suburban stream sediments in the Helsinki region, Finland.
The purpose of this study was to statistically analyze the effect of different suburban land use types on trace metal contamination of suburban streams. Acid extractable metal concentrations (Cu, Zn, Pb, Cd) of stream bed sediments (<63 μm) and high-flow suspended sediments were determined for 61 suburban and six baseline catchments in the Helsinki metropolitan region, Finland. Our results showed that the average suburban metal concentrations were 3-5-fold compared to baseline values for stream bed sediments and 2-9-fold for suspended sediments. Correlation analyses revealed moderate relationships between the land use parameters of the contributing catchment and the metal concentrations. Metals, particularly Zn and Cu, were most strongly correlated with proportions of dense suburban land use and imperviousness. In addition, industrial land use appeared to be particularly important for describing the variations of suspended sediment metal concentrations. Our findings present statistical evidence that the intensity of urbanization and industrial land use provides an indication of metal contamination even within the suburban environment.


[Study in the combining quantity of Con A-binding sites on membrane surface of artesunate-resistance strain of Plasmodium berghei].
To study the production mechanism of plasmodium berghei (PB) in resisting artesunate. The combining quantity of Con A-binding sites on membrane surface of PB trophozoite labelled with fluorescein isothiocyanate (FITC) of Con A was determined by fluoromicrospectrophotometer. The combining quantity of PB artesunate-resistance strain (PBAR) was reduced significantly than that of PB normal strain (P < 0.01). The type of glucose in surface membrane of PBAR has changed and the changes of membrane fluidity could be one of the causes of the change in the combining quantity of Con A-binding sites on membrane of PBAR.


Ultrasound identification of impalpable testicle tumor.
We describe an ultrasound technique that accurately detected an occult testicular primary in a young man with a large retroperitoneal seminoma. A simple water bath system and commonly available ultrasound equipment are used to provide high resolution scans and excellent patient acceptance.


Priorities and practicalities of prescribing diabetes medicines with cardiovascular and renal protective effects: an Australian perspective.
Recent cardiovascular safety trials on sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated the significant cardiovascular and renal benefits of these medications. Diabetes organisations have revised their medication guidelines to include a focus on disease outcomes for cardiovascular disease, heart failure and renal disease. This article summarises latest evidence, guideline recommendations and current Australian Pharmaceutical Benefits Scheme requirements.


Synchronous colorectal cancer and abdominal aortic aneurysm treated simultaneously. Is a one-stage surgery a feasible treatment?
The finding of synchronous abdominal aortic aneurysm and colorectal cancer is rare. There is no consensus on which is the best surgical approach, so its management remains uncertain. A 64-year-old man was diagnosed with synchronous abdominal aortic aneurysm and rectal cancer. One-stage treatment was performed: He underwent endovascular aortic repair followed by simultaneous laparoscopic tumor resection. In our experience, one-stage minimally invasive surgery could be a safe and feasible treatment for concomitant abdominal aortic aneurysm and colorectal cancer.


A two-staged classifier to reduce false positives: On device detection of atrial fibrillation using phase-based distribution of poincaré plots and deep learning.
Mobile Cardiac Outpatient Telemetry (MCOT) can be used to screen high risk patients for atrial fibrillation (AF). These devices rely primarily on algorithmic detection of AF events, which are then stored and transmitted to a clinician for review. It is critical the positive predictive value (PPV) of MCOT detected AF is high, and this often leads to reduced sensitivity, as device manufacturers try to limit false positives. The purpose of this study was to design a two stage classifier using artificial intelligence (AI) to improve the PPV of MCOT detected atrial fibrillation episodes whilst maintaining high levels of detection sensitivity. A low complexity, RR-interval based, AF classifier was paired with a deep convolutional neural network (DCNN) to create a two-stage classifier. The DCNN was limited in size to allow it to be embedded on MCOT devices. The DCNN was trained on 491,727 ECGs from a proprietary database and contained 128,612 parameters requiring only 158 KB of storage. The performance of the two-stage classifier was then assessed using publicly available datasets. The sensitivity of AF detected by the low complexity classifier was high across all datasets (>93%) however the PPV was poor (<76%). Subsequent analysis by the DCNN increased episode PPV across all datasets substantially (>11%), with only a minor loss in sensitivity (<5%). This increase in PPV was due to a decrease in the number of false positive detections. Further analysis showed that DCNN processing was only required on around half of analysis windows, offering a significant computational saving against using the DCNN as a one-stage classifier. DCNNs can be combined with existing MCOT classifiers to increase the PPV of detected AF episodes. This reduces the review burden for physicians and can be achieved with only a modest decrease in sensitivity.


Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer.
Radiation is known to induce DNA damage resulting in the onset of apoptosis. The apoptosis is modulated by p53, Bcl2 and Bax proteins. High level of wild type p53 is required for radiation induced apoptosis. The p53 status, therefore, may be a crucial determinant of radiosensitivity of tumor cells. Overexpression of Bcl2, however, inhibits apoptosis via hetero- and homodimeric interaction. Bax might function as a cell death effector molecule that is neutralized by Bcl2. The aim of the present study is to investigate the correlation between p53, Bcl2, Bax and c-myc levels and the clinical response of head and neck cancer patients to radiation. The base line and 30 GY gamma radiation induced values of p53, Bcl2, Bax and c-myc were estimated by Western blot in 40 biopsies of head and neck cancers. We found that the radiosensitivity of head and neck cancer patients depends on the ratio of p53, Bcl2 and Bax protein levels. High Bcl2 levels resulted in radioresistance of cancer patients. Overexpression of Bax and c-myc may ensure the radiosensitivity of head and neck cancer patients. Our studies indicate that prediction of radiation sensitivity of tumors could be based on the simultaneous evaluation of p53, Bax and Bcl2 levels.


Comparison of the immune response in serum and bucco-pharyngeal secretions following immunization by different routes with a live hog cholera virus vaccine (Thiverval strain).
The influence of vaccination route on local and systemic immune response was studied with hog cholera virus vaccine. Kinetics of antibody synthesis in serum and bucco-pharyngeal secretion was observed. Results show that, whatever the vaccination route (intranasal or intramuscular) a good systemic and local immune response were induced and pigs resisted to a virulent challenge. However the highest local immune response was obtained by intranasal vaccination with large vaccine dosage (10(7) P.F.U./pig). After a virulent challenge performed by intranasal route, no clear anamnestic immune response was detected in bucco-pharyngeal secretions.


Refractive Surgery Survey 2001.
In February 2001, a questionnaire on the practice of refractive surgery was sent worldwide to all 8196 members of the American Society of Cataract and Refractive Surgery; 1511 responses (18.4%) were received. Although laser in situ keratomileusis (LASIK) was the most common refractive procedure reported, phakic intraocular lenses, clear lens extraction, and photorefractive keratectomy were also widespread. Nineteen percent of the respondents said they had had refractive surgery, and that group reported performing significantly more procedures than those who had not had a refractive procedure (P < .0001). The most common complication of LASIK was dry eyes, occurring in more than half of the cases in one fourth of the practices; however, only 30% of surgeons said they perform a Schirmer test before surgery. High-volume surgeons reported seeing fewer cases of flap striae (P = .002) and slipped flaps (P = .02) than low-volume surgeons. Seventy-seven percent said that wavefront LASIK ablation will increase the quality of vision and of those already performing wavefront ablation, 92% stated they believe it will improve outcomes.


Segmenting renal whole slide images virtually without training data.
Digital pathology is a field of increasing interest and requires automated systems for processing huge amounts of digital data. The development of supervised-learning based automated systems is aggravated by the fact that image properties can change from slide to slide. In this work, the focus is on the segmentation of the glomeruli constituting the most important regions-of-interest in renal histopathology. We propose and investigate a two-stage pipeline consisting of a weakly supervised patch-based detection and a precise segmentation. The proposed methods do not need any previously obtained training data. For adapting and optimizing this model, a kernel two-sample test is applied. For the segmentation stage, unsupervised segmentation methods including level-set and polygon-fitting approaches are adapted, combined and evaluated. Overall, with the best performing polygon-fitting segmentation method, 51% of glomeruli were segmented with sufficient accuracy (DSC > 0.8). 42% of the detections were false positives. Due to the difficult application scenario in combination with the small required training corpus, the obtained performance is assessed as good. Strategies for increasing the segmentation performance even further are discussed in detail.


An investigation of the impact of left-censored soil contamination data on the uncertainty of descriptive statistical parameters.
Left-censored concentration data are frequently encountered because measuring instruments cannot detect concentrations below the instrument detection limit. For statistical analysis of left-censored data, the environmental literature mainly refers to the following methods: maximum likelihood estimator, regression on order statistics using log-normal and gamma assumption (rROS and GROS, respectively), and Kaplan-Meier. A number of simulation experiments examined the performance of these methods in terms of bias and/or mean square error. However, no matter which method is adopted, some uncertainty is introduced into outcomes because all that is known about a left-censored observation is that the concentration falls between 0 and the detection limit. The data used in the present study come from analysis of soil samples collected for a site characterization in Montreal, Canada. Employing nonparametric bootstrap, the authors quantify the uncertainty and bias in the mean and standard deviation estimates obtained by the maximum likelihood estimation (under log-normal, Weibull, and gamma distributions), rROS, GROS, and Kaplan-Meier methods. First, the authors demonstrate that the highest uncertainty is associated with the maximum likelihood estimator under log-normality and Weibull assumptions, whereas a gamma assumption leads to estimates with less uncertainty. Second, the authors show that although an increase in sample size improves the uncertainty, it reduces the bias only in the rROS, GROS, and Kaplan-Meier methods. Finally, comparing percentage uncertainty in the mean of contaminant data, the authors illustrate that adopting an inappropriate estimator results in large uncertainties. Environ Toxicol Chem 2016;35:2623-2631. © 2016 SETAC.


Corrigendum to 'Health-Promoting Lifestyle in Colorectal Cancer Survivors: A Qualitative Study on the Experiences and Perspectives of Colorectal Cancer Survivors and Healthcare Providers' [Asia-Pacific J Oncol Nursing 8 (2021) 696-710].
[This corrects the article DOI: 10.4103/apjon.apjon-2132.].


Harmful algae and pressure-impact relationship: Noxious blooms and toxic microalgae occurrence from coastal waters of the Apulia region (Adriatic and Ionian Seas, Mediterranean).
The spatial distribution of harmful microalgal taxa along the coasts of the Apulia region (Mediterranean Sea) based on results of eight years (2012-2019) of routine monitoring program and a series of sporadic observations is presented. A total number of 69 potentially harmful taxa were found during the study period. Occurrence, abundance and richness of harmful taxa (toxic, potentially toxic and high biomass producers) varied along the Apulian coasts. The occurrence of harmful species was significantly higher where most of anthropogenic pressures overlap than only a few or no pressures existed. The physical alteration of coast is the most important pressure determining this pattern. Despite the variety and the abundances of the harmful microalgae, to our knowledge, no human health problems or risks have been ever recorded, nor were full-blown consequences on marine organisms such as fish kills during algal blooms. However, blooms coupled with water discoloration phenomena could become a big issue to tourism and recreational activities that have locally important socio-economic value.


Spurious cross-reactions between plant viruses and monoclonal antibodies can be overcome by saturating ELISA plates with milk proteins.
It has been claimed recently [Dietzgen (1986) Arch Virol 91: 163-173] that a series of monoclonal antibodies (Mabs) produced against the nepovirus, arabis mosaic virus (ArMV) cross-reacted with the tobamovirus, tobacco mosaic virus (TMV). In the present report, this alleged cross-reactivity was re-examined by two ELISA procedures using Mabs produced against each of the two viruses. It was found that when highly concentrated preparations of Mabs were used, all antibodies reacted in a nonspecific manner with several plant viruses. However, when defatted milk instead of bovine serum albumin was used both as blocking agent and as diluent for the Mabs, the spurious cross-reactions between unrelated viruses were abolished. The use of milk as blocking agent did not prevent the detection of genuine cross-reactions between related nepoviruses.


The impact of low-threshold methadone maintenance treatment on mortality in a Canadian setting.
Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the setting's universal medical insurance plan. Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with time-dependent variables. Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1-3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR]=0.73, 95% CI: 0.61-0.88). While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use.


Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice.
Many clinical studies have shown that low humidity has a deleterious effect on skin, but the mechanisms involved are poorly understood. To clarify the changes that occur in skin, we examined epidermal cell proliferation in mice kept in a dry (relative humidity < 10%) or a moist (relative humidity > 90%) environment. In animals exposed to low humidity, epidermal DNA synthesis started to increase within 12 h, reaching twice the original level, and the increased level was maintained for up to 5 days. The transepidermal water loss (TEWL) of mice kept for 12 h in the dry environment was the same as that of mice kept in the moist environment, but the skin conductance was lower. The increase in epidermal DNA synthesis following exposure to the dry environment was inhibited by topical application of petrolatum. It is concluded that loss of water from the stratum corneum induces epidermal cell proliferation within 12 h, and this change occurs in the absence of apparent cutaneous barrier dysfunction.


pH-dependent rearrangement determines the iron-activation and antitumor activity of artemisinins.
The action mechanisms of artemisinins remains elusive for decades, and one long-standing question is whether the indispensable peroxide group is activated by iron or heme. Although heme usually reacts faster with artemisinins than iron does, we have found that rearrangement of dihydroartemisinin (DHA) into monoketo-aldehyde-peroxyhemiacetal (MKA) under physiological conditions can significantly enhance its reaction towards iron. The rearrangement is pH-dependent and the derived MKA is identified by LC-MS in the cellular metabolites of DHA in cancer cells. MKA reacts quickly with ferrous irons to afford reactive carbon-centered radicals and can inhibit enzyme activities in vitro. Moreover, MKA oxidizes ferrous irons to ferric irons, which may explain the effect of DHA on decreasing cellular labile iron pool (LIP). Both addition of exogenous iron and increase in LIP via triggering ferroptosis can enhance the cytotoxicity of DHA against cancer cells. While artesunate (ATS) can also decompose to MKA after hydrolyzing into DHA, the other artemisinins of lower antitumor activity, e.g. artemisinin (ART), artemether (ATM) and arteether (ATE), exhibit negligible hydrolysis and rearrangement under the same conditions. Our study reveals the vital role of molecular rearrangement to the activation and activity of artemisinins and provides a new strategy for designing antitumor molecules containing endoperoxide group.


Does ophthalmic-grade silicone oil possess antimicrobial properties?
To test the antimicrobial properties of silicon oil (Aurosil 1000 cSt, Aurosil Plus 5000 cSt) on in vitro growth of common microorganisms causing endophthalmitis. Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, multi-drug resistant (MDR) strain of Klebsiella pneumoniae, Escherichia coli, Candida albicans, and Aspergillus flavus were prepared to 0.5 McFarland turbidity. The bacteria and fungi were inoculated into the silicone oils, brain heart infusion (BHI) broth for bacteria and Sabouraud dextrose agar (SDA) broth for fungi, respectively, and cultured aerobically for 30 days. From each sample, 10 μl was plated onto nutrient agar and potato dextrose agar (PDA) for testing growth of bacteria and fungi respectively. Cultures from specimens, overnight incubation, and CFU counting were repeated on days 1, 3, 5, 7, 14, 21, 24, and 30. Negative controls were brain heart infusion and physiologic saline as well as silicone oils without any inoculations. All bacteria showed a decrease in CFUs by the fifth day and eliminated between 21 and 30 days in silicone oil. The silicon oil, irrespective of its viscosity, had only fungistatic effect up to 30 days. Colony-forming units of microorganisms remained stable in physiologic saline during the study. In BHI and Sabouraud broth, both bacteria and fungi showed a growth pattern that was compatible with the growth curve of microorganisms. Medical-grade silicone oil used in ophthalmology exhibited in vitro bactericidal and fungistatic activity over 30 days. Insertion of silicone oil in vitrectomy for endophthalmitis, when required, could supplement the antimicrobial activities of intravitreal antibiotics in management of endophthalmitis.


The yeast RER2 gene, identified by endoplasmic reticulum protein localization mutations, encodes cis-prenyltransferase, a key enzyme in dolichol synthesis.
As an approach to understand the molecular mechanisms of endoplasmic reticulum (ER) protein sorting, we have isolated yeast rer mutants that mislocalize a Sec12-Mfalpha1p fusion protein from the ER to later compartments of the secretory pathway (S. Nishikawa and A. Nakano, Proc. Natl. Acad. Sci. USA 90:8179-8183, 1993). The temperature-sensitive rer2 mutant mislocalizes different types of ER membrane proteins, suggesting that RER2 is involved in correct localization of ER proteins in general. The rer2 mutant shows several other characteristic phenotypes: slow growth, defects in N and O glycosylation, sensitivity to hygromycin B, and abnormal accumulation of membranes, including the ER and the Golgi membranes. RER2 and SRT1, a gene whose overexpression suppresses rer2, encode novel proteins similar to each other, and their double disruption is lethal. RER2 homologues are found not only in eukaryotes but also in many prokaryote species and thus constitute a large gene family which has been well conserved during evolution. Taking a hint from the phenotype of newly established mutants of the Rer2p homologue of Escherichia coli, we discovered that the rer2 mutant is deficient in the activity of cis-prenyltransferase, a key enzyme of dolichol synthesis. This and other lines of evidence let us conclude that members of the RER2 family of genes encode cis-prenyltransferase itself. The difference in phenotypes between the rer2 mutant and previously obtained glycosylation mutants suggests a novel, as-yet-unknown role of dolichol.


Methyl isobutyl ketone metabolites and potentiation of the cholestasis induced in rats by a manganese-bilirubin combination or manganese alone.
Methyl isobutyl ketone (MIBK) has recently been shown to potentiate the cholestasis induced by manganese-bilirubin (Mn-BR) or manganese (Mn) in rats. In this study, we investigated the effect of 4-methyl-2-pentanol (4MPOL) and 4-hydroxymethyl isobutyl ketone (4-OHMIBK), two major metabolites of MIBK, on these models of cholestasis. Dosages varying from 1.88 to 15 mmol/kg 4MPOL or 4-OHMIBK were administered once, 18 hr prior to the administration of a cholestatic Mn-BR combination. The cholestatic effect of the manganese-bilirubin combination was enhanced with dosages of 4MPOL of 3.75 mmol/kg and larger. On the other hand, dosages smaller than 15 mmol/kg of 4-OHMIBK did not potentiate the Mn-BR cholestasis. Daily pretreatment for 3 days resulted in an increased response to the cholestatic challenges of either Mn-BR or Mn alone. 4MPOL administered repetitively was a better potentiator than 4-OHMIBK with the Mn-BR model of cholestasis. However, with Mn alone, 4-OHMIBK proved to be more effective. 4MPOL and 4-OHMIBK per se were devoid of cholestatic properties, since the bile flow measured prior to the cholestatic challenge was not decreased and in some cases was significantly greater than that of vehicle-pretreated animals. These results show that MIBK metabolites can potentiate the cholestatic form of hepatotoxicity.


A comprehensive insight into binding of hippuric acid to human serum albumin: a study to uncover its impaired elimination through hemodialysis.
Binding of hippuric acid (HA), a uremic toxin, with human serum albumin (HSA) has been examined by isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), molecular docking, circular dichroism (CD) and fluorescence spectroscopy to understand the reason that govern its impaired elimination through hemodialysis. ITC results shows that the HA binds with HSA at high (K b ~10(4)) and low affinity (K b ~10(3)) sites whereas spectroscopic results predict binding at a single site (K b~10(3)). The HA form complex with HSA that involves electrostatic, hydrogen and hydrophobic binding forces as illustrated by calculated thermodynamic parameters. Molecular docking and displacement studies collectively revealed that HA bound to both site I and site II; however, relatively strongly to the later. Esterase-like activity of HSA confirms the involvement of Arg410 and Tyr411 of Sudlow site II in binding of HA. CD results show slight conformational changes occurs in the protein upon ligation that may be responsible for the discrepancy in van't Hoff and calorimetric enthalpy change. Furthermore, an increase in T(1)(m) and T(2)(m) is observed from DSC results that indicate increase in stability of HSA upon binding to HA. The combined results provide that HA binds to HSA and thus its elimination is hindered.


Kanamycin acetyltransferase gene from kanamycin-producing Streptomyces kanamyceticus IFO 13414.
A kanamycin producer, Streptomyces kanamyceticus IFO 13414 is highly resistant to kanamycin. Cloning of the kanamycin resistance genes in S. lividans 1326 with pIJ702 gave several kanamycin resistant transformants. Two transformants, S. lividans SNUS 90041 and S. lividans SNUS 91051 showed similar resistance patterns to various aminoglycoside antibiotics. Gene mapping experiments revealed that plasmids pSJ5030 and pSJ2131 isolated from the transformants have common resistant gene fragments. Subcloning of pSJ5030 gave a 1.8 Kb gene fragment which showed resistance to kanamycin. Cell free extracts of S. lividans SNUS 90041, S. lividans SNUS 91051 and subclone a S. lividans SNUS 91064 showed kanamycin acetyltransferase activity. The detailed gene map is included.


Analysis of RNA-Protein Interaction Networks Using RNP-MaP.
RNA-protein interactions regulate a myriad of biological functions through formation of ribonucleoprotein complexes. These complexes may consist of one or more RNA-protein interaction network(s) providing additional layers of regulatory potential to the RNA. Moreover, since the protein-binding also regulates local and global structure of the RNA by structurally remodeling the latter, it is important to correlate RNA nucleotide flexibility with the site of protein-binding. We have discussed methods for chemical probing of structure of the RNA in the protein-free and protein-bound states in the preceding chapters. In this chapter, we describe a ribonucleoprotein mutational profiling (RNP-MaP) method for probing RNA-protein interaction networks.


Estimation of the flow rate of pyrolysis gasoline, ethylene, and propylene in an industrial olefin plant using machine learning approaches.
Light olefins, as the backbone of the chemical and petrochemical industries, are produced mainly via steam cracking route. Prediction the of effects of operating variables on the product yield distribution through the mechanistic approaches is complex and requires long time. While increasing in the industrial automation and the availability of the high throughput data, the machine learning approaches have gained much attention due to the simplicity and less required computational efforts. In this study, the potential capability of four powerful machine learning models, i.e., Multilayer perceptron (MLP) neural network, adaptive boosting-support vector regression (AdaBoost-SVR), recurrent neural network (RNN), and deep belief network (DBN) was investigated to predict the product distribution of an olefin plant in industrial scale. In this regard, an extensive data set including 1184 actual data points were gathered during four successive years under various practical conditions. 24 varying independent parameters, including flow rates of different feedstock, numbers of active furnaces, and coil outlet temperatures, were chosen as the input variables of the models and the outputs were the flow rates of the main products, i.e., pyrolysis gasoline, ethylene, and propylene. The accuracy of the models was assessed by different statistical techniques. Based on the obtained results, the RNN model accurately predicted the main product flow rates with average absolute percent relative error (AAPRE) and determination coefficient (R2) values of 1.94% and 0.97, 1.29% and 0.99, 0.70% and 0.99 for pyrolysis gasoline, propylene, and ethylene, respectively. The influence of the various parameters on the products flow rate (estimated by the RNN model) was studied by the relevancy factor calculation. Accordingly, the number of furnaces in service and the flow rates of some feedstock had more positive impacts on the outputs. In addition, the effects of different operating conditions on the propylene/ethylene (P/E) ratio as a cracking severity factor were also discussed. This research proved that intelligent approaches, despite being simple and straightforward, can predict complex unit performance. Thus, they can be efficiently utilized to control and optimize different industrial-scale units.


Combining impregnation and co-pyrolysis to reduce the environmental risk of biochar derived from sewage sludge.
Sewage sludge derived biochar has great potential for agricultural application, whereas the risk of heavy metals in sewage sludge is a key challenge for utilization. This study investigated the synergetic effect of co-pyrolysis and ZnCl2 impregnation treatment on the surface characteristics and potential ecological risk of heavy metals in sewage sludge derived biochar. It was concluded that ZnCl2 impregnation led to an increase in biochar yield, O and S content, but decrease the ash content and pH. Additionally, the thermal stability of ZnCl2-added biochar was decreased. Semi-quantitive specific functional groups analysis suggested that ZnCl2 impregnation had a negative effect on the content of CO and C-O, while promoted the formation of aromatic CC. And the functional group of CO was retained in biochar by co-pyrolysis with Camellia oleifera shell due to its high content of potassium. For heavy metal passivation, ZnCl2 impregnation decreased total content of heavy metals by chlorination, while the oxidizable fraction (F3) of heavy metals showed an increasing tendency. Results of potential ecological risk assessment indicated that combining ZnCl2 impregnation and co-pyrolysis had great potential to reduce the ecological risk of heavy metals in sewage sludge derived biochar.


The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis.
Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH-RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti-UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by which the different antibody isotypes act still have to be unraveled.


Global research trends on epigenetics and neuropathic pain: A bibliometric analysis.
Neuropathic pain (NP) is a common disease that manifests with pathological changes in the somatosensory system. In recent years, the interactions of NP with the epigenetic mechanism have been increasingly elucidated. However, only a few studies have used bibliometric tools to systematically analyze knowledge in this field. The objective of this study is to visually analyze the trends, hotspots, and frontiers in epigenetics and NP research by using a bibliometric method. Studies related to epigenetics and NP were searched from the Science Citation Index-Expanded of the Web of Science Core Collection database. Search time is from inception to November 30, 2022. No restrictions were placed on language. Only articles and reviews were included as document types. Data on institutions, countries, authors, journal distribution, and keywords were imported into CiteSpace software for visual analysis. A total of 867 publications met the inclusion criteria, which spanned the period from 2000 to 2022. Over the years, the number of publications and the frequency of citations exhibited a clear upward trend in general, reaching a peak in 2021. The major contributing countries in terms of the number of publications were China, the United States, and Japan. The top three institutions were Rutgers State University, Xuzhou Medical University, and Nanjing Medical University. Molecular Pain, Pain, and Journal of Neuroinflammation contributed significantly to the volume of issues. Among the top 10 authors in terms of the number of publications, Tao Yuan-Xiang contributed 30 entries, followed by Zhang Yi with 24 and Wu Shao-Gen with 20. On the basis of the burst and clusters of keywords, "DNA methylation," "Circular RNA," "acetylation," "long non-coding RNA," and "microglia" are global hotspots in the field. The bibliometric analysis indicates that the number of publications related to epigenetics and NP is exhibiting a rapid increase. Keyword analysis shows that "DNA methylation," "Circular RNA," "acetylation," "long non-coding RNA" and "microglia" are the most interesting terms for researchers in the field. More rigorous clinical trials and additional studies that explore relevant mechanisms are required in the future.


Selection of mitotic Chinese hamster ovary cells from microcarriers. Cell cycle-dependent induction of mutation by 5-bromo-2'-deoxyuridine and ethyl methanesulfonate.
Large quantities of mitotic cells may be collected by mitotic detachment from a population of Chinese hamster ovary cells growing on positively charged dextran microcarriers in suspension culture. Exponentially growing cells are treated for 2.5 h with colcemid and mitotic cells are detached from the microcarriers by increasing the stirring speed. A yield of 4-6% of the total population is obtained and, of the cells collected, 85-95% are arrested in metaphase. Using this means to synchronize cells we have determined the cell cycle dependence of the toxic and mutagenic effects of 5-bromo-2'-deoxyuridine (BUdR) and ethyl methanesulfonate (EMS). Mutation was measured at two independent loci: resistance to 6-thioguanine and resistance to ouabain. Both mutagens were more toxic during S phase as compared to G1 or G2 or mitosis. BUdR induced significant mutation only during S phase. The maximum induction of 6-thioguanine resistance was observed in cultures treated 10 h after plating of mitotic cells (2 h into S phase), while the maximum induction of ouabain resistance was observed in cultures treated 10-12 h after plating of mitotic cells (2-4 h into S phase). EMS induced significant mutation at all points in the cell cycle. Mutation induction reached a minimum during S phase but the magnitude of difference between any two points in the cell cycle was found to be less than two-fold.


Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis.
The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.


Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4.
The antiviral activity of UV-4 was previously demonstrated against dengue virus serotype 2 (DENV2) in multiple mouse models. Herein, step-wise minimal effective dose and therapeutic window of efficacy studies of UV-4B (UV-4 hydrochloride salt) were conducted in an antibody-dependent enhancement (ADE) mouse model of severe DENV2 infection in AG129 mice lacking types I and II interferon receptors. Significant survival benefit was demonstrated with 10-20 mg/kg of UV-4B administered thrice daily (TID) for seven days with initiation of treatment up to 48 h after infection. UV-4B also reduced infectious virus production in in vitro antiviral activity assays against all four DENV serotypes, including clinical isolates. A set of purified enzyme, in vitro, and in vivo studies demonstrated that inhibition of endoplasmic reticulum (ER) α-glucosidases and not the glycosphingolipid pathway appears to be responsible for the antiviral activity of UV-4B against DENV. Along with a comprehensive safety package, these and previously published data provided support for an Investigational New Drug (IND) filing and Phases 1 and 2 clinical trials for UV-4B with an indication of acute dengue disease.


Alternative splicing of exons 29 and 30 in the neurofibromatosis type 1 gene.
Alternative splicing of exons 29 and 30 of the human neurofibromatosis type 1 (NF1) gene was detected by reverse transcription/polymerase chain reaction (RT-PCR). Three different isoforms that omitted either one or both exons were identified (ex29-, ex30-, and ex29/30-). The alternatively spliced transcripts exhibited tissue-specific differences, with the ex30- variant apparent only in brain. All three isoforms altered the reading frame and introduced a stop codon in the adjacent downstream exon. Alternative splicing of this region of the NF1 gene also was detected in RNA from rats, although only the ex30- variant was observed. RNA from mice revealed only constitutive expression in this region of the NF1 gene. This study adds a new site of alternative processing to the complex expression of NF1.


Children as voices and images for medicinal cannabis law reform.
This article situates the movement for the legalisation of medicinal cannabis within the bigger picture of the impetus toward recreational cannabis legalisation. It describes the role played by children with epileptic syndromes in the medicinal cannabis law reform campaigns in the United Kingdom, and Queensland, New South Wales and Victoria in Australia. Noting the 'rule of rescue' and the prominence in media campaigns of children in Australian and English cases of parental disputation with clinicians about treatment for their children, it reviews whether paediatric epilepsy is a suitable test case for the legalisation of medicinal cannabis. Taking into account the vested commercial interests of Big Cannabis, the current medico-scientific knowledge of the efficacy of medicinal cannabis in controlling paediatric epileptic seizures, and issues of dignity, health privacy, and the enduring digital footprints of media coverage, the article commences discussion about the ethics of the media, parents, politicians and entrepreneurial doctors utilising parents' testimonials about the effects of medicinal cannabis as part of the cannabis law reform movement.


Contralateral cervical seventh nerve transfer for spastic arm paralysis via a modified prespinal route: a cadaveric study.
We proposed contralateral cervical seventh nerve transfer for spastic arm paralysis after central neurological injury in the New England Journal of Medicine (NEJM) in 2018. In this surgery, we applied a new surgical route for nerve transfer, the Huashan prespinal route. The objective of this study was to elaborate our new surgical technique, clarify its relationship to the vertebral artery, and provide anatomical data on this novel method. The effectiveness and safety of the Huashan prespinal route in contralateral C7 nerve transfer were evaluated anatomically. Nine cadavers (4 males, 5 females) were available for this study. Among these, anatomical parameters of the vertebral artery were obtained from 6 cadavers, and the anastomosis of the bilateral cervical seventh nerve was observed on 3 cadavers undergoing contralateral C7 nerve transfer via the Huashan prespinal route. Tension-free anastomosis of the bilateral cervical seventh nerve was achieved through the Huashan prespinal route. The tilt angle of the vertebral artery to the sagittal plane (with thyroid cartilage as the origin) was 25.5 ± 4.5°, at 22.5 ± 1.6° and 28.7 ± 4.3° on the left and right side, respectively. The safe drilling angle to penetrate through the longus colli muscles for the creation of a longus colli muscle tunnel to avoid injury to the vertebral artery in our surgical technique was above 33.2°. The cadaveric study confirms that the presented technique allowed simple, effective, and safe contralateral C7 nerve transfer. This technique can be used in the treatment of hemiplegia and brachial plexus injury. There is a safe scope of drilling angle for creating the longus colli muscle tunnel required for this surgical route. The anatomical parameters obtained in this study will be helpful for the performance of this operation.


Correction to: Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.
Following publication of the original article [1], the authors have reported that the following sentence "While of the same IgG1 class as ipilimumab, preclinical data suggests this molecule may have enhanced activity against T regulatory cells".


Prevalence and characteristics of symptomatic and asymptomatic tuboovarian masses in women with HIV: an ultrasonographic study.
HIV-positive women with pelvic inflammatory disease have been reported to have an increased prevalence of tuboovarian masses (TOMs). The aim of this study was to assess the prevalence of asymptomatic ultrasonographic TOMs in women with HIV and to identify associated factors in order to formulate a selective ultrasonographic screening strategy. Two-hundred and four HIV outpatients underwent transvaginal ultrasonography. Eight (3.9%) had a diagnosis of TOM (5 were asymptomatic). Two profiles of patients at risk for TOM were identified who could be considered for selective screening strategies: the 'long-term infected' (age>35 years, diagnosis of HIV infection more than 5 years ago, HIV clinical category C, CD4 counts below 200/mm(3), >5 lifetime partners and on antiretroviral therapy) and the 'recently diagnosed with HIV' (African ethnicity, age 25-35, HIV diagnosis in the previous year, >5 lifetime partners, HIV clinical category C and not on antiretroviral therapy).


Comparison of upper airway collapse during general anaesthesia and sleep.
Measurement of the collapsibility of the upper airway while a patient is awake is not a good guide to such collapsibility during sleep, presumably because of differences in respiratory drive, muscle tone, and sensitivity of reflexes. To assess whether a relation existed between general anaesthesia and sleep, we measured collapsibility of the upper airway during general anaesthesia and severity of sleep-disordered breathing in 25 people who were having minor surgery on their limbs. Anaesthetised patients who needed positive pressure to maintain airway patency had more severe sleep-disordered breathing than did those whose airways remained patent at or below atmospheric pressure. Such an association was strongest during rapid-eye-movement (REM) sleep. Our findings suggest that sleep-disordered breathing should be considered in all patients with a pronounced tendency for upper airway obstruction during anaesthesia or during recovery from it.


Inhalation challenge testing of latex-sensitive health care workers and the effectiveness of laminar flow HEPA-filtered helmets in reducing rhinoconjunctival and asthmatic reactions.
There are few data relating latex aeroallergen concentrations to biologic responses in latex-sensitized persons. We sought to investigate acceptable latex aeroallergen concentrations below which latex-sensitive health care workers do not experience symptoms and to study the effect of high-efficiency particle arrest (HEPA)-filtered laminar flow helmets in preventing latex-induced symptoms. Under challenge chamber conditions, latex-sensitive health care workers underwent 7 sequential inhalation challenge tests by donning and discarding either vinyl gloves (challenge 1), low latex-allergen powder-free gloves (challenge 2), or high latex-allergen powdered gloves (challenges 3 to 7) for up to 1 hour. Volunteers wore a laminar flow helmet during all challenges; HEPA filters in the helmet were in place only during challenges 3 and 4. Flow-volume loops, symptom scores, and latex aeroallergen concentrations were measured before and during each test. At 60 minutes, latex aeroallergen concentrations during challenges 3 to 7 (mean, 7600 ng/m3; range, 93 to 54,000 ng/m3 ) were significantly higher than during challenges 1 or 2 (mean, 65 ng/m3; range, nondetectable to 100 ng/m3 ) (P <.001). During challenges 5 and 6, mean maximum percent falls in FEV1 (-16% and -11%, respectively) were significantly greater compared with those measured during challenges 3 and 4 (-3% and -1%, respectively) (P =.03). Mean maximum change from baseline symptom scores during challenges 5 and 6 was significantly higher than that during challenges 3 and 4 (P =.006). During challenges with high latex-allergen gloves, 4 volunteers had reproducible FEV1 falls of 20% or greater at cumulative inhaled latex aeroallergen doses ranging from less than 100 ng to 1500 ng. The laminar flow helmets were effective in reducing latex-induced symptoms. Only 1 volunteer exhibited a fall in FEV1 of 20% or greater after a cumulative inhaled latex aeroallergen dose of less than 100 ng, and no volunteer showed a decline in FEV1 after exposure to powder-free low allergen gloves.


The Winners and the Losers: Tax Incidence of Gambling in Finland.
Gambling markets have grown rapidly for the last few decades. As a result, gambling is also a very important and common source of tax income for many governments these days. This raises a question about the overall fairness of the gambling taxation systems. In this paper, we aim to study the tax incidence of gambling in Finland. First, we analyse who are the expected payers of the gambling taxes and second, who are expected to be the receivers of the gambling-tax based contributions. In the first part of the study, we analyse the demographic incidence of gambling taxation by using the Finnish gambling 2015 population survey combined with registry based variables. Our data contains 3776 individuals. In the second part of the study, we use data of county level gambling-taxation based contributions to different organisations to analyse how the gambling expenditures are distributed back to citizens in a form of public spending. This study shows that different socio-demographic factors have diverse association with the decisions whether or how much to gamble. The results also suggest that more disadvantaged, i.e. lower income, less educated and rural area living, individuals are expected to be the "losers" of the Finnish gambling taxation system. In other words, the Finnish gambling system is found to be regressive by nature.


Development of a Communication Tool for Handoffs Involving Patients Cared for by Sitters: An Evidence-Based Practice Project.
Communication has been found to be central to patient safety and colleague engagement. Poor communication was identified in a Level III trauma hospital in the midwestern US between "sitters" (staff members assigned to monitor patients identified as having safety concerns) and the nurses assigned to care for those patients, including lack of a formal handoff process. A Patient/Problem, Intervention, Comparison, Outcome (PICO) statement guided an evidence-based project and identification of an intervention to improve the handoff process. Using the evidence-based format of Situation/Background/Assessment/Recommendation (SBAR), a Patient Safety Attendant Handoff Form was developed and implemented. Initially, Registered Nurses (RNs), Licensed Practical Nurses (LPNs), or Certified Nursing Assistants (CNAs) were used as sitters, taking them away from other responsibilities. A formal position, Patient Safety Attendant (PSA), was created to perform the sitter role. The Patient Safety Attendant Handoff tool was made an official hospital form and implemented as a new standard of practice. Analysis of data from completed forms identified the top reasons for assigning a sitter were mental health and behavioral concerns. In a six-month post-implementation survey, most PSAs reported receiving adequate information about the patients during handoffs using the new form. Using SBAR for the Patient Safety Attendant Handoff Form improved communication between RNs and PSAs and also enhanced communication between PSAs. A key safety feature of the form is the Recommendation section which includes "triggers to avoid," de-escalation techniques, and things the patient enjoys. Developing a structural model from the aggregated data on the completed forms helped in analyzing the information.


Micronodular cirrhosis after thiabendazole.
Hepatotoxicity secondary to the administration of thiabendazole has been rare since this drug was produced in 1964. In 14 of 15 patients reported previously in the literature, severe intrahepatic cholestasis resolved within seven months of the onset of illness. A recent report documented the progression to cirrhosis in a 15th patient. We report the second case of a patient with intrahepatic cholestasis that developed after treatment with thiabendazole and progressed to severe micronodular cirrhosis.


A scoring system for the preoperative evaluation of prognosis in spinal infection: the MSI-20 score.
Spinal infection (SI) is a life-threatening condition and its treatment remains challenging. Recent studies have supported early and aggressive surgery, but mortality still reaches 5% to 10% and it remains unclear, if an aggressive surgical strategy also applies for severely sick patients. The aim of this analysis was to generate an assessment score to predict mortality of SI in order to facilitate decision-making. Retrospective risk factor analysis. Two hundred fifty-two patients were retrospectively analyzed. Physiologic measures, functional measures. Diagnosis was based on clinical presentation, imaging findings and inflammatory markers. Factors associated with mortality were identified by multivariate analysis, weighted according to their relative risk ratio (RR) and included in the novel assessment score. Eight parameters were included: (1) BMI, (2) ASA score, (3) presence of sepsis, (4) age-adjusted Charlson Comorbidity Index, (5) presence and degree of renal failure, (6) presence of hepatopathy, (7) neurological deficits and (8) CRP levels at diagnosis. Each parameter was assigned a certain range of points, resulting in a maximum total score of 20. The mortality in spinal infection (MSI-20) score - indicating poorer status with higher values - was obtained for each patient and correlated with mortality. An MSI-20 score of 11 or more points seems to identify the small group of patients being "too sick to undergo surgery," while early surgery can be recommended in the remainder (MSI-20 ≤10). Our results need to be confirmed in prospective studies, but may give guidance for indicating surgery even in rather sick and comorbid patients.


Decolorization and degradation of dyes with mediated fenton reaction.
A mediated Fenton system has been evaluated for decolorization of several types of dyes. The result shows that the Fenton system with a dihydroxybenzoic acid (DHBA) chelator-mediator effectively reduced the color of a diluted solution of Carta Yellow RW liquid, Carta Yellow G liquid, and Cartasol Red 2GF liquid dye to a colorless level after 90 minutes of treatment with 100 microM iron II (Fe[II]), 100 microM DHBA, and 10 mM hydrogen peroxide (H2O2) at room temperature. Our results show that compared to a neat Fenton process, the mediated Fenton decolorization process increased the production, and therefore the effective longevity, of hydroxyl radical (OH) species to increase the decolorization efficiency. Our results suggest that application of this system would also result in an increase in dissolved oxygen (DO) in solution, which in turn would result in reduction of chemical oxygen demand (COD), biochemical oxygen demand (BOD), and total organic carbon (TOC).


Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1.
Circulating tumour cells (CTCs), especially mesenchymal CTCs, are important determinants of metastasis, which leads to most recurrence and mortality in hepatocellular carcinoma (HCC). However, little is known about the underlying mechanisms of CTC colonisation in pre-metastatic niches. Detection and classification of CTCs in patients were performed using the CanPatrol™ system. A lentiviral vector expressing Prrx1-targeting shRNA was constructed to generate a stable HCC cell line with low expression of Prrx1. The effect of Prrx1 knockdown on stemness, migration, and drug resistance of the cell line was assessed, including involvement of SDF-1/CXCR4 signalling. Promising clinical applications of an inhibitor of STAT3 tyrosine phosphorylation, C188-9, and specific blockade with CXCR4 antibody were explored. The number of mesenchymal CTCs in blood was closely associated with tumour recurrence or metastasis. Pre-metastatic niche-derived SDF-1 could downregulate Prrx1, which induced the stemness, drug resistance, and increased expression of CXCR4 in HCC cells through the STAT3 pathway in vitro. In vivo, mice bearing tumours of Prrx1 low-expressing cells had significantly shorter survival. In xenograft tumours and clinical samples, loss of Prrx1 was negatively correlated with increased expression of CXCR4 in lung metastatic sites compared with that in the primary foci. These findings demonstrate that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC.


Whole-brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non-small cell lung cancer: A single-institution study.
To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.


Curcumin Promotes Cell Cycle Arrest and Inhibits Survival of Human Renal Cancer Cells by Negative Modulation of the PI3K/AKT Signaling Pathway.
Curcumin possesses anti-cancer effects. In the current study, we tested the effect of curcumin on cell proliferation, viability, apoptosis, cell cycle phases, and activation of the PI3K/Akt pathway in the renal cell carcinoma (RCC) cell line RCC-949. We observed that cell proliferation and viability were markedly inhibited by curcumin, while cell apoptosis was promoted. The latter effect was associated with increased expression of Bcl-2 and diminished expression of Bax (both: mRNA and protein). The cells treated with curcumin increasingly went into cell cycle arrest, which was likely mediated by diminished expression of cyclin B1, as seen in curcumin-treated cells. In addition, curcumin decreased activation of the PI3K/AKT signaling pathway. In conclusion, our results demonstrate that curcumin exerts anti-cancer effects by negative modulation of the PI3K/AKT signaling pathway and may represent a promising new drug to treat RCC.


Erratum: Therapeutic ultrasound combined with microbubbles improves atherosclerotic plaque stability by selectively destroying the intraplaque neovasculature: Erratum.
[This corrects the article DOI: 10.7150/thno.39553.].


Long-term follow-up of cardiac resynchronization therapy: mechanical resynchronization and reverse left ventricular remodeling are predictive for long-term transplant-free survival.
We sought to determine whether correction of mechanical left ventricular (LV) dyssynchrony as defined by tissue Doppler imaging (TDI) is predictive for transplant-free long-term survival in patients (pts.) undergoing cardiac resynchronization therapy (CRT). In 76 CRT recipients TDI curves from the septal, lateral, anterior, and inferior basal LV were obtained at baseline and after 6 ± 4 months. A time difference between regional electromechanical delays (EMD) of ≥40 ms was considered dyssynchronous. At follow-up, pts. were classified as TDI-responders (TDI-R: dyssynchrony at baseline, corrected by CRT) versus non-responders (TDI-NR: either not dyssynchronous at baseline, or persisting dyssynchrony). Pts. were then followed by standard echocardiography over 21 ± 6 months and were re-classified as LV remodelers (LV-R: LV volume reduction of >10%) versus non-remodelers (LV-NR). The end-point during clinical long-term follow-up of 65 ± 38 months was all-cause mortality or heart transplantation. 44 out of the 76 pts. (58%) were classified as TDI-R, 32 (42%) as TDI-NR. Significant reverse LV remodeling was observed in 41 (54%) pts., while 35 (46%) did not improve LV size and function. TDI-R was associated with LV-R in 35 pts. (85%; P < 0.001). During long-term follow-up, 38 pts. (50%) reached the end point, 11 (30%) in the TDI-R group, and 27 (70%) in the TDI-NR group (P < 0.0003). Mechanical resynchronization as defined by TDI translates into a significant survival benefit in CRT recipients.


ERCP update: diagnostic and therapeutic applications.
Endoscopic retograde cholangiopancreatography (ERCP) is currently utilized to evaluate jaundice, both intra- and extrahepatic, and can differentiate between these by demonstrating specific anatomic lesions. ERCP is definitive in the evaluation of gallbladder disease when other modalities are indefinite. For the first time outside the operating room, the pancreatic duct can be opacified by ERCP. The newest application of ERCP, endoscopic papillotomy (EP), has revolutionized the treatment of common bile duct gallstones and stenosis of the duct, offering a safe and effective alternative to repeated surgery, especially in those patients at risk. Because of these diverse and effective applications, ERCP has become firmly established in our diagnostic armamentarium.


Reduction in bioavailability of 6-mercaptopurine on simultaneous administration with cow's milk.
The authors present a case where the simultaneous administration of 6-mercaptopurine (6-MP) and cow's milk during maintenance treatment for acute lymphoblastic leukemia led to elevated full blood counts resistant to increasing doses of chemotherapy. The blood counts returned to the expected range after milk intake with chemotherapy was discontinued.


The epidemiology of bovine ostertagiasis in the north temperate regions of North America.
Ostertagia ostertagi is widely distributed and is the most pathogenic of the parasitic nematodes affecting cattle in this region. Clinical ostertagiasis is seen mainly in calves and yearlings but outbreaks tend to be sporadic; the subclinical disease is of greater importance. Studies on the population dynamics of the free-living stages have shown that infective larvae can survive on pasture over the relatively severe winter conditions encountered in this region but that such pasture contamination declines during the succeeding grazing season and is lost by midsummer. In the host there is gradual acquisition of worms from pasture over the summer period, with relatively high burdens accumulating in the autumn. A dramatic shift in the proportion of adult to immature worms occurs during the autumn (October). By the time calves are housed, the proportion of larvae (mainly L4) is greater than 80%. This relative distribution of adults to larvae continues through the winter months until early spring when there appears to be a shift to a higher proportion of adults, presumably due to resumption of development of the L4. These persistent L4 stages are considered to be undergoing hypobiosis. Spring infections of calves appear to be mainly acquired from larvae that have successfully overwintered on pasture, and availability of these larvae is drastically reduced by midsummer. There appears to be negligible development of the eggs that result from the spring infections until late summer and early autumn. At this time because of favorable climatic conditions there is rapid larval development which can result in heavy infections in susceptible calves in the autumn.(ABSTRACT TRUNCATED AT 250 WORDS)


Circulating miRNA-181b-5p, miRNA-223-3p, miRNA-210-3p, let 7i-5p, miRNA-21-5p and miRNA-29a-3p in patients with localized scleroderma as potential biomarkers.
Localized scleroderma (LoSc) is a rare disease manifested by an inflammation and sclerosis of the skin. The latest studies focused on glycoprotein Krebs von den Lungen-6, surfactant protein-D, chemokine ligand 18 and dipeptidylpeptidase 4 as potential biomarkers of skin fibrosis in systemic scleroderma. Our study aimed to identify 6 miRNAs with elevated or decreased levels in 38 LoSc patients (31 females, 7 males) compared to healthy volunteers (HVs) and to correlate the selected miRNAs' serum levels with the severity and the clinical symptoms of LoSc and some laboratory parameters with the selected miRNAs' serum levels. The serum levels of miRNAs, i.e. miRNA-181b-5p, miRNA-223-3p, miRNA-21-5p, let 7i-5p, miRNA-29a-3p and miRNA-210-3p were significantly increased in the LoSc patients compared to the HVs. The level of let-7i increase in the female LoSc patients correlated negatively with BSA (r = - 0.355, p = 0.049) and mLoSSI (r = - 0.432, p = 0.015). Moreover, the female patients with inactive LoSc had significantly higher level of let-7i (2.68-fold on average) in comparison to those with active disease (p = 0.045). The exact role of those molecules has not been revealed in LoSc and a long-term longitudinal research is pivotal to confirm their prognostic value.


Satisfaction with antiepileptic drugs in children and adolescents with newly diagnosed and chronic epilepsy.
To assess incidence, indicators and outcome of satisfaction with antiepileptic drugs in children. Multicenter, observational, open, prospective survey of children and adolescents with epilepsy with three-month follow-up. Included were patients aged 3-17 years with newly diagnosed ("new diagnosis") or chronic epilepsy ("old diagnosis") requiring treatment start or change. Satisfaction was assessed with the Hedonic Visual Scale or direct questions, depending on patient's age. Quality of life of adolescents (QOLIE-48) and of caregivers (SF-36) and predictors of (dis)satisfaction were also assessed. 293 patients completed the study. Most had generalized idiopathic epilepsy, and a disease lasting <12 months. Newly diagnosed patients were 60.8%. Patients declaring satisfaction were 70.6% at one month and 75.8% at three months. Compared to old diagnosis, new diagnosis carried a higher satisfaction rate and improved satisfaction at end of follow-up. Independent predictors of dissatisfaction were an old diagnosis, adverse events and SF-36 score. The latter remained the only independent predictor of persisting dissatisfaction when adjusting for the presence of and the interaction with adverse events. About one-fourth of children and adolescents with epilepsy are dissatisfied with treatment. Chronic epilepsy, adverse events, and parents/caregivers with poor quality of life predict dissatisfaction.