Dual-Therapeutics-Loaded Mesoporous Silica Nanoparticles Applied for Breast Tumor Therapy.
A material that possesses high loading efficiency (in terms of delivering small molecular drugs, nucleic acids, peptides, and proteins) has various medical applications, such as in tumor diagnosis and gene therapy or chemotherapy of tumors. Mesoporous silica nanoparticles are ideal nanocarriers for constructing drug delivery systems because of the unique mesoporous channels for encapsulation and the sustainable release of anticancer drugs. Herein, we demonstrate a doxorubicin (DOX)-peptides double-loaded and -response nanodrug (DMK nanoplatforms) as a multifunctional nanoplatform for chemotherapy of tumors. The nanoparticles are prepared by a surface modification strategy. The KLAK and DOX release in an acidic/reductive tumor microenvironment, which efficiently penetrate cell nuclei and generate the antitumor effect. Our study provides a new approach for developing a smart drug delivery nanosystem, particularly for peptides-guided pH-sensitive chemotherapy.


Evidence-Based Musculoskeletal Care for Swimmers: A Critical Analysis Review.
Swimming is a popular activity with numerous health benefits. Swimming involves complex biomechanical movements that, especially if performed incorrectly, can lead to musculoskeletal injuries. The shoulder is the most commonly affected joint, although lower-extremity and spine injuries have also been reported.


The neurophysiology of continuous action monitoring.
Monitoring actions is essential for goal-directed behavior. However, as opposed to short-lasting, and regularly reinstating monitoring functions, the neural processes underlying continuous action monitoring are poorly understood. We investigate this using a pursuit-tracking paradigm. We show that beta band activity likely maintains the sensorimotor program, while theta and alpha bands probably support attentional sampling and information gating, respectively. Alpha and beta band activity are most relevant during the initial tracking period, when sensorimotor calibrations are most intense. Theta band shifts from parietal to frontal cortices throughout tracking, likely reflecting a shift in the functional relevance from attentional sampling to action monitoring. This study shows that resource allocation mechanisms in prefrontal areas and stimulus-response mapping processes in the parietal cortex are crucial for adapting sensorimotor processes. It fills a knowledge gap in understanding the neural processes underlying action monitoring and suggests new directions for examining sensorimotor integration in more naturalistic experiments.


Patient- and Nutrition-Derived Outcome Risk Assessment Score as a Predictor of Mortality in Critically Ill Surgical Patients: A Retrospective, Single-Center Observational Study.
The Patient- And Nutrition-Derived Outcome Risk Assessment (PANDORA) was recently validated for predicting mortality in hospitalized patients; however, its utility in the intensive care unit (ICU) remains unknown. We investigated whether PANDORA is associated with 30, 90, and 180 day mortality in critically ill surgical patients by performing logistic regressions, controlling for age, sex, race, body mass index, macronutrient deficit, and length of stay. The area under the receiver operating characteristic curves (AUC) of PANDORA vs Acute Physiology and Chronic Health Evaluation (APACHE) II scores for mortality at each time point were also compared. 312 patients comprised the analytic cohort. PANDORA was associated with mortality at 30 (OR 1.08; 95% CI 1.04-1.13; P < .001), 90 (OR 1.09; 95% CI 1.03-1.12; P < .001), and 180 days (OR 1.10; 95% CI 1.06-1.15; P < .001). PANDORA and APACHE II were comparable for mortality prediction at 30 (AUC: 0.69, 95% CI 0.62-0.76 vs 0.74, 95% CI 0.67-0.81; P = .29), 90 (AUC: 0.71, 95% CI 0.63-0.77 vs 0.74, 95% CI 0.67-0.80; P = .52), and 180 days (AUC: 0.73, 95% CI 0.67-0.79 vs 0.75, 95% CI 0.69-0.81; P = .66). In surgical ICU patients, PANDORA was associated with mortality and was comparable with APACHE II for mortality prediction at 30, 90, and 180 days after initiation of care. Prospective studies are needed to assess whether nutrition support, stratified by PANDORA scores, can improve outcomes in surgical ICU patients.


[The transcriptional regulation study on human delta globin gene with CAAT box C-->T point mutation in its promoter].
To study the transcriptional regulation of human delta globin gene with C-->T point mutation at -64 in its promoter. Human delta globin genes including wild CAAT box and mutant CAAT box (-64C-->T) were separately cloned into eukaryotic expression vector pcDNA3.1 (-)/Myc-His A which was cut out the strong promoter CMV, transfected MEL cells, and induced by DMSO to express. The transcriptional regulation of human delta globin gene was analysed using semi-quantitative RT-PCR. The expression level of human delta globin gene with mutant CAAT box was 2.2-fold as high as that with wild CAAT box. The defective CAAT box of human delta globin gene promoter region may be one of the major reasons for its low expression level.


Adverse events, quality of life, and recurrence rates after laparoscopic adhesiolysis and recurrent incisional hernia mesh repair in patients with previous failed repairs.
The aim of this study was to determine the impact of laparoscopic adhesiolysis and mesh repair on adverse event rates, quality-of-life (QoL) scores, and recurrence rates in patients with recurrent incisional hernia after failed repairs after multiple laparotomies. Data on consecutive patients were included prospectively. Recurrent incisional hernia was defined as a fascia defect > 5 cm. Adhesions were classified according to time needed for lysis. A standardized repair with IP polytetrafluoroethylene mesh, transabdominal sutures, and tacks was developed by the surgeons during a pretrial routine. QoL was assessed by the Gastrointestinal Quality of Life Index (GIQLI) before operation and at 24-month followup. Values are median (range). There were 85 consecutive patients aged 55 years (range 29 to 93 years); 45% were men; body mass index, 31 (range 23 to 39); American Society of Anesthesiologists grade I: 27%, II: 70%, III: 2%; comorbidity, 75%; previous laparotomies; 5 (range 2 to 18); previous colectomy, 87%; previous failed repairs, 4 (range 2 to 15); previous mesh repair, 98%; and midline hernia site, 98%. Fascia defect was 255 cm(2) (range 48 to 416 cm(2)), mesh size, 600 cm(2) (range 285 to 884 cm(2)), and operating time 145 minutes (80 to 210 minutes). There was one conversion. Length of stay was 2 days (1 to 9 days). A 15.2% adverse event rate included 1% port-site cellulitis, 7% seroma, and 7% persistent pain. Hernia recurrence rate was 3.5% at 41-month (range 24 to 61 months) followup. GIQLI total scores were significantly improved at followup (98 versus 116; p < 0.001). Domain GIQLI scores were improved at followup for symptoms (54 versus 63; p < 0.001), emotional function (12 versus 16; p < 0.001), and physical function (15 versus 21; p < 0.001). Laparoscopic adhesiolysis and recurrent hernia mesh repair resulted in a low rate of adverse events, a substantially improved health-related QoL, and a risk of recurrence similar to the rates associated with first-time hernia repair.


From sodium intake restriction to nitrate supplementation: Different measures with converging mechanistic pathways?
Endothelial nitric oxide synthase is at the centre of endothelial physiology producing nitric oxide which dilates blood vessels, inhibits platelet aggregation and smooth muscle cell proliferation and reduces adhesion molecule production. The laminar shear stress is a common test used usually as the flow mediated dilatation test (FMD) which is sensitive to saturated fat, sodium and potassium although with the latter ion it is possible potassium has direct effects on ion channels in the smooth muscle cell as well as the endothelial cell. High blood pressure and blood cholesterol both reduce nitric oxide production, the latter probably by increasing caveolin-1 which binds nitric oxide synthase. Saturated fat reduces nitric oxide by elevating LDL cholesterol and caveolin-1 while insulin stimulates nitric oxide synthase activity by serine phosphorylation. Polyphenols from tea, coffee and cocoa and virgin olive oil enhance FMD and eNOS activity is essential for this activity. Wine polyphenols produce mixed results and it is not clear at present that they are beneficial. Blackberries and other polyphenol-rich fruit also enhance FMD. Dietary nitrate from beetroot and green leafy vegetables is converted to nitrite by salivary microbes and then to nitric oxide and this acts directly on the smooth muscle to lower blood pressure particularly in a low oxygen environment. Dietary nitrate also improves work efficiency and improves flow mediated dilatation.


Validation of the Chinese version of the Malocclusion Impact Questionnaire (MIQ).
To translate and cross-culturally adapt the Malocclusion Impact Questionnaire (MIQ) into Chinese and to assess the psychometric properties of the Chinese version of the MIQ (MIQ/C) for use among adolescents with malocclusion in China. First, the MIQ/C was developed according to international guidelines. Then, the MIQ/C was filled out by 536 adolescents between 10 and 16 years of age. This study used exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, internal consistency, and test-retest reliability to evaluate the psychometric properties of the MIQ/C. Following EFA, three domains were extracted, accounting for 65.950% of the total variance. The CFA results showed that the fit indices of each factor in the three-factor model all reached the standard (chi-square/DF = 2.591, GFI = 0.919, TLI = 0.926, CFI = 0.928, RMSEA = 0.076). The scale evidenced a good relationship with the two global questions, indicating good convergent validity. The Cronbach alpha value and the intraclass correlation coefficients (ICC) value of the MIQ/C were 0.929 and 0.893, respectively. The MIQ/C demonstrated good reliability and validity and can be further studied and applied in Chinese adolescents with malocclusion. The MIQ/C can be applied to assess the psychosocial impact of malocclusion among Chinese adolescents.


Combination of isothermal titration calorimetry and time-resolved luminescence for high affinity antibody-ligand interaction thermodynamics and kinetics.
For experiments using synthetic ligands as probes for biological experiments, it is useful to determine the specificity and affinity of the ligands for their receptors. As ligands with higher affinities are developed (K(A)>10(8)M(-1); K(D)<10(-8)M), a new challenge arises: to measure these values accurately. Isothermal titration calorimetry measures heat produced or consumed during ligand binding, and also provides the equilibrium binding constant. However, as normally practiced, its range is limited. Displacement titration, where a competing weaker ligand is used to lower the apparent affinity of the stronger ligand, can be used to determine the binding affinity as well as the complete thermodynamic data for ligand-antibody complexes with very high affinity. These equilibrium data have been combined with kinetic measurements to yield the rate constants as well. We describe this methodology, using as an example antibody 2D12.5, which captures yttrium S-2-(4-aminobenzyl)-1, 4, 7, 10-tetraazacyclododecanetetraacetate.


More obvious association between short-term ambient nitrogen dioxide and atrial fibrillation outpatient visits in cool seasons: A hospital-based study in northwestern China.
Atrial fibrillation (AF) is the most common sustained heart rhythm disorder associated with high mortality and morbidity. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and AF attacks. This study aimed to explore the association between short-term ambient nitrogen dioxide (NO2) exposure and outpatient visits for AF in Xi'an, China. Data on daily AF outpatient visits and air pollutants from 2013 to 2019 (2555 days) were obtained. A time-series approach using over-dispersed Poisson generalized additive model (GAM) was employed, and stratified analyses were performed to investigate the potential modifying effects by season, age, and gender. A total of 8307 outpatient visits for AF were recorded. Increased levels of NO2 were associated with increased AF outpatient visits, and the most significant effect estimates were observed at lag 03: A 10 μg/m3 increase of NO2 at lag 03 was related to an elevation of 5.59% (95% CI: 2.67%, 8.51%) in daily outpatient visits for AF. Stratified analyses showed that there were no gender and age difference in the effect of NO2, while more obvious association was observed in cool seasons (October to March) than in warm seasons (April to September). In summary, short-term ambient NO2 exposure can be positively associated with daily outpatient visits for AF, especially in cool seasons. This work provided novel data that the association between air pollutants and AF can vary by seasons, further supporting that the prevention of cardiovascular health effects should be strengthened in winter.


The impact of female sex on the outcomes of endovascular treatment for iliac lesions.
The aim of this study was to evaluate early and long-term outcomes of stenting for iliac obstructive disease in women, comparing their results with those of men. A single-center retrospective analysis of iliac stenting procedures performed from 2010 to 2017 was conducted. Perioperative clinical, anatomic, and operative data, including mean artery diameters and stent diameters, were collected in a dedicated database. Early outcomes and long-term patency rates were compared between men and women; Cox proportional hazards modeling was used to identify independent predictors of patency. There were 210 patients (298 limbs; women, n = 80 limbs [33%]; men, n = 218 limbs [66%]) treated. In comparing women with men, there were no differences in comorbidities (Society for Vascular Surgery score: women, 0.81 ± 0.54; men, 0.84 ± 0.60; P = .69) and TransAtlantic Inter-Society Consensus (TASC) classification (P = .49). At presentation, women had more advanced symptoms (Rutherford categories 5 and 6: women, 36.2%; men, 23.8%; P = .039) and smaller diameter at the level of the aortic bifurcation (women, 14.5 ± 3.6 mm; men, 16.0 ± 3.3 mm; P = .017), common iliac artery (women, 9.3 ± 1.5 mm; men, 10.0 ± 1.6 mm; P < .001), external iliac artery (EIA; women, 8.7 ± 1.5 mm; men, 10.1 ± 2.6 mm; P = .006), and common femoral artery (women, 7.3 ± 2.0 mm; men, 8.5 ± 2.1 mm; P = .034); similarly, the mean stent diameter was smaller (women, 8.9 ± 1.7 mm; men, 10.1 ± 4.4 mm; P = .03). The 30-day medical (P = .22) and surgical (P = .50) complication rates were similar. At 72 months, women had lower primary patency (women, 71%; men, 88%; P = .020) and secondary patency (women, 83%; men, 97%; P < .001) rates compared with men, whereas limb salvage rate was similar (women, 96%; men, 99%; P = .501). Multivariable analysis showed that female sex (hazard ratio [HR], 2.49; P = .04), ischemic tissue loss (HR, 2.48; P = .04), and stent diameter ≤7 mm (HR, 2.86; P = .01) were overall negative predictors of patency. Within women, EIA involvement (HR, 2.01; P = .04) and stent diameter ≤7 mm (HR, 3.79; P = .12) were also negative predictors. Iliac stenting shows similarly good early outcomes in women and men. However, in the long term, primary and secondary patency rates are significantly lower in women, and this may be explained by smaller arterial diameter. In particular, a stent diameter ≤7 mm and EIA stenting were negative predictors of patency.


The association between increased maternal PARK7 (DJ-1) levels and the occurrence of preterm premature rupture of membranes - A randomized prospective study
Parkinson's disease protein 7 (PARK7/DJ-1) is an important antioxidant multiprotein against inflammation and oxidative stress. We therefore planned this study to demonstrate the association between maternal PARK7 levels and the occurrence of preterm premature rupture of membranes (PPROM). We enrolled 80 pregnant women; 50 PPROM patients and 30 healthy controls, into this cross- sectional study between the 24th and 36th gestational weeks. Furthermore, we measured serum PARK 7 levels using enzyme-Linked immunosorbent assay method. Plasma PARK7 levels were higher in PPROM patients compared to those in the healthy controls (p<0.001). With a cutoff value of 2.57 pg/mL; PARK 7 had a 92% sensitivity, 86% specificity, 88% positive predictive value and 83% negative predictive value (p<0.01) for PPROM. PARK7 had positive correlation with blood leukocyte levels (p<0.001), C-reactive protein levels (p<0.001), and negatively correlated with birth weight and birth week. PARK 7 is overexpressed in PPROM patients. Due to its anti-inflammatory and antioxidant properties, PARK7 may be a novel marker in better understanding the pathophysiology and prediction of the prognosis PPROM. Further large-scale studies are needed.


Adjusting for reverse causation to estimate the effect of obesity on mortality after incident heart failure in the Atherosclerosis Risk in Communities (ARIC) study.
The lower mortality rate of obese patients with heart failure (HF) has been partly attributed to reverse causation bias due to weight loss caused by disease. Using data about weight both before and after HF, this study aimed to adjust for reverse causation and examine the association of obesity both before and after HF with mortality. Using the Atherosclerosis Risk in Communities (ARIC) study, 308 patients with data available from before and after the incidence of HF were included. Pre-morbid and post-morbid obesity were defined based on body mass index measurements at least three months before and after incident HF. The associations of pre-morbid and post-morbid obesity and weight change with survival after HF were evaluated using a Cox proportional hazard model. Pre-morbid obesity was associated with higher mortality (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.04 to 2.49) but post-morbid obesity was associated with increased survival (HR, 0.57; 95% CI, 0.37 to 0.88). Adjusting for weight change due to disease as a confounder of the obesity-mortality relationship resulted in the absence of any significant associations between post-morbid obesity and mortality. This study demonstrated that controlling for reverse causality by adjusting for the confounder of weight change may remove or reverse the protective effect of obesity on mortality among patients with incident HF.


Delineating the dynamic transformation of gluten morphological distribution, structure, and aggregation behavior in noodle dough induced by mixing and resting.
To understand the formation of gluten network and its regulation on noodle qualities upon mixing and resting, the dynamic distribution and molecular transformation of gluten were tracked and quantified. Confocal laser scanning microscopy and scanning electron microscopy images showed that appropriate mixing (8 min) and resting (60 min) induced a compact gluten network with higher gluten junctions. Both height and width of protein molecular chains were increased by hydration during mixing and reduced after excessive resting (90 min). According to the size exclusion/reversed phase-HPLC profiles, mixing induced slight depolymerization of large glutenin polymer, and α-gliadin subunits were more susceptible to polymerization after appropriate mixing and resting. Increased mixing time was accompanied by the strengthening of ionic and hydrogen bonds, and the weakening of hydrophobic interaction. PCA and correlation analysis revealed the accurate regulation of mixing and resting induced dynamic distribution and evolution of gluten on the macroscopic noodle qualities.


Histone demethylation and steroid receptor function in cancer.
Steroid receptors recruit various cofactors to form multi-protein complexes which locally alter chromatin structure and control DNA accessibility in order to regulate gene transcription. Some of these factors are enzymes that add or remove histone marks in the vicinity of regulatory regions of target genes. Numerous histone modifications added by specific writer enzymes and removed by eraser enzymes have been identified. Histone methylation is a modification with a complex outcome, as it can lead to gene activation or repression, depending on the modified residue and the context. Methylation marks are added by different enzyme families displaying exquisite substrate specificity. Lysine methylation is reversible and two different demethylase families have been identified in humans, the Jumonji C and the lysine-specific demethylase families. A regulatory role of histone demethylases in fine-tuning the function of steroid receptors, especially the androgen receptor and estrogen receptor, has emerged in recent years. This is mostly inferred from in vitro studies, but more recently first in vivo data have further supported this concept. This and the deregulated expression observed for several histone demethylases suggest a role in tumours such as prostate and breast cancer.


NMDA receptor activation modulates programmed cell death during early post-natal retinal development: a BDNF-dependent mechanism.
Glutamate is a classical excitotoxin of the central nervous system (CNS), but extensive work demonstrates neuroprotective roles of this neurotransmitter in developing CNS. Mechanisms of glutamate-mediated neuroprotection are still under scrutiny. In this study, we investigated mediators of glutamate-induced neuroprotection, and tested whether this neurotransmitter controls programmed cell death in the developing retina. The protective effect of N-methyl-d-aspartate (NMDA) upon differentiating cells of retinal explants was completely blocked by a neutralizing antibody to brain-derived neurotrophic factor (BDNF), but not by an antibody to neurotrophin-4 (NT-4). Consistently, chronic activation of NMDA receptor increased the expression of BDNF and trkB mRNA, as well as BDNF protein content, but did not change the content of NT-4 mRNA in retinal tissue. Furthermore, we showed that in vivo inactivation of NMDA receptor by intraperitoneal injections of MK-801 increased natural cell death of specific cell populations of the post-natal retina. Our results show that chronic activation of NMDA receptors in vitro induces a BDNF-dependent neuroprotective state in differentiating retinal cells, and that NMDA receptor activation controls programmed cell death of developing retinal neurons in vivo.


Natalisin, a tachykinin-like signaling system, regulates sexual activity and fecundity in insects.
An arthropod-specific peptidergic system, the neuropeptide designated here as natalisin and its receptor, was identified and investigated in three holometabolous insect species: Drosophila melanogaster, Tribolium castaneum, and Bombyx mori. In all three species, natalisin expression was observed in 3-4 pairs of the brain neurons: the anterior dorso-lateral interneurons, inferior contralateral interneurons, and small pars intercerebralis neurons. In B. mori, natalisin also was expressed in two additional pairs of contralateral interneurons in the subesophageal ganglion. Natalisin-RNAi and the activation or silencing of the neural activities in the natalisin-specific cells in D. melanogaster induced significant defects in the mating behaviors of both males and females. Knockdown of natalisin expression in T. castaneum resulted in significant reduction in the fecundity. The similarity of the natalisin C-terminal motifs to those of vertebrate tachykinins and of tachykinin-related peptides in arthropods led us to identify the natalisin receptor. A G protein-coupled receptor, previously known as tachykinin receptor 86C (also known as the neurokinin K receptor of D. melanogaster), now has been recognized as a bona fide natalisin receptor. Taken together, the taxonomic distribution pattern of the natalisin gene and the phylogeny of the receptor suggest that natalisin is an ancestral sibling of tachykinin that evolved only in the arthropod lineage.


Sex determination of blood stains with a recombinant DNA probe: comparison with radioactive and non-radioactive labeling methods.
A recombinant DNA probe hybridizing specifically to human repeat DNA sequence (pHY10) of which about 3000 copies are present on the Y chromosome was used for sex determination of degraded DNA samples of blood stains. Human blood stains of male and female origin were readily differentiated with the pHY10 DNA probe. This radioactive technique enabled reliable and sensitive sex determination from blood or dried blood stains greater than 20 years old. Less than 1 microliter of blood or 1 piece of 0.5 cm length thread of blood stain from cotton fabric was sufficient for the test using dot blot hybridization. Compared with the radioactive labeling method, the photobiotin labeling method showed one thirtieth to one fiftieth lower sensitivity and presented some problems which are expected to be resolvable.


[On preparation the monoclonal antibody against synthetic antigen of cyclosporine A].
To study the methods for preparing the monoclonal antibody against synthetic antigen of cyclosporine A. These included using photochemical reaction to couple cyclosporine A with poly-L-lysine as synthetic antigen, immunizing BALB/c mice, fusing spleen cells and SP2/0 cells. Then hybridoma cells were repeatedly screened and subcloned. The monoclonal antibodies were identified by indirect ELISA. Four hybridoma cells in secreting anti-cyclosporine A monoclonal antibodies were obtained. Only two showed high titer and some specificity. The methods of antigen synthesis and immunization were practicable. But the methods of antibody preparation and preservation need to be improved.


Bioactivity of Acanthus mollis - Contribution of benzoxazinoids and phenylpropanoids.
Acanthus mollis is a plant native to the Mediterranean region, traditionally used as diuretic, anti-inflammatory and soothing of the mucous membranes of the digestive and urinary tract and externally as healing of wounds and burns, also demonstrating analgesic and anti-inflammatory activities. However, studies focused on its phytochemical composition as well as scientific proof of Acanthus mollis efficacy are scarce. The proposed work aims to perform a phytochemical characterization and evaluation of the therapeutic potential of Acanthus mollis, based on biological properties that support its traditional uses. In this study, an 96% ethanol extract from Acanthus mollis leaves was obtained and its phytochemical composition evaluated using High Performance Liquid Chromatography with Photodiode Array Detector coupled to Electrospray Ionization Mass Spectrometry (HPLC-PDA-ESI/MSn). The chemical structure of the compound isolated was elucidated using 1H and 13C Nuclear Magnetic Resonance (NMR), 1H-correlation spectroscopy (1H-COSY), heteronuclear single quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC). The quantification of the constituents was performed using two external standards (2,4-dihydroxy-1,4-benzoxazin-3-one and verbascoside). The antioxidant activity was determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) assay. Anti-inflammatory activity was determined measuring the inhibition of nitric oxide production by RAW 264.7 macrophages stimulated with the TLR4 agonist lipopolysaccharide (LPS) and through lipoxygenase (LOX) inhibition assay. The cytotoxicity was screened on two lines (RAW 264.7 and HaCaT) using the resazurin assay. Compounds such as verbascoside and its derivatives, as well as benzoxazinoids were found as the main constituents. A percentage of 5.58% was verified for the 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) derivatives. DIBOA was the main compound of the extract. Significant concentrations were also found for phenylpropanoids, which constitute about 4.39% of the total compounds identified. This extract showed antioxidant capacity against DPPH (IC50 = 40.00 ± 1.59 μg/mL) and superoxide anion (IC50 = 29.42 ± 1.99 μg/mL). It also evidenced anti-inflammatory potential in RAW 264.7 macrophages, presenting capacity for nitric oxide reduction (IC50 = 28.01 μg/mL). Moreover, in vitro studies have shown that this extract was able to inhibit the lipoxygenase, with an IC50 of 104.39 ± 4.95 µg/mL. Importantly, all effective concentrations were devoid of cytotoxicity in keratinocytes, thus highlighting the safety of the extract for the treatment of skin inflammatory related diseases. Concerning macrophages it was also possible to disclose concentrations showing anti-inflammatory activity and without cytotoxicity (up to 30 µg/mL). The benzoxazinoid DIBOA demonstrated a considerable anti-inflammatory activity suggesting its important contribution to this activity. These results corroborate the anti-inflammatory properties traditionally attributed to this plant. Among the compounds identified in this study, benzoxazinoids exhibited a significant anti-inflammatory activity that was never previously described. Ethanol seems to be a good option for the extraction of these bioactive compounds, since relevant antioxidant/anti-radical and anti-inflammatory activities were found for this extract.


Hearing Loss and Noise Exposure Among Commercial Fishermen in the Gulf Coast.
Noise is a hazard in commercial fishing. This cross-sectional study associates occupational noise exposure with hearing loss in commercial fishermen. A comprehensive survey and audiometric testing were administered to 227 participants in the Gulf Coast. Sound-level measurements were obtained aboard a sample of fishing vessels. Criteria specific for hearing impairment (HI) and noise-induced hearing loss (NIHL) were applied to each audiogram. The majority of these fishermen work shifts more than 16 hours for an extended duration. Hazardous noise levels were measured in the engine rooms ranging from 94.8 to 105.0 dBA. NIHL was significantly associated with years spent fishing, but not with age. HI was significantly associated with age, but not with years fishing. Commercial fishermen in the Gulf may be at a considerable risk of occupational NIHL and would benefit from hearing conservation programs.


The cDNA of cucumber mosaic virus-associated satellite RNA has in vivo biological properties.
Two isolates of cucumber mosaic virus (CMV)-associated satellite RNA, differing in their biological properties, have been reverse transcribed. One was able to induce the tomato necrotic syndrome whereas the other one attenuated fernleaf symptoms on tomato plants after co-inoculation with the helper virus. cDNAs representing partial or full-length copies have been cloned in the plasmid pAT 153 and sequenced. The two RNAs showed a very limited number of variations (2 to 5 substitutions depending on the clones and a one base deletion). Full-length cDNA copies possessed the same biological properties that characterized the parent satellite RNA. Efficiency of the cDNA depended upon its form in the inoculum (circular or linear plasmid or excised cDNA) and upon the form of the helper virus (viral RNAs or virions) with which it seemed to compete for installation and/or expression.


Chiari-like Malformation.
Chiari-like malformation is a condition of the craniocervical junction in which there is a mismatch of the structures of the caudal cranial fossa causing the cerebellum to herniate into the foramen magnum. This herniation can lead to fluid buildup in the spinal cord, also known as syringomyelia. Pain is the most common clinical sign followed by scratching. Other neurologic signs noted are facial nerve deficits, seizures, vestibular syndrome, ataxia, menace deficit, proprioceptive deficits, head tremor, temporal muscle atrophy, and multifocal central nervous system signs. MRI is the diagnostic of choice, but computed tomography can also be used.


The EBV-carrying, beta2M/HLA deficient Burkitt lymphoma line Daudi is sensitive to EBV-specific killer T-cells of mononucleosis patients.
The beta2-microglobulin/HLA deficient Burkitt lymphoma line Daudi was tested for sensitivity to EBV-specific cytotoxicity mediated by natural killer (NK)-depleted T-cells from acute mononucleosis patients. While the Daudi line was not as sensitive as the reference EBV-genome-positive target line, it was clearly sensitive in the majority of cases. This would speak against a major role of syngeneic restriction in this system.


Large-scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma.
Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. The plasma proteome was evaluated using an aptamer-based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under-explored. This investigational study evaluating the plasma proteome in clinically-phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.


Site mapping and small molecule blind docking reveal a possible target site on the SARS-CoV-2 main protease dimer interface.
The SARS-CoV-2 virus is causing COVID-19 resulting in an ongoing pandemic with serious health, social, and economic implications. Much research is focused in repurposing or identifying new small molecules which may interact with viral or host-cell molecular targets. An important SARS-CoV-2 target is the main protease (Mpro), and the peptidomimetic α-ketoamides represent prototypical experimental inhibitors. The protease is characterised by the dimerization of two monomers each which contains the catalytic dyad defined by Cys145 and His41 residues (active site). Dimerization yields the functional homodimer. Here, our aim was to investigate small molecules, including lopinavir and ritonavir, α-ketoamide 13b, and ebselen, for their ability to interact with the Mpro. The sirtuin 1 agonist SRT1720 was also used in our analyses. Blind docking to each monomer individually indicated preferential binding of the ligands in the active site. Site-mapping of the dimeric protease indicated a highly reactive pocket in the dimerization region at the domain III apex. Blind docking consistently indicated a strong preference of ligand binding in domain III, away from the active site. Molecular dynamics simulations indicated that ligands docked both to the active site and in the dimerization region at the apex, formed relatively stable interactions. Overall, our findings do not obviate the superior potency with respect to inhibition of protease activity of covalently-linked inhibitors such as α-ketoamide 13b in the Mpro active site. Nevertheless, along with those from others, our findings highlight the importance of further characterisation of the Mpro active site and any potential allosteric sites.


A mini-review on Sirtuin activity assays.
Sirtuins belong to the class III histone deacetylase family with NAD-dependent protein lysine deacylase activities, which has been shown to play important roles in many physiological processes, including the regulation of transcription, DNA repair, metabolism and protein secretion. Small molecules that can modulate Sirtuin activity are important for fundamental studies of Sirtuin biology and drug development. High-throughput assays to screen for small molecule modulators of Sirtuins have been approved to be very useful tools for the development of therapeutics and research tools targeting Sirtuins. In this review, we will summarize the reported assays (during 2000-2015) for Sirtuins and discuss how these assays show different performances for the possibility of screening Sirtuin modulators and the application of high-throughput format screening.


Diagnostic value of CD103 expression in bronchoalveolar lymphocytes in sarcoidosis.
Pulmonary sarcoidosis is frequently characterized by a CD4(+)/CD8(+) ratio ≥3.5 in bronchoalveolar lavage fluid (BALF), although up to 40% of the cases present a normal or even decreased ratio, pointing out its variability and limitation as a diagnostic marker for sarcoidosis. Lung lymphocytes within the bronchial epithelium, the alveolar walls, and BALF express the integrin CD103. Our aim was to compare the expression of CD103 in BALF T-lymphocytes between sarcoidosis and other interstitial lung diseases (ILD) and to evaluate its relevance as a BALF diagnostic marker for sarcoidosis. A total of 86 patients with ILD (mean age ± standard deviation, 42.6 ± 16.6 years; 60.5% female), who underwent BALF as part of their initial diagnostic work-up, were enrolled into 2 groups: sarcoidosis (n = 41) and other ILD (n = 45). Area under the receiver operating characteristic (ROC) curve (AUC) was used to describe the performance of CD103 for sarcoidosis diagnosis. Sarcoidosis patients presented a significantly reduced CD103 expression in BALF T-lymphocytes, more pronounced in the CD4(+) subset. The BALF CD103(+)CD4(+)/CD4(+) ratio for a cutoff point of 0.45 was associated with a better diagnostic performance for sarcoidosis (AUC: 0.86 [95% confidence interval (95% CI): 0.78-0.94]; sensitivity: 81%; specificity: 78%), even for those with a CD4(+)/CD8(+) ratio <3.5 (AUC: 0.79 [95% CI: 0.64-0.93]; sensitivity: 75%; specificity: 78%). Assessment of CD103 expression in BALF CD4(+) T-lymphocytes may be a reliable tool for sarcoidosis diagnosis, independently of CD4(+)/CD8(+) ratio, pointing out the relevance of evaluating the CD103(+)CD4(+)/CD4(+) ratio in the ILD diagnostic work-up.


The role of acetylcholinesterase and butyrylcholinesterase activity in the development of delirium in acute stroke.
Our study aimed to test whether plasma acetylcholinesterase and butyrylcholinesterase enzyme activity were related to the presence and intensity of delirium in acute stroke patients. We carried out a matched (age and gender) case-control study, in a sample of consecutive patients with an acute infarct or intracerebral haemorrhage (≤7 days). We assessed delirium using the DSM-5 criteria and the Delirium Rating Scale, and we measured plasma acetylcholinesterase and butyrylcholinesterase enzyme activity after the patient's admission in the stroke unit and before hospital discharge. Mantel-Haenszel's chi-square was used to test bivariate associations between cases (delirious patients) and controls (non-delirious patients). At admission in the stroke unit, cases and controls did not present significant differences in plasma acetylcholinesterase or butyrylcholinesterase activity. At hospital discharge (18 cases and 21 controls) patients who have had delirium at admission had higher levels of butyrylcholinesterase activity. Butyrylcholinesterase activity may secondarily increase due to the inflammatory process associated with neuronal dysfunction in delirium patients.


Salvage of pyrimidine nucleosides by Trichomonas vaginalis.
Trichomonas vaginalis is incapable of de novo pyrimidine biosynthesis because it cannot incorporate bicarbonate, aspartate or orotate into its pyrimidine nucleotides or nucleic acids. The organism can salvage exogenous cytidine greater than uridine greater than uracil and thymidine, and incorporate them into the nucleotide pool. A portion of cytidine is converted to CMP, CDP and CTP by cytidine phosphotransferase and nucleotide kinases. Some cytidine and most of uracil are, however, converted first to uridine by cytidine deaminase and uridine phosphorylase respectively; uridine is then incorporated into UMP, UDP and UTP by uridine phosphotransferase and nucleotide kinases. The two phosphotransferases, found mainly in the non-sedimentable fraction of T. vaginalis, provide the main avenue of pyrimidine salvage. No significant levels of pyrimidine phosphoribosyl transferase or nucleoside kinases can be detected in the extract. T. vaginalis has no appreciable dihydrofolate reductase or thymidylate synthetase; it grows normally in millimolar concentrations of methotrexate, pyrimethamine, or trimethoprim, and cannot incorporate labels from exogenous uracil or uridine into DNA. It has an enzyme thymidine phosphotransferase in the sedimentable fraction which converts thymidine to TMP. Thymidine salvage in T. vaginalis is thus totally isolated from the rest of the pyrimidine salvage.


An X-ray analysis of adjuvant arthritis in the rat. The effect of prednisolone and indomethacin.
A detailed evaluation has been made of the radiological changes occurring in the hindfeet of rats with adjuvant arthritis from 0 to 50 days after injection with Freund's Complete Adjuvant (FCA). The results were compared with concomitant foot swelling and the presence of histopathological abnormalities at the end of the experiment. In addition, the effects of oral administration of prednisolone and indomethacin administered either from one day before injection with FCA to 21 days afterwards, or from 21 to 35 days after injection with FCA, has been investigated on all these changes. The main radiological changes were osteoporosis of the tarsals and metatarsals, erosions of the tarsals and periosteal reactions in the metatarsals which were visible on day 10 and progressed up until 21-24 days after injection with FCA. Cystic fibrosis was noted in the metatarsals on day 14 and in the tibia, fibula and tarsals on day 21 and progressed to become the dominant abnormality by day 35. Cystic fibrosis and subsequent calcification, which was apparent on day 35, were the main features of the disease when the animals were killed on day 50. 10 and 30 mg/kg prednisolone and 0.3 and 3 mg/kg indomethacin both reduced the total X-ray score when administered either from day - 1 to 21, or from day 21-35, but did not at any time inhibit the osteoporosis or erosions. Their effect was mainly on preventing the cystic fibrosis and calcification which occurred later in the disease. Prednisolone and indomethacin also reduced the periosteal reaction when administered from one day before injection with FCA, but they were inactive in this respect when dosing was started on day 21 when the periosteal reaction was well established. Therefore, the results suggest that prednisolone and indomethacin inhibit the later sequelae of the disease and do not interfere with either the initial events or the disease process itself. There was a good correlation between the toal X-ray score, foot size and total histopathology score at the end of the experiment, and also an apparent correlation between total X-ray score and foot size throughout the experiment. Although this suggests that foot size is sufficient to indicate the overall reaction in adjuvant arthritis, X-ray analysis may detect clinically useful anti-rheumatoid activity which might not be evident from measurements of foot size alone.


Use of high- and low-value care among US adults by education levels.
Healthcare reform in the United States has focused on improving the value of health care, but there are some concerns about the inequitable delivery of value-based care. We examine whether the receipt of high- and low-value care differs by education levels. We employed a repeated cross-sectional study design using data from the 2010-2019 Medical Expenditure Panel Survey. Our outcomes included 8 high-value services across 3 categories and 9 low-value services across 3 categories. Our primary independent variable was education level: (i) no degree, (ii) high school diploma, and (iii) college graduate. We conducted a linear probability model while adjusting for individual-level characteristics and estimated the adjusted values of the outcomes for each education group. In almost all services, the use of high-value care was greater among more educated adults than less educated adults. Compared to those with no degree, those with a college degree were significantly more likely to receive all high-value services except for HbA1c measurement, ranging from blood pressure measurement (4.5 percentage points [95% CI: 3.9-5.1]) to colorectal cancer screening (15.6 percentage points [95% CI: 13.9-17.3]). However, there were no consistent patterns of the use of low-value care by education levels. Our findings suggest that more educated adults were more likely to receive high-value cancer screening, high-value diagnostic and preventive testing, and high-value diabetes care than less educated adults. These findings highlight the importance of implementing tailored policies to address education-based inequities in the delivery of high-value services in the United States.


The dehydrogenation of butane on metal-free graphene.
The dehydrogenation of alkane feedstock to produce alkenes is a significant and energy intensive industrial process, generally occurring on metals and metal oxides. Here, we investigate a catalytic mechanism for the dehydrogenation of butane on single-layer, metal-free graphene using a combination of ab initio quantum chemical calculations and adsorption microcalorimetry. Dispersion-corrected Density Functional Theory (DFT) is employed to calculate transition states and energy minima that describe the reaction pathways connecting butane to the two possible products, but-1-ene and but-2-ene. The deprotonations occur with moderate energy barriers in the 0.54 eV-0.69 eV range. A strong agreement is observed between the results of the adsorption energies calculated by DFT (0.40 eV) and the measured differential heat of adsorption of n-butane on a graphitic overlayer. We conclude that the active-site for this catalytic reaction is a metal-free graphene vacancy, created by removing a carbon atom from a single-layer graphene sheet.


This drunk doesn't have to die!
Addiction treatment programs and after-care provide needed help to aid alcoholics in making fully recovery. They instruct, guide, and support the alcoholic back to a normal life. Ninety-three percent who abstain for five years remain sober.


[New perspectives in the approach to age-related macular degeneration].
The approval of aflibercept for the neovascular form of age-related macular degeneration has opened up the possibility of treating patients with fewer injections, since the drug can be administered once every two months. Aflibercept can also be used as rescue therapy in patients with suboptimal response to other antiangiogenic treatments. The present study reviews the scientific evidence on aflibercept, both in treatment-naïve patients and in those with an unsatisfactory response to conventional treatments.


A statistical method for enhancing the production of succinic acid from Escherichia coli under anaerobic conditions.
The most influential parameters for succinic acid production obtained through one at a time method were sucrose, tryptone, magnesium carbonate, inoculum size and incubation period. These resulted in the production of 7.0 g L(-1) of succinic acid in 60 h from Escherichia coli W3110 under anaerobic conditions. Based on these results, a statistical method, face centered central composite design (FCCCD) falling under response surface method (RSM) was employed for further enhancing the succinic acid production and to monitor the interactive effect of these parameters, which resulted in a twofold increase in yield (14.3 g L(-1) in 48 h). The analysis of variance (ANOVA) showed the adequacy of the model and the verification experiments confirmed its validity. On subsequent scale-up in a 10-L bioreactor using conditions optimized through RSM, 24.2 g L(-1) of succinic acid was obtained in 30 h. This clearly indicated that the model stood valid even on large-scale. Thus, the statistical optimization strategy led to a 3.5-fold increase in the yield of succinic acid. This is the first report on the use of FCCCD to improve succinic acid production from E. coli.


Reduced time to skin grafting in chronic wounds using an esterified hyaluronic acid matrix and negative pressure wound therapy.
The use of NPWT and eHAM can aid in the closure of chronic wounds with exposed bone and tendon. The authors examined the time to skin grafting and wound closure in 10 patients after treatment with either NPWT with eHAM (group 1, n = 5) or NPWT without eHAM (group 2, n = 5). The average time to closure was similar between group 1 and group 2 (15.2 weeks vs 14.6 weeks) despite a nearly twofold greater initial wound area. However, the rate of wound closure per week was better in group 1 than in group 2 in terms of both area (9.0 cm2 vs 6.8 cm2) and volume (12.3 cm3 vs 5.4 cm3). In addition, the rate of wound closure per week at skin grafting was better in group 1 than group 2 in terms of both area (4.5 cm2 vs 3.8 cm2) and volume (25.9 cm3 vs 4.1 cm3). All patients in group 1 received skin grafts within 2 to 3 weeks after their second eHAM application. The results of this small case series suggest that eHAM has a synergistic effect when used in combination with NPWT for the treatment of chronic wounds with exposed bone and tendon.


Electron microscopy study of the central retinal fovea in Pied flycatcher: evidence of a mechanism of light energy transmission through the retina.
We present unique ultrastructural data on avian retinal cells. Presently and earlier (Zueva et al., 2016) we explored distribution of intermediate filaments (IFs) in retinal cells of the Pied flycatcher (Ficedula hypoleuca, Passeriformes, Aves) in the central foveolar zone. This retinal zone only contains single and double cone photoreceptors. Previously we found that continuous IFs span Müller cells (MC) lengthwise from the retinal inner limiting membrane (ILM) layer up to the outer limiting membrane (OLM) layer. Here we describe long cylindrical bundles of IFs (IFBs) inside the cone inner segments (CIS) adjoining the cone plasma membrane, with these IFBs following along the cone lengthwise, and surrounding the cone at equal spacing one from the other. Double cones form a combined unit, wherein they are separated by their respective plasma membranes. Double cones thus have a common external ring of IFBs, surrounding both cone components. In the layer of cilia, the IFBs that continue into the cone outer segment (COS) follow on to the cone apical tip along the direction of incident light, with single IFs separating from the IFB, touching, and sometimes passing in-between the light-sensitive lamellae of the COS. These new data support our previous hypothesis on the quantum mechanism of light energy propagation through the vertebrate retina (Zueva et al., 2016, 2019).


Deciphering complex rearrangements at the breakpoint of an apparently balanced reciprocal translocation t(4:18)(q31;q11.2)dn and at a cryptic deletion: Further evidence of TLL1 as a causative gene for atrial septal defect.
When a de novo balanced reciprocal translocation is identified in patients with multiple congenital abnormalities, attempts are often made to infer the relationship between the phenotype of the patient and genes in the proximity of the breakpoint. Here, we report a patient with intellectual disability, atrial septal defect, syndactyly, and cleft lip and palate who had an "apparently balanced" de novo reciprocal translocation t(4:18)(q31;q11.2) as well as a 7-Mb cryptic deletion spanning the HOXD cluster on chromosome 2q31 that was unrelated to the reciprocal translocation. Further analysis using a nanopore long-read sequencer showed complex rearrangements on both derivative chromosomes 4 and 18 and the deleted chromosome 2. First, the TLL1 locus, which is associated with atrial septal defect, was disrupted by the rearrangement involving chromosome 4. Second, the deleted interval at 2q31 included the entire HOXD cluster, the deletion of which is known to cause toe syndactyly, and the DLX1 and DLX2 loci, which are responsible for cleft lip and palate. Among the haplo-sensitive genes within the deleted interval on 2q31, only the RAPGEF4 gene is known to be associated with an autistic phenotype. Hence, most of the clinical features of the patient could be ascribed to specific genomic rearrangements. We have shown the effectiveness of long-read sequencing in defining, in detail, the likely effects of an apparently balanced translocation and cryptic deletion. The results of the present analysis suggest the possibility of phenotypic prediction through a detailed analysis of structural abnormalities, including balanced translocations and deletions.


[Cytoprotection of gastric mucosa induced by tripotassium-dicitrato bismuthate against ethanol stress. Dependent mechanisms of sulfhydryl, dopaminergic and endogenous prostaglandin].
In groups of white Wistar rats, the cytoprotective effect induced by TDB on the gastric mucosa against the ethanol injury, was studied; where macroscopic protection and histologic cytoprotection in gastric corpus was found, and no in antrum mucosa. The cytoprotective mechanism give by TDB, were studied by the test of Indomethacin, Cl2Hg, Domperidone, Chlorpromazine and Acetazolamide, where each drug was given as pretreatment. Was conclude that TDB give gastric cytoprotection by the mechanism of the nonprotein sulfhydryl, by to be one peripheral agonist of the neuronal dopamine receptors, by increase of endogenous prostaglandin, by little increment of cAMP and no participate the gastric bicarbonate secretion.


Kisspeptins and the reproductive axis: potential applications to manage reproduction in farm animals.
Kisspeptins (Kp) are a family of neuropeptides produced mainly by two hypothalamic neuronal cell populations. They have recently emerged as a major regulator of the gonadotropin axis and their action is located upstream of the gonadotropin-releasing hormone (GnRH) cell population. In less than 10 yr a growing body of literature has demonstrated the involvement of these peptides in most, if not all, aspects of reproductive axis maturation and function. In contrast to these abundant basic research studies, few experiments have evaluated the potential application of Kp as tools to manipulate reproduction in domestic animals. In mammals, exogenous Kp administration potently stimulates gonadotropin secretion. This action is exerted mainly, if not exclusively, through the stimulation of GnRH release. Intravenous, intraperitoneal, or subcutaneous administration of Kp induced a robust and rapid increase in plasma gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]). However, this stimulatory effect is of short duration. Prolonged LH and FSH release over several hours can be achieved only when Kp are given as repeated multiple bolus or as an infusion. Kp administration was used in two experimental models, ewe and pony mare, with the aim of inducing well-timed and synchronized ovulations. During the breeding season, progesterone-synchronized ewes were given an intravenous infusion of Kp starting 30 h after the removal of progesterone implants. An LH surge was induced in all Kp-treated animals within 2 h of infusion onset. In contrast, in pony mares a constant infusion of Kp for 3 d in the the late follicular phase was unable to induce synchronized ovulation. Another set of studies showed that Kp could be used to activate reproductive function in acyclic animals. Pulsatile administration of Kp in prepubertal ewe lambs was shown to activate ovarian function, leading to enhanced ovarian steroidogenesis, stimulation of LH preovulatory surge, and ovulation. In anestrous ewes, an intravenous infusion of a low dose of Kp induced an immediate and sustained release of gonadotropins, followed a few hours later by an LH surge. This hormonal pattern mimicked hormonal changes normally observed during the estrous cycle follicular phase and was associated with a high percentage of ovulating animals (80%). In summary, exogenous administration of Kp appears to be a new tool to manipulate reproduction. However, optimal doses and periods of treatment should be defined for each species, and the development of powerful analogs or long-term release formulations is necessary before large-scale applications in domestic animals could be envisaged.


Strains and clones of Trypanosoma cruzi differ in their expression of a surface antigen identified by a monoclonal antibody.
Four Trypanosoma cruzi strains and 50 clones derived from a total of 10 strains were assayed with a monoclonal antibody, WIC 29.26 Ab, for expression of an epitope previously demonstrated to be on the carbohydrate portion of a 72 000 Da surface glycoprotein of Y strain epimastigotes. WIC 29.26 Ab bound to only 2 of the 4 strains and 23 of the 50 clones tested. A group of 10 cloned isolates from one strain contained both reactive and non-reactive clones. Competitive inhibition studies with soluble extracts of the reactive and non-reactive isolates suggested that in addition to being absent from the surface membrane, the antigenic determinant is not synthesized by the non-reactive parasites. These data indicate that the epitope recognized by WIC 29.26 Ab is not present on all T. cruzi epimastigotes, and provide the first demonstration of clone-specific differences in a parasite antigen detected by a monoclonal antibody. No correlation was found between the reactivity of isolates with WIC 29.26 Ab and the previously investigated parameters of growth rate and modal volume.


Hand lacerations and job design characteristics in line-paced assembly.
This study investigated risk factors for laceration injuries among workers employed in line-paced manufacturing assembly operations. Most lacerations (76% of 576) occurred on the hands and fingers (grouped as "hand" lacerations). On average, 37% of surveyed workers reported at least one laceration to the hand in the preceding year, resulting in an overall hand laceration rate of 83 per 100 workers per year. An inverse relationship was found between level of job routinization and hand lacerations, with progressively higher rates of hand lacerations occurring among workers assigned to less routine (more variable) work patterns. Fabricated metal parts handling and job variability may be related to increased risk of hand lacerations in line-paced work environments where personal protective equipment is the primary strategy to control exposure to sharp objects.


Functional brain imaging in voiding dysfunction.
Voiding dysfunction (VD) is morbid, costly, and leads to urinary tract infections, stones, sepsis, and permanent renal failure. Evaluation and diagnosis of VD in non-obstructed patients can be challenging. Potential diagnostic and therapeutic options beyond the bladder, such as brain centers involved in voiding have been proposed as promising targets. This review focuses on current and future applications of functional neuroimaging in human in voiding and in patients with VD. The current understanding of brain centers, and their roles in initiating, maintaining and/or modulating voiding, is rudimentary in humans and in patients with VD. With the advent and advancement in functional neuroimaging we are gaining more insight into specific brain regions involved in the voiding phase of micturition. In healthy individuals, right dorsomedial pontine tegmentum, periaqueductal grey, hypothalamus, and the inferior, medial and superior frontal gyrus have been identified as regions of interest in voiding. Functional neuroimaging could suggest new diagnostic methods and provides crucial steps towards therapeutic options for the morbid and intractable VD condition, in patients with neurogenic (e.g. MS or Strokes) or non-neurogenic VD (e.g. underactive bladder or Fowler's syndrome).


A Single Site Phosphorylation on Hsp82 Ensures Cell Survival during Starvation in Saccharomyces cerevisiae.
Unicellular organisms live under diverse stressful conditions and must respond and adapt quickly to these stresses. When these stresses persist, cells favor a transition to quiescence. There are changes to many processes when cells begin their entry into quiescence. It has been reported that Hsp82 plays an important role in several such processes, and its distribution and activity change according to nutrient conditions. In this study, we found that the subcellular distribution of Hsp82 is regulated by its co-chaperone Ppt1. Under starvation conditions, Ppt1 expression was significantly reduced by a TOR-independent pathway. Furthermore, we found that Ppt1 regulates Hsp82 distribution in the cytoplasm and nucleus by dephosphorylating the S485 residue on Hsp82. The Hsp82S485A strain has impaired membrane-related protein transport, and its cell size did not become larger in quiescence compared to log phase, resulting in failure to survive during starvation.


Neuroprotective effect of quercetin and Zingiber officinale on sodium arsenate-induced neurotoxicity in rats.
The study was aimed at determining the ameliorative potential of quercetin and Zingiber officinale (ZO) against sodium arsenate-induced neurotoxicity in male Wistar rats. Thirty adult animals were randomly allocated to five groups (n = 6). Group I served as control, groups II and IV were treated with ZO [300 mg/kg, PO (per os)/day], and group V animals were administered quercetin (50 mg/kg, PO/day) for 18 days. Groups III, IV, and V were injected with sodium arsenate (20 mg/kg, intraperitoneally/day) for 4 days starting from day 15. The administration of sodium arsenate resulted in a significant decrease in total antioxidant status, total thiols, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and aryl esterase in brain tissue of the animals compared with the control group. In addition, a significant increase was observed in malondialdehyde, advanced oxidation protein product and plasma nitric oxide levels, indicating oxidative stress-mediated neuronal damage. However, these arsenic-induced alterations were significantly reversed by quercetin or ZO in the treatment groups, indicating their ameliorative potential. These positive effects were further confirmed by histopathological examination of brain tissue revealing the suppression of severe neuronal injury, spongiosis and gliosis in the samples pretreated with quercetin and ZO. Our results suggest that inclusion of ZO and quercetin-rich foods in the diet can help in preventing the neurotoxic effects in areas with elevated levels of arsenic in food chain and ground water.


Effects of increasing salinity on anArtemia population from Mono Lake, California.
Salinity increased from 48 to 93 g/l total dissolved solids (TDS) in Mono Lake, California between 1941 and 1982, and is expected to fluctuate between 169 and 248 g/l at equilibrium by the middle of the next century. In order to predict the consequences of this trend on the Mono Lake ecosystem, we determined effects of salinity on survival, growth, reproduction and hatching ofArtemia monica, Mono Lake's only macrozooplankton species. Seven salainities ranging from 76 to 179 g/l were tested in a long-term experiment to determine both lethal and sublethal responses. The salt tolerance limit for subadultA. monica was between 159 and 179 g/l. Adult size, growth rates, and brood sizes decreased, and female mortality during reproduction increased, as salinity increased. Hatching of diapause eggs was delayed and total percent hatch decreased as salinity increased, and hatching failed at 159 g/l. The life-time reproductive potential of individual females decreased linearly over the seven salinities tested. Based on this study, we predict a decrease in the productivity of theA. monica population in Mono Lake and extinction of the species is probable before the lake reaches equilibrium.


Differential effect of transporter Tap 2 gene introduction into RMA-S cells on viral antigen processing.
The protein products of the Tap (Transporter associated with antigen processing) 1 and 2 genes are presumed to deliver peptides across the endoplasmic reticulum (ER) for assembly with major histocompatibility complex (MHC) class I molecules. The antigen processing-defective cell line RMA-S (H-2b) has a premature stop in the Tap 2 gene and probably therefore fails to deliver peptides into the ER, which leads to a low level of cell surface MHC class I molecules. Transfection of a Tap 2 gene restores to RMA-S both MHC class I molecule expression and the ability to present influenza viral antigens. We investigated the ability of RMA-S cells transfected with a Tap 2 gene to process and present alloantigens, Sendai and Rauscher viral antigens to allogeneic and virus-specific cytotoxic T lymphocytes. We found that allogeneic peptides as well as Rauscher and Sendai viral peptides can be processed and presented by RMA-S but at reduced levels. Transfection of a Tap 2 gene of mouse (BALB/c, H-2d) or rat origin into RMA-S increased the presentation of Sendai viral antigens and partially restored the presentation of allogeneic antigens. The already low level of Rauscher viral peptides presented by RMA-S is not elevated by transfection of either Tap 2 gene into RMA-S. This indicates a differential effect of transfection of a Tap 2 gene of rat or allogeneic mouse origin into RMA-S on viral antigen processing.


Strong and insusceptible photo-emissions from an intramolecular weak hydrogen bond strengthened twisted fluorophore.
Intramolecular weak hydrogen bonds of CHO and CH/Pi were introduced into a twisted fluorophore backbone of 1,4-bis(2,2-diphenylvinyl)benzene, which enables the fluorophore to emit violently and stably in both solubilized and aggregated states, and be inert to solvent environments and preserve over 10% quantum yield at temperature as high as 90 °C in solution.


Protective effect of potassium and chitosan supply on growth, physiological processes and antioxidative machinery in sunflower (Helianthus annuus L.) under drought stress.
Drought stress is one of the extreme effects of climate change causing large losses in production of crop plants. The risk of recurrent droughts has increased in next decades hence, the development of shot-gun, inexpensive and effective approaches is essential to ensure high yield of crops in drought-prone areas of the world. Exogenous application of nutrients such as potassium (K) has been reported to increase abiotic resistance and improve yield in crops however, knowledge regarding interaction of K with osmoprotectants like chitosan (Ct) still remains elusive. Here, we report the effects of individual or combined K (using K2SO4 as a source) or Ct application on growth, physiological processes and antioxidative defense system of sunflower under drought stress. At first, various doses of K (0, 5, 10, 15, 20, 25 g/l) and Ct (0, 0.1, 0.2, 0.3, 0.4, 0.5 g/l) were foliar applied to evaluate their role in improving plant biomass, water status and total chlorophyll in drought-induced seedlings of sunflower. The optimized K (11.48 g/l) and Ct (0.28 g/l) doses were further tested in second experiment to understand the underlying mechanisms of drought tolerance. Foliar K + Ct spray markedly enhanced the leaf gas exchange characteristics, increased proline, soluble proteins, and free amino acids, upregulated antioxidant defense system and helped to maintain plant water status in sunflower exposed to drought stress. The impact of drought stress was more pronounced at vegetative than reproductive stage and positive effects of combined K and Ct application were related to improved physiological and metabolic processes to improve yield and quality of sunflower under drought stress.


The oculocardiac reflex: a graphic and statistical analysis in infants and children.
A new method for the detection and recording of the oculocardiac reflex (OCR) is described and applied to 49 healthy infants and children (six months to nine years old) undergoing strabismus surgery under halothane anaesthesia with spontaneous ventilation. Eighty-one extraocular muscles were studied. Square wave stimuli (abrupt and sustained tractions) were definitely more reflexogenic than slow slope stimuli (very gradual, progressive and gentle tractions). Vagal escape, as well as fatigue of the OCR, are graphically documented and analysed. In this series, using well-defined and controlled tractions, the medial rectus was not more reflexogenic than the other extraocular muscles. Hypercapnia was an important adjuvant factor of the OCR. Controlled ventilation is recommended. The routine use of intravenous anticholinergic drugs is briefly discussed. Prevention of the OCR, and prophylaxis of cardiac arrhythmias during strabismus surgery, now seem to be placed on a more rational basis.


Women's experiences of living with increased inter-recti distance after childbirth: an interview study.
Although an increased inter-recti distance, also known as diastasis recti, is common after pregnancy, evidence-based knowledge about the condition is relatively limited. In particular, little is known about the consequences as perceived by the women. The objective of the present study was to describe how postpartum women with increased inter-recti distance experience the condition as well as the contacts they have had with healthcare providers regarding their symptoms. A purposeful sampling approach was used to recruit 19 participants from an existing study cohort of 144 women. All participants had an inter-recti distance of at least two finger widths and at least one child, with the youngest child between the ages of 1 and 6 years. Individual interviews based on a semi-structured interview guide were performed and subsequently analysed using qualitative content analysis. Four categories emerged from the interviews: the body's function and ability has changed; the body does not look like it used to; uncomprehending attitudes and treatment in their surroundings; and trying to acquire an understanding of and strategies to cope with the diastasis. The findings reveal that women with increased inter-recti distance might experience fear of movement and engage in avoidance behaviour. In combination with feelings of physical instability in the midsection of their bodies and body dissatisfaction, many of the women restrict their everyday lives and physical activities. The findings indicate that increased inter-recti distance is a complex phenomenon that affects the women in a multitude of ways, highlighting the importance of considering the condition for each individual in her own context from a biopsychosocial perspective.


Surgery of calculous hydrocalyx (calyceoplastic surgery).
A modified surgical technique for calculous hydrocalyx, based on partial calyceal resection with simultaneous correction of the morphological abnormality responsible for stone formation is described. Access to the calyx is gained by a modified marginopolar resection. The modification developed by the authors consists in carrying the resection line laterally to the vertical axis of the kidney. The parenchyma is closed by U-shaped "hair-pin" stitches. Preparation of the limbic, pelvic and ureteral areas is abstained from, thus avoiding scarring which might affect renal lymph and blood flow and interfere with urinary transport. The results obtained in 85 cases of calculous hydrocalyx over an 8-year period were satisfactory. The rate of calculous recurrences was not higher than 3.5 per cent.


Lateral asymmetries of pupillary responses.
We wanted to learn if pupillary changes induced by looking and attending to stimuli on the right and left are asymmetrical. In humans, there are hemispheric asymmetries in the control of attention-arousal systems. Because attention and arousal may influence pupil size, asymmetric pupillary responses may be seen when looking and attending in different directions. Twelve right-handed, healthy volunteers served as subjects. Using infrared pupillography, we recorded changes of pupillary diameter while subjects were looking and attending to the stimuli on the right and left sides of space. For the one second following a saccade, there are three phasic pupillary responses, an initial constriction (C1) then a dilation (D1), followed by constriction (C2). Evaluation of these three responses revealed right-left asymmetries with more pupil dilation (D1) when looking to the stimulus on the right. Our results suggest that subjects are more aroused when looking to the right than when looking to the left.


Adolescents and Trust in Online Social Interactions: A Qualitative Exploratory Study.
Social media have become increasingly embedded in adolescents' daily lives. Although these contexts have been widely studied, how trust in online relationships is built among adolescents is still an unexplored issue. By adopting the theoretical socio-cognitive model of trust, this study aims to explore the components of online trust as far as today's teenagers are concerned. The study involved 10 adolescents aged between 12 and 18 (M = 15.5). The data were collected using individual semi-structured, audio-recorded, and faithfully transcribed interviews. A deductive-inductive content analysis carried out with the NVivo10 software was performed on the textual material. Results show that adolescents seem to be aware of online trust value in "selecting" peers to be trusted. To protect themselves from the risks they are exposed to, they choose to interact with peers/friends who are already known in real life or are similar to them in terms of interests, ways of thinking, passions, and age. Additionally, others' competencies and willingness play an important role in adolescents' evaluations and decisions to rely on others online. The results of this study could be useful for developing awareness-raising interventions on the risks that adolescents are exposed to in order to promote "safe" relationships of trust and emphasize the possible positive use of technologies (e.g., by building online trust relationships using peer "safe" models).


Recent advances in pediatric liver transplantation.
Pediatric liver transplantation has matured into a well-established, highly successful treatment for advanced pediatric liver disease. Recent 1-year success rates range from 85% to 95%. This unprecedented achievement is the result of careful selection criteria and optimal timing of transplantation, technical advances in surgical technique, and improved treatment following transplant. This report highlights many recent published findings representing advances that have led to current successful approaches.


IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS.
Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction.


CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells.
Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process. In this study, the presence of CD44v on B cell lines from different stages of development was analyzed by flow cytometry and a role in adhesion to stromal cells from different tissues was evaluated in in vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma cell growth. Binding studies using CD44 isoform- specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell binding resulted in a significant induction of IL-6 secretion by bone marrow stromal cells. Large differences in quantitative plasma cell binding to stromal cells from different tissues were observed. These, however, could not be related to a differential use of CD44v in these binding processes. The role of CD44v9 in adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent plasma cell lines may explain the previously observed correlation between CD44v9 expression and adverse prognosis in multiple myeloma.


Bilateral traumatic extradural haematomas: report of 12 cases with a review of the literature.
We are reporting 12 cases of traumatic bilateral extradural haematomas. The incidence was 4.8% of all cases of extradural haematomas. The most common site was the frontal region. CT scan examination was necessary for early diagnosis. Ten patients were operated upon while one patient was treated conservatively. Two patients died. The relevant literature is reviewed.


Hemolytic uremic syndrome induced by lipopolysaccharide and Shiga-like toxin.
Induction of experimental hemolytic uremic syndrome (HUS) by simply administering Shiga-like toxin (Stx) to rodents has not yet been successful. Attention has been paid to the role of lipopolysaccharide (LPS) in the pathogenesis of HUS. In this study, we showed successful induction of an experimental HUS in LPS responder mice by administering Stx together with LPS. Intraperitoneal administration of 200 ng of Stx 2 for 2 days, followed by 250 microg of LPS on the 2nd day of Stx administration, caused a significant decrease of thrombocytes and deterioration of renal function, with proteinuria and hematuria. Electron microscopy revealed alterations of glomerular endothelial cells. Administration of Stx alone or LPS alone caused neither hematological nor histopathological changes, as were observed with Stx and LPS co-administration. Interestingly, when LPS was administered before Stx, no hematological and histological changes were observed. The results showed that LPS was essential for the induction of HUS, but LPS pretreatment might protect against Stx toxicity. The order of LPS and Stx administration is important for the induction of experimental HUS.


Structure of SNX9 SH3 in complex with a viral ligand reveals the molecular basis of its unique specificity for alanine-containing class I SH3 motifs.
Class I SH3 domain-binding motifs generally comply with the consensus sequence [R/K]xØPxxP, the hydrophobic residue Ø being proline or leucine. We have studied the unusual Ø = Ala-specificity of SNX9 SH3 by determining its complex structure with a peptide present in eastern equine encephalitis virus (EEEV) nsP3. The structure revealed the length and composition of the n-Src loop as important factors determining specificity. We also compared the affinities of EEEV nsP3 peptide, its mutants, and cellular ligands to SNX9 SH3. These data suggest that nsP3 has evolved to minimize reduction of conformational entropy upon binding, hence acquiring stronger affinity, enabling takeover of SNX9. The RxAPxxP motif was also found in human T cell leukemia virus-1 (HTLV-1) Gag polyprotein. We found that this motif was required for efficient HTLV-1 infection, and that the specificity of SNX9 SH3 for the RxAPxxP core binding motif was importantly involved in this process.


Newer antiarrhythmic drugs.
The effective management of cardiac arrhythmias remains a major challenge in cardiovascular therapeutics. The management of arrhythmias encompasses a wide spectrum of supraventricular and ventricular tachyarrhythmias occurring in patients with various cardiac diagnoses and different degrees of myocardial dysfunction. A number of the newer antiarrhythmic drugs that have either recently been released or appear promising are reviewed in this article. Drugs are described with respect to their basic pharmacology, electrophysiologic actions, pharmacokinetics and metabolism, hemodynamics, antiarrhythmic effects, side effects, interactions, indications, and dosage.


Techniques of the Single-Port Totally Laparoscopic Distal Gastrectomy.
Single-port laparoscopic surgery for patients with early gastric cancer has been rarely reported. Our aim was to introduce techniques of the single-port totally laparoscopic distal gastrectomy (TLDG) in patients with early gastric cancer. This procedure was performed using only one 3-3.5 cm skin incision on the umbilicus. One 12 mm and two 10 mm ports were used, and the flexible scope was used during the operation. Partial omentectomy with D1 + β or more lymph node dissection was performed. Bowel continuity was restored by intracorporeal gastroduodenostomy using two linear staplers. A total of 30 patients underwent single-port TLDG from June to August 2014. Median age of patients was 55 years (range 33-77) and median body mass index of patients was 21.2 kg/m(2) (range 15.7-26.1). Sixteen of 30 patients (53.3 %) were female. Operating times were 122.6 min, and blood losses during operations were 103.2 ml on average. The median length of postoperative hospital stay was 7 days, and the median number of dissected lymph nodes was 40 (range 16-67). No patients had dissected lymph nodes <15. The rate of complications was 20 % (6/30 patients), and no patients had an incisional hernia. Two patients experienced ileus (6.7 %), another two patients experienced delayed gastric emptying (6.7 %), and one patient suffered from small bowel obstruction. There were no postoperative mortalities. The single-port TLDG for patients with early gastric cancer is feasible in very selected patients and in specialized gastric cancer centers with experience in multi-trocar laparoscopy and single-port laparoscopic surgery.


Sequence analysis of peptide fragments from the intrinsic membrane protein of calf lens fibers MP26 and its natural maturation product MP22.
Calf lens fiber plasma membranes, containing only the intrinsic membrane protein MP26 and its maturation product MP22 were treated with proteolytic enzymes such as trypsin, protease V8 from S. aureus or with chemical agents as CNBr in formic acid. The cleavage products, purified by electrophoresis, were analysed for their amino acid composition and N-terminal sequences. Proteolysis gave rise to peptides which were mainly shortened at the C-terminal end of the molecules. While the V8 protease produced a fragment with a similar N-terminal sequence as the maturation product MP22, trypsin yielded another cleavage product. Chemical hydrolysis yielded large fragments (11-15 kDa) with hydrophobic N-terminal sequences. Our results suggest that MP26 is characterised by an N-terminal signal sequence and possesses other hydrophobic domains which could function as untranslocated insertion sequences.


Centralized radiation oncologic review of cross-sectional imaging of Hodgkin's disease leads to significant changes in required involved field-results of a quality assurance program of the German Hodgkin Study Group.
To guarantee the treatment quality of involved-field radiotherapy (IF-RT) of patients in the Hodgkin's disease (HD)10 and HD11 trials of the German Hodgkin Study Group, with 460 participating study centers, a quality assurance program was conducted. It was based on a central prospective radiation oncologic review of all patients' entire diagnostic imaging and clinical findings. An individual RT prescription was provided for every study patient. The purpose of the present investigation was to assess the feasibility of such a procedure and its impact on the final definition of disease extension and patient treatment. Between 1998 and 2002, 1371 patients were enrolled into the HD10 trial (early-stage disease) and 1570 patients into the HD11 trial (intermediate-stage disease). The HD10 trial tested four cycles of Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD) against two cycles of ABVD followed by 20 Gy of IF-RT vs. 30 Gy of IF-RT (four study arms). The HD11 trial compared four cycles of ABVD with four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline followed by 20 Gy IF-RT vs. 30 Gy IF-RT in a four-arm design. All study centers were required to score disease involvement at a total of 34 possible anatomic sites on case report forms and send them, together with all diagnostic imaging, to the RT reference center in Cologne, Germany. Images were reviewed there by a panel of expert radiation oncologists and radiologists and compared with the case report form. Differences between the disease involvement documented by the participating center and the reference center were recorded. Subsequently, an individualized treatment proposal was compiled. Complete sets of documentation were submitted to the reference center for 89% of the patients in both HD10 and HD11. A considerable proportion of involved sites were incorrectly recorded on the corresponding case report form by the participating center. For patients with early-stage HD (HD10), there was a correction of disease involvement in 49% (593 of 1214 patients) and for patients with intermediate-stage HD (HD11) in 67% (936 of 1397 patients). Most discrepancies were seen in the lower mediastinum (23%), infraclavicular (17%), upper cervical (16%), supraclavicular (13%), and pulmonary hilar region (13%). This resulted in a change of disease stage in 41 of those 1,529 patients whose documented disease involvement had to be corrected (2.7%). Ninety-three patients had to be treated in a different protocol, because of changes in stage and risk factors. Owing to incorrect lymph node documentation of the participating centers, the RT treatment volume had to be enlarged in 891 (34%) and reduced in 82 (3%) of 2,611 patients. A central prospective review of patient data and consecutive prescription of individual RT treatment volume is feasible within large multicenter trials for HD. Such a procedure has a significant impact on the correctness of stage definition, allocation to treatment groups, and extent of the IF treatment volume.


Bluetongue virus surveillance in the Islamic Republic of Mauritania: Is serotype 26 circulating among cattle and dromedaries?
In March 2013, EDTA-blood and serum samples were collected from 119 cattle and 159 dromedaries at the slaughterhouse of Nouakchott, the capital city of the Islamic Republic of Mauritania. Serum samples were screened for the presence of Bluetongue (BT) antibodies by competitive ELISA (cELISA). Positive samples were then tested by serum-neutralization (SN) to determine BTV serotype. RNA from blood samples was first tested by a genus-specific quantitative RT-PCR assay which is able to detect all 27 existing BTV serotypes (RT-qPCR1-27). Positive samples were further screened by a RT-qPCR assay which, instead, is able to detect the classical 24 BTV serotypes only (RT-qPCR1-24). Of the 278 serum samples tested, 177 (mean=63.7%; 95% CI: 57.9%-69.1%) resulted positive by cELISA. Of these, 69 were from cattle (mean=58.0%; 95% CI: 49.0%-66.5%) and 108 from dromedaries (mean=67.9%; 95% CI: 60.3%-74.7%). BTV-26 neutralizing antibodies were by far the most frequently found as they were detected in 146 animals with titres ranging from 1:10 to 1:80. Out of 278 blood samples, 25 (mean=9.0%; 95% CI: 6.2%-12.9%) were found positive for BTV by RT-qPCR1-27, 20 (mean=16.8%; 95% CI: 11.2%-24.6%) were from cattle and 5 (mean=3.1%; 95% CI: 1.4%-7.1%) from dromedaries. When tested by RT-qPCR1-24 the 25 BTV positive samples were negative. Unfortunately, no genetic information by molecular typing or by next generation sequencing has been obtained as for the very low levels of RNA in the blood samples.


1H NMR metabolomic profiling of human cerebrospinal fluid in aging process.
The molecular process of biological aging might be accompanied by significant metabolic derangement, especially in the central nervous system (CNS), since the brain has an enormous energy demand. However, the metabolic signature of the aging process in cerebrospinal fluid (CSF) has not been thoroughly investigated, especially in the Asian population. In this prospective cohort study on CSF metabolomics using proton nuclear magnetic resonance (NMR) spectroscopy, fasting CSF samples from 75 cognitively unimpaired patients aged 20-92 years without diabetes or obesity, undergoing spinal anesthesia for elective surgery were analyzed. Several metabolites in CSF samples were identified as having a significant association with the aging process in cerebral circulation; among the metabolites, the levels of alanine, citrate, creatinine, lactate, leucine, tyrosine, and valine significantly increased in old patients compared to those in young patients. The combined CSF metabolite alterations in citrate, lactate, leucine, tyrosine, and valine had a superior correlation with the aging process in all age groups. In conclusion, our pilot study of aging CSF metabolomics in the Taiwanese population presents significantly altered CSF metabolites with potential relevance to the aging process. These metabolic alterations in CSF samples might imply increasing anaerobic glycolysis, mitochondrial dysfunction, and decreasing glucose utilization in cerebral circulation in aged patients.


Primary extranodal and nodal non-Hodgkin's lymphoma. A survey of a population-based registry.
In a population-based registry, there were 580 patients with non-Hodgkin's lymphoma (NHL); 236 had primary extranodal lymphoma (41%). The initial localization of the primary extranodal lymphomas varied markedly, although 36% were primary gastrointestinal lymphomas. Histological classification was performed by a regional panel of pathologists according to the Kiel Classification and the International Working Formulation. Twelve per cent of the patients with nodal NHL had a localized disease in contrast to 40% with primary extranodal NHL. Low grade lymphomas were encountered in 30 and 10% of the patients with primary nodal and extranodal NHL, respectively. Recurrence-free survival rate for patients with localized low-grade malignancy and disseminated intermediate grade NHL is significantly better for extranodal lymphoma than for nodal NHL. Patients with disseminated high-grade extranodal NHL had the worst prognosis of all. We conclude that primary nodal and primary extranodal lymphomas should be considered as distinctive and separate entities.


Author Reply "Comment on Prediction of Successful Spontaneous Breathing Trial and Extubation of Trachea by Lung Ultrasound in Mechanically Ventilated Patients in Intensive Care".
How to cite this article: Rajbanshi LK. Author Reply "Comment on Prediction of Successful Spontaneous Breathing Trial and Extubation of Trachea by Lung Ultrasound in Mechanically Ventilated Patients in Intensive Care". Indian J Crit Care Med 2023;27(8):597-598.


Fetal-maternal bleed in the second trimester of pregnancy. A report of two cases.
Two cases of nontraumatic fetal-maternal bleeding occurred in the second trimester. Both presented with mild, lower quadrant tenderness similar to round ligament pain, illustrating the potential for a misdiagnosis.


Vortioxetine for major depressive disorder: An indirect comparison with duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, using number needed to treat, number needed to harm, and likelihood to be helped or harmed.
Vortioxetine is approved for the treatment of major depressive disorder and differs from other antidepressants in terms of its pharmacodynamic profile. Given the limited number of head-to-head studies comparing vortioxetine with other antidepressants, indirect comparisons using effect sizes observed in other trials can be helpful to discern potential differences in clinical outcomes. Data sources were the clinical trial reports for the pivotal short-term double-blind trials for vortioxetine and from publicly available sources for the pivotal short-term double-blind trials for two commonly used generic serotonin specific reuptake inhibitor antidepressants (sertraline, escitalopram), two commonly used generic serotonin-norepinephrine reuptake inhibitor antidepressants (venlafaxine, duloxetine), and two recently introduced branded antidepressants (vilazodone, levomilnacipran). Response was the efficacy outcome of interest, defined as a≥50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale or Hamilton Depression Rating Scale. The tolerability outcome of interest was discontinuation because of an adverse event. Number needed to treat (NNT) and number needed to harm (NNH) for these outcomes vs. placebo were calculated, as well as likelihood to be helped or harmed (LHH) to contrast efficacy vs. tolerability. The analysis included 8 studies for duloxetine, 3 studies for escitalopram, 5 studies for levomilnacipran, 1 study for sertraline, 4 studies for venlafaxine, 2 studies for vilazodone, and 11 studies for vortioxetine. NNTs for response vs. placebo were 6 (95% CI 5-8), 7 (5-11), 10 (8-16), 6 (4-13), 6 (5-9), 8 (6-16), and 9 (7-11), respectively. NNHs for discontinuation because of an adverse event vs. placebo were 25 (17-51), 31 (19-92), 19 (14-27), 7 (5-12), 8 (7-11), 27 (15-104), and 43 (28-91), respectively. LHH values contrasting response vs. discontinuation because of an adverse event were 4.3, 4.6, 1.8, 1.2, 1.4, 3.3, and 5.1 respectively. Subjects were all participants in carefully designed and executed clinical trials and may not necessarily reflect patients in clinical settings who may have complex psychiatric and non-psychiatric comorbidities. The measured outcomes come from different studies and thus comparisons are indirect. Vortioxetine demonstrates similar efficacy to that observed for duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, however overall tolerability as measured by discontinuation because of an adverse event differs. Vortioxetine is 5.1 times more likely to be associated with response than discontinuation because of an adverse event when compared to placebo.


Orbital complications of ethmoiditis.
Orbital infections are due to sinusitis in 75 per cent of cases and the ethmoid sinus is the most likely culprit. Aggressive and timely treatment is crucial if permanent disability and death are to be prevented.


Infections Are a Very Dangerous Affair: Enterobiasis and Death.
Enterobiasis or oxyuriasis from Enterobius vermicularis is an infection usually localized in the large bowel and cecum. Generally, the symptoms are characterized by anal itching, and intestinal or nervous disorders. Rarely, it is responsible for death. A forensic autopsy of a 52-year-old white male inmate who died 5 days after hospitalization was performed. Histological and toxicological analyses were also performed. The death occurred by localization of Enterobius vermicularis in the duodenum and in the proximal ileum, with intestinal haemorrhage, inflammation, and peritonitis documented by histological examination. This is a common infectious disease, and can rarely occur with a fatal outcome, even in advanced populations. The lack of knowledge related to the rarity of death from enterobiasis disease can determine a dangerous concern.


Lung alveolar septation defects in Ltbp-3-null mice.
Latent transforming growth factor (TGF)-beta binding proteins (LTBPs) modulate the secretion and activation of latent TGF-beta. To explore LTBP function in vivo, we created an Ltbp-3(-/-) mouse that has developmental emphysema with decreased septation in terminal alveoli. Differences in distal airspace enlargement were obvious at day 6 after birth. Secondary septation was inhibited, so by days 21 to 28 the mean linear intercept was approximately twofold greater in mutant versus control lungs. There were no differences in lung collagen and elastin, visualized by immunohistochemistry, or in myofibroblast numbers, determined by alpha-smooth muscle actin-positive cells, between mutant or wild-type lungs as the animals aged, other than differences associated with altered lung structure in mutant animals. However, from day 10 there was twice the number of alveolar type II cells in mutant alveoli compared to controls. At days 6 and 10, a transient enhancement in cell proliferation in the mutant lungs was observed by both 5-bromo-2'-deoxy-uridine and proliferating cell nuclear antigen labeling, accompanied by enhanced numbers of terminal dUTP nick-end labeling-positive cells at days 4, 6, and 10. Finally, there was a transient decrease in TGF-beta signaling at days 4 to 6 in Ltbp-3(-/-) lungs. These results indicate that in the absence of Ltbp-3, a temporary decrease in TGF-beta signaling in the lungs at days 4 to 6 alters cell proliferation, correlating with inhibition of septation and developmental emphysema.