Utility of ICD-9-CM Codes for Identification of Allergic Drug Reactions.
The epidemiology of allergic drug reactions is poorly understood due, in large part, to difficulty in identifying true cases in population data sets. Use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes is a potentially valuable approach that requires formal evaluation. To better understand the utility of ICD-9-CM codes for identification of allergic drug reactions, including the validation of specific codes by chart review. We reviewed randomly sampled medical records of patients treated in the emergency department (ED) between January 1, 2001, and December 31, 2006, with ICD-9-CM codes for drug allergy and E codes (E930-949) for adverse drug reactions. During the 6-year period, 11,130 charts were identified by ICD-9-CM and E codes and 1,634 were reviewed. Allergic drug reactions were found in 444 (27%) of the reviewed ED visits. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0; 87%), adverse reaction to drug (995.2; 52%), and anaphylaxis (995.0; 38%). Patients with both an ICD-9-CM code and an E code had a high likelihood of having an allergic drug reaction (76%). Most allergic drug reactions were attributed to antibiotics (42%), intravenous contrast (7%), and nonsteroidal anti-inflammatory drugs (6%). The estimated frequency of allergic drug reactions increased from 0.49% of ED visits in 2001 to 0.94% in 2012. Specific ICD-9-CM and E codes can be used in combination to identify allergic drug reactions. Further study of these codes in the inpatient and outpatient settings is necessary to better understand the utility of diagnosis codes for improving epidemiologic research on drug allergy.


Characteristics of meso-particles formed in coagulation process causing irreversible membrane fouling in the coagulation-microfiltration water treatment.
In coagulation-membrane filtration water treatment processes, it is still difficult to determine the optimal coagulation condition to minimize irreversible membrane fouling. In microfiltration (MF), meso-particles (i.e., 20 nm-0.5 μm) are thought to play an important role in irreversible membrane fouling, especially their characteristics of particle number (PN) and zeta potential (ZP). In this study, a new nanoparticle tracker combined a high-output violet laser with a microscope was developed to identify the physicochemical characteristics of these microscopic and widely dispersed meso-particles. The effects of pH and coagulant dose on ZP and PN of micro-particles (i.e., >0.5 μm) and meso-particles were investigated, and then coagulation-MF tests were conducted. As the result, irreversible membrane fouling was best controlled for both types of membranes, while meso-particle ZP approached zero at around pH 5.5 for both types of natural water. Since PN was greatest under these conditions, ZP is more important in determining the extent of irreversible membrane fouling than PN. However, the acidic condition to neutralize meso-particles is not suitable for actual operation, as considering residual aluminum concentration, pipe corrosion, and chlorination efficiency. It is therefore necessary to investigate coagulants or other methods for the appropriate modification of meso-particle characteristics.


Mobilising a rural community to lose weight: impact evaluation of the WellingTonne Challenge.
To evaluate the impact of the WellingTonne Challenge. Before-after study. The National Action Agenda for the prevention and control of obesity in Australia identified community action and development as a key theme. The WellingTonne Challenge was a whole-of-community project designed to support a small rural community to lose weight and reduce their risk of chronic disease. Adult residents of the Wellington Local Government Area who were overweight or obese. The project successfully engaged the community with around 10% of the target group formally participating in the Challenge. Participants achieved a weight reduction of around 3 kg each, as well as positive changes in diet and physical activity. A total of 59% of those who signed up for the Challenge achieved an accumulated loss of 687 kg at the end of the 12-week program--less than the community goal of 1000 kg. The WellingTonne Challenge is a promising intervention. Wider implementation of this approach in other small rural communities might make a significant contribution to the national effort. The opportunity should be taken to undertake a more rigorous evaluation to determine whether this approach benefits communities in the longer term.


Pyogenic Liver Abscess After Pancreaticoduodenectomy: A Single-Center Experience.
Pancreaticoduodenectomy (PD) is a complex procedure with a morbidity rate of 40%-50%. We evaluated the incidence, associated factors, etiologic characteristics, and outcome of pyogenic liver abscess (PLA), a rare infectious complication of PD. We retrospectively assessed the data of patients who underwent PD (n = 326) between January 2012 and February 2017 at a single institution. Patients who developed PLA after PD were matched (1:3) for age, sex, and pathologic diagnosis with patients without PLA after PD. Patients who developed PLA without abdominal operation history (n = 77) were also reviewed in the same period. Eleven patients (3.4%) developed PLA after PD; diabetes (5/11, 45.5% versus 4/33, 12.1%; P = 0.031) increased the risk of PLA after PD. The preoperative and postoperative fasting blood glucose (FBG) was significantly higher in PLA+ group than PLA- group: preoperative FBG (median: 7.39 versus 4.49; P < 0.01), postoperative FBG (median: 8.98 versus 5.68; P < 0.01). The occurrence of multiple liver abscess was significantly higher in patients with PLA after PD than patients who developed PLA without abdominal operation history (7/11 versus 22/77; P = 0.036). Microbial pus culture was positive in eight patients with PLA after PD (n = 8/11) and in forty-one patients who developed PLA without abdominal operation history (n = 41/77). Klebsiella pneumoniae was the most commonly isolated microorganism in PLA patients with or without a history of PD (5/8, 62.5% versus 34/41, 82.9%; P = 0.333). Patients with diabetes (including impaired fasting plasma glucose) have a higher risk of developing PLA after PD. Multiple liver abscess was the most common type of PLA after PD; K pneumoniae should be covered when empirically treated patients with PLA.


Reproductive value and the evolution of altruism.
Altruism is favored by natural selection provided that it delivers sufficient benefits to relatives. An altruist's valuation of her relatives depends upon the extent to which they carry copies of her genes - relatedness - and also on the extent to which they are able to transmit their own genes to future generations - reproductive value. However, although relatedness has received a great deal of attention with regard to altruism, reproductive value has been surprisingly neglected. We review how reproductive value modulates patterns of altruism in relation to individual differences in age, sex, and general condition, and discuss how social partners may manipulate each other's reproductive value to incentivize altruism. This topic presents opportunities for tight interplay between theoretical and empirical research.


Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity.
Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and AKT signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases.


High-Fidelity Simulation With Debriefing: Best Practice Education for Flight Nurses?
High-fidelity simulation with debriefing has been shown to be effective in maintaining high-risk, low-volume proficiencies in nursing. The purpose of this evidence-based practice project was to implement high-fidelity simulation with debriefing to measure improvements in flight nurse skill acuity and retention when performing intubations. This was a prospective evidence-based project conducted before and after a debriefing intervention that took place at HealthNet Aeromedical Services, Charleston, WV. Participants were flight nurses who were asked to intubate during a high-fidelity simulation session and participate in a debriefing session to reflect on their performance. They were then tested on 7-month skill retention. Eight subjects completed all stages of the study and were included in the analysis. The mean ± standard deviation time to successful intubation predebriefing was 26.9 ± 11.9 seconds; for postdebriefing, it was 24.8 ± 5.8 seconds. The mean ± standard deviation checklist score before debriefing was 7.9 ± 0.4 points, whereas for postdebriefing it was 9.4 ± 0.7 points. The implementation of debriefing after simulation improved the time to intubation and produced better clinical judgment and mastery while performing the intubation.


Acute graft-vs.-host disease correlates with the disparity for the PECAM-1 S536N polymorphism only in the HLA-B44-like positive Tunisian recipients of HSCs.
GVHD is the major cause of mortality after HLA-identical HSCT. Such complication has been widely linked to donor/recipient disparity for minor histocompatibility antigens (MiHAgs). PECAM-1 is one of potential human MiHAgs but its effect on the GVHD occurrence remains not clear. In order to examine such association in the Tunisian cohort of HSCs recipients, we performed a retrospective study on patients who undergone HLA-identical HSCT between 2000 and 2009. Genotyping of the three selected PECAM-1 polymorphisms (rs668, rs12953 and rs1131012) was performed with SSP-PCR method. Univariate analyses showed that grades II-IV acute GVHD were considerably linked to the non-identity for rs12953 only in HLA-B44-like positive patients (p=0.010, OR=10.000). Multivariate analysis for chronic GVHD showed that this outcome may be affected only by the adulthood and the conditioning regimen. Our findings support the previously reported data suggesting a significant association between the PECAM-1 disparity and the risk of acute GVHD.


Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.
Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors.


Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer.
Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD-L1 expression in a large-scale consecutive cohort from East-Asian patients with non-small cell lung cancer (NSCLC). PD-L1 testing was conducted using 22C3 assays, and cases were categorized into the high, low, and no expression of PD-L1 based on the tumor proportion score (TPS). Target-capture next-generation sequencing was used to identify molecular events. A total of 4550 patients and 4622 tests of PD-L1 expression were enrolled. There were 3017 (66.3%) patients with no PD-L1 expression (TPS < 1%), 1013 (22.3%) with low PD-L1 expression (TPS 1-49%), 520 (11.4%) with high PD-L1 expression (TPS ≥ 50%). Higher proportions of positive PD-L1 expression (TPS ≥ 1%) were observed in smokers, males, squamous cell carcinoma, and high-grade lung adenocarcinoma. Further analyses revealed fair agreement in primary and metastatic lesions (kappa = 0.533), poor agreement in multi-focal primary tumors (kappa = 0.045), and good agreement in biopsy and resection samples (kappa = 0.662) / two biopsy samples (kappa = 0.711). Mutational analyses revealed association between high PD-L1 expression (TPS ≥ 50%) and EGFR wild-type, KRAS mutation, ALK rearrangement, and TP53 mutation. The study reveals the unique distribution pattern of PD-L1 expression in a large-scale East-Asian cohort with NSCLC, the concordance of multiple PD-L1 tests, and the association between PD-L1 expression and molecular events. The results shed a light on the optimization of PD-L1 testing in clinical practice.


Hollow nitrogen-containing core/shell fibrous carbon nanomaterials as support to platinum nanocatalysts and their TEM tomography study.
Core/shell nanostructured carbon materials with carbon nanofiber (CNF) as the core and a nitrogen (N)-doped graphitic layer as the shell were synthesized by pyrolysis of CNF/polyaniline (CNF/PANI) composites prepared by in situ polymerization of aniline on CNFs. High-resolution transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared and Raman analyses indicated that the PANI shell was carbonized at 900°C. Platinum (Pt) nanoparticles were reduced by formic acid with catalyst supports. Compared to the untreated CNF/PANI composites, the carbonized composites were proven to be better supporting materials for the Pt nanocatalysts and showed superior performance as catalyst supports for methanol electrochemical oxidation. The current density of methanol oxidation on the catalyst with the core/shell nanostructured carbon materials is approximately seven times of that on the catalyst with CNF/PANI support. TEM tomography revealed that some Pt nanoparticles were embedded in the PANI shells of the CNF/PANI composites, which might decrease the electrocatalyst activity. TEM-energy dispersive spectroscopy mapping confirmed that the Pt nanoparticles in the inner tube of N-doped hollow CNFs could be accessed by the Nafion ionomer electrolyte, contributing to the catalytic oxidation of methanol.


Polyp size of 1 cm is insufficient to discriminate neoplastic and non-neoplastic gallbladder polyps.
A significant proportion of gallbladder polyps are non-neoplastic, for which resection is not necessary. However, international guidelines advocate cholecystectomy for all polyps ≥ 1 cm. This study assessed a national cohort of histopathologically proven gallbladder polyps to distinguish neoplastic from non-neoplastic polyps. PALGA, the nationwide network and registry of histo- and cytopathology, was searched to identify all histopathologically proven gallbladder polyps between 2003 and 2013. All polyps and (focal) wall thickenings > 5 mm were included, and classified as neoplastic or non-neoplastic. Polyp subtype, size, distribution, presentation as wall thickening or protruding polyp, and presence of gallstones were assessed for neoplastic and non-neoplastic polyps. A decision tree to distinguish neoplastic and non-neoplastic polyps was made and diagnostic accuracy of 1 cm surgical threshold was calculated. A total of 2085 out of 220,612 cholecystectomies contained a polyp (0.9%). Of these polyps, 56.4% were neoplastic (40.1% premalignant, 59.9% malignant) and 43.6% non-neoplastic (41.5% cholesterol polyp, 37.0% adenomyomatosis, 21.5% other). Polyp size, distribution, and presence of gallstones were reported in 1059, 1739 and 1143 pathology reports, respectively. Neoplastic polyps differed from non-neoplastic polyps in size (18.1 mm vs 7.5 mm, p < 0.001), singularity (88.2% vs 68.2%, p < 0.001), wall thickening (29.1% vs 15.6%, p < 0.001), and presence of gallstones (50.1% vs 40.4%, p = 0.001). However, adenomyomatosis presented with similar characteristics as neoplastic polyps. Fifty percent of polyps were ≥ 1 cm surgical threshold (optimal surgical threshold based on ROC-curve); sensitivity for indicating neoplastic polyps was 68.1%, specificity was 70.2%, and positive and negative predictive values were 72.9% and 65.1%. The prevalence of gallbladder polyps on cholecystectomy is low and many of the polyps are non-neoplastic. Clinicopathological characteristics differ between neoplastic and non-neoplastic polyps in general, but these cannot properly indicate neoplasia. The 1 cm surgical threshold has moderate diagnostic accuracy and is insufficient to indicate surgery for neoplastic gallbladder polyps.


Improvement of the signal to noise ratio for fluorescent imaging in microfluidic chips.
Microfluidics systems can be fabricated in various ways using original silicon glass systems, with easy Si processing and surface modifications for subsequent applications such as cell seeding and their study. Fluorescent imaging of cells became a standard technique for the investigation of cell behavior. Unfortunately, high sensitivity fluorescent imaging, e.g., using total internal reflection fluorescence (TIRF) microscopy, is problematic in these microfluidic systems because the uneven surfaces of the silicon channels' bottoms affect light penetration through the optical filters. In this work, we study the nature of the phenomenon, finding that the problem can be rectified by using a silicon-on-insulator (SOI) substrate, defining the channel depth by the thickness of the top Si layer, and halting the etching at the buried SiO2 layer. Then the fluorescent background signal drops by = 5 times, corresponding to the limit of detection drop from = 0.05 mM to = 50 nM of fluorescein. We demonstrate the importance of a flat surface using TIRF-based single-molecule detection, improving the signal to a noise ratio more than 18 times compared to a conventional Si wafer. Overall, using very high-quality SOI substrates pays off, as it improves the fluorescence image quality due to the increase in signal-to-noise ratio. Concerning the cost of microfluidic device fabrication-design, mask fabrication, wafer processing, and device testing-the initial SOI wafer cost is marginal, and using it improves the system performance.


Activation of the PKB/AKT pathway by ICAM-2.
We identified intracellular adhesion molecule-2 (ICAM-2) in a genetic screen as an activator of the PI3K/AKT pathway leading to inhibition of apoptosis. ICAM-2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation, resulting in phosphatidylinositol 3,4,5 production, PDK-1 and AKT activation, and subsequent phosphorylation of AKT targets BAD, GSK3, and FKHR. ICAM-2 clustering protected primary human CD19+ cells from TNFalpha- and Fas-mediated apoptosis as determined by single-cell analysis. ICAM-2 engagement by CD19+ cells of its natural receptor, LFA-1, on CD4+ naive cells specifically induced AKT activity in the absence of an MHC-peptide interaction. These results attribute a novel signaling function to ICAM-2 that might suggest mechanisms by which ICAM-2 signals intracellular communication at various immunological synapses.


Neuronal activation and plasticity in Schistosoma mansoni infected mice.
Schistosomiasis leads to structural and functional changes which may result from unbalanced release of some inflammatory mediators. The aim of the study was to investigate the effect of intestinal parasitic infection on nitric oxide release and to evaluate the neural plasticity that leads to motility disturbance. Experiments were performed in Swiss mice 8- and 12-weeks following infection with Schistosoma mansoni compared to untreated controls. Jejunal motility was assessed using a Trendelenburg preparation to study aboral directed peristaltic pressure waves. Histological examination was used to determine the pathological characteristics of inflammation. Parasitic infection produces diffuse inflammatory infiltrate in both 8- and 12-weeks infected animals. Inflammation had significant effect on peristaltic pressure waves amplitude and intervals at 8-weeks compared to control; whereas, in 12-weeks post infection there was a significant decrease in peristaltic pressure waves amplitude and interval compared to 8- weeks and control. Nitric oxide synthase inhibitor (L-NAME 100 μM) induced a significant increase in amplitude and decrease in intervals in control, 8- and 12- weeks infected animals. In conclusion, parasitic infection leads to disturbance in the release of the inflammatory mediators. This study indicated the role of nitric oxide in developing granulomatous inflammation and participating in motility disturbance.


Effect of temperature on albumin cobalt binding and its influence on ischemia-modified albumin levels in patients with suspected acute coronary syndrome.
Ischemia-modified albumin (IMA) has been shown to be a rapidly rising and sensitive biochemical marker especially for the diagnosis of myocardial ischemia. The aim of this study was to evaluate the influence of temperature on the capacity of cobalt binding to human albumin and the influence of this variable on IMA measurement. The following temperatures of incubation were tested for human albumin standard 25 degrees C, 28 degrees C, 31 degrees C, 34 degrees C, and 37 degrees C and for patients with suspected acute coronary syndrome, room temperature and 37 degrees C. IMA was measured by cobalt-albumin binding assay. There was a strong positive correlation (r = 0.98, p < 0.001) between IMA and the assay temperatures. IMA levels were 0.68 +/- 0.25 absorbance units (ABSU) at room temperature and 0.92 +/- 0.33 ABSU (p < 0.001) at 37 degrees C in the study participants. IMA values were influenced by the assay temperature.


Differences in the patterns of phenytoin-induced malformations following stiripentol coadministration in three inbred mouse strains.
Differences in the patterns of congenital malformations observed in three inbred mouse strains (SWV, LM/Bc, and C57BL/6J) were compared following exposure to phenytoin monotherapy and a polytherapeutic regimen of phenytoin and stiripentol. Treatment groups containing no fewer than 10 dams were chronically exposed to the test compound(s) prior to and throughout gestation. The pattern of fetal defects observed included abnormalities of the neural, cardiac, urogenital, and skeletal systems. The coadministration of the cytochrome P-450-inhibiting antiepileptic drug stiripentol significantly reduced the incidence of fetal malformations in all three strains, primarily by reducing phenytoin's deleterious effects on congenital abnormalities related directly to fetal growth and development. In the SWV fetuses, there were significantly more soft tissue defects (neural and renal) than were evident in the LM/Bc fetuses. Overall, the C57BL/6J fetuses were the most sensitive to the induction of skeletal defects, with a preponderance of defects in the ossification of the craniofacial bones. It is hypothesized that the reduction in fetal defects was the result of limiting the biotransformation of phenytoin to highly teratogenic oxidative metabolites, which interfere with normal fetal growth.


Butyl 4-(butyryloxy)benzoate functions as a new selective estrogen receptor beta agonist and induces GLUT4 expression in CHO-K1 cells.
Estrogen receptors (ERs) belong to nuclear hormone receptor superfamily and can be activated by estrogens and regulate many target genes. Two ER isoforms, ERalpha and ERbeta have been discovered to date and ERbeta was indicated to involve in anti-inflammatory and anti-diabetogenic effects. Recently, some studies also demonstrated an association between ERbeta and GLUT4 expression. The development of selective ERbeta ligand has facilitated probing its novel biological functions and clinical benefits. In this work, a new ERbeta selective agonist, butyl 4-(butyryloxy)benzoate (DCW234), was discovered as investigated by surface plasmon resonance (SPR) technology, yeast two-hybrid and cell-based transcription-based assays. SPR results demonstrated that DCW234 has a higher binding affinity against ERbeta over ERalpha and induces a strong and selective stimulation on ERbeta/SRC1 interaction, which could be efficiently blocked by Tamoxifen. Meanwhile, the yeast two-hybrid technology-based assay indicated that DCW234 exhibits a higher agonistic activity ( approximately 13-fold) in stimulating ERbeta ligand-binding domain (LBD) interaction with SRC1 (EC(50)=2.5 microM) than ERalpha-LBD/SRC1 interaction (EC(50)=32.7 microM). The cell-based transcriptional assay further proved the potency and selectivity of DCW234. Moreover, DCW234 was found to be able to induce GLUT4 expression in CHO-K1 cell. The discovered DCW234 might be hopefully developed as a potential lead compound for further research.


Management of acute severe upper airway obstruction in children.
There are many causes of acute severe upper airway obstruction (UAO) in children. The timing of symptom onset and the presence of fever will help to distinguish infectious from non-infectious conditions. Signs and symptoms from congenital malformations often present at birth but may also develop over time. The most common cause of UAO in children is croup. Choking on a foreign body also occurs relatively frequently. Evaluation of the child with UAO starts with a detailed history followed by a thorough physical examination, including an assessment of severity. Severe airway obstruction will result in respiratory failure. This situation requires an immediate response. A child with partial airway obstruction may initially have an adequate airway. However, this situation can deteriorate rapidly. Therefore, providing supportive care and mobilizing resources for definitive airway management may be the most appropriate interventions.


Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin-exposed humans with chloracne.
Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue of chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne.


Fusidic acid is an effective treatment against Toxoplasma gondii and Listeria monocytogenes in vitro, but not in mice.
Fusidic acid is a bacteriostatic antibiotic that inhibits the growth of bacteria by preventing the release of translation elongation factor G (EF-G) from the ribosome. The apicomplexan parasite Toxoplasma gondii has an orthologue of bacterial EF-G that can complement bacteria and is necessary for parasite virulence. Fusidic acid has been shown to be effective in tissue culture against the related pathogen Plasmodium falciparum, and current drug treatments against T. gondii are limited. We therefore investigated the therapeutic value of fusidic acid for T. gondii and found that the drug was effective in tissue culture, but not in a mouse model of infection. To determine whether this trend would occur in another intracellular pathogen that elicits a T helper 1-type immune response, we tested the efficacy of fusidic acid for the bacterium Listeria monocytogenes. Similar to its effects on T. gondii, fusidic acid inhibits the growth of L. monocytogenes in vitro, but not in mice. These findings highlight the necessity of in vivo follow-up studies to validate in vitro drug investigations.


Nucleotide binding sites on mitochondrial F1-ATPase. Electron spin resonance spectroscopy and photolabeling by azido-spin-labeled adenine nucleotides support an adenylate kinase-like orientation.
A spin-labeled photoaffinity ATP analog, 2-N3-2',3'-SL-ATP (2-N3-SL-ATP) was specifically loaded at catalytic (exchangeable) or noncatalytic (nonexchangeable) nucleotide-binding sites on nucleotide-depleted mitochondrial F1-ATPase. Photolysis of the enzyme complexes resulted in the specific modification of beta-Tyr-345 when the catalytic sites were occupied and beta-Tyr-368 when noncatalytic sites were filled. These are the same amino acid assignments that were made previously using 2-N3ATP. The results demonstrate that the attachment of a spin label moiety to the ribose ring does not prevent proper binding of the analog at both types of nucleotide sites on F1-ATPase and suggest that the probe can be used for investigations of the nucleotide-binding sites using ESR spectroscopy. Enzyme that is in complex with the 2-N3-SL-ATP exhibits an ESR spectrum that is typical for highly immobilized nitroxyl radicals both in the dark or after photolysis. Additional peaks in the high- and low-field regions arise due to dipolar spin interactions most likely involving a pair of catalytic and noncatalytic sites. The two sites are calculated to be approximately 15 A apart. This distance, obtained through ESR spectroscopy, combined with the finding that the 2 labeled amino acids are only 23 residues apart from each other, further supports an adenylate kinase-like arrangement of nucleotide binding sites on F1-ATPase where catalytic and noncatalytic sites are in close proximity (Vogel, P. D., and Cross, R. L. (1991) J. Biol. Chem. 266, 6101-6105).


Antagonism of neuronal kainate receptors by lanthanum and gadolinium.
The effects of lanthanum and gadolinium on currents evoked by excitatory amino acids were studied in cultured rat hippocampal and cortical neurons, in freshly dissociated dorsal root ganglion neurons, and in human embryonic kidney 293 cells expressing the GluR6 kainate receptor subunit. In all of these cells, currents mediated by kainate-preferring receptors were antagonized by low micromolar concentrations of the trivalent ions. At negative holding potentials, the IC50 values for inhibition in DRG cells were 2.8 microM for La and 2.3 microM for Gd. Kainate receptor-mediated currents in hippocampal neurons and in 293 cells expressing GluR6 were blocked by La with IC50 values of 2.1 and 4.4 microM, respectively. Steady-state inhibition by the lanthanides showed very slight dependence on membrane potential, however, we were not able to resolve any systematic variation with membrane potential in the kinetics of block onset or recovery. Inhibition was not use-dependent and was not overcome by increasing the concentration of agonist. These results indicate that lanthanides probably do not bind deep within the ion pore or directly compete for the agonist binding site. In contrast to neuronal AMPA receptors, which require more than 100 microM lanthanides for half-maximal blockade, the inhibition of neuronal and recombinant kainate receptors by these ions displays significantly higher potency.


Neferine mitigates cisplatin-induced acute kidney injury in mice by regulating autophagy and apoptosis.
The nephrotoxicity caused by cisplatin severely limits the application and affects related platinum-based therapeutics. Neferine is a dibenzylisoquinoline alkaloid extracted from a Chinese medicinal herb (Nelumbo nucifera Gaertn), which can decrease cisplatin-induced apoptosis of NRK-52E cells by activating autophagy in vitro in our previous study. In this article, we aimed to further investigate the protective effect of neferine, against to the cispltain-induced kidney damage in mice. Six groups were designed in our study. Renal index, mice serum creatinine and blood urea nitrogen levels were detected after the mice were killed. HE staining was used to observe the pathological changes of each group. The apoptosis of mouse kidney tissue was detected by TUNEL. Immunofluorescence and Western blot were used to detect the expression of cleaved-caspase3 and LC3. The transmission electron microscope was used to reveal the changes of apoptosis and autophagy of renal tubular epithelial cells in different groups. In our findings, the pathological changes of acute kidney injury were easily observed in cisplatin-treated mice while those in the neferine-pretreated groups were significantly alleviated. The apoptosis induced by cisplatin in mice increased evidently compared with the control group, which was decreased in the mice with neferine pretreatment. What' more, we found that autophagy increased obviously in mice pretreated by neferine contrast to the cisplatin-treated mice. In our study, neferine can effectively alleviate cisplatin-induced renal injury in mice, as well act as an autophagy-regulator in kidney protection.


The effect of tobacco smoking on the frequency of sister chromatid exchanges in human lymphocyte chromosomes.
The incidence of sister chromatid exchange (SCE) was investigated in the lymphocyte chromosomes of 24 bidi smokers, 18 cigarette smokers, and 20 normal nonsmoking controls. Bidi and cigarette smokers had a mean SCE per cell of 10.12 +/- 2.41 and 8.15 +/- 1.62, respectively, which were significantly higher than the mean value of 5.48 +/- 1.29 found in controls. Higher frequencies of SCE were also observed in individuals who smoked more than ten bidis or cigarettes per day, compared with people who smoked less than ten bidis or cigarettes per day, respectively. Individuals who smoked bidis or cigarettes for more than 10 years also showed an increased frequency of SCE as compared with those who smoked bidis or cigarettes for less than 10 years.


A Review of Consent Documents From Canadian IVF Clinics, 1991 to 2014.
We reviewed the content of IVF consent documents (i.e., consent forms and accompanying information sheets) used by Canadian IVF clinics in 1991, 2004, and 2014, paying particular attention to the inclusion of information that should be provided to patients in accordance with minimum ethical standards for disclosure. We contacted all Canadian IVF clinics in operation in 1991 (17 clinics), 2004 (24 clinics), and 2014 (35 clinics) by mail and requested blank copies of their IVF consent documents. Documents received were reviewed for the inclusion of information about the nature of IVF, the potential benefits of IVF, the potential harms and inconveniences of IVF, confidentiality, voluntariness, and options for the use or discarding of embryos not transferred in the original stimulated cycle (sometimes referred to as supernumerary, excess, or spare embryos). We received responses from 11 of 17 clinics operating in 1991 (response rate 65%), 14 of 24 clinics operating in 2004 (response rate 58%), and 11 of 35 clinics operating in 2014 (response rate 31%). In general, comparisons of the 1991, 2004, and 2014 data sets showed a long-term decrease in documented disclosure of information that should be provided to patients in accordance with minimum ethical standards. The only cases in which this trend appeared to be reversed was with disclosure about the probability of supernumerary embryos, long-term risks of treatment, the right to revoke consent to the use or discarding of supernumerary embryos, and some of the options for the use of supernumerary embryos. In these few instances, there was a notable improvement in the disclosure of relevant information between 1991 and 2014. The disclosure of information relevant to the interests of those undergoing IVF and those who are born as a result of IVF appears to be decreasing. Furthermore, the information that increasingly is being disclosed in consent documents appears to be directing the orientation and content of these documents away from the primary interests of the relevant women, couples, and children. These two trends are inconsistent with the goal of informed consent.


Changes in Objectively Measured Physical Activity Are Associated With Perceived Physical and Mental Fatigability in Older Men.
Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established. Community-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to <3.0), moderate-to-vigorous PA (MVPA, METs ≥ 3.0), and sedentary behavior (SB, METs ≤ 1.5, excluding sleep). Perceived physical and mental fatigability were measured (Year 14) with the Pittsburgh Fatigability Scale (PFS, higher score = greater fatigability; range = 0-50). Associations between each metric of percent changes in PA and fatigability were examined using linear regression, adjusted for demographics, change in health conditions, and Year 7 step count or total PA (METs > 1.5). Men declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores. Older men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.


Revision of fossil species of Dryinus belonging to lamellatus group, with description of a new species (Hymenoptera, Dryinidae).
Dryinus rasnitsynisp. n. is described from amber collected in the Dominican Republic. A revision and a key to the fossil Neotropical species of Dryinus Latreille, 1804 belonging to the lamellatus species group is presented.


Tunable nanoplasmonic sensor based on the asymmetric degree of Fano resonance in MDM waveguide.
We first report a simple nanoplasmonic sensor for both universal and slow-light sensing in a Fano resonance-based waveguide system. A theoretical model based on the coupling of resonant modes is provided for the inside physics mechanism, which is supported by the numerical FDTD results. The revealed evolution of the sensing property shows that the Fano asymmetric factor p plays an important role in adjusting the FOM of sensor, and a maximum of ~4800 is obtained when p = 1. Finally, the slow-light sensing in such nanoplasmonic sensor is also investigated. It is found that the contradiction between the sensing width with slow-light (SWS) and the relevant sensitivity can be resolved by tuning the Fano asymmetric factor p and the quality factor of the superradiant mode. The presented theoretical model and the pronounced features of this simple nanoplasmonic sensor, such as the tunable sensing and convenient integration, have significant applications in integrated plasmonic devices.


High-level, heat-regulated synthesis of proteins in eukaryotic cells.
Plasmids have been constructed in which promoters of 70-kDa heat-shock protein genes (hsp70) of human and Drosophila origin were linked to three different eukaryotic genes encoding human growth hormone (hGH), chicken lysozyme (cL) and a human influenza haemagglutinin (HA). Following transfection into widely divergent eukaryotic cells, the hybrid genes direct the transient, heat-regulated synthesis of the three proteins. hGH and cL are secreted into the medium. A human hsp70-hGH construct was used to establish stable mouse fibroblast lines that are capable of producing and secreting hGH at high levels following heat induction: hGH is secreted at a 500-1200-fold higher rate by heat-treated than by untreated cells.


Correction: Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents, Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B₁. Toxins 2017, 9, 371.
The authors wish to make the following correction to their paper [...].


Detection of specific IgE antibodies towards cat flea (Ctenocephalides felis felis) in patients with suspected cat allergy.
Cat flea sensitivity is considered one of the most important skin diseases in cats and dogs. Cat fleas, however, are also a growing allergen problem for humans. Cat flea-specific IgE antibodies were studied in serum samples from 70 patients with suspected cat allergy, using RAST-based techniques and the nitrocellulose immunoblotting method. Results from RAST studies, using cat and cat flea as allergosorbents, showed that 46% of the patients were RAST positive against both cat and cat flea. 9% of the patients were RAST positive only against the cat flea. The nitrocellulose immunoblotting experiments were in agreement with the RAST results showing specific IgE to cat flea. The results indicate that some cat-allergic patients have specific IgE both towards cat and cat flea but also that some of the patients with suspected cat allergy might have specific IgE towards the cat flea and not the cat. RAST-inhibition and immunoblotting experiments also indicate that the allergen composition of cat flea extract differs from that of cat extract, even if common allergens have been detected, leading to cross-reactivity in some sera.


Image-guided brachytherapy for gynecologic surgeons.
Brachytherapy is a fundamental component of the definitive treatment of many advanced gynecologic malignancies, most notably cancers of the uterine corpus and cervix, and allows high radiation doses to be delivered to the target while minimizing the normal tissue dose. However, dose specification has been based primarily on points visible on plain radiographs, with limited correlation to a patient's anatomy and extent of disease. Recent advances have allowed more customized volume-based specification of dose, which has allowed improvements in outcomes. This article reviews these advances using cervical cancer as a model, and looks to future directions with this promising treatment.


The lack of a physiologic effect of the stress-induced decrease of the proestrous prolactin surge in the rat.
Experiments were performed to determine whether the restraint stress-induced decrease in the proestrous prolactin (PRL) surge blocked luteolysis of the corpora lutea (CL), affected ovulation, or prevented the induction of pregnancy/pseudopregnancy in the next cycle. In all experiments rats were either stressed on proestrus and estrus, administered daily sc injections of 1 mg/day of 2-Br-alpha-ergocryptine (CB-154) for 4 days starting on diestrus II or not treated. In one experiment animals were sampled on the afternoon of proestrus to determine the effect of restraint stress on plasma PRL values and sacrificed on the morning of proestrus in the next cycle. Ovaries were removed, weighed, fixed and examined for number of CL. Restraint stress resulted in a significant increase in ovarian weight when compared to controls; CB-154 resulted in significant increases in ovarian weight when compared to stress and control animals. However, only CB-154-treated animals had a significant increase in the number of CL when compared to controls. In another experiment, animals were sacrificed on estrus of the next cycle and the oviducts examined for the number of ova. There were no differences among groups. In the final experiment, animals were placed with males of proven fertility on proestrus of the next cycle and examined for evidence of sperm in the vaginal lavage and/or vaginal plugs. CB-154 prevented the induction of pregnancy or pseudopregnancy due to a carry over effect of the drug on PRL surges. Restraint stress had no significant effect on the induction of pregnancy or pseudopregnancy. We conclude that there is no physiological significance to the stress-induced decrease of the proestrous PRL surge with respect to ovarian function or fertility.


Developmental temperature alters the thermal sensitivity of courtship activity and signal-preference relationships, but not mating rates.
Mating behaviors are sensitive to novel or stressful thermal conditions, particularly for ectothermic organisms. An organism's sensitivity to temperature, which may manifest in altered mating outcomes, can be shaped in part by temperatures experienced during development. Here, we tested how developmental temperature shapes the expression of adult mating-related behaviors across different ambient conditions, with a focus on courtship behavior, mating rates, and mating signals and preferences. To do so, we reared treehoppers under two temperature regimes and then tested the expression of male and female mating behaviors across a range of ambient temperatures. We found that developmental temperature affects the thermal sensitivity of courtship behavior and mating signals for males. However, developmental temperature did not affect the thermal sensitivity of courtship or mate preferences in females. This sex-specific plasticity did not alter the likelihood of mating across ambient temperatures, but it did disrupt how closely mating signals and preferences matched each other at higher ambient temperatures. As a result, developmental temperature could alter sexual selection through signal-preference de-coupling. We further discuss how adult age may drive sex-specific results, and the potential for mismatches between developmental and mating thermal environments under future climate change predictions.


Proteomics of FACS-sorted heterogeneous Corynebacterium glutamicum populations.
The metabolic status of individual cells in microbial cultures can differ, being relevant for biotechnology, environmental and medical microbiology. However, it is hardly understood in molecular detail due to limitations of current analytical tools. Here, we demonstrate that FACS in combination with proteomics can be used to sort and analyze cell populations based on their metabolic state. A previously established GFP reporter system was used to detect and sort single Corynebacterium glutamicum cells based on the concentration of branched chain amino acids (BCAA) using FACS. A proteomics workflow optimized for small cell numbers was used to quantitatively compare proteomes of a ΔaceE mutant, lacking functional pyruvate dehydrogenase (PD), and the wild type. About 800 proteins could be quantified from 1,000,000 cells. In the ΔaceE mutant BCAA production was coordinated with upregulation of the glyoxylate cycle and TCA cycle to counter the lack of acetyl CoA resulting from the deletion of aceE. Metabolic pathways in C. glutamicum WT and ΔaceE, devoid of functional pyruvate dehydrogenase, were compared to understand proteome changes that contribute to the high production of branched chain amino acids (BCAA) in the ΔaceE strain. The data complements previous metabolome studies and corroborates the role of malate provided by the glyoxylate cycle and increased activity of glycolysis and pyruvate carboxylase reaction to replenish the TCA cycle. A slight increase in acetohydroxyacid synthase (ILV subunit B) substantiates the previously reported increased pyruvate pool in C. glutamicumΔaceE, and the benefit of additional ilv gene cluster overexpression for BCAA production.


A novel glycosaminoglycan-like polysaccharide from abalone Haliotis discus hannai Ino: purification, structure identification and anticoagulant activity.
A novel glycosaminoglycan-like sulfated polysaccharide (AAP) from the pleopods of Haliotis discus hannai Ino was purified by DEAE ion exchange chromatography followed with S-300 HR geltrion chromatography. Chemical composition analysis indicated that AAP was composed of galactosamine, glucuronic acid, fucose, galactose with a ratio of 2.14:2.37:2.94:1, the content of sulfate was 15.5%. The average molecular weight (M(w)) was 56.2 kDa in a TSK G4000 column. Further IR, 1D, 2D NMR spectroscopic analysis of the correlation signals of different sugar units gave a proposal repeating structure, as follows: [chemical structure: see the text] In vitro anticoagulant assay indicated AAP prolonged both the activated partial thromboplastin time (APTT) and thrombin time (TT), with a 22.5 U/mg and 72.0 U/mg compared with standard heparin, respectively. The anticoagulant property of AAP was mainly attributed to powerful potentiation thrombin by anti-thrombin III.


Studying the mechanism of sperm DNA damage caused by folate deficiency.
Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double-strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = -0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC-2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ-H2AX, that is, DNA injury marker protein, and increased sensitivity of GC-2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.


Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation.
Variants of the transthyretin (TTR) gene cause hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis (v for variant), which results from deposition of misfolded TTR protein as amyloid in organs and tissues. Patisiran is an RNA interference (RNAi) therapeutic that suppresses the hepatic production of TTR protein. Patisiran improves multiple clinical manifestations of hATTR amyloidosis in patients without liver transplantation (LT). Because the liver is the predominant source of circulating TTR, LT has been prescribed to eliminate the production of the variant TTR. However, the continued production of wild-type TTR can contribute to disease progression after LT. Patisiran could potentially address an unmet need in these affected patients. This clinical trial was conducted to evaluate the safety, efficacy, and pharmacokinetics (PK) and pharmacodynamics (PD) of patisiran in patients with hATTR amyloidosis with polyneuropathy progression after LT. In this paper, we describe the PK/PD of patisiran in post-LT patients and compare it with prior patisiran studies in healthy subjects and patients without LT. In an open-label study, patients (N = 23) with hATTR amyloidosis with polyneuropathy progression after LT received 0.3 mg/kg patisiran intravenously every 3 weeks (q3w) for 12 months. As a post hoc analysis, the PK and PD results from the current study were compared with prior patisiran studies in healthy volunteers from a Phase 1 study and in patients with hATTR amyloidosis without LT from Phase 2 and 3 studies. The PK profile of patisiran siRNA (ALN-18328) and its 2 lipid excipients, DLin-MC3-DMA and PEG2000-C-DMG, in hATTR amyloidosis patients after LT was consistent with prior patisiran studies in non-LT subjects. Plasma PK profiles of ALN-18328 and DLin-MC3-DMA exhibited 2 phases, the first characterized by a short distribution half-life and the second by a minor peak and relatively long elimination half-life. The plasma concentrations of PEG2000-C-DMG reached Cmax at the end of infusion and declined in a multiphasic manner. There was no appreciable accumulation at steady state. Consistent with prior studies in non-LT subjects, the post-LT patients showed a robust, and sustained TTR reduction; with median TTR reduction from baseline of 91% (average of Month 6 and Month 12). No anti-drug antibodies were observed in any patient. The consistency of patisiran PK and PD between patients with and without LT suggests that neither LT nor concomitantly administered immunosuppressants influence hepatic uptake or RNAi activity of patisiran. The patisiran dosing regimen of 0.3 mg/kg q3w is appropriate for hATTR amyloidosis patients with or without LT. NCT03862807.


Case report: Evaluation of supernumerary teeth with computerized tomography.
Radiographs play an important role in assessment of both the location and the typing of supernumerary teeth. In general, periapical, occlusal, and/or panoramic radiographs are sufficient for providing the information required by the clinician. These modalities, however, do not provide detailed information concerning the 3-dimensional relationship between supernumerary or ectopically impacted teeth and adjacent structures. This case report discusses the value of computerized tomography (CT) for evaluation of the root relationships of supernumerary teeth located palatally to maxillary permanent central incisors. CT accurately demonstrated the relationship between the supernumerary teeth and the permanent tooth roots.


The pattern of sesame sensitivity among infants and children.
Recently, we found sesame to be a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE-mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients 'outgrew' their allergy within 1-2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut - a major cause of severe food allergic reactions.


Mutational profiling of lung adenocarcinoma in China detected by next-generation sequencing.
NSCLC is the most common type of lung cancers. The purpose of this study is to screen cancer-related mutations in early LUAD in China through NGS technology, determine their correlation with clinical characteristics and provide basis for treatment decisions. In this study, we performed a 583 gene panel to detect the mutational spectrum of the tumors which were collected from 98 LUAD patients. The sequencing data and clinical characteristics were analyzed. Mutations were identified in 94.9% of patients. EGFR had the highest mutation frequency which was detected in 66% of the patients and was significantly associated with female gender and non-smoking history. Other genes with high mutation frequency were TP53 (37%), ERBB2 (24%), BCOR (22%), ZFHX3 (19%), BTG1 (17%), ATR (16%), WWTR1 (15%), etc. TP53 mutations were significantly associated with medium and low differentiation of tumors; BCOR and BLM mutations with gender; WWTR1 mutations with age; and ATR mutations with visceral pleura invasion were observed. 61% of the patients harbored at less one actionable alteration associated with FDA-recognized or investigational drugs. Multiple mutations in LUAD patients in this study have not previously been reported in NSCLC. Moreover, mutations in driver genes including EGFR, TP53, BCOR, BLM, WWTR1, and ATR were significantly related to clinical features. The panel used in this study is an effective approach for molecular analysis and can be applied in personalized treatment decision-making and drug development.


Combating diabetes complications by 1-Fe, a corrole-based catalytic antioxidant.
The potent corrole-based ROS/RNS decomposition catalyst 1-Fe was examined regarding its effect on the development of diabetes complications, in parallel with studies that addressed safety and toxicity issues that are crucial for forwarding the compound towards clinical trials. Cardiotoxicity and mutagenic potential were addressed by applying the hERG and AMES tests on 1-Fe, revealing that it is safe enough for further development. General toxicity studies in rats disclosed the appearance of mild adverse effect only at a dose of 300 mg/kg/day. In the streptozotocin-induced rat model of diabetes, 20 mg/kg/day 1-Fe prevented cataract incidents and reduced its severity, displayed a favorable effect on kidney function, and also decreased serum cholesterol and triglyceride levels. Comparisons with alpha lipoic acid, a compound with reported benefits in the same mouse model, indicate that the benefits of 1-Fe are due to the combination of its ability to disarm ROS/RNS and its positive effect on lipid profile.


The stability and latent profiles of mental health problems among Dutch young adults in the past decade: A comparison of three cohorts from a national sample.
The aim of the study reported here was to assess whether the prevalence of mental health problems (MHP) among Dutch 19-24 year old adults increased in the past decade and/or whether the distribution of latent profiles of mental health problems changed over the years. For this purpose, data was extracted from the LISS panel, based on a representative national sample of the Dutch population. We focused on three exclusive groups who were 19-24 years old in 2007 (n = 383), 2012 (n = 351) or 2017 (n = 362). Multivariate logistic regression analyses showed that the 2012 and 2017 group did not have more MHP according to seven mental health-related indicators including mental health services utilization. Latent profile analysis identified 4 classes of MHP profiles, labeled "healthy" (82.2%), "at risk" (9.6%), "clinical" (4.2%) and "treatment" (3.9%). The 2007, 2012 and 2017 cohorts were equally distributed across these four classes. However, females had systematically more health problems than males and more often belonged to the "at risk", "clinical" and "treatment" class. In sum, our findings do not support concerns about an increase in MHP or that problems have become more complex among Dutch young adults over the past decade.


Is adjuvant chemotherapy beneficial for stage II-III goblet cell carcinoid/goblet cell adenocarcinoma of the appendix?
Goblet cell carcinoma (GCC), formerly known as goblet cell carcinoid, of the appendix constitutes less than 14% of all primary appendiceal neoplasms. Surgical resection is the main treatment and the role of adjuvant chemotherapy (AC) is not established. This study aims to evaluate the impact of AC in stage II-III appendiceal GCC. Patients with pathological stage II and III GCC who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3 (goblet cell carcinoid) and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. A total of 619 patients were identified. 54.4% males and 89.0% Caucasian; median age 56 (range, 23-90) years. Distribution across pathological stages II-III was 82.7% (N = 512) and 17.3% (N = 107) respectively. AC was administered in 9.4% (N = 48) of stage II and 47.7% (N = 51) of stage III patients. For stage II patients, AC was not associated with better OS in univariate (HR 0.32; 95% CI 0.04-2.34; p = 0.261) or multivariable analyses (HR 0.29; 95% CI 0.04-2.12; p = 0.221). By contrast, in stage III patients, AC was associated with better OS in univariate (HR 0.35; 95% CI 0.17-0.71; p = 0.004) and multivariable analyses (HR 0.25; 95% CI 0.07-0.88; p = 0.031). In the entire cohort 5-year OS for patients that received AC was 85.5% (74.0%, 92.1%) versus 82.7% (77.5%, 86.8%) (p = 0.801) with no AC. For stage II patients, 5-year OS was 96.9% with AC vs. 89.1% with no AC (p = 0.236). For stage III patients, 5-year OS was 77.1% with AC vs. 42.8% with no AC (p = 0.003). AC was associated with improved OS in patients with pathological stage III GCC of the appendix, but not with pathological stage II.


A feasibility study of different commercially available serum-free mediums to enhance lentivirus and adeno-associated virus production in HEK 293 suspension cells.
Lentivirus and adeno-associated viruses are invaluable tools for biotechnology applications due to their genetic material delivery abilities both in vitro and in vivo. However, their large-scale productions with Good Manufacturing Practices yield low efficiency when adherent and serum dependent HEK293 (Human Embryonic Kidney) cells are used as the host. To increase production efficiency, HEK293 cells are adapted to grow in suspension using commercially available and chemically defined serum-free mediums. Suspended cells can be transiently transfected for viral vector production; however, significant improvements are still needed to increase yield and thereby cost effectiveness. Here, we evaluated four most preferred commercially available mediums that are IVY, FreeStyle293, LV-MAX, and BalanCD HEK293 for the transient transfection feasibility of lentiviral (LV) and adeno-associated virus serotype 2 (AAV2) production in FlorabioHEK293 suspension cells. The highest transfection efficiency was over 90% and obtained by using polyethyleneimine (PEI) 25 K and by media adaptation in IVY without using any transfection enhancer. For the first time the feasibility of HEK293 cells, which were adapted to grow in suspension culture by Florabio and IVY media, were tested for virus production. This study demonstrates the best transfection medium for scalable and optimized production of Lentivirus and Adeno-Associated Virus in suspended HEK293 cell culture. The online version contains supplementary material available at 10.1007/s10616-022-00551-1.


Prognostic factors in severe community-acquired pneumonia in patients without co-morbid illness.
We wished to determine the prognostic factors and the impact of initial empirical antibiotic therapy on the outcome of severe community-acquired pneumonia in patients without underlying co-morbid illness. This is a retrospective record review of consecutive patients with severe community-acquired pneumonia who were divided into those with and without underlying co-morbid illness. There were 182 patients including 112 primary (no co-morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The overall mortality was 41.8% and there were no differences in APACHE II score or mortality when comparing cases with primary (37.5%) and secondary infections (48.6%). The mortality was significantly higher in patients with negative microbiology. Univariate analysis identified a number of parameters and various antibiotic regimens, which appeared to be associated with a significantly poorer outcome. On multivariate analysis multilobar pulmonary consolidation, need for mechanical ventilation, inotropes and dialysis were documented to be independent predictors of mortality. Only in their absence could different antibiotic regimens be shown to have an apparent impact on outcome and further analysis suggested that the reason for these differences related predominantly to differences in the severity of the infection. Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.


Combined smooth and saccadic ocular pursuit during the transient occlusion of a moving visual object.
Accurate ocular pursuit during a transient occlusion interval would minimize retinal position and velocity error, and could provide an advantage when discriminating object characteristics at reappearance. This study was designed to examine how the smooth and saccadic response extrapolates the trajectory of a moving visual object during a transient occlusion. We confirmed that subjects could not maintain unity gain smooth pursuit during the transient occlusion. Eye velocity decayed significantly without visual feedback but then in the majority of subjects, there was a recovery that brought eye velocity back towards object velocity. However, eye velocity did not increase to a level that eliminated the developing position error. Subjects corrected for the resulting error in eye position by releasing saccades that generally placed the eye ahead of the occluded object's extrapolated position. The majority of saccadic correction occurred between 220 and 600 ms of the occlusion interval, and when combined with the smooth response enabled accurate pursuit of a 10 degrees/s object for up to 1,200 ms of occlusion. The lack of saccadic correction after 600 ms of occlusion combined with the reduced eye velocity resulted in significant undershoot of eye position at the moment of object reappearance when pursuing an 18 degrees/s object. We suggest that extra-retinal information regarding eye velocity and smooth eye displacement could be available from a continually updating efference copy of eye motion in MST, whereas a veridical representation of extrapolated object velocity and displacement could be obtained from persistent activity in FEF.


Veterinary parasitology in Australia--a short history.
As an important producer and exporter of livestock products, animal health has always been of major significance to the Australian economy, and research into efficient parasite control has continued since the 1800s. With substantial research achievements also involving parasites of companion animals and wildlife, Australian parasitologists have made numerous contributions of global significance. This summary outlines the development of investigations into parasite biology and parasitic disease in Australia.


Protective effect of nitronyl nitroxide against hypoxia-induced damage in PC12 cells.
Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. HPN (4'-hydroxyl-2-substituted phenyl nitronyl nitroxide), a stable nitronyl nitroxide, has excellent free radical scavenging properties. The purpose of this study was to investigate the protective effects of HPN on hypoxia-induced damage in PC12 cells. It was shown that HPN significantly attenuated hypoxia-induced loss of cell viability, release of lactate dehydrogenase (LDH), and morphological changes in PC12 cells. Moreover, hypoxic PC12 cells had increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), and expression of HIF-1α and VEGF, but had reduced levels of superoxide dismutase (SOD) and catalase (CAT), and HPN reversed these changes. HPN also inhibited hypoxia-induced cell apoptosis via suppressing the expression of Bax, cytochrome c, and caspase-3, and inducing the expression of Bcl-2. These results indicate that the protective effects of HPN on hypoxia-induced damage in PC12 cells is associated with the suppression of hypoxia-induced oxidative stress and cell apoptosis. HPN could be a promising candidate for the development of a novel neuroprotective agent.


Job demands and job control among occupational therapists in public sector in Finland.
Although health care professionals' increased job demands and strain have generated much public debate in recent years, the way in which occupational therapists' job strain has developed remains unknown. To examine how Finnish occupational therapists working in municipalities experienced job demands and control in 2014-2018 compared with physiotherapists and registered nurses. Occupational therapists (OT, n = 107), physiotherapists (PT, n = 331) and registered nurses (RN, n = 1389) responded to repeated surveys in the Finnish Public Sector Study in 2014-2018. We used the Job Content Questionnaire and analyzed the data using repeated measures analysis of variance and multiple linear regression with generalized estimating equations to identify the trends and differences. More OTs had lower job demands and higher job control than PTs and RNs in each year of study. These differences were statistically significant. Most OTs had low job strain. The changes in job control and job demands of participants in different years were not statistically significant. The OTs consistently experienced low job strain as compared to the PTs and RNs. Developing good practices in OT's work may be beneficial for improving employee health and well-being and high-quality client care.


Rod-cone interaction in monocular but not binocular pathways.
Photopic background stimulation elevates scotopic increment thresholds (rod-cone interaction) at moderate background levels when both test and concentric disk-background stimuli enter the same eye (monocular condition) but not when they enter different eyes (dichoptic condition). Only when background levels are made extremely high is there any measurable dichoptic interaction, and this interaction does not resemble that observed monocularly. Rod-cone interaction, as usually studied, is a property of monocular pathways in human vision.


Major histocompatibility complex markers in patients with nomifensine-induced immune hemolytic anemia.
To evaluate a possible role of major-histocompatibility-complex (MHC)-related immune-response genes for the selective production of drug-induced antibodies, HLA class I (ABC), class II (DR, DQ), class III (BF, C2, C4A, C4B) as well as glyoxalase-1 allotypes were investigated in 26 patients with nomifensine-induced immune hemolytic anemia. No statistically significant deviations of MHC antigen frequencies were noted. The possible implications of these findings are discussed.


Evaluation of immunomodulatory effects of Boswellia sacra essential oil on T-cells and dendritic cells.
Boswellia sacra resin has been commonly used as analgesic, antimicrobial, and anti-inflammatory properties, which reflect its immunomodulatory activity. Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) and sentinel cells that regulate the immune response. This study aims at investigating whether crude essential oil extracted from Boswellia sacra resin (BSEO), has a potential effect on the phenotype and functions of human monocyte-derived DCs. Oil extract from the resin of Boswellia sacra was prepared by hydrodistillation using a custom made hydrodistiller. BSEO-mediated cell viability has been initially studied on human skin dermis cells (HSD) and DC precursors using quantitative and qualitative assays before applying on DCs. Human DCs were generated from differentiated peripheral blood monocytes cultured in media containing both GM-CSF and IL-4. DCs were exposed to 5 μg/mL or 10 μg/mL of BSEO in vitro. Morphological, phonotypical, and functional properties studied with microscopy, flow cytometry, and ELISA. Crude BSEO was found to interfere with the maturation and differentiation of DCs from precursor cells in the presence or absence of lipopolysaccharide (LPS). BSEO-treated DCs, cultured in the presence of LPS, reduced the ability of allogeneic T cells to proliferate compared to that co-cultured with LPS-stimulated DCs only. In addition, the endocytic capacity and secretion of IL-10 by DCs treated with BSEO was enhanced in comparison to LPS treated cells. Analysis of the chemical composition of BESO using GC-MS (Clarus 500 GC/MS, PerkinElmer, Shelton, CT) revealed the presence of compounds with several biological activities including antibacterial, antioxidant, and anti-inflammatory properties. Results indicated that BSEO deviates the differentiation of monocytes into immature DCs. Furthermore, stimulation of immature DCs with BSEO was unable to generate full DC maturation. However, these findings may potentially be employed to generate DCs with tolerogenic properties that are able to induce tolerance in diseases with hypersensitivity, autoimmunity as well as transplantation.


Financial Burden of Tuberculosis Patients - China, 2020.
Tuberculosis (TB) is often referred to as "a disease of poverty," yet the information regarding the financial burden of TB care is limited and regionally representative. This manuscript reported the national representative total and breakdown costs associated with TB care in China. The total cost per patient was 1,185 USD, of which 88% was direct cost and 37% was incurred prior to TB treatment. TB patients experience a significant financial burden, and disparities exist among different regions and populations. Current TB care policies and packages are not sufficient to address this issue.


Determination of deoxynivalenol-sulfonate (DONS) in cereals by hydrophilic interaction chromatography coupled to tandem mass spectrometry.
Deoxynivalenol (DON) is one of most widespread mycotoxins in cereal commodities, and animal feed is prevalently contaminated at high concentrations. This poses a problem in animal nutrition as especially pigs are very sensitive to DON. An effective process for the reduction of the DON concentration is the treatment of contaminated feed with sodium bisulfite (SBS) whereby DON is transformed into DON-sulfonate (DONS). Although the success of this treatment has been confirmed in several feeding studies, it is unexplained if the decrease of DON is accompanied with a coincident increase of DONS. For this reason, we developed a method for the analysis of DONS using hydrophilic interaction chromatography coupled to tandem mass spectrometry. In order to investigate the correlation between DON and DONS concentrations during SBS-treatment, DON-contaminated wheat was treated with SBS and stored for up to 36 days. At defined timepoints of this treatment, samples were analyzed for DON and DONS using stable isotope labeled standards. The preparation, purification, and structure elucidation of DONS, and the HILIC-HPLC-MS/MS method for the analysis of DONS as well as the results of two storage experiments are presented in this paper.


Atypical manifestations of typhoid fever.
High fever, toxaemia, constipation during first week of fever, complicated by encephalopathy and perforation during third week of fever are the typical manifestations of typhoid fever. However, the classical presentation of typhoid fever has considerably changed now. To study atypical presentations of typhoid fever. A teaching unit of a hospital in South India All culture-positive adult patients of typhoid fever admitted over a period of seven years were studied Thirty-two adult patients were admitted. Fifteen (46.9%) patients presented with atypical manifestations. Atypical manifestations observed were burning micturition with normal urine examination (n= 5, 15.6%) diarrhoea in first week (6.2%), encephalopathy in first week (3.1%), isolated hepatomegaly (6.2%), pneumonitis (3.1%) and bone marrow depression (6.2%). Out of 32 Salmonella typhi culture positive patients, 10 (31.3%) patients had multidrug resistant (MDR) strain. Patients with MDR strains had atypical manifestations (5/10=50%) not significantly more often than patients having multidrug sensitive strains (10/22=45.5%) (Z <2). All patients responded to treatment. It appears atypical manifestations do not necessarily mean a worse prognosis in typhoid fever. Patients having high fever presenting with pneumonia, early encephalopathy, early diarrhoea or bone marrow depression in a typhoid endemic area, should be suspected for this disease.


Racism, racialization, and health equity in Canadian residential long term care: A case study in Toronto.
To date, most of the interdisciplinary scholarly literature pertaining to care work and labor studies of marginalized groups, such as women, visible minorities, and immigrants, has focused on emotional labor as well as concerns about high stress and high turnover. However, few mention racism and racialization. Using a single-case study research design of a long term care ("LTC") home in Toronto, Ontario, Canada, this paper contributes to our understanding of racism and racialization by analyzing participants' experiences of work. It documents how particular social determinants of health ("SDoH"), such as race and racialization, can manifest themselves in the lives of workers. Drawing on critical race theory and feminist political economy, this study examines the ways in which the participants discuss their experiences of care work, with closer attention to racism and racialization.


IL-10 and IL-17 expression by CD4+ T cells is altered in corticosteroid refractory immune thrombocytopenia (ITP).
Corticosteroids remain the first-line treatment for patients with immune thrombocytopenia (ITP). However, 20% to 30% of patients do not respond to treatment at tolerable doses. This variation in corticosteroid efficacy is replicated in other autoimmune diseases and may have an adaptive immune basis. To test the hypothesis that CD4+ T-cell responses to corticosteroids are different in patients with clinically defined corticosteroid refractory ITP. In this prospective cohort study, CD4+ T cells from patients with ITP were cultured in the presence or absence of dexamethasone (Dex). Intracellular cytokine expression was then quantified by flow cytometry and compared with patients' clinical response to corticosteroid treatment. A control cohort of patients with autoimmune uveitis was also studied to evaluate whether our findings were limited to ITP or are potentially generalizable across autoimmune diseases. The ratio of interleukin (IL)-10 to IL-17 expression following CD4+ T cell culture with Dex was able to discriminate between ITP patients with a clinically defined complete (n = 33), partial (n = 12) or nonresponse (n = 11) to corticosteroid treatment (P = .002). These findings were replicated in patients with autoimmune uveitis (complete response n = 14, nonresponse n = 22; P = .01). There is a relative abrogation of IL-10 and persistence of IL-17 expression in the CD4+ T cells of patients who clinically fail corticosteroid therapy. This observation has potential to inform both our mechanistic understanding of the action of corticosteroids in the treatment of ITP, and as a biomarker for steroid refractory disease, with potential application across a range of hematological and nonhematological conditions.


Obstetric outcomes: A comparison of teenagers and adults in the Cape Coast metropolis, Ghana.
Prevalence of teenage pregnancy is very high in the Central Region of Ghana. Although, pregnant teenagers are perceived to be high-risk mothers, very little has been documented about obstetric outcomes among these mothers in Ghana. This case-control observational study compared maternal and perinatal outcomes between teen and adult mothers in the Cape Coast metropolis. Data on maternal and perinatal outcome variables were collected with a data extraction form from maternal history record and delivery record books of 505 teens and 501 adults. Maternal and perinatal outcomes for the two groups were compared using chi-square or Fisher's exact test and odds ratios at 95% confidence interval. Prenatal services utilization was high among the participants. Prevalence of adverse maternal and perinatal outcomes were low, which is comparable between the two groups. Spontaneous vaginal delivery was higher in the teens with the adults having higher predisposition for caesarean section. The adult mothers were more likely to have preterm delivery and babies with low minute 1 APGAR score, the teens on the other hand had babies with significantly lower birth weight. The favourable and comparable pregnancy outcomes among the participants could be attributed to the high prenatal service utilization. Improved access to prenatal service utilization would produce better pregnancy outcomes.


Two-stage orchiopexy with laparoscopic clip ligation of the spermatic vessels in prune-belly syndrome.
A 1-year-old boy with prune-belly syndrome underwent unilateral laparoscopic clip ligation of the spermatic vessels with the hope of developing vasal collateral circulation. Six months later, the patient underwent ipsilateral second-stage orchiopexy on the right testis after division if the ligated spermatic vessels and contralateral Fowler-Stephens orchiopexy on the left testis in combination with major urinary tract reconstructions and abdominoplasty. For the following 1-year period, both testes were growing and comparable in size.


The advantages and disadvantages of using high technology in hand rehabilitation.
A brief review of the history of occupational therapy shows that the relationship between health and activity was of great concern to the founders of the Occupational Therapy (OT) field, and continues to be of concern to today's occupational therapists. Today, computers and Virtual Reality (VR) take the place of clay and the weaving loom. The goal of this article is to describe both known and innovative computerized equipment being used in interventions for hand rehabilitation and evaluations, as well as answer the question: 'what are the advantages and disadvantages of using technology in hand rehabilitation?' Our conclusion, based on clinical experience and supported by the literature, appears to emphasize that advanced technology can enrich treatment and help patients who are unable to visit the clinic regularly, to get appropriate treatment. However, advanced technology has not been found to be superior to traditional treatment and cannot replace the occupational therapist.


Simultaneous determination of pinoxaden, cloquintocet-mexyl, clodinafop-propargyl ester and its major metabolite in barley products and soil using QuEChERS modified with multi-walled carbon nanotubes coupled with LC-MS/MS.
Herein, a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with multi-walled carbon nanotube (MWCNT) as a dispersive solid-phase extraction was developed for simultaneous determination of pinoxaden (PXD), cloquintocet-mexyl (CLM), clodinafop-propargyl ester (CPE) and its major metabolite (clodinafop, CP) in barley grass powder, barley grain, and soil using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that MWCNT as an absorbent could improve the recoveries of the tested analytes, particularly CP, in complex matrices. Under the optimum conditions, the established MWCNT-modified QuEChERS coupled with LC-MS/MS method exhibited excellent linearity (R2 ) of ≥0.9912, low limits of detection (LODs) and quantification (LOQs) of 0.02-0.07 and 0.29-1.26 μg kg-1 , and acceptable recoveries of 80-130% with intra- and inter-day relative standard deviations (RSDs) < 10.5%. No strong matrix effect (ME) has been observed on the respective samples. The method was successfully applied to monitor the tested analytes in the representative field incurred samples. Conclusively, the proposed method is sensitive and reliable and could be used to monitor the residues of PDX, CLM, CPE, and CP in complicated agro-products and soil matrices.


Decreased gray matter concentration and local synchronization of spontaneous activity in the motor cortex in Duchenne muscular dystrophy.
Patients with DMD have demonstrated functional abnormalities in the motor-related brain areas in previous PET, MRS, and TMS studies. We applied structural MR imaging and RS-fMRI in patients with DMD for the first time, and aimed to investigate the GMC and ReHo or local synchronization of spontaneous activity in the motor cortex. Ten boys with DMD (6.4-14.0 years of age) and 15 healthy controls (7.9-15.1 years of age) underwent brain structural MR imaging and RS-fMRI scanning. GMC and local synchronization of spontaneous activity in the motor cortex were analyzed by using VBM and ReHo approaches, respectively. Compared with healthy controls, boys with DMD showed decreased GMC in the left PSMC and decreased ReHo in the bilateral PMSC as well as in the supplementary motor area (P < .05, corrected). The current results indicate that boys with DMD have both GMC loss and decreased local synchronization of spontaneous activity in the motor cortex, which might be due to the deficiency of dystrophin in the brain.


Cellulose nanocrystal mediated fast self-healing and shape memory conductive hydrogel for wearable strain sensors.
Electro-conductive hydrogel (ECH) with self-healing, shape memory and biocompatible properties is highly urgent for wearable strain sensors to prolonging their lifespan, endowing programmable shape control property, and improving affinity to skin during service. However, most of synthetic polymer-based ECH usually involve potential toxicity, long healing and shape drive time. Herein, a fast healable and shape memory ECH with excellent biocompatibility is reported for the first time by incorporating cellulose nanocrystals grafted phenylboronic acid (CNCs-ABA) and multiwalled carbon nanotubes (MWCNTs) into polyvinyl alcohol (PVA). CNCs-ABA is designed as dispersant and crosslinker in hydrogel. pH-induced dynamic borate bonds give hydrogel excellent shape recovery and fixity ratio of 82.1% and 78.2%, respectively. Meanwhile, 97.1% healing efficiency is obtained within 2 min depending on remarkable photothermal effect of MWCNTs and reversible microcrystallization. Double crosslinking networks endow excellent mechanical properties to hydrogel, whose tensile strength, strain and elastic modulus reach 227.0 kPa, 395.0% and 9.0 kPa, respectively. Furthermore, the synergistic effect of MWCNTs and NaOH enhance the conductivity of hydrogel with value of 3.8×10-2 S/m. In addition, the hydrogel can act as strain sensor for detecting human motion with superior biocompatibility and fast resistance response to applied strain, which is suitable for human health management.


Health decline in prison and the effects of sporting activity: results of the Hessian prison sports study.
Previous studies about health in prisons conclude that incarceration has detrimental consequences for physical and mental health. It is associated with weight gain, decreased fitness, increased cardiovascular risks, and increased risks for mental illnesses, like depression and anxiety. This article examines the relationships between sports activity and health developments among prisoners. We analyze data from the Hessian Prison Sports Study, conducted in 12 prisons of the federal state of Hesse, Germany. Based on quantitative survey data of 568 prisoners in regular custody, our empirical findings show that inmates perceive substantial health declines since incarceration. They report substantial decreases in general health (d=-0.52) and life satisfaction (d=-0.84) as well as an increased number of health problems (d = 0.71). However, sport has a potential to buffer this decline of health. Prisoners engaged in sports report a less negative development of their health compared to inactive prisoners. The greater the amount of time spent with sports activities, the better are the health trajectories found. Findings add to the public health and prison sport literature by demonstrating health benefits of sporting activities in a vulnerable population group that almost inevitably is exposed to manifold strains and burdens.


Tissue proteome analysis for profiling proteins associated with lymph node metastasis in gallbladder cancer.
Lymph node (LN) metastasis is the earliest sign of metastatic spread and an established predictor of poor outcome in gallbladder cancer (GBC). Patients with LN positive GBC have a significantly worse survival (median survival- 7 months) than patients with LN negative disease (median survival- ~ 23 months) in spite of standard treatment which includes extended surgery followed by chemotherapy, radiotherapy and targeted therapy. This study aims at understanding the underlying molecular processes associated with LN metastasis in GBC. Here, we used iTRAQ-based quantitative proteomic analysis using tissue cohort comprising of primary tumor of LN negative GBC (n = 3), LN positive GBC (n = 4) and non-tumor controls (Gallstone disease, n = 4), to identify proteins associated with LN metastasis. A total of 58 differentially expressed proteins (DEPs) were found to be specifically associated with LN positive GBC based on the criteria of p value ≤ 0.05, fold change ≥ 2 and unique peptides ≥ 2. These include the cytoskeleton and associated proteins such as keratin, type II cytoskeletal 7 (KRT7), keratin type I cytoskeletal 19 (KRT19), vimentin (VIM), sorcin (SRI) and nuclear proteins such as nucleophosmin Isoform 1 (NPM1), heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 (HNRNPA2B1). Some of them are reported to be involved in promoting cell invasion and metastasis. Bioinformatic analysis of the deregulated proteins in LN positive GBC using STRING database identified 'neutrophil degranulation' and 'HIF1 activation' to be among the top deregulated pathways. Western blot and IHC analysis showed a significant overexpression of KRT7 and SRI in LN positive GBC in comparison to LN negative GBC. KRT7, SRI and other proteins may be further explored for their diagnostics and therapeutic applications in LN positive GBC.


Effect of triangular roof angle on dispersion of gaseous pollutants and particulate matter.
The Euler-Lagrangian method is adopted to simulate the dispersion of gaseous pollutants and particulate matter (PM) in isolated street canyons, and the influences of the roof angle on the flow structures and distributions of gaseous pollutants and PM are analyzed in detail. Numerical simulation results indicate that gaseous pollutants and PM in the canyons present three typical single main clockwise vortex, transition vortex, and double vortex structures, which are identified at increasing roof slopes. Gaseous pollutants and PM demonstrate the lowest concentration of pollutants when a single vortex structure exists. The concentration of gaseous pollutants and PM reaches the highest value in pedestrian-level areas when the flow field is in a transitional vortex structure. Unlike gaseous pollutants, the concentration of PM does not always decrease with increasing altitude, and higher PM concentrations sometimes occur in the mid-level areas of the canyon. A small roof incline angle is generally recommended for discharging gaseous pollutants and PM.


In-depth analysis of the effect of catalysts on plasma technologies for treatment of various wastes.
Energy security and waste management are gaining global attention. The modern world is producing a large amount of liquid and solid waste as a result of the increasing population and industrialization. A circular economy encourages the conversion of waste to energy and other value-added products. Waste processing requires a sustainable route for a healthy society and clean environment. One of the emerging solutions for waste treatment is plasma technology. It converts waste into syngas, oil, and char/slag depending on the thermal/non-thermal processes. Most of all the types of carbonaceous wastes can be treated by plasma processes. The addition of a catalyst to the plasma process is a developing field as plasma processes are energy intensive. This paper covers the detailed concept of plasma and catalysis. It comprises various types of plasma (non-thermal and thermal) and catalysts (zeolites, oxides, and salts) which have been used for waste treatment. Catalyst addition improves gas yield and hydrogen selectivity at moderate temperatures. Depending on the properties of the catalyst and type of plasma, comprehensive points are listed for the selection of the right catalyst for a plasma process. This review offers an in-depth analysis of the research in the field of waste-to-energy using plasma-catalytic processes.


Dose linearity and monitor unit stability of a G4 type cyberknife robotic stereotactic radiosurgery system.
Dose linearity studies on conventional linear accelerators show a linearity error at low monitor units (MUs). The purpose of this study was to establish the dose linearity and MU stability characteristics of a cyberknife (Accuray Inc., USA) stereotactic radiosurgery system. Measurements were done at a depth of 5 cm in a stereotactic dose verification phantom with a source to surface distance of 75 cm in a Generation 4 (G4) type cyberknife system. All the 12 fixed-type collimators starting from 5 to 60 mm were used for the dose linearity study. The dose linearity was examined in small (1-10), medium (15-100) and large (125-1000) MU ranges. The MU stability test was performed with 60 mm collimator for 10 MU and 20 MU with different combinations. The maximum dose linearity error of -38.8% was observed for 1 MU with 5 mm collimator. Dose linearity error in the small MU range was considerably higher than in the medium and large MU ranges. The maximum error in the medium range was -2.4%. In the large MU range, the linearity error varied between -0.7% and 1.2%. The maximum deviation in the MU stability was -3.03%.


Qualitative screening of veterinary anti-microbial agents in tissues, milk, and eggs of food-producing animals using liquid chromatography coupled with tandem mass spectrometry.
A method for the analysis of 120 drugs in animal derived food was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These analytes belong to 12 families of veterinary anti-microbial agents (quinolones, macrolides, β-lactams, nitroimidazoles, sulfonamides, lincomycines, chloramphenicols, quinoxalines, tetracyclines, polypeptides, and antibacterial synergists) as well as other compounds not assigned to a particular drug family. The animal derived food samples include muscle and liver of swine, bovine, sheep, and chicken, as well as hen eggs and dairy milk. The sample preparation included ultrasound-assisted extraction (UAE) with acetonitrile-water and a final clean-up with auto solid-phase extraction (SPE) on HLB cartridges. The detection and quantification of 120 anti-microbial agents was performed using LC-MS/MS in positive and negative ion mode. The chromatographic separation was performed on a C18 column using acetonitrile and 0.1% formic acid as the mobile phase. The limit of detection (LOD) and limit of quantification (LOQ) of all drugs in food-producing animals were 0.5-3.0μg/kg and 1.5-10.0μg/kg, respectively. The developed method was successfully utilized to monitor real samples, which demonstrated that it is a simple, fast, and robust method, and could be used as a regulatory to screen for the presence of residues from veterinary anti-microbial drugs in animal-derived foods.