Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma.
Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA-damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy.


Interaction of exercise and diet on GLUT-4 protein and gene expression in Type I and Type II rat skeletal muscle.
We determined the interaction of exercise and diet on glucose transporter (GLUT-4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high-fat (FAT, n=24) or high-carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week-1 of 1000 m @ 28 m min-1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT-4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT-4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet-training interaction on GLUT-4 mRNA, such that expression was increased in both the soleus (100% upward arrowP < 0.05) and EDL (142% upward arrowP < 0.01) in CHO-fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL ( downward arrow 45%, P < 0.05) but not the soleus ( downward arrow 14%, NS). We conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein were largely preserved, suggesting that control of GLUT-4 protein and gene expression are modified independently by exercise and diet.


Organic or antibiotic-free labeling does not impact the recovery of enteric pathogens and antimicrobial-resistant Escherichia coli from fresh retail chicken.
We investigated the implied health benefits of retail chicken breast labeled as "organic" or "antibiotic-free" when compared to conventional products based on frequency of contamination by Salmonella spp., Campylobacter spp., and coliform bacteria resistant to fluoroquinolones, extended-spectrum cephalosporins, or carbapenems. We purchased 231 prepackaged chicken breasts from 99 grocery stores representing 17 retail chains in Ohio, Michigan, and Pennsylvania from June to September 2012. Ninety-six (41.5%) packages were labeled "antibiotic free" and 40 (17.3%) were labeled "organic," with the remaining 95 (41.1%) making neither label claim. Salmonella were recovered from 56 (24.2%) packages, and the recovery rate was not different between product types. Five percent of packages contained Salmonella carrying the extended-spectrum cephalosporin resistance gene bla(CMY-2), representing 21.4% of Salmonella isolates. Campylobacter spp. were recovered from 10.8% of packages, with observed recovery rates similar for the three product types. Using selective media, we recovered Escherichia coli harboring bla(CMY-2) from over half (53.7%) of packages, with similar recovery rates for all product types. In addition, we recovered E. coli carrying bla(CTX-M) from 6.9% of packages, and E. coli with QRDR mutations from 8.2% of packages. Fluoroquinolone-resistant E. coli recovered using selective media were more common (p<0.05) in conventional (18.9%) compared to organic (0) and antibiotic-free (2.1%) packages. Our results indicate that, regardless of product type, fresh retail chicken breast is commonly contaminated with enteric pathogens associated with foodborne illness and commensal bacteria harboring genes conferring resistance to critically important antimicrobial drugs.


Emerging applications of anticytokine vaccines.
Most chronic inflammatory diseases have an unknown etiology but all involve cytokine cascade in their development. Several cytokines have been identified as major targets in various autoimmune diseases, resulting in the development of monoclonal antibodies against those cytokines. Even if monoclonal antibodies are indeed efficient, passive immunotherapies present some disadvantages and are expensive. To counter this, several strategies have been developed, including active immunotherapy, based on vaccination principles. The aim of such a strategy is to induce a B-cell response and to obtain autoantibodies able to neutralize the interaction of the self-cytokine to its receptor. Efficient vaccines have to induce a short-term response to avoid permanent inhibition of a given cytokine. This review focuses on the different therapeutic vaccination strategies with cytokines in preclinical studies; the benefit-risk ratio of such a strategy and the present development of clinical trials in some autoimmune diseases are also discussed.


Ureteroscopy-assisted retrograde nephrostomy for an obese patient.
Obesity is associated with increased surgical morbidity and mortality. We previously reported on the usefulness of ureteroscopy assisted retrograde nephrostomy (UARN) and here we report a case of renal calculi successfully treated with UARN during percutaneous nephrolithotomy (PCNL) in an obese patient. A 63-year-old female with left renal calculi was referred to Department of Urology, Ohguchi Higashi General Hospital. Her body mass index was 34.0 kg/m(2). Stone fragments were completely extracted. URS-assisted puncture from the renal collecting system to the skin under fluoroscopic guidance was a safe and easy procedure in our obese patient.


Scaffold Proteins in Autoimmune Disorders.
Cells transmit information to the external environment and within themselves through signaling molecules that modulate cellular activities. Aberrant cell signaling disturbs cellular homeostasis causing a number of different diseases, including autoimmunity. Scaffold proteins, as the name suggests, serve as the anchor for binding and stabilizing signaling proteins at a particular locale, allowing both intra and intercellular signal amplification and effective signal transmission. Scaffold proteins play a critical role in the functioning of tight junctions present at the intersection of two cells. In addition, they also participate in cleavage formation during cytokinesis, and in the organization of neural synapses, and modulate receptor management outcomes. In autoimmune settings such as lupus, scaffold proteins can lower the cell activation threshold resulting in uncontrolled signaling and hyperactivity. Scaffold proteins, through their binding domains, mediate protein-protein interaction and play numerous roles in cellular communication and homeostasis. This review presents an overview of scaffold proteins, their influence on the different signaling pathways, and their role in the pathogenesis of autoimmune and auto inflammatory diseases. Since these proteins participate in many roles and interact with several other signaling pathways, it is necessary to gain a thorough understanding of these proteins and their nuances to facilitate effective target identification and therapeutic design for the treatment of autoimmune disorders.


Electron attachment and detachment and the electron affinity of cyclo-C4F8.
New measurements have been made of rate constants for electron attachment to c-C(4)F(8) (octafluorocyclobutane) and thermal electron detachment from the parent anion, c-C(4)F(8) (-), over the temperature range 298-400 K in 133 Pa of He gas in a flowing-afterglow Langmuir-probe apparatus. From these data the electron affinity for c-C(4)F(8) was determined, EA(c-C(4)F(8))=0.63+/-0.05 eV. The motivation was to resolve a discrepancy between our earlier EA estimate and a higher value (EA=1.05+/-0.10 eV) reported from a recent experiment of Hiraoka et al. [J. Chem. Phys. 116, 7574 (2002)]. The electron attachment rate constant is 9.3+/-3.0x10(-9) cm(3) s(-1) at 298 K. The electron detachment rate constant is negligible at room temperature but climbs to 1945+/-680 s(-1) at 400 K. G3(MP2) calculations were carried out for the neutral (D(2d), (1)A(1)) and anion (D(4h), (2)A(2u)) and yielded EA(c-C(4)F(8) (-))=0.595 eV. Bond energies were also calculated for loss of F from c-C(4)F(8) and loss of F or F(-) from c-C(4)F(8) (-). From these, dissociative electron attachment is found to be endothermic by at least 1.55 eV.


Slice imaging of the UV photodissociation of CH2BrCl from the maximum of the first absorption band.
The photodissociation dynamics of bromochloromethane (CH2BrCl) have been investigated at the maximum of the first absorption band, at the excitation wavelengths 203 and 210 nm, using the slice imaging technique in combination with a probe detection of bromine-atom fragments, Br(2P3/2) and Br*(2P1/2), via (2 + 1) resonance enhanced multiphoton ionization. Translational energy distributions and angular distributions reported for both Br(2P3/2) and Br*(2P1/2) fragments show two contributions for the Br(2P3/2) channel and a single contribution for the Br*(2P1/2) channel. High level ab initio calculations have been performed in order to elucidate the dissociation mechanisms taking place. The computed absorption spectrum and potential energy curves indicate the main contribution of the populated 4A″, 5A', and 6A' excited states leading to a C-Br cleavage. Consistently with the results, the single contribution for the Br*(2P1/2) channel has been attributed to direct dissociation through the 6A' state as well as an indirect dissociation of the 5A' state requiring a 5A' → 4A' reverse non-adiabatic crossing. Similarly, a faster contribution for the Br(2P3/2) channel characterized by a similar energy partitioning and anisotropy than those for the Br*(2P1/2) channel is assigned to a direct dissociation through the 5A' state, while the slower component appears to be due to the direct dissociation on the 4A″ state.


Effects of prostaglandin F2 alpha and pregnant mares' serum gonadotropin (PMSG) on the reproductive performance of fluorogestone acetate PMSG-treated ewes.
Two experiments were conducted to examine the effect of prostaglandin F2 alpha (PGF2 alpha) and pregnant mares' serum gonadotropin (PMSG) on the reproductive performance (fertility, prolificacy and fecundity) of ewes previously treated with fluorogestone acetate (FGA) and PMSG. In the first experiment, 29 ewes were synchronized for estrus with FGA and PMSG but not bred at the postsynchronization estrus. On day 10 of the first post-synchronization estrous cycle, they were injected IM with 15 mg PGF2 alpha and 500 IU PMSG and exposed to experienced, fertile, raddled rams. Twenty-four of the 29 ewes (83%) had viable fetuses 9 weeks after the PGF2 alpha-PMSG treatment. In the second experiment, 64 ewes were treated with FGA-PMSG, and 33 were exposed to fertile, raddled rams at the synchronized estrus. A second group of 31 ewes was not bred at the synchronized estrus, but on day 12 of the postsynchronized estrous cycle, they were injected IM with 15 mg PGF2 alpha and 500 IU PMSG and exposed to fertile, raddled rams. Sixty-six percent of the 33 ewes lambed in the FGA-PMSG-treated group and 60% of the 31 ewes lambed in the PGF2 alpha-PMSG-treated group. Differences in reproductive performance between these two treatment groups were not statistically significant. The results suggest that the PGF2 alpha-PMSG treatment combination does not adversely affect reproductive performance of ewes.


Predictors of acute hematologic toxicity attributable to palliative radiotherapy: Analysis of patient characteristics and bone marrow dose-volume parameters.
As predictors of hematologic toxicity (HT) after palliative radiotherapy (RT) have been studied insufficiently, we explored predictors of leukopenia, neutropenia, and thrombocytopenia attributable to palliative RT. We retrospectively assessed patients with various solid tumors who had received palliative RT at our institution. Excluded from our study were patients who had undergone chemotherapy from one month before to one month after the start of RT. To measure the bone marrow dose, all bones were delineated, and the absolute volume of bone marrow that had received 5, 10, 20, and 30 Gy was recorded. Univariate and multivariate logistic regression analysis was performed to identify variables associated with leukopenia, neutropenia, or thrombocytopenia of grade 2 or higher (HT2+). Of 68 patients, 17 (25%) developed HT2+. Grade ≥ 2 leukopenia developed in 13 patients (19%), neutropenia in 8 (12%), and thrombocytopenia in 6 (9%). Only one patient experienced ≥ grade 3 toxicity. The median baseline and nadir white blood cell count (WBC) was 6.950 and 4.650x109/l, respectively; the absolute neutrophil count (ANC) was 5.236 and 3.307x109/l, respectively, and the platelet count was 249 and 177.5x109/l, respectively. Multivariate analysis revealed that female gender and a lower baseline WBC and ANC were significant independent predictors of HT2+. No bone marrow dose-volume parameter was a significant predictor of HT2+. Overall, HT was relatively mild. Female gender and lower baseline WBC and ANC may be predictors of HT elicited by palliative RT.


Friendship Quality Over Time in Youth With Spina Bifida Compared to Peers.
Examine friendship qualities (i.e., control, prosocial skills, positive affect, support, companionship, conflict, help, security, and closeness) and perceived self-efficacy in friendships of children with spina bifida (SB) and chosen peers over time through observed behaviors and self-report. Families of children with SB (aged 8-15) were asked to invite the child's "best friend" to participate in-home assessment visits; 127 friendship dyads were included in the current study. Mixed-effects models were used to examine children with SB and their peers across age on observed behaviors and self-reported data about their friendships. For observed behaviors, peers displayed more control (p = .002) and prosocial behaviors (p = .007) with age than youth with SB. Male peers displayed higher control in their interactions as they aged (p = .04); and males with SB maintained their level of prosocial behaviors with age, compared to an increase in prosocial behaviors with age for all other groups (p = .003). For self-reported data, there was no evidence to suggest significant differences in friendship qualities across age (ps ≥ .2), with the exception of increased help (p = .002). Female peers reported increases in companionship across age compared to the other groups (p = .04). Differing from previous examinations of social characteristics in SB, most longitudinal trends in friendship qualities did not differ for youth with SB compared to their peers. Promotion of this existing social strength may be a key intervention target for future strategies that promote positive outcomes for youth with SB.


Effect of the shapes of the oscillometric pulse amplitude envelopes and their characteristic ratios on the differences between auscultatory and oscillometric blood pressure measurements.
Oscillometric noninvasive blood pressure (NIBP) devices determine pressure by analysing the oscillometric waveform using empirical algorithms. Many algorithms analyse the waveform by calculating the systolic and diastolic characteristic ratios, which are the amplitudes of the oscillometric pulses in the cuff at, respectively, the systolic and diastolic pressures, divided by the peak pulse amplitude. A database of oscillometric waveforms was used to study the influences of the characteristic ratios on the differences between auscultatory and oscillometric measurements. Two hundred and forty-three oscillometric waveforms and simultaneous auscultatory blood pressures were recorded from 124 patients at cuff deflation rates of 2-3 mmHg/s. A simulator regenerated the waveforms, which were presented to two NIBP devices, the Omron HEM-907 [OMRON Europe B.V. (OMCE), Hoofddorp, The Netherlands] and the GE ProCare 400 (GE Healthcare, Tampa, Florida, USA). For each waveform, the paired systolic and paired diastolic pressure differences between device measurements and auscultatory reference pressures were calculated. The systolic and diastolic characteristic ratios, corresponding to the reference auscultatory pressures of each oscillometric waveform stored in the simulator, were calculated. The paired differences between NIBP measured and auscultatory reference pressures were compared with the characteristic ratios. The mean and standard deviations of the systolic and diastolic characteristic ratios were 0.49 (0.11) and 0.72 (0.12), respectively. The systolic pressures recorded by both devices were lower (negative paired pressure difference) than the corresponding auscultatory pressures at low systolic characteristic ratios, but higher than the corresponding auscultatory pressures at high systolic pressures. Conversely, the differences between the paired diastolic pressure differences were higher at low diastolic characteristic ratios, compared with those at high diastolic characteristic ratios. The paired systolic pressure differences were within +/-5 mmHg for those waveforms with systolic characteristic ratios between 0.4 and 0.7 for the Omron and between 0.3 and 0.5 for the ProCare. The paired diastolic pressure differences were within +/-5 mmHg for those waveforms with diastolic characteristic ratios between 0.4 and 0.6 for the Omron and between 0.5 and 0.8 for the ProCare. The systolic and diastolic paired oscillometric-auscultatory pressure differences varied with their corresponding characteristic ratios. Good agreement (within 5 mmHg) between the oscillometric and auscultatory pressures occurred for oscillometric pulse amplitude envelopes with specific ranges of characteristic ratios, but the ranges were different for the two devices. Further work is required to classify the different envelope shapes, comparing them with patient conditions, to determine if a clearer understanding of the different waveform shapes would improve the accuracy of oscillometric measurements.


Does preinterventional flat-panel computer tomography pooled blood volume mapping predict final infarct volume after mechanical thrombectomy in acute cerebral artery occlusion?
Decreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT). Twenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day. In 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion. PBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.


Lysophosphatidic acid modulates ovarian cancer multicellular aggregate assembly and metastatic dissemination.
Epithelial ovarian cancer (EOC) metastasis occurs by exfoliation of cells and multicellular aggregates (MCAs) from the tumor into the peritoneal cavity, adhesion to and retraction of peritoneal mesothelial cells and subsequent anchoring. Elevated levels of lysophosphatidic acid (LPA) have been linked to aberrant cell proliferation, oncogenesis, and metastasis. LPA disrupts junctional integrity and epithelial cohesion in vitro however, the fate of free-floating cells/MCAs and the response of host peritoneal tissues to LPA remain unclear. EOC MCAs displayed significant LPA-induced changes in surface ultrastructure with the loss of cell surface protrusions and poor aggregation, resulting in increased dissemination of small clusters compared to untreated control MCAs. LPA also diminished the adhesive capacity of EOC single cells and MCAs to murine peritoneal explants and impaired MCA survival and mesothelial clearance competence. Peritoneal tissues from healthy mice injected with LPA exhibited enhanced mesothelial surface microvilli. Ultrastructural alterations were associated with restricted peritoneal susceptibility to metastatic colonization by single cells as well as epithelial-type MCAs. The functional consequence is an LPA-induced dissemination of small mesenchymal-type clusters, promoting a miliary mode of peritoneal seeding that complicates surgical removal and is associated with worse prognosis.


Evaluation of the AutoSCAN-3, a device for reading microdilution trays.
The AutoSCAN-3 (American MicroScan, Mahwah, N.J.) is an instrument capable of automated reading of commercially available microdilution trays for identification and quantitative susceptibility testing of rapidly growing bacteria. This study compared the results of visual and automated reading of microdilution trays for determination and interpretation of minimum inhibitory concentrations of 471 selected gram-negative and gram-positive clinical bacterial isolates. Visual and automated readings were performed in a double-blind fashion, and all discrepancies were examined by a referee. A quantitative comparison of minimum inhibitory concentrations was performed for 201 organisms, yielding 2,472 drug-organism combinations. After exclusion of off-scale values, complete quantitative agreement was obtained in 94% of 959 on-scale combinations, and agreement within +/- 1 well was obtained in 99.3%. Considering the minimum inhibitory concentration interpretations routinely furnished by the instrument, a qualitative comparison was performed for all 471 organisms. Complete agreement in interpretation was obtained in 97.6% of 5,843 drugs-organism combinations, with very major discrepancies accounting for only 0.1% and major discrepancies accounting for 0.2% of all combinations tested.


Female-directed aggression predicts paternal behavior, but female prairie voles prefer affiliative males to paternal males.
In the socially monogamous prairie vole, Microtus ochrogaster, male affiliation and parental care are influenced by the neuropeptide arginine vasopressin and expression of its receptor V1aR. If parental care and adult affiliation can be considered a behavioral syndrome, females might use male affiliative behavior as a cue to choose a good father. We investigated three questions: (1) do females prefer affiliative males; (2) do males that are affiliative with females demonstrate paternal behavior with pups; and (3) is male V1aR expression related to male behavior or female preference? We evaluated paternal behavior of individual males, then offered sexually receptive females a choice between paternal and non-paternal males and measured the proportion of time each male spent engaging in affiliative behavior with the choosing female. Females showed a preference for more affiliative males, but affiliation was not predictive of paternal care. Thus females did not discriminate between paternal and non-paternal males. Perhaps surprisingly, paternal behavior was correlated with the relative amount of aggression males directed toward females. Finally, females did not discriminate between males with high or low V1aR expression and V1aR expression did not predict male affiliative behavior or parental care. These data suggest that male affiliative behavior, but not paternal care, is associated with female mate choice.


Radiation hazards to vascular surgeon and scrub nurse in mobile fluoroscopy equipped hybrid vascular room.
The aim of the present study was to identify the radiation hazards to vascular surgeons and scrub nurses working in mobile fluoroscopy equipped hybrid vascular operation rooms; additionally, to estimate cumulative cancer risk due to certain exposure dosages. The study was conducted prospectively in 71 patients (53 men and 18 women) who had undergone vascular intervention at our hybrid vascular theater for 6 months. OEC 9900 fluoroscopy was used as mobile C-arm. Exposure dose (ED) was measured by attaching optically stimulated luminescence at in and outside of the radiation protectors. To measure X-ray scatter with the anthropomorphic phantom model, the dose was measured at 3 distances (20, 50, 100 cm) and 3 angles (horizontal, upward 45°, downward 45°) using a personal gamma radiation dosimeter, Ecotest CARD DKG-21, for 1, 3, 5, 10 minutes. Lifetime attributable risk of cancer was estimated using the approach of the Biological Effects of Ionizing Radiation report VII. The 6-month ED of vascular surgeons and scrub nurses were 3.85, 1.31 mSv, respectively. The attenuation rate of lead apron, neck protector and goggle were 74.6%, 60.6%, and 70.1%, respectively. All cancer incidences among surgeons and scrub nurses correspond to 2,355 and 795 per 100,000 persons. The 10-minute dose at 100-cm distance was 0.004 mSv at horizontal, 0.009 mSv at downward 45°, 0.003 mSv at upward 45°. Although yearly radiation hazards for vascular surgeons and scrub nurses are still within safety guidelines, protection principles can never be too stringent when aiming to minimize the cumulative harmful effects.


Benefit Type and Care Source in Relation to Mammography Screening and Breast Cancer Stage at Diagnosis Among DoD Beneficiaries.
Type of insurance and out-of-pocket costs influence the use of medical care. Specifically, type of insurance can impact an individual's likelihood of receiving a screening mammogram. Additionally, variation in tumor stage at diagnosis exists for patients with different types of insurance. It is not clear whether different benefit types and care sources differ in breast cancer care and outcomes among Department of Defense (DoD) beneficiaries. The objective of this study was to examine differences in screening mammography and tumor stage at diagnosis between different benefit types (TRICARE Prime vs. non-Prime) and among different care sources (direct care, purchased care, and both) in the DoD Military Health System. Study subjects were women 40 to 64 years of age, diagnosed with malignant breast cancer between 2003 and 2007. Multivariable logistic regression analyses were conducted to assess differences by benefit type and care source in receipt of screening mammography before diagnosis and tumor stage at diagnosis. A total of 2,668 women were included in this study. Patients with Prime were more likely to receive a screening mammography and have an earlier tumor stage than those with non-Prime. Women with direct care were more likely to have an earlier tumor stage but less likely to receive a screening mammogram than those with purchased care. In an equal access health care system, the use of mammography screening and tumor stage at diagnosis may differ by benefit type and care source among DoD beneficiaries. To our knowledge, this was the first study to assess mammography screening and tumor stage differences by benefit type and care source in the Military Health System. Although underlying reasons for the differences are not clear, they may be related to out-of-pocket costs, distance from medical treatment facilities, and frequency of doctor visits for other medical problems. Further research is needed to assess these differences and related factors among DoD beneficiaries.


Prism adaptation treatment improves spatial neglect after severe traumatic brain injury: A case series.
Spatial neglect (SN) after traumatic brain injury (TBI) is common, hindering rehabilitation progress and functional outcomes. Most research has focused on SN treatment after stroke with few published instances of post-TBI SN treated using prism adaptation treatment (PAT) in inpatient rehabilitation. This case series characterizes the dose, after-effect, and treatment response of PAT in patients with SN after severe TBI. Six patients exhibiting severe (n = 2), moderate (n = 2), or mild (n = 2) SN after severe TBI received 5 to 10 PAT sessions during their inpatient rehabilitation stay. Functional improvement in SN was measured by the Catherine Bergego Scale (CBS). Patients presented with a mean initial CBS score of 16.8 (range: 8.8-24.3). Prism after-effect was present after PAT. Following 5-10 sessions, the mean CBS score improved by 11.6 points to 5.2 (range: 7.8-21.8); the change in initial versus final CBS scores was significant (P = 0.031). This study is the first to demonstrate prism after-effect and functional SN improvement in individual patients with TBI. Patients showed a clinically meaningful improvement in mild, moderate, and severe SN following 5 to 10 PAT sessions. Additional studies are needed to assess tolerability, benefit, and optimal PAT dose for SN after TBI.


COVID-19 sentiment analysis via deep learning during the rise of novel cases.
Social scientists and psychologists take interest in understanding how people express emotions and sentiments when dealing with catastrophic events such as natural disasters, political unrest, and terrorism. The COVID-19 pandemic is a catastrophic event that has raised a number of psychological issues such as depression given abrupt social changes and lack of employment. Advancements of deep learning-based language models have been promising for sentiment analysis with data from social networks such as Twitter. Given the situation with COVID-19 pandemic, different countries had different peaks where rise and fall of new cases affected lock-downs which directly affected the economy and employment. During the rise of COVID-19 cases with stricter lock-downs, people have been expressing their sentiments in social media. This can provide a deep understanding of human psychology during catastrophic events. In this paper, we present a framework that employs deep learning-based language models via long short-term memory (LSTM) recurrent neural networks for sentiment analysis during the rise of novel COVID-19 cases in India. The framework features LSTM language model with a global vector embedding and state-of-art BERT language model. We review the sentiments expressed for selective months in 2020 which covers the major peak of novel cases in India. Our framework utilises multi-label sentiment classification where more than one sentiment can be expressed at once. Our results indicate that the majority of the tweets have been positive with high levels of optimism during the rise of the novel COVID-19 cases and the number of tweets significantly lowered towards the peak. We find that the optimistic, annoyed and joking tweets mostly dominate the monthly tweets with much lower portion of negative sentiments. The predictions generally indicate that although the majority have been optimistic, a significant group of population has been annoyed towards the way the pandemic was handled by the authorities.


Functional Casein-Poly saccharide Conjugates Prepared by Controlled Dry Heating.
Casein was conjugated with dextran and galactomannan in a controlled dry state at a relative humidity of 79% and at 60°C for 24 hr. The covalent attachment of polysaccharides to casein was confirmed by SDS-PAGE and HPLC. The emulsifying activity of the casein-dextran and casein-galactomannan conjugates was 1.5 times higher than that of casein. The emulsion stability of the casein-dextran and casein-galactomannan conjugates was 10 times higher than that of casein. The improvement in these emulsifying properties reached a steady state when the conjugation of casein with polysaccharide was done for 24 hr in a controlled dry state, suggesting the rapid formation of conjugates through a Maillard reaction in the case of casein. Compared to commercial emulsifiers, the casein-polysaccharide conjugates showed better emulsifying properties in acidic and high-salt concentration systems.


Development of a Short Self-Report Disability Questionnaire for Health Conditions.
For use in mental epidemiological survey research, a short self-report questionnaire measuring current disability is needed to assess the severity of health symptoms of respondents. A questionnaire, measuring current disability at the somatic, mental, and social domains in the environments of work, family (social) life, and leisure time was made along guidelines issued at the 54th World Health Assembly regarding the acceptance of the International Classification of Functioning, Disability and Health. This article presents the reliability and validity of the Self-Report Disability Questionnaire (SRDQ). A short self-report questionnaire was designed and completed by an adult population sample of a Dutch health region, participating in a mental health survey. The SRDQ measures current disability independent from disorder entity. The data show good reliability. Study outcomes confirm the validity of the SRDQ. Positive correlations were found between the score on the SRDQ and amount of medical and mental health consumption, as well as evidence for divergent validity. Positive correlations emerged with the number of symptoms on various mental health measures and psychiatric comorbidity. Nonretired respondents dependent on social services, elderly respondents, and low-educated respondents are populations commonly at risk, scoring higher on the SRDQ than other populations. The SRDQ is usable both as a disability screener and as an effect instrument for treatments and community interventions because its reliability and validity are found to be good. The combined use of the SRDQ with specific symptom screeners downsizes the proportion of persons who actually need help.


Family and social environmental factors associated with aggression among Chinese adolescents.
Family and school environments are assumed to be associated with and influence aggressive behaviors. However, which specific risk factors within these environments that are associated with aggressive behavior are unclear. The goal of this study is to identify family and social environmental qualities that are related to aggression among Chinese adolescents. Survey data were obtained from 3,213 randomly selected urban high school students ages 10 through 18 in southern China. Lower parental attachment, higher family income, mother's higher education levels, father's parenting goals, rough or changeable parenting styles, unsuitable peer relationships, and inadequate social atmospheres at school serve as risk factors for aggression among Chinese adolescents. Our findings provide some implications for understanding aggression among adolescents and suggests possible interventions to help overcome potential environmental risk factors and thus to prevent aggressive behavior in school.


A Call To Action: Cholangiocarcinoma in the Setting of Sustained Hepatitis C Virologic Response - Case Report and Review of Literature.
The incidence of cholangiocarcinoma, an aggressive malignancy with poor prognosis, is increasing. Hepatitis B and C have been well established as predisposing factors for this malignancy. The availability and efficacy of treatment for hepatitis C infection has led to a substantial reduction in viral hepatitis-related cholangiocarcinoma mortality. Despite treatment, the potential for developing cholangiocarcinoma continues to exist for patients with underlying cirrhosis. We present a patient who was effectively treated for hepatitis C with direct-acting antiviral therapy eight years prior. He presented with malaise, fatigue, and an unintentional weight loss of 40 pounds. Imaging revealed a metastatic malignancy, and a liver biopsy confirmed the diagnosis of cholangiocarcinoma and the absence of underlying cirrhosis in the background liver. This case highlights the persistent risk of developing cholangiocarcinoma despite achieving sustained virological response to treatment for hepatitis C. We review the associated literature and briefly discuss the predisposing conditions that might result in such an outcome. We also encourage the need for long-term surveillance for such patients and the importance of conducting more multi-center studies to identify at-risk patients and develop cost-effective screening protocols.


[Effect of corticotrophin-releasing hormone on connexin-43 phosphorylation and gap junction intercellular communication in human myometrial smooth muscle cells].
To determine the effect of human corticotrophin-releasing hormone (CRH) on the expression of connexin-43 phosphate (P-Cx43) in human myometrial smooth muscle cells (SMCs) and the function of cell gap junction intercellular communication in SMCs. Human non-conceive myometial SMCs were cultured with different concentrations of CRH (0, 5.85, 58.5, 585 and 5850 pmol/L). Western blot was used to test P-Cx43 and Cx43 non-phosphate (NP-Cx43) of protein expression. Cell scratch was used to test cell gap junction intercellular communication opening status in human myometrial SMCs. Compared with the control group, the expression of P-Cx43 was higher in the CRH groups (P<0.01), and was concentration-dependent. There was no significant difference in NPCx43 between the control group and the CRH groups (P>0.05). The transmission of cell layers in the CRH groups was higher than that in the control group (P<0.01), and as the concentration of CRH increased, the time was concentration-dependent (P<0.01). CRH can enhance the expression of P-Cx43 and the function of gap junction intercellular communication in the primary cultured myometrial SMCs.


Compact automated displacement gas metering system for measurement of low gas rates from laboratory fermentors.
An automated metering system was developed for measuring biogas production from laboratory scale biogas digestors. The gas metering system is based on the principle of liquid displacement with a 100-mL reversible cycle and registration. The gas meter is made entirely of plastic and rubber materials resistant to the corrosive components of biogas (e.g., H(2)S) and requires a 12 to 15 VDC power supply.


Schizophrenia: recent advances in LC-MS/MS methods to determine antipsychotic drugs in biological samples.
Schizophrenia is one of the most debilitating and costly illnesses worldwide. First-generation antipsychotics such as chlorpromazine and haloperidol succeeded in controlling the positive symptoms of schizophrenia, but had significant extrapyramidal effects that led to the search for new agents and the release of second-generation (or atypical) antipsychotics. These drugs had a lower risk of adverse motor symptoms. Therapeutic drug monitoring has become a useful tool to optimize schizophrenia treatment and HPLC-MS/MS has been considered the primary technique to monitor antipsychotics. This review comprises three sections: schizophrenia pathophysiology and treatment; recent advances in LC-MS/MS methods designed to measure levels of antipsychotics and their metabolites in plasma samples (selectivity, matrix effect and sensitivity); and the importance of therapeutic drug monitoring.


An online randomised controlled trial of mental contrasting with implementation intentions as a smoking behaviour change intervention.
Objective: We assessed the effectiveness of mental contrasting with implementation intentions (MCII), an established self-regulatory strategy, as a brief online smoking behaviour change intervention. We expected that MCII would enhance smoking reduction among the highly cigarette dependent because MCII is most effective for challenging pursuits. Design: Participants interested in reducing or quitting smoking were recruited online via Amazon Mechanical Turk. At Time 1, we assessed cigarette dependence using the Cigarette Dependence Scale (CDS-5), then administered one of two brief self-help interventions: MCII (n = 172) or a government-promoted control strategy (n = 174). Participants were invited to complete an online follow-up survey 4 weeks later (Time 2). Main Outcome Measure: At Time 1 and Time 2, we measured recent cigarette smoking with a retrospective, self-report questionnaire. We used these reports to compute smoking reduction scores, with an intent-to-treat approach. Results: MCII increased smoking reduction compared to the control strategy at high, but not low, levels of cigarette dependence. Conclusion: We found preliminary evidence consistent with MCII, delivered as a brief online intervention, as an effective smoking reduction strategy for highly dependent cigarette smokers. Further research is needed on MCII as a smoking behaviour change intervention.


Interleukin-12 and interleukin-18 induce indoleamine 2,3-dioxygenase (IDO) activity in human osteosarcoma cell lines independently from interferon-gamma.
In this study we evaluated the ability of inducing activation of the enzyme indoleamine 2,3-dioxygenase (IDO) for the development of a new adjuvant therapy of osteosarcomas. The pathway that has described in the literature states that IDO activity is elevated by IFN-gamma. This mechanism is important because the increased IDO activation induces an intracellular degradation of the essential amino acid tryptophan and thereby activates apoptosis in human osteosarcoma cells. Four different well-established human osteosarcoma cell lines (MNNG/HOS, KHOS-240, HOS and MG-63) were investigated in vitro. Several cytokines were tested for their ability to induce IDO activity. However special emphasis was placed to evaluate the synergistic effects of Interleukin-12 (IL-12) in combination with Interleukin-18 (IL-18). In the first series of experiments IDO induction was investigated by direct application of the cytokines IFN-gamma, TNF-alpha, IL-12 and IL-18 in different concentrations. Secondly, the increase of IDO expression from osteosarcoma cell lines was analysed in the presence of activated lymphocytes with or without cytokine application. Our results demonstrated that the combined application of IL-12 and IL-18 enhanced IDO activity in the human osteosarcoma cell lines HOS and MG-63, in the presence of activated lymphocytes. In the absence of activated lymphocytes, no significant enhancement could be detected. In all our experiments the increase in IDO expression was only partly inhibited by blocking INF-gamma. The presented study demonstrates that IL-12 and IL-18, or even more a combined application of both cytokines, induce IDO expression besides the known pathway via IFN-gamma. These mechanisms have been shown herein for the first time in human osteosacoma cell lines. Since IDO expression could still be shown after complete blocking of IFN-gamma, we conclude that at least a second pathway is responsible for inducing IDO activity. This is in contrast to the present knowledge about IDO activation.


Effects of solar UV radiation on morphology and photosynthesis of filamentous cyanobacterium Arthrospira platensis.
To study the impact of solar UV radiation (UVR) (280 to 400 nm) on the filamentous cyanobacterium Arthrospira (Spirulina) platensis, we examined the morphological changes and photosynthetic performance using an indoor-grown strain (which had not been exposed to sunlight for decades) and an outdoor-grown strain (which had been grown under sunlight for decades) while they were cultured with three solar radiation treatments: PAB (photosynthetically active radiation [PAR] plus UVR; 280 to 700 nm), PA (PAR plus UV-A; 320 to 700 nm), and P (PAR only; 400 to 700 nm). Solar UVR broke the spiral filaments of A. platensis exposed to full solar radiation in short-term low-cell-density cultures. This breakage was observed after 2 h for the indoor strain but after 4 to 6 h for the outdoor strain. Filament breakage also occurred in the cultures exposed to PAR alone; however, the extent of breakage was less than that observed for filaments exposed to full solar radiation. The spiral filaments broke and compressed when high-cell-density cultures were exposed to full solar radiation during long-term experiments. When UV-B was screened off, the filaments initially broke, but they elongated and became loosely arranged later (i.e., there were fewer spirals per unit of filament length). When UVR was filtered out, the spiral structure hardly broke or became looser. Photosynthetic O(2) evolution in the presence of UVR was significantly suppressed in the indoor strain compared to the outdoor strain. UVR-induced inhibition increased with exposure time, and it was significantly lower in the outdoor strain. The concentration of UV-absorbing compounds was low in both strains, and there was no significant change in the amount regardless of the radiation treatment, suggesting that these compounds were not effectively used as protection against solar UVR. Self-shading, on the other hand, produced by compression of the spirals over adaptive time scales, seems to play an important role in protecting this species against deleterious UVR. Our findings suggest that the increase in UV-B irradiance due to ozone depletion not only might affect photosynthesis but also might alter the morphological development of filamentous cyanobacteria during acclimation or over adaptive time scales.


Management of neuroform stent dislodgement and misplacement.
A self-expanding stent has recently been introduced for the treatment of wide-neck aneurysms. We describe two cases of stent malposition within large aneurysms. In the first case, the stent was dislodged during microcatheterization. This was managed by placement of a second stent through the interstices of the first followed by aneurysm coiling. In the second case, after deployment, the proximal portion of the stent moved into the aneurysm as the exchange guidewire was removed. This patient was treated by vessel sacrifice.


Heart Transplant Immunosuppression Strategies at Cedars-Sinai Medical Center.
Heart transplant is the optimal treatment for selected patients with end-stage heart failure. Immunosuppression after heart transplantation has significantly reduced the incidence of rejection and improved patient outcomes with the routine use of calcineurin inhibitors. Antimetabolites and proliferation signal inhibitors add to the improvement in patient outcomes as well. The goal of induction therapy is to provide intense immunosuppression when the risk of allograft rejection is highest. Most maintenance immunosuppressive protocols employ a 3-drug regimen consisting of a calcineurin inhibitor, an antimetabolite agent and glucocorticoids. The management of rejection proceeds in a stepwise fashion based on the severity of rejection detected on biopsy and the patient's clinical presentation. This review will cover induction, maintenance, rejection therapy and some special considerations including sensitization, renal sparing protocol, and corticosteroid weaning. It will end in consideration of potential future directions in immunosuppressive strategies to promote patient and graft survival.


Bronchial matrix and inflammation respond to inhaled steroids despite ongoing allergen exposure in asthma.
Inflammatory and structural changes of the airway mucosa are chronic features of asthma. The mechanisms underlying these changes and their modulation by steroid prophylaxis have not been clarified. We postulated that asymptomatic ongoing allergen exposure could drive airway inflammation as well as changes in the extracellular matrix (ECM), and that inhaled steroids could prevent this. Therefore, we exposed patients with mild asthma to 2 weeks of repeated low-dose allergen, with concomitant inhaled steroid or placebo treatment. Bronchial biopsies, which were taken before and after this exposure, were stained and digitally analysed. The ECM proteins in asthmatics were also compared with a normal control group. Low-dose allergen exposure alone resulted in a significant increase of bronchial epithelial macrophages. Despite ongoing allergen exposure, inhaled steroids reduced the numbers of mucosal eosinophils, neutrophils and T lymphocytes. At baseline, the mean density of the proteoglycans (PGS) biglycan and decorin were, respectively, higher and lower in the bronchial mucosa of asthmatics as compared with normal controls. Steroid treatment, during allergen exposure, increased the mean density of the PGS biglycan and versican. We conclude that chronic allergen exposure induces inflammatory changes in the bronchial mucosa. Despite ongoing allergen exposure, steroid treatment decreases mucosal inflammatory cells while altering PG density. The latter observation highlights the need to examine steroid-induced changes closely in the airway structure in patients with asthma.


Soil temperature, nitrogen concentration, and residence time affect nitrogen uptake efficiency in citrus.
We try to elucidate which environmental and soil factors control nitrogen uptake efficiency in citrus. Effects of residence time and nitrogen (N) concentration (three 500-mL applications of 7 mg N L(-1), representative of reclaimed water used for citrus irrigation in central Florida, or one 150-mL application of 70 mg N L(-1)) on nitrogen uptake efficiency (NUE) of young citrus seedlings were studied. Increasing residence times from 2 to 8 h increased NUE from 36 to 82% and from 17 to 34% for high and low application frequencies, respectively. We developed a model to predict N uptake based on root density, N concentration, and soil temperature (Ts). Assuming a base temperature (Tb) of 10 degrees C, N uptake temperature sum (UTS) = sigma(Ts - Tb)/24 (degrees CdN, degree day units of N uptake). To eliminate the risk of N leaching for young seedlings, minimum uptake periods of 5 and 16 degrees CdN were required at initial soil N concentrations of 0.9 and 2.5 mg N L(-1), respectively. After correcting for differences in root length, this information was then used to predict the effect of irrigation practices on N uptake from reclaimed water for mature trees. Applying 2500 mm yr(-1) vs. 400 mm yr(-1) reclaimed water reduced the NUE of N in this water from 100 to 63% during the summer and from 100 to 28% during the winter. Reductions in NUE at higher irrigation rates appeared to be related to N displacement below the root zone prior to complete N uptake.


Synthesis of Intelligent pH Indicative Films from Chitosan/Poly(vinyl alcohol)/Anthocyanin Extracted from Red Cabbage.
In this study, pH indicative films were successfully synthesized from hydrogels made by blending 1% poly(vinyl alcohol) (PVA) and 1% chitosan (CS) with anthocyanin (ATH) and sodium tripolyphosphate (STPP). Particularly, ATH extracted from red cabbage was used as the pH indicator, while STPP was utilized as the cross-linking agent to provide better mechanical properties of the cast films. FT-IR spectra confirmed the existence of the ATH in the cast films. Moreover, the tensile strength, the elongation-at-break, and the swelling indices of the cast films were measured. In general, these properties of pH indicative films were profoundly influenced by the compositions of PVA/CS and the STPP dosage applied in the hydrogels. For example, the tensile strength could change from 43.27 MPa on a film cast from pure PVA hydrogel to 29.89 MPa, if 35% of the PVA hydrogel was substituted with CS. The cast films were applied as a food wrap that could be used to monitor visually the quality of the enwrapped food via the color change of the film upon the variation in pH values of the enwrapped food. In practice, a sequential change in color was successfully observed on the pH indicative films partially enwrapping the pork belly, indicating the spoilage of the meat.


Optimization of reaction conditions for REM resin-bound quaternization reactions.
A study into the effect of reaction variables on the quaternization of REM resin-bound tertiary amines was undertaken. The influence of resin matrix, solvent, reaction time, temperature, and amount of quaternization agent on the outcome of reaction was evaluated by reaction monitoring using (19)F NMR. The highest yields of tertiary amine products were seen when DMSO was used as reaction solvent in conjunction with a reaction time of 18 h at room temperature. The use of heating for extended reaction times tended to depress yields, indicating product cleavage during quaternization. Quaternization on PS-DVB resin was found to be more robust than reaction on PS-PEG matrices where yields were generally considerably lower than the observed conversions. DMSO was the most efficient reaction solvent for both resins despite poor swelling of the quaternization starting material.


Whether vitamin A supplementation is effective in T-bet and IFN-ɣ gene expression reduction?
The aim of present study is evaluation of vitamin A supplementation efficacy on IFN-ɣ and T-bet gene expression in atherosclerotic patients. Thirty-one patients and 15 healthy controls participated in this study. Healthy control and patients in Vitamin A group received 25 000 IU retinyl palmitate daily for 4 months. Control patients also received 1 pearl of placebo per day up to 4 months. Gene expression levels were assessed by real-time PCR using SYBR green detection method. IFN-γ gene expression in fresh cells of patients taking vitamin A declined slightly (0.85-fold, p = 0.068), whereas the expression of this gene was increased in patients taking placebo, and in healthy control subjects 1.2-fold (p = 0.267) and 1.7-fold (p = 0.580), respectively. There were no significant difference (p = 0.159) between 3 groups in terms of IFN-γ gene expression in cells stimulated with PHA. In order to determine whether PHA stimulation of PBMCs in vitro had an effect on T-bet expression, we measured the difference between the 3 groups of studied. The results showed significant differences between the groups (p = 0.046). IFN-γ gene expression in cells activated with ox-LDL in healthy control subjects and patients taking vitamin A, was reduced 0.43 (p = 0.0001) and 0.41 (p = 0.001) respectively, but in placebo patients was increased 2.2-fold (p = 0.959). Considering role of vitamin A on suppression of Th1 cells in atherosclerotic patients, it can be concluded that vitamin A supplementation may be advantageous for these patients.


Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-gamma genes in the Korean population.
Cytokines play a crucial role in regulating the immune and inflammatory responses. The collective influence of several cytokines can regulate immune responses as complex as those underlying allograft rejections or autoimmune diseases. Polymorphisms in the regulatory regions of the cytokine genes may influence their expression. Therefore, the polymorphisms of cytokine genes are potentially important as genetic predictors of the disease susceptibility or clinical outcome. In 311 unrelated healthy Korean individuals, we investigated the polymorphisms of cytokine genes (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, and interferon-gamma [IFN-gamma]), which had been previously reported to be associated with a number of immune diseases, transplant complications, and direct or indirect influences on the level of expression and production. And we also compared the results to those published for other populations. The genotype distributions were consistent with the assumption of the Hardy-Weinberg equilibrium, with the exceptions of IL-1B +3954 and IL-6-174 polymorphisms. The polymorphisms examined in this study were almost similar to that observed in Asian populations. There were significant differences of the polymorphisms, except for IL-4 receptor alpha +1902, between Korean and other populations. Comparing the alleles associated with higher level of expression and production, IL-1B +3954*T, IL-2-330*G, and IL-4-590*T alleles were significantly higher, and IL-1RN*A2, IL-10-1082*G, and IFN-gamma*2 alleles were lower in Koreans than other populations. Especially in IL-6 promoter -174 polymorphism, we found only the G allele associated with higher plasma IL-6 levels. In haplotype analysis of IL-10 promoter polymorphisms, the GCC haplotype, associated with higher expression of IL-10, was significantly lower in Koreans. These results may be helpful for understanding transplant-related complications, immune or autoimmune diseases, and malignant diseases in the Korean population.


Probing RNA-Small Molecule Interactions Using Biophysical and Computational Approaches.
Interest in small molecules that target RNA is flourishing, and the expectation set on them to treat diseases with unmet medical needs is high. However, several challenges remain, including difficulties in selecting suitable tools and establishing workflows for their discovery. In this context, we optimized experimental and computational approaches that were previously employed for the protein targets. Here, we demonstrate that a fluorescence-based assay can be effectively used to screen small molecule libraries for their ability to bind and stabilize an RNA stem-loop. Our screen identified several fluoroquinolones that bind to the target stem-loop. We further probed their interactions with the target using biolayer interferometry, isothermal titration calorimetry (ITC), and nuclear magnetic resonance spectroscopy. The results of these biophysical assays suggest that the fluoroquinolones bind the target in a similar manner. Armed with this knowledge, we built models for the complexes of the fluoroquinolones and the RNA target. Then, we performed fragment molecular orbital (FMO) calculations to dissect the interactions between the fluoroquinolones and the RNA. We found that the binding free energies obtained from the ITC experiments correlated strongly with the interaction energies calculated by FMO. Finally, we designed fluoroquinolone analogues and performed FMO calculations to predict their binding free energies. Taken together, the results of this study support the importance of conducting orthogonal assays in binding confirmation and compound selection and demonstrate the usefulness of FMO calculations in the rational design of RNA-targeted small molecules.


Study of historical evacuation drill data combining regression analysis and dimensionless numbers.
The time needed to evacuate a building depends on many factors. Some are related to people's behavior, while others are related to the physical characteristics of the building. This paper analyzes the historical data of 47 evacuation drills in 15 different university buildings, both academic and residential, involving more than 19 000 persons. We propose the study of the data presented using a dimensionless analysis and statistical regression in order to give a prediction of the ratio between exit time and the number of people evacuated. The results obtained show that this approach could be a useful tool for comparing buildings of this type, and that it represents a promising research topic which can also be extended to other types of buildings.


Latent autoimmune diabetes in adults.
Latent autoimmune diabetes in adults (LADA) is a special form of diabetes that is clinically similar to type 2 diabetes but with positivity for pancreatic autoantibodies. The frequency of LADA patients among all patients diagnosed as type 2 varies between 6-50% in various populations. The frequency is higher in younger age groups. It is clear, however, that the frequency of autoimmune diabetes among adults is underestimated. Clinical features such as age and severity of symptoms are of no help in identifying these patients. Body mass index and C peptide levels in the general population increase with age, and these parameters are of limited use in identifying LADA patients. Determination of autoantibodies is necessary in order to correctly classify the type of diabetes. Among antibodies, GADA is the most frequently occurring autoantibody, followed by ICA. The natural course of these patients shows that C peptide will decrease with time in parallel with the curve for C peptide in classical type 1 diabetic patients. Most of the LADA patients will require insulin within three years. Our recommendation is that all patients be tested for pancreatic islet autoantibodies at diagnosis of diabetes to enable correct diagnosis and to avoid future failure of hypoglycemic agents and risk of complications due to hyperglycemia. It is still unclear whether early treatment with insulin is beneficial for the remaining beta cells.


Association between beliefs and care-seeking behavior for low back pain.
Cross sectional population-based survey. To investigate the relationship between low back pain (LBP) beliefs and care seeking in LBP. Not all people experiencing LBP seek care for their problem. Consistent predictors of care-seeking behavior seem to be female sex and high perceived disability; the role of beliefs about LBP has not been investigated sufficiently. A questionnaire booklet was mailed to a random sample of 2860 individuals otherwise participating in an epidemiological study of musculoskeletal health. It contained the Back Beliefs Questionnaire (BBQ), the Fear-Avoidance Beliefs Questionnaire (FABQ; physical activity and work scales), and questions about sociodemographics, LBP characteristics, and LBP-related care seeking in the last month ("yes" = visit to specialist, general practitioner, physiotherapist, or other health care practitioner; "no" = none of these). Logistic regression was used to identify whether beliefs made a significant contribution to care-seeking behavior, beyond known predictors conceptualized in the behavioral model of health services use. A total of 2507 of 2860 (88%) individuals completed the questionnaire; 1071 (43%) reported current LBP, 301 (28%) of which had sought care. In univariate analyses the following were all significantly related to care seeking (all P < 0.01): female sex; increasing age; not working full time; lower income; greater LBP frequency, LBP intensity, and limitations in activities of daily living; worse general health; higher FABQ-Physical Activity, FABQ-Work, and Back Beliefs Questionnaire scores. In multiple regression, female sex (odds ratio [OR], 1.731; 95% confidence interval [CI], 1.174-2.551; P = 0.006), LBP frequency (OR, 1.492; 95% CI, 1.249-1.783; P < 0.0001), limitations in activities of daily living (OR, 1.010; 95% CI, 1.001-1.020; P = 0.037), and high FABQ-Work Scores (OR, 1.025; 95% CI, 1.005-1.044, P = 0.012) contributed significantly to the final model. That the odds of seeking care are higher in fear-avoidant individuals, even when controlling for other established predictors, emphasizes the importance of addressing such beliefs during the consultation; public health education programs may serve to underpin the delivery of positive messages, ultimately reducing health care demands.


Penetration and Toxicity of Nanomaterials in Higher Plants.
Nanomaterials (NMs) comprise either inorganic particles consisting of metals, oxides, and salts that exist in nature and may be also produced in the laboratory, or organic particles originating only from the laboratory, having at least one dimension between 1 and 100 nm in size. According to shape, size, surface area, and charge, NMs have different mechanical, chemical, electrical, and optical properties that make them suitable for technological and biomedical applications and thus they are being increasingly produced and modified. Despite their beneficial potential, their use may be hazardous to health owing to the capacity to enter the animal and plant body and interact with cells. Studies on NMs involve technologists, biologists, physicists, chemists, and ecologists, so there are numerous reports that are significantly raising the level of knowledge, especially in the field of nanotechnology; however, many aspects concerning nanobiology remain undiscovered, including the interactions with plant biomolecules. In this review we examine current knowledge on the ways in which NMs penetrate plant organs and interact with cells, with the aim of shedding light on the reactivity of NMs and toxicity to plants. These points are discussed critically to adjust the balance with regard to the risk to the health of the plants as well as providing some suggestions for new studies on this topic.


A comparison between panoramic digital and digitized images to detect simulated periapical lesions using radiographic subtraction.
This study compared digital and digitized panoramic radiographs to detect incipient periapical lesions using the digital subtraction radiography (DSR) technique. Bone defects were created in 77 apical sites of dried human mandibles through the application of 70% perchloric acid. Conventional and digital radiographs were obtained twice at time zero and 2, 4, and 6 hours after application of the acid solution. Conventional radiographs were digitized by using the same attributes than direct digital radiographs. The baseline images were subtracted of the negative control and experimental groups and assessed by an experienced and blinded observer who assigned score 0 (normal) or 1 (mineral loss) to each image. The sensitivity of both modalities was statistically different in relation to experimental times. The percentage of correct responses significantly increased regarding experimental times. The specificity was high both for digitized and digital images. DSR of panoramic images, both digitized and digital, allows for the diagnosis of incipient-simulated periapical lesions with no differences in their performance.


Particulate Matter Emissions of Four Different Cigarette Types of One Popular Brand: Influence of Tobacco Strength and Additives.
The inhalation of particulate matter (PM) in second-hand smoke (SHS) is hazardous to health of smokers and non-smokers. Tobacco strength (amount of tar, nicotine, and carbon monoxide) and different additives might have an effect on the amount of PM. This study aimed to investigate the influence of tobacco strength or additives on PM. Four cigarette types of the brand Marlboro with different strengths and with or without additives were analyzed in comparison to the 3R4F reference cigarette. SHS was generated by an automatic environmental tobacco smoke emitter (AETSE) in an enclosed space with a volume of 2.88 m³. PM concentrations (PM10, PM2.5, PM₁) were measured with a laser aerosol spectrometer followed by statistical analysis. The two strongest Marlboro brands (Red and Red without additives) showed the highest PM concentrations of all tested cigarettes. The measured mean concentrations Cmean of PM10 increased up to 1458 µg/m³ for the Marlboro Red without additives (PM2.5: 1452 µg/m³, PM₁: 1263 µg/m³). The similarly strong Marlboro Red showed very similar PM values. The second strongest type Marlboro Gold showed 36% (PM10, PM2.5) and 32% (PM₁) lower values, respectively. The "lightest" type Marlboro Silver Blue showed 54% (PM10, PM2.5) or 50% (PM₁) lower PM values. The results indicate that the lower the tar, nicotine, and carbon monoxide amounts, as well as the longer the cigarette filter, the lower are the PM levels. An influence of additives could not be determined.


The argument from transfer.
Utilitarian arguments on bioethical issues regarding human reproduction typically start with the view that it is wrong, other things being equal, not to procreate when this would have resulted in an additional being with a life worth living. The paper takes this view for granted and examines the common utilitarian claim that overpopulation and destitution in the world mean that, in practice, this obligation to procreate, other things being equal, often turns into a (categorical) obligation not to procreate. A version of this argument is defended -- a version called the argument from transfer -- according to which, rather than having additional children and care for them in order to make them happy, many people in the West ought to abstain from procreation and take care of destitute children already existing. The reasoning leading up to this conclusion raises some philosophical questions, seldom discussed in connection with bioethics, which indicate that the argument from transfer, although supporting the claim above, cannot neutralise the obligation to create more happy people as easily as assumed by utilitarians. It is argued that the argument from transfer may place many people facing the choice of procreation in a peculiar moral dilemma.


Toward a humanistic model in health communication.
Since the key to effective health communication lies in its ability to communicate well, some of its core problems are those that relate to the sharing of meaning between communicators. In elaborating on these problems, this paper offers two key propositions: one, health communication has to pass through the filter of a particular world view that creates a discrepancy between expected and actual message reception and response. Two, the assumption of a rational human actor made implicitly by most health psychological models is a contestable issue, as many times message recipients do not follow a cognitive judgment process. The phenomenon of resisting health messages by reasonable people asks the question whether we ought to rethink our adherence to a particular vision of human health as many times the adverse reaction to behaviour modification occurs as the result of a particular dialogical or discursive situation. At the same time, most motivational decisions in people's daily routines are automatic and use a concept known as self-identity to give stability to their behaviour patterns. Finally, health communication as part of organised government practices adheres to predominant value perspectives within health promotion practice that affect the manner in which health issues become problematised. This paper proposes a humanistic model that aims to pay attention to the intricacies of human communication by addressing all of the above problems in turn. It interprets the sharing of meaning element in human communication and addresses the question of how the idea of health is created through discourse. As such, it offers a complementary and constructive paradigm and set of approaches to understand health, its meanings and communication.


IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway.
This study was established to investigate the contribution of high mobility group nucleosome-binding protein 1 (HMGN1)/ Toll-like receptor 4 (TLR4) pathway in diabetic nephropathy (DN). And as an intervention of the potential mechanism above, the insulin growth factor 1 receptor (IGF-1R) inhibitor was examined for its therapeutic effect in the diabetic mice. Male C57BL/6J mice were administered streptozotocin(STZ) to induce diabetes and thus divided into 5 groups: the untreated group (DN group), the benazepril-treated group (BEN-DN group), the insulin-treated group (INS-DN group) and the IGF-1R inhibitor-treated group (IGF-DN group). Immunohistochemistry and in situ hybrization were performed to detect the expression of HMGN1 and TLR4 in renal tissue. To evaluate the effect of IGF-1R inhibitor, levels of blood glucose and kidney/ body weight (KW/BW) were measured. And morphological changes and mesangial matrix expansion in kidneys were also detected. Increased expression of HMGN1 and TLR4 in renal tissue of STZ-induced type1 diabetic mellitus (T1DM) mice models was observed. IGF-1R inhibitor attenuate the established nephropathy with reduced expression of TLR4 protein, as revealed by a decrease in mesangial index. IGF-1R inhibitor might have therapeutic potential in DN through inhibition of HMGN1/TLR4 pathway.


Emulating the gut-liver axis: Dissecting the microbiome's effect on drug metabolism using multiorgan-on-chip models.
The homeostatic relationship between the gut, its microbiome, and the liver is crucial for the regulation of drug metabolism processes. Gut microbes are known to influence human health and disease by enhancing food metabolism and providing a first line of defense against pathogens. In addition to this, the gut microbiome also plays a key role in the processing of exogenous pharmaceutical compounds. Modeling the highly variable luminal gut environment and understanding how gut microbes can modulate drug availability or induce liver toxicity remains a challenge. However, microfluidics-based technologies such as organ-on-chips could overcome current challenges in drug toxicity assessment assays because these technologies are able to better recapitulate complex human responses. Efforts are being made to create in vitro multiorgan platforms, tailored for an individual patient's microbial background. These platforms could be used as a tool to predict the effect of the gut microbiome on pharmacokinetics in a personalized way.


The Chronic Effects of Narghile Use on Males' Cardiovascular Response During Exercise: A Systematic Review.
Narghile use has regained popularity throughout the world. Public opinion misjudges its chronic harmful effects on health, especially on the cardiovascular system. This systematic review aimed to evaluate the chronic effects of narghile use on cardiovascular response during exercise. It followed the preferred reporting items for systematic reviews guidelines. Original articles from PubMed and Scopus published until January 31, 2020, written in English, and tackling the chronic effects of narghile use on human cardiovascular response during exercise were considered. Five studies met the inclusion criteria. Only males were included in these studies. They were published between 2014 and 2017 by teams from Tunisia (n = 4) and Jordan (n = 1). One study applied the 6-min walk test, and four studies opted for the cardiopulmonary exercise test. Narghile use was associated with reduced submaximal (e.g., lower 6-min walk distance) and maximal aerobic capacities (e.g., lower maximal oxygen uptake) with abnormal cardiovascular status at rest (e.g., increase in heart rate and blood pressures), at the end of the exercise (e.g., lower heart rate, tendency to chronotropic insufficiency) and during the recovery period (e.g., lower recovery index). To conclude, chronic narghile use has negative effects on cardiovascular response to exercise with reduced submaximal and maximal exercise capacities.


Isolated congenital histiocytosis in the palpebral conjunctiva in a newborn.
To report a rare case of congenital histiocytosis in a newborn without skin involvement. Interventional case-report. A full-term baby presented with a mass over the palpebral conjunctiva of his left upper lid. Ophthalmic examination was otherwise normal, and the baby was healthy. There were no skin lesions. The lesion was completely removed surgically. Pathologic examination demonstrated a cellular infiltrate composed of eosinophils and histiocytes. Immunohistochemistry disclosed positive stain for protein S-100 and CD1 antigenic determinant. Pediatric oncology evaluation was completely normal. Eighteen months after presentation, the patient remained healthy without recurrence of the lesion. Rare cases of congenital histiocytosis can present as a solitary lesion over the palpebral conjunctiva, without skin or systemic involvement.


On the role of TolC in multidrug efflux: the function and assembly of AcrAB-TolC tolerate significant depletion of intracellular TolC protein.
TolC channel provides a route for the expelled drugs and toxins to cross the outer membrane of Escherichia coli. The puzzling feature of TolC structure is that the periplasmic entrance of the channel is closed by dense packing of 12 α-helices. Efflux pumps exemplified by AcrAB are proposed to drive the opening of TolC channel. How interactions with AcrAB promote the close-to-open transition in TolC remains unclear. In this study, we investigated in vivo the functional and physical interactions of AcrAB with the closed TolC and its conformer opened by mutations in the periplasmic entrance. We found that the two conformers of TolC are readily distinguishable in vivo by characteristic drug susceptibility, thiol modification and proteolytic profiles. However, these profiles of TolC variants respond neither to the in vivo stoichiometry of AcrAB:TolC nor to the presence of vancomycin, which is used often to assess the permeability of TolC channel. We further found that the activity and assembly of AcrAB-TolC tolerates significant changes in amounts of TolC and that only a small fraction of intracellular TolC is likely used to support efflux needs of E. coli. Our findings explain why TolC is not a good target for inhibition of multidrug efflux.


Products of tryptophan catabolism induce Ca2+ release and modulate the cell cycle of Plasmodium falciparum malaria parasites.
Intraerythrocytic malaria parasites develop in a highly synchronous manner. We have previously shown that the host hormone melatonin regulates the circadian rhythm of the rodent malaria parasite, Plasmodium chabaudi, through a Ca2+-based mechanism. Here we show that melatonin and other molecules derived from tryptophan, i.e. N-acetylserotonin, serotonin and tryptamine, also modulate the cell cycle of human malaria parasite P. falciparum by inducing an increase in cytosolic free Ca2+. This occurs independently of the extracellular Ca2+ concentration, indicating that these molecules induce Ca2+ mobilization from intracellular stores in the trophozoite. This in turn leads to an increase in the proportion of schizonts. The effects of the indolamines in increasing cytosolic free Ca2+ and modulating the parasite cell cycle are both abrogated by an antagonist of the melatonin receptor, luzindole, and by the phospholipase inhibitor, U73122.


Hydrogen bonding and thermoplastic elastomers - a nice couple with temperature-adjustable mechanical properties.
Styrene-butadiene copolymers are modified with varying fractions of benzoic acid moieties being able to perform hydrogen bonding. This is done by using a simple synthetic approach which utilizes click chemistry. Temperature-dependent dynamic mechanical properties are studied, and it turns out that even the apparently rather simple hydrogen bonding motif has a marked impact on the material properties due to the fact that it facilitates the formation of a supramolecular polymer network. Besides a glass transition, the investigated functionalized copolymers exhibit a second endothermic transition, known as a quasi-melting. This is related to the opening of the hydrogen bonding complexes. Additionally to dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), temperature-dependent infrared (IR) spectroscopy and small angle X-ray scattering (SAXS) are used to understand the structure-property relationships.


Peripheral and central fatigue after high intensity resistance circuit training.
The aim of this study was to investigate the effects of high intensity resistance circuit (HIRC) and traditional strength training (TST) on neuromuscular fatigue and metabolic responses. Twelve trained young subjects performed HIRC and TST in a counterbalanced order with 1 week rest in-between. The amount of workload and the inter-set time for each local muscle group were matched (180 s), however, the time between successive exercises differed. The twitch interpolation technique was used to test neuromuscular function of the knee extensor muscles. Blood lactate concentration was used to evaluate metabolic responses. Maximum voluntary contraction and resting potentiated twitch amplitude (Qtw ) were significantly reduced after HIRC, but there were not changes after TST, while reductions in voluntary activation were similar. Lactate concentration increased significantly more after HIRC. The higher lactate concentration after HIRC probably impaired excitation-contraction coupling, indicating larger peripheral fatigue than after TST. Muscle Nerve 56: 152-159, 2017.


Are there two functionally distinguished Neu5Gc pools with respect to rouleau formation on the bovine red blood cell?
Bovine red blood cells (RBCs) do not exhibit any aggregation tendency in autologous plasma and, therefore, all bovine rouleaux obtained in vitro are regarded as artificial. The present study reports the bovine RBC rouleau formation by either bovine or human fibrinogen and Ca2+ ions. The phenomenon was induced through two-step cell incubation: in 0.9% NaCl and 1% bovine albumin at 37 degrees C for 30 min followed by 20 hrs incubation at 30 degrees C in the fresh solution supplemented with 10 mM glucose. Its mechanism is unknown. During the incubation the number of N-glycolylneuraminic acid molecules per cell decreased from 48.1 to 44.9 amoles, which accounted for 7%. The treatment of RBCs with V. cholerae sialidase under the same conditions resulted in a 94% drop in the Neu5Gc quantity and did not induce the rouleau formation in the same fibrinogen preparation. The preliminary results rise a question whether the bulk of sialic acid is required in the aggregation of bovine erythrocytes under static conditions. Only a minor pool of Neu5Gc seems to be responsible for suppression of the phenomenon.


Real-Time Dual Video Conferencing of Simulated Tracheostoma Maturation During Residency Interviews.
There are few reports of dexterity tests being done in a distance telecommunication setting for residency applicant evaluation. To report the feasibility and suitability of a virtual suturing skills assessment during residency interviews when added to the standard assessment process. A suturing simulation was developed and implemented during otolaryngology-head and neck surgery (OHNS) residency interviews for the 2020-2021 cycle at one program. On the day of the interview, the activity was completed in real time using 2-camera video conferencing with the 2 resident assessors providing a numerical assessment based on an adapted scoring rubric from prior suturing activities at the institution. The exercise involved suturing a 3/4-inch Penrose drain circumferentially with half-vertical mattress stitches to simulate the maturation of a tracheostoma. The residency selection committee then completed a 7-item Likert-type survey, developed by the authors, to evaluate the simulation exercise. Fifty-one applicants representing all interviewees in the cycle successfully completed this assessment without technologic disruptions. The total cost associated with obtaining and providing the necessary supplies to applicants was $34.78 per interviewee. Time required to complete the suturing task was estimated to range from 10 to 20 minutes. The residency selection committee viewed this exercise as a success (14 of 16, 87.5%) and viewed the results as a valuable adjunct in the overall assessment of candidates (15 of 16, 93.8%). A simple motor exercise completed over real-time telecommunication was feasible and perceived as helpful to the residency selection committee when assessing OHNS residency candidates.


Acute Paraparesis Caused by Spinal Epidural Fluid After Balloon Kyphoplasty for Traumatic Avascular Necrosis: A Case Report.
Minimally invasive procedures, such as percutaneous vertebroplasty or balloon kyphoplasty (BK), eliminate motion at the fracture site and relieve pain associated with traumatic avascular necrosis when conservative treatment fails. However, these are associated with complications, most of which are directly related to cement leakage. Herein, we report a rare case of acute paraparesis caused by spinal cord compression by epidural fluid following BK for the treatment of Kummell's disease in the absence of cement leakage. To the best of our knowledge, this is the first report describing this complication.


Formononetin, a Beer Polyphenol with Catabolic Effects on Chondrocytes.
Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1β for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.


Extraction of rye bran by supercritical carbon dioxide: influence of temperature, CO2, and cosolvent flow rates.
Process parameter optimization for the supercritical CO(2) extraction of rye bran to obtain alkylresorcinols (AR) was studied by carrying out a two-level fractional design experiment. Four parameters, temperature, CO(2) flow rate, cosolvent percentage, and extraction time, presumed to influence the extraction process, were analyzed. A tentative fractionation of the crude extract was also carried out and is discussed. The best extracts were achieved when the CO(2) flow rate and extraction time or temperature and cosolvent addition were kept high. It was found that temperature increase was not statistically significant within the range of the study performed, and the extraction time was thus the most important factor. A preliminary fractionation process in two cyclone separators yielded two fractions, one rich in AR components with higher molecular weights and the other rich in AR components with low molecular weight.


Trust and the Ethical Conduct of Community-Engaged Research.
Community-engaged research (CEnR), which emphasizes equal participation of academic and community partners in research, seeks to improve public trust in science. Unfortunately, there is a dearth of rigorous empirical research on trust as a core component of ethical conduct of CEnR. Drawing on data collected from a project on the ethics of CEnR, this commentary discusses benefits and risks of trust and uses the concept of embeddedness to explain how public trust in science may be increased. We argue that in developing and maintaining trust, partners must balance scientific rigor with community relevance and cultural appropriateness of research. They must strike a balance between working with the same limited pool of trusted partners, which can speed research but slow wider acceptance of science, and extending their trust to new partners, which can broaden acceptance of science but slow research. Practitioners may facilitate the development of trust in science by gradually expanding the pool of partners they choose their collaborators from.


Causes Of Chronic Non-Infectious Diarrhoea In Infants Less Than 6 Months Of Age: Rarely Recognized Entities.
Non-infectious causes of chronic diarrhoea are important and easily missed. The study was done with the objectives to identify different causes of chronic non-infectious diarrhoea in infants less than 6 months of age. All patients less than 6 months of age presenting for the first time to a Paediatric Gastroenterology tertiary care centre with a history of chronic diarrhoea and negative stool cultures were enrolled over a period of 8 months. Demographical profile and various factors under observation were recorded in this observational study. Collected data was analysed using SPSS version 20. Chi square test was applied as a test of significance for any qualitative variable, p value (p<0.05) was taken as significant. Among 72 enrolled patients, female to male ratio was1.05:1. Age at onset of symptoms was between 15 days to 6 months. Aetiology found was Cow's milk protein allergy (CMPA) in 58 (80.6%), Primary intestinal lymphangiectasia (PIL) 6 (8.3%), Cystic fibrosis (CF) 3 (4.2%), Immunodeficiency (SCID) 2 (2.8%), 1 (1.4%) for each Abetalipoproteinemia (ABL), Glucose galactose malabsorption (GGM) and Congenital chloride diarrhoea (CCD). Among noninfectious causes of chronic diarrhoea in early infancy, cow's milk protein allergy is most common followed by Primary intestinal lymphangiectasia and Cystic fibrosis.


X-ray polarimetry with the microstrip gas chamber.
A two-dimensional microstrip gas chamber (MSGC) with a 5 cm x 5 cm detection area has been developed. It has 254 anodes and 255 back strips, both with 200 micro m pitches. Using this MSGC, linear polarization of X-rays was successfully measured in the energy range 6-14 keV. In addition, the performance of the MSGC as an X-ray imaging polarimeter has been simulated using the EGS4 program (Electron Gamma Shower, Version 4) modified for this purpose. In this article, the results of both the polarization measurement and the simulation are reported.


Epidermal growth factor-like domain 8 inhibits the survival and proliferation of mouse thymocytes.
Thymic epithelial cells (TECs) play a critical role in T-cell development through their intercellular interactions and by producing various soluble proteins, such as growth factors, cytokines and chemokines. In this study, we report a new role for epidermal growth factor-like domain 8 (EGFL8) in the regulation of the survival and proliferation of mouse thymocytes. Mouse recombinant EGFL8 (rEGFL8) protein was produced using an E. coli system and its biological role in mouse thymocytes was determined. The injection of rEGFL8 in mice in vivo resulted in a decrease in the weight of the thymus, as well as in the number of total thymocytes; rEGFL8 also inhibited thymocyte proliferation and induced thymocyte apoptosis. Furthermore, rEGFL8 suppressed the expression of the Notch downstream targets, Hes1 and Hey1, in mouse thymocytes and TECs, indicating that EGFL8 negatively regulates the Notch signaling pathway in these cells. The identification of the role of EGFL8 in thymocytes may aid in the determination of the fate of thymocytes during T-cell development.


[Risks in mountaineering and trekking].
Mass tourism in the mountains is on the increase. The climbers often do not know much about the possible risks which include death, invalidity and sickness. In this article, risks such as AMS (acute mountaine sickness), HACE (high altitude cerebral edema) and HAPE (high altitude pulmonale edema) are shown. These facts should be taken into account for risk assessment in the private insurance industry.


Continuing the journey of leadership: song of degrees.
The author discusses how her experiences at Project LEAD have improved her ability to be an effective administrator and faculty member through her "songs of degrees." She discusses her journey as an African American leader and how the principles learned in Project LEAD impacted her leadership style and ability to collaborate with peers and colleagues. Leaders who spoke during workshops provided blueprints for mentoring and discussed the journeys of notable leaders, which provided attendees with insights into the successes and challenges of leadership. During Project LEAD, Dr. Hattie Bessent focused upon five leadership principles and applied Structural, Human Resource, Political, and Symbolic Frames. The author determined she primarily used the Structural and Political Frames after studying the frames of Bolman and Deal (2003) discussed by Dr. Bessent. The Project LEAD model focused allowed her to grow as a mentor and guided mentees to the successful completion of projects.


Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care.
Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm(3) or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran-Armitage test, and independent correlates of late initiation were identified using logistic regression. In total, 8942 participants (18% female) of median age 40 years (Q1-Q3 33-47) were included. The median baseline CD4 count increased from 190 cells/mm(3) (Q1-Q3 80-320) in 2000 to 360 cells/mm(3) (Q1-Q3 220-490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm(3) or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm(3)), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.


Influence of isradipine treatment on the morphology of the aorta in spontaneously hypertensive rats.
To investigate the influence of hypertension and of treatment with the vasodilator hydralazine or with the dihydropyridine calcium antagonist isradipine on the morphology of the thoracic aorta in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP), body weight and morphology of the thoracic aorta were evaluated. The ultrastructure of the smooth muscle component of the aorta and of the tunica intima were analysed by transmission and scanning electron microscopy. The SHR were divided into three groups: a control group, which was left untreated, and two treatment groups, one with 1 mg/kg per day hydralazine and the other with 0.1 mg/kg per day isradipine. Three age-matched groups of Wistar-Kyoto (WKY) rats were included in the study: one group was left untreated and was used as a normotensive reference group, the other two groups were treated with 1 mg/kg per day hydralazine or with 0.1 mg/kg per day isradipine. The SBP did not change in the WKY rats treated with hydralazine, with isradipine or untreated, but was significantly increased in the SHR as a function of age. Both hydralazine and isradipine significantly reduced the SBP in the SHR after the second week of treatment. Light microscopy analysis of the thoracic aorta revealed thickening of the wall of the tunica media as well as an increase in the wall: lumen ratio in the SHR. Treatment with hydralazine had no effect on the morphometric parameters evaluated, whereas isradipine administration significantly reduced the thickening of both the wall and the tunica media of the aorta, and reduced the wall: lumen ratio. No significant modifications in the structure of the thoracic aorta were noticed in the hydralazine- or isradipine-treated WKY rats compared with untreated WKY rats. Transmission and scanning electron microscopy analysis demonstrated in control SHR hypertrophy of smooth muscle cells of the tunica media, an increased size and impairment of the internal elastic lamina, and a widening of the subendothelial space. Hypertrophy of the endothelium was also noticeable in the SHR. Treatment with isradipine reduced the hypertrophy of smooth muscle cells of the tunica media and the structural impairment of the tunica intima. No effect of isradipine treatment on the morphology of the aorta was noticed in the WKY rats. The present results show that the effect of isradipine was different from that of hydralazine. Both compounds lowered the SBP, but only isradipine countered the structural changes of the aorta in the SHR. The effect of isradipine administration is particularly pronounced on the hypertension-dependent changes of endothelium. This suggests that isradipine may have a protective effect on the endothelium.