COMMUNITY COLLEGE RE-ENROLLMENT AFTER HURRICANE KATRINA.
In this study, we explored predictors of community college re-enrollment after Hurricane Katrina among a sample of low-income women (N = 221). It was predicted that participants' pre-hurricane educational optimism would predict community college re-enrollment a year after the hurricane. The influence of various demographic and additional resources (e.g., social support, childcare, hours of employment, psychological well-being) was also explored. High levels of pre- and post-hurricane educational optimism were significant predictors of re-enrollment, as were lower post-hurricane psychological distress and fewer post-hurricane hours employed. In addition, experiencing a greater number of moves since the hurricane was a marginally significant predictor of post-hurricane re-enrollment.


An outbreak of community-acquired Legionnaires' disease pneumonia.
In October 1981, an outbreak of 29 cases of community-acquired pneumonia occurred among adult residents of Johnson County, Iowa. Retrospective study revealed 12 cases (41 per cent) had laboratory evidence of Legionnaires' disease (LD). No significant differences in clinical or epidemiological features were found between LD cases and the other pneumonias in the outbreak. All LD cases received erythromycin; one case died for a case-fatality rate of 8 per cent. The outbreak's focus could not be identified.


Extreme Early Image Recognition Using Event-Based Vision.
While deep learning algorithms have advanced to a great extent, they are all designed for frame-based imagers that capture images at a high frame rate, which leads to a high storage requirement, heavy computations, and very high power consumption. Unlike frame-based imagers, event-based imagers output asynchronous pixel events without the need for global exposure time, therefore lowering both power consumption and latency. In this paper, we propose an innovative image recognition technique that operates on image events rather than frame-based data, paving the way for a new paradigm of recognizing objects prior to image acquisition. To the best of our knowledge, this is the first time such a concept is introduced featuring not only extreme early image recognition but also reduced computational overhead, storage requirement, and power consumption. Our collected event-based dataset using CeleX imager and five public event-based datasets are used to prove this concept, and the testing metrics reflect how early the neural network (NN) detects an image before the full-frame image is captured. It is demonstrated that, on average for all the datasets, the proposed technique recognizes an image 38.7 ms before the first perfect event and 603.4 ms before the last event is received, which is a reduction of 34% and 69% of the time needed, respectively. Further, less processing is required as the image is recognized 9460 events earlier, which is 37% less than waiting for the first perfectly recognized image. An enhanced NN method is also introduced to reduce this time.


Anterior Subcutaneous Transposition of the Ulnar Nerve Affects Elbow Range of Motion: A Mean 13.5 Years of Follow-up.
Surgical decompression of the ulnar nerve is effective for cubital tunnel syndrome. However, deep approaches may result in iatrogenic elbow stiffness. This long-term study was to evaluate the range of motion (ROM) of the elbow and functional outcomes after anterior subcutaneous transposition. A total of 115 patients (78 male and 37 female; mean age: 46.6 years) who underwent anterior subcutaneous transposition of the ulnar nerve between 2001 and 2005 were evaluated retrospectively; mean follow-up was 13.5 years. Elbow ROM was measured as flexion arc, flexion, and extension preoperatively and at the final follow-up, and compared via a mixed analysis of variance adjusting for age. Neuropathy was assessed preoperatively using a modified McGowan neuropathy grade and postoperatively using modified Wilson-Krout criteria. An ordinal logistic regression analysis used postoperative modified Wilson-Krout criteria as the outcome and preoperative factors as predictors. Preoperative McGowan grades were Grade 1 in 14 patients (12.2%), Grade 2A in 28 (24.3%), Grade 2B in 53 (46.1%), and Grade 3 in 20 (17.4%) patients. Postoperatively, 66 patients (57.4%) had excellent results, 26 (22.6%) had good results, 16 (13.9%) had fair results, and 7 (6.1%) had poor results at the final follow-up, as per the Wilson-Krout criteria. There were no complications. Pre- and postoperative elbow ROM was significantly decreased in patients with previous trauma or surgery of the elbow compared with those without (P < 0.05). Anterior subcutaneous transposition of the ulnar nerve did not significantly affect elbow ROM regardless of previous trauma or surgical history nor preoperative ROM (P > 0.05), after adjusting for age. Patients with prolonged symptoms prior to surgery and worse neuropathy tended to have less satisfactory functional outcomes (P < 0.05), after adjusting for covariates. Anterior subcutaneous transposition of the ulnar nerve is an effective and reliable treatment of cubital tunnel syndrome with satisfactory outcomes and minimal effect on elbow ROM.


[JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms].
To investigate JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPN) and the clinical characteristics of patients with JAK2 exon 12 mutants. Allele-specific PCR (AS-PCR) was applied to identify JAK2 V617F mutation. Genomic DNA corresponding to exon 12 of JAK2 gene and epigenetic regulator gene (TET2, ASXL1, EZH2) were amplified by polymerase chain reaction (PCR). Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. SNP genotyping of two 46/1 tag SNPs, rs12340895 and rs10974944, was analyzed using commercially available Taqman assays on the 7500HT real-time PCR instrument according to standard protocols. No JAK2 exon 12 mutation was detected in patients with ET, PMF or JAK2 V617F positive PV. Among 13 JAK2 V617F negative PV patients, JAK2 exon 12 mutation was detected as N542-E543del in 2(15.4%) patients who presented with a phenotype of predominant erythrocytosis and erythroid colonic grown from their bone marrow samples in the absence of exogenous EPO, reduced serum erythropoietin (EPO) level, and no mutations in TET2, ASXL1 or EZH2 genes. One of the affected patients was heterozygous for 46/1 but the second was negative for this haplotype. There was no need to detect JAK2 exon 12 mutation in ET, PMF or MPN-U patients without JAK2 V67F mutation. Ph negative MPN patients with JAK2 exon 12 mutations had somewhat unique clinical and laboratory features.


Heart rate is a useful marker of adherence to beta-blocker treatment in hypertension.
Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients' heart rates to their serum beta-blocker levels. We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4 vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p = .041) in comparison to adherent patients. Heart rate above 75.5 beats per minute predicted non-adherence to beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate cutoff might be applicable for nebivolol but was not determined due to the low number of patients treated with nebivolol. We concluded that heart rate was shown to be a good predictor of non-adherence to beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.


Nanostructured layered double hydroxide aerogels with enhanced adsorption properties.
Aerogels of layered double hydroxides were prepared by a simple and eco-friendly method involving a quick coprecipitation followed by supercritical CO(2) drying. Such aerogels display high surface areas and enhanced adsorption behavior.


From hitting to tattling to gossip: an evolutionary rationale for the development of indirect aggression.
Adult humans are characterized by low rates of intra-group physical aggression. Since children tend to be more physically aggressive, an evolutionary developmental account shows promise for explaining how physical aggression is suppressed in adults. I argue that this is achieved partly through extended dominance hierarchies, based on indirect reciprocity and linguistic transmission of reputational information, mediated by indirectly aggressive competition. Reviewing the literature on indirect and related forms of aggression provides three pieces of evidence for the claim that evolutionarily old impulses towards physical aggression are socialized into indirect aggression in humans: (i) physical aggression falls in early childhood over the same age range at which indirect aggression increases; (ii) the same individuals engage in both direct and indirect aggression; and (iii) socially dominant individuals practice indirect aggression more frequently. Consideration of the developmental course of indirect aggression is complemented by analysis of similar developments in verbal behaviors that are not always thought of as aggressive, namely tattling and gossip. An important puzzle concerns why indirect aggression becomes more covert, and tattling more derogated, in preadolescence and adolescence. This may be due to the development of new strategies aimed at renegotiating social identity and friendship alliances in the peer group.


[Correlation of selected hemodynamic parameters of pulmonary circulation and indices of pulmonary function in patients with mitral stenosis].
The aim of this study was to test if the lung compliance and other indices of pulmonary function correlated with hemodynamic parameters in patients with secondary pulmonary hypertension due to mitral stenosis. 36 patients (mean age 50 years) with mitral stenosis (mean mitral valve area-1.2 cm2), without history of lung diseases were analyzed in the study. 16 patients (group A) were in the II-nd and 20 patients (group B) were in the III-rd and IV-th NYHA class. All patients underwent Swan-Ganz catheterization with evaluation of pulmonary pressures, resistances and pulmonary veins compliance. Pulmonary function tests (spirometry, plethysomography, lung compliance) were also performed. In both analyzed groups the pulmonary artery pressure and pulmonary vein compliance correlated significantly with pulmonary compliance.


A local electrostatic change is the cause of the large-scale protein conformation shift in bacteriorhodopsin.
During light-driven proton transport bacteriorhodopsin shuttles between two protein conformations. A large-scale structural change similar to that in the photochemical cycle is produced in the D85N mutant upon raising the pH, even without illumination. We report here that (i) the pKa values for the change in crystallographic parameters and for deprotonation of the retinal Schiff base are the same, (ii) the retinal isomeric configuration is nearly unaffected by the protein conformation, and (iii) preventing rotation of the C13-C14 double bond by replacing the retinal with an all-trans locked analogue makes little difference to the Schiff base pKa. We conclude that the direct cause of the conformational shift is destabilization of the structure upon loss of interaction of the positively charged Schiff base with anionic residues that form its counter-ion.


LMP1 promotes expression of insulin-like growth factor 1 (IGF1) to selectively activate IGF1 receptor and drive cell proliferation.
Epstein-Barr Virus (EBV) is a gammaherpesvirus that infects the majority of the human population and is linked to the development of multiple cancers, including nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is considered the primary oncoprotein of EBV, and in epithelial cells it induces the expression and activation, or phosphorylation, of the epidermal growth factor receptor kinase. To identify effects on additional kinases, an unbiased screen of receptor tyrosine kinases potentially activated by LMP1 was performed. Using a protein array, it was determined that LMP1 selectively activates insulin-like growth factor 1 receptor (IGF1R). This activation takes place in fibroblast, epithelial, and nasopharyngeal cell lines that express LMP1 stably and transiently. Of note, LMP1 altered the phosphorylation, but not the expression, of IGF1R. The use of LMP1 mutants with defective signaling domains revealed that the C-terminal activating region 2 domain of LMP1 increased the mRNA expression and the secretion of the ligand IGF1, which promoted phosphorylation of IGF1R. IGF1R phosphorylation was dependent upon activation of canonical NF-κB signaling and was suppressed by IκBα and a dominant negative form of TRAF6. Inhibition of IGF1R activation with two small-molecule inhibitors, AG1024 and picropodophyllin (PPP), or with short hairpin RNA (shRNA) directed against IGF1R selectively reduced proliferation, focus formation, and Akt activation in LMP1-positive cells but did not impair LMP1-induced cell migration. Expression of constitutively active Akt rescued cell proliferation in the presence of IGF1R inhibitors. These findings suggest that LMP1-mediated activation of IGF1R contributes to the ability of LMP1 to transform epithelial cells. EBV is linked to the development of multiple cancers in both lymphoid and epithelial cells, including nasopharyngeal carcinoma. Nasopharyngeal carcinoma is a major cancer that develops in specific populations, with nearly 80,000 new cases reported annually. LMP1 is consistently expressed in early lesions and continues to be detected within 50 to 80% of these cancers at later stages. It is therefore of paramount importance to understand the mechanisms through which LMP1 alters cell growth and contributes to tumorigenesis. This study is the first to determine that LMP1 activates the IGF1R tyrosine kinase by regulating expression of the ligand IGF1. Additionally, the data in this paper reveal that specific targeting of IGF1R selectively impacts LMP1-positive cells. These findings suggest that therapies directed against IGF1R may specifically impair the growth of EBV-infected cells.


The metyrapone test in manic patients and healthy subjects.
The metyrapone (Metopiron) test (MT), a useful and reliable procedure for assessing hypothalamic-pituitary-adrenal (HPA) axis function, was applied to manic patients and healthy subjects. Three out of 11 patients had high normal responses to metyrapone, as observed in patients with Cushing's disease. One patient exhibited a subnormal response to metyrapone, as occurs in patients with adrenal insufficiency. No such abnormalities were detected in 11 matched healthy control subjects. These preliminary results suggest that the HPA axis activity patterns in mania may be more complex than previously reported.


Influence of ethnic origin on predictive parameters of performance in sprint running in prepubertal boys.
Afro-American and Caribbean athletes have long dominated sprint running, although the reasons for their disproportionate success remain unclear. The studies of sprinting ability in blacks versus whites have shown contradictory results. This study compared the anthropometric measurements and the physical test results (vertical jump and sprint) of Caucasian and Afro-Caribbean prepubertal boys. Seventeen healthy untrained prepubertal boys, 8 Caucasians and 9 Afro-Caribbeans (11.49 +/- 0.74 years) performed vertical jump tests (a countermovement jump according to the Sargent method, using Abalakov material) and short sprints (30 m). Age, height, weight, and fat mass percentage were also recorded. The sprints were filmed to determine the number of strides over the 30 m. No significant difference was noted for sprint performance between the Caucasians and Afro-Caribbeans (respectively, 5.59 seconds +/- 0.44 vs. 5.51 s +/- 0.50). The predictors of sprint performance differed between the two groups: the vertical jump test was the main predictor for the Caucasian group, whereas the stride number/height ratio was the main predictor for the Afro-Caribbean group. This last group had better ratio (0.14 +/- 0.15 vs. 0.16 +/- 0.02, p < 0.05) and better jump test results (36.77 cm +/- 2.90 vs. 31.12 cm +/- 4.76, p < 005). The prepubertal Afro-Caribbeans seemed to be endowed to run faster but they did not. We hypothesize that they were unable to use their greater leg strength to develop an optimal stride. Further study is needed to investigate what occurs at other maturational stages.


Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study.
Several methods are used to treat focal chondral and osteochondral defects on the weightbearing surfaces of synovial joints. Autologous osteochondral grafting is 1 option used to replace hyaline cartilage in the defect. Mosaicplasty is effective in returning elite athletes to participation in sports. Case series; Level of evidence, 4. In 3 institutes, 354 of 383 patients were followed from 2 to 17 years (average, 9.6 years). The results of mosaicplasty were prospectively evaluated at 6 weeks, 3 months, 6 months, and yearly with patient-reported outcomes measures and radiographs. Slight or moderate degenerative changes (Fairbank grade I or II) were detected preoperatively in 27% of the cases and in 36% of the cases at follow-up. Fairbank grade III changes were observed in 5 cases. An average radiographic deterioration of 0.32 on the Fairbank scale was detected (preoperative, 0.34; postoperative, 0.66). Good to excellent results were found in 91% of femoral mosaicplasties, 86% of tibial, and 74% of patellofemoral; 92% of talar mosaicplasties had similar results (Hannover ankle scoring system). Patellofemoral pain related to graft harvest was observed in 5% of cases. Second-look arthroscopies revealed good, congruent, gliding surfaces of the transplants and acceptable fibrocartilage coverage of donor sites in 16 patients and degenerative changes of the transplants in 5 cases. Histological evaluation revealed good graft incorporation in all 11 cases. Two infections and 3 deep venous thromboses occurred. Despite a higher rate of preoperative osteoarthritic changes in the athletic patients, clinical outcomes of mosaicplasty in this group demonstrated a success rate similar to that of less athletic patients. Higher motivation resulted in better subjective evaluation. Slight deterioration in results occurred during the 9.6-year follow-up; thus, autologous osteochondral mosaicplasty may be a useful alternative for the treatment of 1.0- to 4.0-cm(2) focal chondral and osteochondral lesions in competitive athletes.


Two new diterpenoids from Croton crassifolius.
Two new clerodane-type diterpenoids were isolated from the roots of Croton crassifolius Geisel. The structures of these compounds were elucidated as 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acid (1) and methyl 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic ester (2) by spectroscopic methods.


The course of fatigue in patients with gynecologic and breast cancer.
The objective of this study is to examine the course of fatigue in female cancer patients during the first months after treatment. We examined a sample of 110 patients suffering from gynecological or breast cancer. Fatigue was assessed with two questionnaires, the Multidimensional Fatigue Inventory (MFI) and the fatigue scale of the quality of life questionnaire European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30). Participants were tested during their stay in the hospital (t1), two weeks after discharge (t2), and three months after discharge (t3). Fatigue in the patients' sample was markedly higher than the general population reference values. At t1, the effect sizes are d=0.81 (MFI) and d=1.21 (EORTC QLQ-C30 fatigue scale). Age and tumor stage had no significant influence on fatigue, but patients with a long time since diagnosis had higher fatigue levels than patients with a shorter time since diagnosis. From t1 to t3, fatigue mean scores decreased. The correlations between the t1 and the t3 fatigue scores were weak, with correlation coefficients of only about 0.30. Though the mean scores of fatigue, averaged across all patients, decreased over the first three months, the individual courses could not be predicted from the t1 score.


Acute venous thromboembolic disease and paradoxical embolism.
We report two cases of paradoxical cerebral embolism associated with acute venous thromboembolic disease. The first case corresponds to a 49-year-old woman with sudden onset of dyspnea and syncope, followed by right upper extremity paresis, aphasia and dysarthria. The admission brain computed tomography (CT) was unremarkable, but lung CT showed multilobar and multisegmentary pulmonary embolism. Echocardiography showed dilated right ventricle with impaired systolic function, moderate tricuspid regurgitation, moderate pulmonary hypertension and positive bubble test, suggestive of a patent foramen ovale (PFO) which was successfully closed by endovascular Amplatzer device placement. The patient was discharged with anticoagulation therapy and permanent antiplatelet aggregation therapy. The second case is a 60-year-old woman found unconscious. Neurological examination revealed expressive aphasia, right hemianopsia, right central facial paralysis and right-sided paresis with a National institute of Health Stroke Scale of 19. Brain CT showed signs of acute left middle cerebral artery infarction. Later, she developed greater impairment of consciousness. A new brain CT showed significant edema with mass effect requiring a decompressive craniotomy. Echocardiography showed PFO and lower extremities' Doppler ultrasound showed a left infrapopliteal posterior tibial right deep venous thrombosis. An inferior vena cava filter was placed and two days after surgery, anticoagulation was started.


Expression of IP-10 chemokine is regulated by pro-inflammatory cytokines in cultured hepatocytes.
Chemokines are classified in four distinct groups as CXC, CC, CX3C and C, depending on the presence or absence of a motif called ELR (Arg-Leu-Glu) before the first cysteine residue in their structure. CXC chemokines are also subdivided into ELR+ and ELR-. Increasing evidence has indicated the existence of a chemokine network in the liver which is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury. The CXC chemokines play a major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. The aim of this study was to examine the response of cultured hepatocytes to exogenous inflammatory cytokines (TNF-alpha and IFN-gamma) regarding expression of IP-10 and growth regulatory oncogen (Gro) chemokines. In this study we employed western and northern analysis to measure chemokines at the level of protein and mRNA by hepatocytes in response to pro-inflammatory cytokines. We found that, the pro-inflammatory cytokines, TNF-alpha and IFN-gamma, selectively stimulated expression of IP-10 but were without effect on Gro. This confirms a potential direct involvement of these cytokines in chemokine production by hepatocytes. Thus, IFN-gamma and TNF-alpha may play a role in hepatic injury and inflammation and produce some of their biological effects by localized induction of chemokines by hepatocytes. Given the similarity to an acute phase response, we were able to show that IFN-gamma and TNF-alpha mimicked the effects of cell isolation and culture on induction of IP-10 expression. Further, evidence for linkages between IFN- gamma and TNF- alpha and liver injuries is seen in hepatitis C and hepatitis B in which increased levels of TNF- alpha and its soluble receptor were reported.


Natural versus artificial sensors applied in peroneal nerve stimulation.
We have attempted to quantify the performance of natural versus artificial sensors when used in a closed-loop functional electrical stimulation system. Peroneal nerve stimulation was applied during gait to a multiple sclerosis subject with a drop foot. Stimulation was applied only during the swing phase to provide artificially induced dorsiflexion of the foot. Detection of the onset of the stance phase was accomplished using a standard heel contact switch mounted inside the subject's shoe (the artificial sensor) and using processed nerve signals derived from an implanted nerve-cuff electrode (the natural sensor). A detection percentage of at least 85% was achieved using the afferent nerve signal information only. When muscle activity (also recorded in the cuff) and additional information about the gait cycle were incorporated, functional detection ratios approaching 100% were achieved.


Structure of wild-type yeast RNA polymerase II and location of Rpb4 and Rpb7.
The three-dimensional structure of wild-type yeast RNA polymerase II has been determined at a nominal resolution of 24 A. A difference map between this structure and that of the polymerase lacking subunits Rpb4 and Rpb7 showed these two subunits forming part of the floor of the DNA-binding (active center) cleft, and revealed a slight inward movement of the protein domain surrounding the cleft. Surface plasmon resonance measurements showed that Rpb4 and Rpb7 stabilize a minimal pre-initiation complex containing promoter DNA, TATA box-binding protein (TBP), transcription factor TFIIB and the polymerase. These findings suggest that Rpb4 and Rpb7 play a role in coupling the entry of DNA into the active center cleft to closure of the cleft. Such a role can explain why these subunits are necessary for promoter-specific transcription in vitro and for a normal stress response in vivo.


Recent developments in carbon dioxide utilization under mild conditions.
The use of carbon dioxide as a renewable and environmentally friendly source of carbon is highly attractive. This article focuses on recent developments in important new reactions and new catalysts for homogeneous CO(2) transformations under mild reaction conditions. Other than traditional organometallic catalysts, organocatalysts have also been applied in the chemical conversion of CO(2) and have demonstrated very promising ability in this field. As the coupling of epoxides with CO(2) to form cyclic carbonates or polycarbonates has been well documented, it will be excluded from this article.


Shifting terrains: Understanding residential contaminants after flood disasters.
Flood disasters can induce the mass transport of soils and sediments. This has the potential to distribute contaminants and present novel combinations to new locations - including residential neighborhoods. Even when soil contaminants cannot be directly attributed to the disaster, data on bacterial and heavy metal(loids) can facilitate an environmentally just recovery by enabling reconstruction decisions that fill data gaps to minimize future exposure. These data-gathering interventions may be especially useful in poor, rural, and racially diverse communities where there is a high probability of exposure to multiple hazards and a potential dependency on the financial resources of disaster aid as a means of reducing chronic exposures to other environmental pollutants. At the same time, entering these post-disasters spaces is ethically complex. To acknowledge this complexity, we pilot a framework for work that gathers social-ecological hazard information while retaining a fair-minded approach to transdisciplinary work. Assembled a transdisciplinary team to recruit participants from 90 households subjected to flooding in the southeastern US. Participating households agreed to interviews to elicit flood experience and environmental health concerns, soil sampling for fecal bacteria (E. coli) and soil sampling for selected heavy metals and metalloids (Pb, As, Cd) at their flooded residence. Soil sampling found a wide range of E. coli concentrations in soil (0.4-1115.7 CFU/ dry gram). Heavy metal(loid)s were detected at most residences (As 97.9 %; Ca 25.5 %; Pb 100 %). Individually, heavy metal(loid) concentrations did not exceed regulatory thresholds. Hazard, risk, and mitigation concerns expressed during interviews reveal that integrated human-nature concepts complicate common understandings of how hazard perceptibility (smell, sight, touch, and information) affects research-action spaces. Qualitative analysis of interviews and field notes revealed that soil-related hazards addressed by our biophysical protocols were less salient than changes with direct causal associations with flooding. We conclude by discussing the potential for the social-ecological hazard information that is fair-minded and transdisciplinary (SHIFT) framework to advance environmentally just approaches to research-action spaces after disasters.


[Chronic Lung Allograft Dysfunction after Living-donor Lobar Lung Transplantation].
Long-term survival after living-donor lobar lung transplantation (LDLLT) is hampered by the development of chronic lung allograft dysfunction( CLAD), similar to the clinical courses seen in some recipients of cadaveric lung transplantation( CLT). CLAD after bilateral LDLLT has been shown to be characterized by the development in the unilateral lung due to differences in the immunological features of the two donors. Based on this characteristic, we found that lung perfusion scintigraphy, which can show a perfusion shift to the contralateral unaffected lung with the development of CLAD, had the potential to predict unilateral CLAD after bilateral LDLLT. Moreover, we found that CLAD, especially restrictive allograft syndrome, developed significantly later after bilateral LDLLT than after bilateral CLT, although the CLAD-free survival and overall survival after bilateral LDLLT were similar to those after bilateral CLT. We describe our experience of CLAD after bilateral LDLLT since the first case of LDLLT in Japan.


Sesquiterpene benzoxazoles and sesquiterpene quinones from the marine sponge Dactylospongia elegans.
A new sesquiterpene benzoxazole, nakijinol B (3), its acetylated derivative, nakijinol B diacetate (6), and two new sesquiterpene quinones, smenospongines B (4) and C (5), were isolated from the methanol extract of the marine sponge Dactylospongia elegans. Also isolated were the known compounds dactyloquinone B and a 1:1 mixture of ilimaquinone and 5-epi-ilimaquinone. Their structures were determined on the basis of spectroscopic analyses and comparison with literature data. The isolated compounds were assessed for their cytotoxicity against a panel of human tumor cell lines (SF-268, H460, MCF-7, and HT-29) and a normal mammalian cell line (CHO-K1). All compounds were found to have activities in the range 1.8-46 μM and lacked selectivity for tumor versus normal cell lines.


The role of ILC2 in hookworm infection.
Hookworm is a major public health concern, yet still relatively little is known about the immunological responses involved in human infection. Animal studies are mainly confined to using the natural rodent helminth Nippostrongylus brasiliensis as this has been proposed as the most accurate model of hookworm infection in the mouse, with both its life cycle and the immune responses it invokes having been extremely well characterized. In this review, we examine the roles that type 2 innate lymphoid cells (ILC2s) play in immunity and host tolerance to hookworm infection, particularly N. brasiliensis. This includes their role in the initiation and regulation of immune responses, as well as in the resolution and limitation of tissue damage required after an infection with a large organism, such as a helminth.


Extended transcervical thymectomy with partial upper sternotomy: results in non-thymomatous patients with myasthenia gravis.
Thymectomy is a recognized treatment for myasthenia gravis (MG), but the optimal surgical approach is yet to be determined. This study analysed the results in non-thymomatous MG patients treated at our institution using an extended transcervical access with partial upper sternotomy (TC-US), in order to describe cumulative incidence of remission and its predictors. In the period 1988-2012, 215 non-thymomatous MG patients underwent thymectomy using the TC-US approach. There were 61 males and 154 females (median age: 33 years). Primary end points were complete stable remission (CSR) and pharmacological remission (PR). Clinico-pathological predictors of CSR/PR were analysed including age, gender, preoperative MG symptom duration, preoperative immunosuppression therapy and disease severity. The median follow-up period was 127 months. The median preoperative duration of MG symptoms was 9 months (interquartile range 4-13). The median operative time was 65 min (range: 45-135). There was no postoperative death. Morbidity rate was 7% (14 patients, no major complication). Ten patients died at the follow-up (3 of MG). MG symptoms improved in 85% (150/176) of the patients. CSR rate was 34%, PR rate was 4%. Cumulative incidence of CSR/PR was 27, 37 and 46% at 5, 10 and 15 years, respectively. Independent predictors of increased CSR/PR rate were age (P = 0.028) and MG symptom duration <6 months (P = 0.013). Our data suggest that in patients with non-thymomatous MG, thymectomy by TC-US has a remission rate not inferior to those reported after trans-sternal or video-assisted thoracic surgery techniques. The short duration of MG symptoms before thymectomy is a predictor of remission. The technique strikes a reasonable balance between the extent of thymic resection, operative and anaesthesia time, patient acceptance, neurological outcome and costs.


Identification of Additives in Polypropylene and Their Degradation under Solar Exposure Studied by Gas Chromatography-Mass Spectrometry.
Additives are absolutely essential in the development of commercial polymeric materials. Accordingly, an exhaustive control of composition and evolution in these additives over time is necessary to validate their performance and safety during their shelf life and, consequently, their ultimate applications. Gas chromatography coupled with mass spectrometry, GC-MS, is described in the present work to identify and analyze the content of a wide variety of additives, commonly used in industrial polymeric materials. First, the identification under the present experimental protocol of additives with a relatively high molecular weight (Irganox 1330 and Irganox 1010) has been successfully attained. Second, the evolution under solar exposure over time has been analyzed by GC-MS for 11 additives and derived substances, which have been identified in a commercial polypropylene sample, estimating the corresponding depletion times. In addition, the resultant increase of carbonyl groups in the polymeric macrochains along the photo-oxidation has been also determined by infrared spectroscopy. Therefore, GC-MS is found to be a reliable tool for the analysis of the evolution of commonly used polymer additives under specific degradation conditions, which can be very useful in the formulation of improved future additivations.


Enhancing effects of phenobarbital and 3-methylcholanthrene on GST-P-positive liver cell foci development in a new medium-term rat liver bioassay using D-galactosamine.
The carcinogenic potential of phenobarbital (PB) and 3-methylcholanthrene (3-MC) was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a nonsurgical method to induce liver cell regeneration in place of partial hepatectomy (PH). Rats were initially given a single ip injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 wk on basal diet received 2 ip injections of DGA (300 mg/kg) at the end of wk 2 and 5. They were treated with one of the test compounds PB or 3-MC in the diet or fed basal diet for wk 3-8 Carcinogenic potential was assessed by comparing the numbers and areas per square centimeter of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of test chemical-treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for PB, which is a nongenotoxic liver tumor promoter, and for 3-MC, which is a genotoxic nonliver carcinogen. Increases of liver/body weight ratios and serum total cholesterol were observed in rats treated with PB or 3-MC. Interestingly, interlobe differences were found on the development of GST-P+ liver cell foci. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive method to screen large-numbers of environmental liver and nonliver carcinogens.


Biochemical evidence that small proline-rich proteins and trichohyalin function in epithelia by modulation of the biomechanical properties of their cornified cell envelopes.
The cornified cell envelope (CE) is a specialized structure involved in barrier function in stratified squamous epithelia, and is assembled by transglutaminase cross-linking of several proteins. Murine forestomach epithelium undergoes particularly rigorous mechanical trauma, and these CEs contain the highest known content of small proline-rich proteins (SPRs). Sequencing analyses of these CEs revealed that SPRs function as cross-bridgers by joining other proteins by use of multiple adjacent glutamines and lysines on only the amino and carboxyl termini and in functionally non-polar ways. Forestomach CEs also use trichohyalin as a novel cross-bridging protein. We performed mathematical modeling of amino acid compositions of the CEs of mouse and human epidermis of different body sites. Although the sum of loricrin + SPRs was conserved, the amount of SPRs varied in relation to the presumed physical requirements of the tissues. Our data suggest that SPRs could serve as modifiers of a composite CE material composed of mostly loricrin; we propose that increasing amounts of cross-bridging SPRs modify the structure of the CE, just as cross-linking proteins strengthen other types of tissues. In this way, different epithelia may use varying amounts of the cross-bridging SPRs to alter the biomechanical properties of the tissue in accordance with specific physical requirements and functions.


Short communication: The Veterans Aging Cohort Study Index is an effective tool to assess baseline frailty status in a contemporary cohort of HIV-infected persons.
The Veterans Aging Cohort Study (VACS) Index has previously been used to identify frail HIV-infected persons. However, data demonstrating the independent association between the VACS Index and baseline frailty status is lacking. Furthermore, the ability of the VACS Index to also reflect transitions in frailty status over time is unknown. We used data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) to determine independent association of baseline frailty status with the VACS Index. We also evaluated VACS Index changes with frailty status transitions over time. We included 303 participants (median age 48 years, 76% men, 57% non-Hispanic white, 91% with plasma HIV RNA <400 copies/ml, and median CD4(+) cell count 595 cells/ml) with baseline and follow-up frailty assessments and used the Fried's criteria to define frailty status. There were 184 (61%) nonfrail, 112 (37%) prefrail, and seven (2%) frail participants at baseline. Prefrail/frail participants had significantly higher median VACS Index scores compared with nonfrail participants (18 versus 10, p<0.001). In multivariable analysis, prefrailty/frailty was independently associated with a higher VACS Index score (odds ratio 1.025, p=0.019). After a median follow-up of 12 months, participants who remained prefrail/frail compared to those who remained nonfrail continued to have higher median VACS Index scores. The VACS Index score did not significantly change with transitions in frailty status over time. Our study highlights the potential utility of the VACS Index in frailty assessment within the clinical setting.


Spatiotemporal clustering of dengue cases in Thiruvananthapuram district, Kerala.
Dengue cases are increasing in Kerala since 2010. Information on clustering of cases across locations and time periods is vital for disease surveillance and timely control. The objective is to study spatiotemporal clustering of dengue cases and their climatic and physioenvironmental correlates in Thiruvananthapuram district during 2010-2014. Health department data on reported cases of dengue were obtained from January 2011 to June 2014. Cases were individually geocoded, using Google Earth. Moran's I index was estimated to analyze spatial autocorrelation using GeoDa software. Space-time clustering across 178 geo-divisions within the district was analyzed using SaTScan software. Correlation analysis was done for space-time clustering with climatic variables. Definite spatial and temporal trends were found on analysis of a total of 8279 dengue cases. Significant spatial autocorrelation (Moran's I = 0.32, P< 0.01) and space-time clusters with very high log-likelihood ratios (P < 0.01) were found across geo-divisions. Pallichal panchayat was the most likely cluster in every year. The monthly incidence of dengue cases showed a significant positive association (P < 0.05) with a 2-month lag of mean minimum temperature (ρ = 0.39), 1-month lag of rainfall (ρ = 0.33), and 1-month lag of humidity (ρ = 0.38). Dengue occurrences showed an inverse association (P < 0.01) with mean maximum temperatures of the respective months (ρ= -0.48). Spatial analysis using epidemiological tools reveals spatial and temporal clustering of dengue cases within the district and their association with climatic parameters. This information can be used in controlling outbreaks in the future. This work upholds scope and feasibility of geospatial research in public health in India.


[Experimental study of the toxic effect of combinations of tobramycin and carbenicillin].
Acute toxicity of tobramycin and carbenicillin used alone and in combination was studied on albino mice. The antibiotics were combined in the following ratios: 1:15, 1:30, 1:45, 1:60, 1:75 and 1:150 (1 refers to tobramycin). The character of the toxic effect of the combinations was estimated with the Loewe graphical method and interaction indices. It was shown that interaction of tobramycin with carbenicillin in the combinations with wide ratio ranges was of an indifferent character. The toxic effect of the combinations did not reach the total toxic effect of the components used alone. It was noted that the combinations of tobramycin with carbenicillin in the ratios of 1:15, 1:30 and 1:150 were most favourable for the drug tolerance. The nephrotoxic effect of tobramycin and carbenicillin used alone and in combination was studied on albino rats. The antibiotics were administered intravenously for 5 days. It was demonstrated that the level and the character of the morphological changes in the kidneys of the rats treated with the combinations of tobramycin and carbenicillin were the same as those after the use of an analogous dose of tobramycin alone. Therefore, the nephrotoxic effect of tobramycin was not potentiated on its combined use with carbenicillin.


Spontaneous coronary artery dissection.
Spontaneous coronary artery dissection (SCAD) should be considered as a cause of the acute coronary syndrome in young patients with few apparent risk factors for coronary artery disease, in females in the peripartum period, and in patients who are at a higher risk for this condition. SCAD can also present as sudden death and cardiogenic shock. Several mechanisms have been described in the pathophysiology of this condition. Urgent coronary angiography is indicated if SCAD is suspected. Percutaneous coronary artery stenting and coronary artery bypass grafting are the main treatment strategies.


RuO2 nanoparticles anchored on g-C3N4 as an efficient bifunctional electrocatalyst for water splitting in acidic media.
The electrolysis of water, particularly proton exchange membrane (PEM) water electrolysis, holds great promise for hydrogen production in industry. However, the catalyst used in this process is prone to dissolution in acidic environments, making it imperative to develop cost-effective, highly efficient, and acid-stable electrocatalytic materials to overcome this challenge and enable large-scale application of PEM water electrolysis technology. Herein, we prepared ruthenium oxide (RuO2)/graphitic carbon nitride (g-C3N4) composites (RuO2/C3N4) via a combination of sol-gel and annealing methods. The g-C3N4 provides a large surface area, while RuO2 is uniformly deposited on the g-C3N4 surface. The interaction between g-C3N4 and RuO2 stabilizes the RuO2 nanoparticles and enhances long-term water oxidation stability. This unique structure and the combined advantages of RuO2 and g-C3N4 yield exceptional electrocatalytic activity toward both the oxygen evolution reaction (OER, 240 mV@10 mA cm-2) and the hydrogen evolution reaction (HER, 109 mV@10 mA cm-2), with excellent durability (over 28 h), and a cell voltage of 1.607 V at 10 mA cm-2 when used in an RuO2/C3N4||RuO2/C3N4 electrolyzer. This study highlights the efficacy of the g-C3N4 support method in designing highly stable Ru-based OER electrocatalysts for efficient acidic water splitting.


The Importance of Physical Activity in Preventing Fatigue and Burnout in Healthcare Workers.
The workers of the health sector are important to the country's economy in many ways. Healthy and rested workers are highly valuable to the public health sector and give a good perception of their work to patients and society. It is thus important to have a sufficient number of healthy working staff in healthcare institutions who do not have work fatigue and burnout. A total of 987 employees-doctors, professional staff, and others-of a large healthcare institution in Hungary voluntarily participated in a survey regarding their lifestyle and physical activity habits and answered the questions anonymously. Women reported less leisure time (p < 0.02), with 54.9% of female respondents saying that they did not exercise regularly, and fatigue was more common among them (p < 0.001). In this respect, the healthcare workers' responses did not differ from those of the overall population. The most common sports were cycling (17.7%), running (15.4%), and working out in a gym (12.3%). Reasons for not participating in sports included lack of time (70.2%) and fatigue (43.9%) as the most frequent responses. Healthcare workers are exposed to a number of risks that require particular attention to maintain their health. Employers should thus focus on implementing programs that prevent burnout and promote healthy lifestyles.


Functional evidence for adenosine A2 receptor regulation of phosphatidylcholine secretion in cultured type II pneumocytes.
We examined the effects of P1 purinoceptor agonists on secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. Adenosine and its nonmetabolizable analogs, 5'-N-ethylcarboxyamidoadenosine (NECA), N6-phenylisopropyladenosine (PIA) and 2-chloroadenosine, increased secretion, and this effect was dependent on concentration. At the highest concentration, all agonists stimulated phosphatidylcholine secretion approximately 2-fold. NECA, with an EC50 of 8.9 X 10(-8) M, was the most potent agonist. The order of potency was NECA greater than 2-chloroadenosine = L-PIA greater than or equal to adenosine greater than D-PIA. The stimulatory effect of 10(-6) M NECA was diminished by the P1 antagonists theophylline and 8-phenyltheophylline. The degree of stimulation by the adenosine analogs as well as its time course was the same as that induced by terbutaline. The effects of the adenosine analogs and of terbutaline were not additive, suggesting a similar mode of action for the beta adrenergic and purinoceptor agonists. Terbutaline and the adenosine analogs increased intracellular cyclic AMP levels. Again, NECA was the most potent adenosine analog. For NECA, L-PIA and adenosine, there was a significant correlation between effects on secretion and on cyclic AMP content. These data suggest that the effect of adenosine on phosphatidylcholine secretion in type II pneumocytes is mediated by the A2 subtype of the P1 purinoceptor.


Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma.
Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.


Operational definition of intrinsically unstructured protein sequences based on susceptibility to the 20S proteasome.
Intrinsically unstructured proteins (IUPs), also known as natively unfolded proteins, lack well-defined secondary and tertiary structure under physiological conditions. In recent years, growing experimental and theoretical evidence has accumulated, indicating that many entire proteins and protein sequences are unstructured under physiological conditions, and that they play significant roles in diverse cellular processes. Bioinformatic algorithms have been developed to identify such sequences in proteins for which structural data are lacking, but still generate substantial numbers of false positives and negatives. We describe here a simple and reliable in vitro assay for identifying IUP sequences based on their susceptibility to 20S proteasomal degradation. We show that 20S proteasomes digest IUP sequences, under conditions in which native, and even molten globule states, are resistant. Furthermore, we show that protein-protein interactions can protect IUPs against 20S proteasomal action. Taken together, our results thus suggest that the 20S proteasome degradation assay provides a powerful system for operational definition of IUPs.


Development and Validation of Verbal Emotion Vignettes in Portuguese, English, and German.
Everyday human social interaction involves sharing experiences verbally and these experiences often include emotional content. Providing this context generally leads to the experience of emotions in the conversation partner. However, most emotion elicitation stimulus sets are based on images or film-sequences providing visual and/or auditory emotion cues. To assimilate what occurs within social interactions, the current study aimed at creating and validating verbal emotion vignettes as stimulus set to elicit emotions (anger, disgust, fear, sadness, happiness, gratitude, guilt, and neutral). Participants had to mentally immerse themselves in 40 vignettes and state which emotion they experienced next to the intensity of this emotion. The vignettes were validated on a large sample of native Portuguese-speakers (N = 229), but also on native English-speaking (N = 59), and native German-speaking (N = 50) samples to maximise applicability of the vignettes. Hierarchical cluster analyses showed that the vignettes mapped clearly on their target emotion categories in all three languages. The final stimulus sets each include 4 vignettes per emotion category plus 1 additional vignette per emotion category which can be used for task familiarisation procedures within research. The high agreement rates on the experienced emotion in combination with the medium to large intensity ratings in all three languages suggest that the stimulus sets are suitable for application in emotion research (e.g., emotion recognition or emotion elicitation).


Nick-dependent and -independent processing of large DNA loops in human cells.
DNA loop heterologies are products of normal DNA metabolism and can lead to severe genomic instability if unrepaired. To understand how human cells process DNA loop structures, a set of circular heteroduplexes containing a 30-nucleotide loop were constructed and tested for repair in vitro by human cell nuclear extracts. We demonstrate here that, in addition to the previously identified 5' nick-directed loop repair pathway (Littman, S. J., Fang, W. H., and Modrich, P. (1999) J. Biol. Chem. 274, 7474-7481), human cells can process large DNA loop heterologies in a loop-directed manner. The loop-directed repair specifically removes the loop structure and occurs only in the looped strand, and appears to require limited DNA synthesis. Like the nick-directed loop repair, the loop-directed repair is independent of many known DNA repair pathways, including DNA mismatch repair and nucleotide excision repair. In addition, our data also suggest that an aphidicolin-sensitive DNA polymerase is involved in the excision step of the nick-directed loop repair pathway.


The human PMR1 endonuclease stimulates cell motility by down regulating miR-200 family microRNAs.
The motility of MCF-7 cells increases following expression of a human PMR1 transgene and the current study sought to identify the molecular basis for this phenotypic change. Ensemble and single cell analyses show increased motility is dependent on the endonuclease activity of hPMR1, and cells expressing active but not inactive hPMR1 invade extracellular matrix. Nanostring profiling identified 14 microRNAs that are downregulated by hPMR1, including all five members of the miR-200 family and others that also regulate invasive growth. miR-200 levels increase following hPMR1 knockdown, and changes in miR-200 family microRNAs were matched by corresponding changes in miR-200 targets and reporter expression. PMR1 preferentially cleaves between UG dinucleotides within a consensus YUGR element when present in the unpaired loop of a stem-loop structure. This motif is present in the apical loop of precursors to most of the downregulated microRNAs, and hPMR1 targeting of pre-miRs was confirmed by their loss following induced expression and increase following hPMR1 knockdown. Introduction of miR-200c into hPMR1-expressing cells reduced motility and miR-200 target gene expression, confirming hPMR1 acts upstream of Dicer processing. These findings identify a new role for hPMR1 in the post-transcriptional regulation of microRNAs in breast cancer cells.


[Gestational surrogacy - sin, whim or necessity].
The authors propose the gestational surrogacy to be permitted but only for medical indications and under exact requirements. The surrogate mother if married, her husband, too, sign with the commissioning adopting couple a legal agreement at the beginning of the procedures.


Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group Protocol 057.
The aim of this study was to identify a safe and tolerable dose of recombinant interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million units of IFN-beta given by daily subcutaneous injection with 500 mg per day of oral zidovudine. At the time of this study, this was standard of care for HIV infection. Patients were sequentially enrolled at three medical centers. Tumor response, drug tolerance, antiviral studies and CD4 changes were assessed. Four patients were enrolled at each dose level, and escalation proceeded when at least four patients had tolerated two weeks of therapy without dose-limiting toxicity. ACTG Kaposi's sarcoma tumor response criteria were used to assess response. Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was well tolerated, and the dose-limiting toxicities were local skin necrosis and systemic symptoms. Despite generally good prognostic characteristics, only two patients achieved a clinical complete response and three addition patients had stable disease for a prolonged period of time (range 24-44 weeks). There was no correlation between baseline CD4 cell counts and tumor response, nor between the antiviral effect of IFN-beta as measured by decreases in immune-complex dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not result in more tumor responses or in greater antiviral activity. The maximum tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was 45 million units by subcutaneous injection per day. IFN-beta is well tolerated in patients with AIDS-related Kaposi's sarcoma when used in conjunction with zidovudine. However, the antitumor response rate in good-prognosis patients is low. Further studies of this agent should be in the context of four-drug antiretroviral regimens where viral suppression is greatest and any antitumor activity of IFN-beta may be observed.


Impacts of low salinity exposure and antibiotic application on gut transport activity in the Pacific spiny dogfish, Squalus acanthias suckleyi.
The role of the marine elasmobranch gastrointestinal tract in nitrogen-recycling and osmotic homeostasis has become increasingly apparent, with the gut microbial community likely playing a significant role converting urea, an important osmolyte in elasmobranchs, into ammonia. The Pacific spiny dogfish can experience and tolerate reduced environmental salinities, yet how this environmental challenge may affect the microbiome, and consequently nitrogen transport across the gut, is as of yet unknown. In the present study, excised gut sac preparations were made from dogfish acclimated to the following: full-strength seawater (C), low salinity for 7 days (LS), and after acute transfer of LS-acclimated fish to full-strength SW for 6 h (AT). Significantly reduced microbial derived urease activity was observed in the mucosal saline of gut sac preparations from the LS (by 81%) and AT (by 89%) treatments relative to the C treatment. Microbial derived cellulase activity from mucosal saline samples tended to follow similar patterns. To further ensure an effective decrease in the spiral valve microbial population, an antibiotic cocktail was applied to the mucosal saline used for in vitro measurements of ion, water, and nitrogen flux in these gut sac preparations. This caused a further 57-61% decrease in the mucosal saline urease activity of the C and LS treatments. Overall, we observed relatively little flux across the stomach for all measured parameters aside from water movement, which switched from a net efflux in control fish to a net influx in acutely transferred fish, indicative of drinking. While no significant differences were observed in terms of nitrogen flux (urea or ammonia), we tended to see the accumulation of ammonia in the spiral valve lumen and a switch from efflux to influx of urea in control versus acutely transferred fish. The increased ammonia production likely occurs as a result of heightened metabolism in a challenging environment, while the retention and acquisition of urea is suggestive of nitrogen scavenging under nitrogen-limiting conditions.


Benign metastasizing leiomyoma of the uterus.
Herein, we report on a well-characterized benign metastasizing leiomyoma, presented in an unusual site. Up to the knowledge of authors, so far, only 76 cases of benign metastasizing leiomyoma have been reported. The tumor presented as a retroperitoneal mass three years after a hysterectomy Performed for leiomyomatosis of the uterus with extensive areas of hyalinization. Histopathologic and immunohistochemical studies of the resected mass were similar to the uterine leiomyoma, showing moderate cellularity of bland looking smooth muscle cells with minimal atypia, inconspicuous mitosis, and no necrosis in a hyalinized background.


Evaluating consumer acceptability and willingness to pay for various beef chuck muscles.
In-home consumer steak evaluations, followed by centralized laboratory-setting auctions, were used to determine consumer (n = 74 consumers) acceptability and willingness to pay for various beef chuck muscles. The infraspinatus (IF), serratus ventralis (SV), supraspinatus (SS), and triceps brachii (TB) from the beef chuck were evaluated against LM steaks from the rib to determine price and trait differentials. Muscles from USDA Choice, boneless, boxed-beef sub-primals were aged 14 d, frozen, and cut into 2.5-cm-thick steaks. Consumers received two steaks from each muscle for in-home evaluations of uncooked steak appearance and cooked steak palatability. After in-home evaluation of steaks, consumers participated in a random nth price auction session to determine willingness to pay for those steaks. Muscles differed (P < 0.05) for overall like of appearance, like of size, like of shape, and like of leanness; LM generally rated the highest. Steaks from the LM rated highest (P < 0.05) for overall like, and steaks from the SS and SV were lowest (P < 0.05) for overall like. Juiciness and beef flavor intensity scores were highest (P < 0.05) for steaks from the LM and IF, whereas SS steaks received the lowest (P < 0.05) juiciness scores, and SS and SV steaks were rated lowest (P < 0.05) for beef flavor intensity. Average auction price differentials differed (P < 0.05) from the LM, and were -0.71 dollars, -0.79 dollars, -1.75 dollars, and -2.44 dollars/0.45 kg for the TB, IF, SS, and SV, respectively. Average appearance trait differentials and average palatability trait differentials were correlated significantly with average price differentials. Results indicate the IF and TB were acceptable to consumers as steaks but only at prices lower than the LM.


Sonneratia apetala (Buch.-Ham.) Fruit Extracts Ameliorate Iron Overload and Iron-Induced Oxidative Stress in Mice.
Iron overload results in oxidative damage to various biomolecules including DNA, proteins and lipids which ultimately leads to cell death. The Sonneratia apetala fruit contains a high content of antioxidants and displays several bioactive properties. Therefore, the powder of the S. apetala fruit was successively fractionated into n-hexane (Hex), chloroform (Chl), and methanol (Met) fractions to evaluate their efficiency in ameliorating iron overload. In vitro, a colorimetric method was used to assess the Fe-chelating activity of the fractions using ferrozine. The fractions were also used in vivo to examine their efficacy in ameliorating iron overload and iron-induced oxidative stress in mice induced by intraperitoneal injection of ferric carboxymaltose at 100 mg/kg body weight (bw). Among the fractions, Met showed the highest Fe-chelation ability with an inhibitory concentration 50 of 165 μg/mL followed by Hex (270 μg/mL), and Chl (418 μg/mL). In vivo, the results showed a significantly (P<0.05) lower iron profile (iron and ferritin concentrations in serum and liver tissue and total iron-binding capacity of serum) in the Met and the Hex treated mice groups than in the iron-overloaded group. Met at 1,000 μg/kg bw completely ameliorated iron overload in the blood and the liver tissue of mice. At this concentration, Met also prevented iron-induced oxidative stress in the liver tissue of iron-overloaded mice by restoring reducing power, total antioxidant capacity, and total protein. Thus, the S. apetala fruit, especially its Met fraction can be used in treating iron overload and associated toxicity.


Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells.
sPLA2 (secretory phospholipase A2) enzymes have been implicated in various biological events, yet their precise physiological functions remain largely unresolved. In the present study we show that group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with an adenovirus. Bronchial epithelial cells and lung fibroblasts pre-expressing group V and X sPLA2s showed marked resistance to adenovirus-mediated gene delivery in a manner dependent on their catalytic activity. Although adenovirus particles were insensitive to recombinant group V and X sPLA2s, direct addition of these enzymes to 293A cells suppressed both number and size of adenovirus plaque formation. Group V and X sPLA2s retarded the entry of adenovirus into endosomes. Moreover, adenoviral infection was suppressed by LPC (lysophosphatidylcholine), a membrane-hydrolytic product of these sPLA2s. Thus hydrolysis of the plasma membrane by these sPLA2s may eventually lead to the protection of host cells from adenovirus entry. Given that group V and X sPLA2s are expressed in human airway epithelium and macrophages and that the expression of endogenous group V sPLA2 is upregulated by virus-related stimuli in these cells, our present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract.


Mulibrey nanism: Two novel mutations in a child identified by Array CGH and DNA sequencing.
In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver-Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X-ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver-Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this. © 2016 Wiley Periodicals, Inc.


Estrogen sulfotransferase expression in endometrial stromal sarcomas: an immunohistochemical study.
Levels and activity of the enzyme estrogen sulfotransferase (EST) have been reported to play an important role in the regulation of in situ estrogen levels in human breast, prostate, and endometrial cancer. To better understand growth progression in endometrial stromal sarcomas (ESS), estrogen-dependent tumors, we analyzed the expression of EST in a series of 29 ESS. Archival formalin-fixed, paraffin-embedded material was analyzed immunohistochemically with a monoclonal antibody to EST using the peroxidase-antiperoxidase method. A score was calculated based on the percentage of positive tumor cells and staining intensity. EST staining was identified in 5 of 29 (18%) ESS and was scored as weakly positive, while 24 of 29 (82%) ESS were negative for EST. We demonstrate that a subset of ESS express EST, which may allow them to inactivate intratumoral estrogens. ESS without EST expression may have increased levels of biologically active estrogen, which explains the tumor progression of this entity and these patients may be at increased risk for recurrences and metastases.


In-depth Characterization of a TCR-specific Tracer for Sensitive Detection of Tumor-directed Transgenic T Cells by Immuno-PET.
A number of different technologies have been developed to monitor in vivo the distribution of gene-modified T cells used in immunotherapy. Nevertheless, in-depth characterization of novel approaches with respect to sensitivity and clinical applicability are so far missing. We have previously described a novel method to track engineered human T cells in tumors using 89Zr-Df-aTCRmu-F(ab')2 targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR. Here, we performed an in-depth in vitro characterization of the tracer in terms of antigen affinity, immunoreactivity, influence on T-cell functionality and stability in vitro and in vivo. Of particular interest, we have developed diverse experimental settings to quantify TCR-transgenic T cells in vivo. Local application of 89Zr-Df-aTCRmu-F(ab')2-labeled T cells in a spot-assay revealed signal detection down to approximately 1.8x104 cells. In a more clinically relevant model, NSG mice were intravenously injected with different numbers of transgenic T cells, followed by injection of the 89Zr-Df-aTCRmu-F(ab')2 tracer, PET/CT imaging and subsequent ex vivo T-cell quantification in the tumor. Using this setting, we defined a comparable detection limit of 1.0x104 T cells. PET signals correlated well to total numbers of transgenic T cells detected ex vivo independently of the engraftment rates observed in different individual experiments. Thus, these findings confirm the high sensitivity of our novel PET/CT T-cell tracking method and provide critical information about the quantity of transgenic T cells in the tumor environment suggesting our technology being highly suitable for further clinical translation.


Women's health, hormonal balance, and personal autonomy.
Hormone-based contraception disrupts hormonal balance, creating artificial states of anovulation and threatening women's health. We reviewed its main adverse effects and mechanisms on accelerated ovarian aging, mental health (emotional disruptions, depression, and suicide), sexuality (reduced libido), cardiovascular (brain stroke, myocardial infarction, hypertension, and thrombosis), and oncological (breast, cervical, and endometrial cancers). Other "collateral damage" includes negative effects on communication, scientific mistrust, poor physician-patient relationships, increased patient burden, economic drain on the healthcare system, and environmental pollution. Hormone-sensitive tumors present a dilemma owing to their potential dual effects: preventing some cancers vs. higher risk for others remains controversial, with denial or dismissal as non-relevant adverse effects, information avoidance, and modification of scientific criteria. This lack of clinical assessment poses challenges to women's health and their right to autonomy. Overcoming these challenges requires an anthropological integration of sexuality, as the focus on genital bodily union alone fails to encompass the intimate relational expression of individuals, complete sexual satisfaction, and the intertwined feelings of trust, safety, tenderness, and endorsement of women's femininity.


[Phylogenomic analysis reveals the significant expansion of gene families of Volvariella volvacea ].
[OBJECTIVE] Cryogenic autolysis of Volvariella volvacea is an unusual phenomenon of abnormal metabolism. The aim of this study was to describe this molecular feature of abnormal metabolism at the genome-level. [METHODS] We used 21 fungal species for the phylogenomic analysis and then selected 9 representative species in basidiomycetes for the comparative genomic analysis. [ RESULTS] The phylogenomic analysis shows that V. volvacea was located at the bottom of the cluster consisting of grass-degrading fungi. Phylogenetic tree shows that basidiomycetes and ascomycetes fungi have independent evolutionary trajectories. Therefore, nine representative species in basidiomycetes were chosen for the comparative genomic analysis. The result shows that compared to other grass-degrading fungi, V. volvacea has the tendency of contraction. The comparison of the number of gene families on a different scale shows that there was a significant expansion of 3 large size ( > 200) gene families (faml, fam4 and fam6) in V. volvacea with their total number significantly more than other species, representing that the molecular feature of V. volvacea is correlated with its abnormal metabolism. [ CONCLUSION] The significant expansion of 3 gene families ( > 200) in V. volvacea indicates the enhancement of their function in specific gene families, which is most likely associated with cryogenic autolysis of V. volvacea.


Horizontally Acquired Polysaccharide-Synthetic Gene Cluster From Weissella cibaria Boosts the Probiotic Property of Lactiplantibacillus plantarum.
Lactiplantibacillus plantarum are probiotic bacteria, maintaining the integrity of the gastrointestinal epithelial barrier, and preventing the infection of pathogenic bacteria. Exopolysaccharides (EPSs) are often involved in the probiotic property of L. plantarum. Here, we identified a new EPS-synthetic gene cluster, cpsWc, carrying 13 genes, laid on a large plasmid in a well-characterized probiotic L. plantarum strain LTC-113. The cpsWc gene cluster was horizontally acquired from Weissella cibaria, enhancing the biofilm formation ability of the host strain and its tolerance to harsh environmental stresses, including heat, acid, and bile. Transfer of cpsWc also conferred the probiotic properties to other L. plantarum strains. Moreover, cpsWc strengthened the adhesion of LTC-113 to intestinal epithelial cells. Both the cpsWc-carrying LTC-113 and its EPSs per se effectively attenuated the LPS-induced pro-inflammatory effect of intestinal epithelial cells, and inhibited the adhesion of pathogenic bacteria, such as S. typhimurium and E. coli by exclusion and competition. The newly identified cpsWc gene cluster emphasized the contribution of mobile EPS-synthetic element on the probiotic activity of L. plantarum, and shed a light on the engineering of probiotic bacteria.


The role of visual representations in college students' understanding of mathematical notation.
Developing understanding of fractions involves connections between nonsymbolic visual representations and symbolic representations. Initially, teachers introduce fraction concepts with visual representations before moving to symbolic representations. Once the focus is shifted to symbolic representations, the connections between visual representations and symbolic notation are considered to be less useful, and students are rarely asked to connect symbolic notation back to visual representations. In 2 experiments, we ask whether visual representations affect understanding of symbolic notation for adults who understand symbolic notation. In a conceptual fraction comparison task (e.g., Which is larger, 5 / a or 8 / a?), participants were given comparisons paired with accurate, helpful visual representations, misleading visual representations, or no visual representations. The results show that even college students perform significantly better when accurate visuals are provided over misleading or no visuals. Further, eye-tracking data suggest that these visual representations may affect performance even when only briefly looked at. Implications for theories of fraction understanding and education are discussed.


Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas.
Medicines for the treatment of rare diseases frequently do not attract the interest of the pharmaceutical industry, and hospital pharmacists are thus often requested by physicians to prepare personalized medicines. Tuberous Sclerosis Complex (TSC) is a rare disease that causes disfiguring lesions named facial angiofibromas. Various topical formulations of rapamycin (=sirolimus) have been proved effective in treating these changes in small case series. The present study provides for the first time characterization of a 0.1% rapamycin cream formulation presenting good rapamycin solubilisation. The first step of the formulation is solubilisation of rapamycin in Transcutol(®), and the second step is the incorporation of the mixture in an oil-in-water cream. A HPLC stability-indicating method was developed. Rapamycin concentration in the cream was tested by HPLC and confirmed that it remained above 95% of the initial concentration for at least 85days, without characteristic degradation peaks. The preparation met European Pharmacopoeia microbial specifications throughout storage in aluminum tubes, including when patient use was simulated. Odour, appearance and colour of the preparation were assessed and no change was evidenced during storage. The rheological properties of the cream also remained stable throughout storage. To conclude, we report preparation of a novel cream formulation presenting satisfactory rapamycin solubilisation for the treatment of TSC cutaneous manifestations, with stability data. The cream is currently being used by our patients. Efficacy and tolerance will be reported later.


Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.
Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.


A comparative clinical study on five types of compression therapy in patients with venous leg ulcers.
The aim of this study was to compare five types of compression therapy in venous leg ulcers (intermittent pneumatic vs. stockings vs. multi layer vs. two layer short stretch bandages vs. Unna boots). Primary study endpoints were analysis of changes of the total ulcer surface area, volume and linear dimensions inside observed groups. The secondary end points were comparisons between all groups the number of completely healed wounds (ulcer healing rates), Gilman index and percentage change of ulcer surface area. In total, 147 patients with unilateral venous leg ulcers were included to this study. Participants were randomly allocated to the groups: A, B, C, D and E. After two months the healing rate was the highest in group A (intermittent pneumatic compression) - 57.14%, 16/28 patients, B (ulcer stocking system) - 56.66%, 17/30 patients and C (multi layer short stretch bandage) - 58.62%, 17/29 patients. Significantly much worse rate found in group D (two layer short stretch bandages) - only 16.66%, 5/30 patients and E (Unna boots) - 20%, 6/30 patients. The analysis of changes of the percentage of Gilman index and wound total surface area confirmed that intermittent pneumatic compression, stockings and multi layer bandages are the most efficient. The two layer short - stretch bandages and Unna boots appeared again much less effective.


Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease.
A series of 2-sulfonyl-4H-3,1-benzoxazinones was prepared that inhibit C1r protease in vitro. Several compounds were found to be selective for C1r verses the related serine protease trypsin. Selected compounds demonstrated functional activity in a hemolysis assay.


Hospital doctors' views of factors influencing their prescribing.
Factors influencing doctors in prescribing of drugs have mostly been studied in primary care. Studies performed in hospital care have primarily focused on new drugs, not prescribing in general. An in-depth understanding of the prescribing process in the more specialized secondary care is not only important for secondary care itself, but because it also influences prescribing in primary care. The aim of this study is therefore to identify factors that secondary care doctors believe influence them in prescribing drugs, using a qualitative approach. Semi-structured interviews were conducted with 15 hospital doctors in different medical specialities and the interviews were analysed from an interpretivist perspective. The information gathered was on how prescribing decisions were made in general and how the doctors chose a specific drug therapy, including information sources used. According to our interviews, the hospital doctors took patient-specific factors and cost into consideration when prescribing, informed by different written information sources and commercial verbal information. Personal practice, colleagues and therapeutic tradition at the hospital or clinic, were influential in the prescribing of drugs. The themes identified should not to be seen as individual influences; many of them probably act in combination. If changes in prescribing behaviour are desired, factors warranting more attention include understanding how to influence therapeutic traditions and the doctor's personal habits for prescribing. The importance of clinical experience and information exchange with colleagues should not be underestimated in providing information about drugs to hospital doctors.


Kinetics of desynchronization and distribution of generation times in synchronized cell populations.
The kinetics of the distribution of generation times in synchronized cells can be analyzed by using Fourier transform analysis. Deviations of the experimental data from the curve of completely asynchronous growth reflect the degree of synchrony at a particular time. Fourier transform analysis of these deviations yields the average generation time as well as information on the distribution of generation times characterizing a synchronized culture. A detailed analysis of synchronized cell cultures does not provide any evidence for the existence of a subcycle or a polymodal distribution in generation times. The data do indicate that cell-cell interaction occurs at cell densities as low as 2.5 X 10(3)/cm2. It is also shown that the Eyring-Stover formalism for the dynamics of survival can correctly describe the distribution of the first round of cell divisions in a synchronized culture.


Conversion of a laboratory-based test for phenylalanine detection to a simple paper-based format and implications for PKU screening in low-resource settings.
Laboratory-based testing does not reach many individuals in lower-resource settings who could benefit from access to appropriate tests for diagnosis and therapy. A critical issue is laboratory-based testing often requires an environment with a high level of resources and supporting infrastructure that is not available in many areas of the world. The current report describes the conversion of a laboratory-based test for phenylalanine detection to a simple paper-based test appropriate for use in low-resource settings. The paper-based test is easy to operate, with all reagents stored dry on the card, is compatible with visible detection for clinically relevant concentrations of phenylalanine, and has a time to result of 10 minutes. Next steps for test development are discussed in the context of the potential for the paper-based Phe test to be used as a newborn PKU screening test in settings that are not well served by existing screening approaches.


Life as an early career researcher: interview with Minhaj Sirajuddin.
Minhaj Sirajuddin talks to Francesca Lake, Head of Open Access Publishing. Minhaj Sirajuddin is currently an Assistant Investigator at the Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bangalore, India. His lab works on understanding biological motility mediated by cytoskeleton elements using biophysics and cell biology. Previously his tenures were at UCSF (CA, USA) for his postdoctoral work and the Max Planck Institute (Dortmund, Germany) for his PhD. Minhaj is a recipient of Wellcome Trust - DBT India Alliance Intermediate Fellowship and the EMBO Young Investigator Award. He was also a finalist in the inaugural Future Science Early Career Research Award.


Postpartum cardiac failure in Sudanese-Sahelian Africa: clinical prevalence in western Niger.
Postpartum cardiac failure (PPCF) is the most frequent clinical form of heart failure in hospitalized women in Sudanese-Sahelian Africa. We have previously studied this disease in a hospital setting. Although the incidence is relatively high in rural areas, no systematic field study has been carried out. In this report, we describe a retrospective study conducted in the western part of Niger in July-August 1991. Sixty-two villages were visited and a thorough search for patients was initiated (from a population of 79,941 inhabitants, 19,941 females 14-40 years of age, corrected census of 1988). Twenty-eight patients from 27 villages were included. The subject patients were those presenting with predefined symptoms (dyspnea and cough) and physical signs (edema of the legs) of congestive heart failure during the six-month period following delivery. Apart from arterial hypertension and previous PPCF, diagnosis of another cardiac disease was an exclusion criterion. The prevalence of PPCF was 1.40 per 1,000 females of child-bearing age. The clinical profiles of these cases were in accordance with those of a previous study in 1989 carried out at Niamey Hospital. These results were a mean +/- SD age of 28 +/- 7 years, multiparity (mean = 4 children), poor socioeconomic status, postpartum ablutions with hot water, and a high sodium intake. This is the first study on the clinical prevalence of PPCF in a Sudanese/Sahelian population living in a rural area.


TNF-α-induced VEGF and MMP-9 expression promotes hemorrhagic transformation in pituitary adenomas.
Pituitary apoplexy is a clinical syndrome with unknown pathogenesis. Therefore, identifying the underlying mechanisms is of high clinical relevance. Tumor necrosis factor alpha (TNF-α) is a critical cytokine mediating various hemorrhagic events, but little is known about its involvement in pituitary apoplexy. Here we show that TNF-α may be an important regulator of hemorrhagic transformation in pituitary adenomas. In this study, sixty surgical specimens of hemorrhagic and non-hemorrhagic human pituitary adenomas were examined. Hemorrhagic pituitary adenomas displayed higher protein and mRNA levels of TNF-α, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) compared with those of non-hemorrhagic tumors. Exposure of MMQ pituitary adenoma cells to TNF-α induced VEGF and MMP-9 expression in vitro. Additionally, TNF-α administration caused hemorrhagic transformation and enhanced VEGF and MMP-9 expression in MMQ pituitary adenoma cell xenografts in mice. Blockers of VEGF or MMP-9, either alone or in combination, attenuated but not abrogated TNF-α mediated hemorrhagic transformation in xenografts. This study suggests that TNF-α may play a role in the development of intratumoral hemorrhage in pituitary adenomas via up-regulation of VEGF and MMP-9.


A histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolution neural network.
Histopathological image analysis plays an important role in the diagnosis and treatment of cholangiocarcinoma. This time-consuming and complex process is currently performed manually by pathologists. To reduce the burden on pathologists, this paper proposes a histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolutional neural networks. Specifically, the proposed model consists of a spatial branch and a channel branch. In the spatial branch, residual structural blocks are used to extract deep spatial features. In the channel branch, a multi-scale feature extraction module and some multi-level feature extraction modules are designed to extract channel features in order to increase the representational ability of the model. The experimental results of the Multidimensional Choledoch Database show that the proposed method performs better than other classical CNN classification methods.


Scavenging of benzylperoxyl radicals by carotenoids.
Carotenoids scavenge simple lipid-like alkylperoxyl radicals. However, the rate constant is too low to be determined directly and the mechanism is likewise not known with certainty [Mortensen, A. and Skibsted, L.H. (1998) FEBS Lett. 426, 392-396]. It is demonstrated that carotenoids react with peroxyl radicals only slightly more reactive than lipidperoxyl radicals neither by electron transfer nor by hydrogen atom donation, but by adduct formation. Benzylperoxyl radicals are scavenged by the carotenoids beta-carotene and canthaxanthin with a second-order rate constant of at least 1 x 10(6) M(-1) s(-1) by formation of an adduct which decays in a first-order reaction.


Regulatory T cells and cytotoxic T cells close to the epithelial-stromal interface are associated with a favorable prognosis.
Cytotoxic T cells and regulatory T cells play a crucial role in the outcome of cancer patients. Besides the density of these cells, it was shown recently that the spatial distribution is equally important. Here, we specifically analyzed the spatial distribution of these T cell subtypes at the epithelial-stromal interface in a rectal cancer cohort and its relevance for prognosis. We studied a cohort of 191 patients with advanced rectal cancer treated by radiochemotherapy (RCT). Tissue microarrays were immunohistochemical double-stained by FoxP3+ and CD+. Cell densities were analyzed in the stromal and epithelial compartment. Additionally, an image analysis software calculated the distances of lymphocytes to the epithelial-stromal interface (ESI). CD8+ and FoxP3+ cell counts decreased clearly after RCT with the decrease of FoxP3+ being more pronounced than of CD8+ cells. In the invasive front, short distances of the ESI to CD8+ and to FoxP3+ cells were associated with improved overall survival. Cell counts in the stromal compartment had no influence on prognosis. No correlation between stromal and epithelial lymphocyte densities was observed. The distance of epithelial-stromal interface to CD8+ and FoxP3+ cells was more accurate in predicting prognosis in the stromal compartment of rectal cancer patients than mere cell counts and could thereby be means of better stratifying patients for therapy. This observation will have to be validated in future prospective studies with regard to other tumor entities and its implications for the responsiveness of tumors to new therapeutic modalities.


The nonlinear relationship between air quality and housing prices by machine learning.
Using a dataset encompassing 228 cities in China spanning from 2005 to 2019, this study explores the nonlinear relationship between air quality and housing prices and devises a strategy that incorporates the instrumental variable and machine learning to address the endogeneity issue. Both traditional models and machine learning models find air pollution affects housing prices in a diminishing manner. The negative impact of air pollution on housing prices decreases when the degree of air pollution intensifies. Such a characteristic is more pronounced in Eastern China and cities with fewer land resource constraints and larger populations. Mechanism analysis also reveals that air pollution could affect residents' perceived air quality and the industrial structure, further contributing to the nonlinear relationship between air quality and housing prices. The further SHapley Additive exPlanations (SHAP) evaluates the importance of air quality in determining housing prices and finds that air quality's contribution outweighs educational and medical resources. The contribution of air quality also shows a distinct regional disparity and has become increasingly important in recent years. The findings refine the benefit assessment accuracy related to air quality improvement.


How a Training Program Is Transforming the Role of Traditional Birth Attendants from Cultural Practitioners to Unique Health-care Providers: A Community Case Study in Rural Guatemala.
In low- and middle-income countries (LMICs), where the rates of maternal mortality continue to be inappropriately high, there has been recognition of the importance of training traditional birth attendants (TBAs) to help improve outcomes during pregnancy and childbirth. In Guatemala, there is no national comprehensive training program in place despite the fact that the majority of women rely on TBAs during pregnancy and childbirth. This community case study presents a unique education program led by TBAs for TBAs in rural Guatemala. Discussion of this training program focuses on programming implementation, curriculum development, sustainable methodology, and how an educational partnership with the current national health-care system can increase access to health care for women in LMICs. Recent modifications to this training model are also discussed including how a change in the clinical curriculum is further integrating TBAs into the national health infrastructure. The training program has demonstrated that Guatemalan TBAs are able to improve their basic obstetrical knowledge, are capable of identifying and referring early complications of pregnancy and labor, and can deliver basic prenatal care that would otherwise not be provided. This training model is helping transform the role of the TBA from a sole cultural practitioner to a validated health-care provider within the health-care infrastructure of Guatemala and has the potential to do the same in other LMICs.


Code Injection Attacks in Wireless-Based Internet of Things (IoT): A Comprehensive Review and Practical Implementations.
The Internet of Things (IoT) has transformed various domains in our lives by enabling seamless communication and data exchange between interconnected devices, necessitating robust networking infrastructure. This paper presents a comprehensive analysis of code injection attacks in IoT, focusing on the wireless domain. Code injection attacks exploit security weaknesses in applications or software and can have severe consequences, such as data breaches, financial losses, and denial of service. This paper discusses vulnerabilities in IoT systems and examines how wireless frames in state-of-the-art wireless technologies, which serve IoT applications, are exposed to such attacks. To demonstrate the severity of these threats, we introduce a comprehensive framework illustrating code injection attacks in the wireless domain. Several code injection attacks are performed on Wireless Fidelity (Wi-Fi) devices operating on an embedded system commonly used in IoT applications. Our proof of concept reveals that the victims' devices become further exposed to a full range of cyber-attacks following a successful severe code injection attack. We also demonstrate three scenarios where malicious codes had been detected inside the firmware of wireless devices used in IoT applications by performing reverse engineering techniques. Criticality analysis is conducted for the implemented and demonstrated attacks using Intrusion Modes and Criticality Analysis (IMECA). By understanding the vulnerabilities and potential consequences of code injection attacks on IoT networks and devices, researchers and practitioners can develop more secure IoT systems and better protect against these emerging threats.