Inhibition of eryptosis and intraerythrocytic growth of Plasmodium falciparum by flufenamic acid.
Non-selective (NSC) cation channels participate in the Ca(2+) leak of human erythrocytes. Sustained activity of these channels triggers suicidal erythrocyte death (eryptosis), which is characterized by Ca(2+)-stimulated cell shrinkage and phosphatidylserine (PS) exposure. PS-exposing erythrocytes are rapidly cleared from circulating blood. PGE(2) activates the NSC channels, and erythrocyte PGE(2) formation is stimulated by a decrease in intra- or extracellular Cl(-) concentration. In addition, the intraerythrocytic malaria parasite Plasmodium falciparum activates the NSC channels, most probably to accomplish Na(+) and Ca(2+) entry into the erythrocyte cytosol required for parasite development. By Ca(2+) uptake the parasite maintains a low Ca(2+) concentration in the erythrocyte cytosol and thus delays the suicidal death of the host erythrocyte. Flufenamic acid has previously been shown to inhibit NSC channels. The present study thus explored the effect of flufenamic acid on erythrocyte Ca(2+) entry, on suicidal erythrocyte death and on intraerythrocytic growth of P. falciparum. Within 48 h, replacement of extracellular Cl(-) with gluconate or application of PGE(2) (50 microM) increased Fluo3 fluorescence reflecting cytosolic Ca(2+) activity, decreased forward scatter reflecting cell volume and increased annexin V binding reflecting PS exposure in FACS analysis. All those effects were significantly blunted in the presence of flufenamic acid (10 microM). Flufenamic acid (25 microM) further significantly delayed the intraerythrocytic growth of P. falciparum and the PS exposure of the infected erythrocytes. The present observations disclose a novel effect of flufenamic acid, which may allow the pharmacological manipulation of erythrocyte survival and the course of malaria.


Toward Precision Medicine in the Cardiorenal Syndrome.
Although the field of oncology has made significant steps toward individualized precision medicine, cardiology and nephrology still often use a "one size fits all" approach. This applies to the intersection of the heart-kidney interaction and the cardiorenal syndrome as well. Recent studies have shown that the prognostic implications of worsening renal function (WRF) in acute heart failure are variable; thus, there is a need to differentiate the implications of WRF to better guide precise care. This may best be performed with biomarkers that can give the clinician a real-time evaluation of the physiologic state at the time of developing WRF. This review will summarize current cardiac and renal biomarkers and their status in the evaluation of cardiorenal syndrome. Although we have made progress in our understanding of this syndrome, further investigation is needed to bring precision medicine into routine clinical practice for the care of patients with cardiorenal syndrome.


The effect of bestatin on patients with acute and chronic leukemia and malignant lymphoma.
The effects of bestatin was studied in 17 patients with acute and chronic leukemia, and three patients with malignant lymphoma with or without concomitant chemotherapy. Complete remission was obtained in eight patients with acute leukemia and in three patients with malignant lymphoma. Definite effects on both clinical and hematological findings have not been observed in patients with chronic myelogenous leukemia. The PPD and PHA skin reactions increased in about 60 percent of the patients examined. Effects of bestatin on hematological and immunological parameters were obtained at a daily dose of from 30 to 90 mg of bestatin everyday for more than 2 weeks. Bestatin appeared to be useful for the maintenance therapy of hematological malignancies. No side effects due to bestatin were detected.


Dalbergia ecastaphyllum (L.) Taub. and Symphonia globulifera L.f.: The Botanical Sources of Isoflavonoids and Benzophenones in Brazilian Red Propolis.
The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids β-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed.


Complex Intrahepatic Lithiasis: A Case Report of Combined Treatment With Surgical Exploration of the Bilioenteric Anastomosis and Laser Lithotripsy by Cholangioscopy.
Intrahepatic lithiasis, or hepatolithiasis, is an endemic disease in southeast Asia, although, with immigration from Eastern countries, the incidence of this pathology is rising worldwide. The Latin American experience demonstrates morbidity and mortality compatible with other Western countries, but minimally invasive procedures are lacking. We demonstrate a case of a combined surgical and endoscopic approach for stone clearance. We present a case of a 47-year-old female patient with biliary enteric anastomosis to treat recurrent pyogenic cholangitis resulting from intrahepatic lithiasis. The patient was admitted to the emergency room, presented with a new episode of cholangitis, and submitted to transcutaneous hepatobiliary drainage. The multidisciplinary approach, including the endoscopic and surgical teams, successfully performed the stone clearance with laser lithotripsy and stone removal by open access. The postoperative period was uneventful, and the patient did not present any sign of recurrence after one year. A combined surgical and endoscopic approach achieved short-term clinical and technical success in this novel case. Moreover, individualizing cases requiring open surgical access is feasible, which allows a combined endoscopic approach with safety.


Special event planning for the emergency manager.
In the domain of emergency management and homeland security there is a lack of a formal planning process at the local level when it comes to special event planning. The unique nature of special event planning demands an understanding of the planning process for both traditional and non-traditional planning partners. This understanding will make certain that local governments apply due diligence when planning for the safety of the public. This paper offers a practical roadmap for planning at the local level. It will address those 'special events' that are beyond routine local events but not of a sufficient scale to be granted National Special Security Event status. Due to the infrequency of 'special events' in most communities, it is imperative that deliberate planning takes place. Upon conclusion, the reader will be able to construct a planning process tailored to the needs of their community, guide both traditional and non-traditional planning partners through the planning process, determine priorities, explore alternatives, plan for contingencies, conduct a confirmation brief, facilitate operations and assemble an after-action report and improvement plan.


Sizing of bdellovibrio during growth.
A technique for the counting and relative sizing of host-independent bdellovibrio during growth, with the aid of a modified Coulter counter, is described.


Optical coherence tomography after pars plana vitrectomy for retinal detachment related to choroidal coloboma.
The purpose was to study the anatomical outcome of choroidal coloboma with retinal detachment managed by pars plana vitrectomy with silicone oil tamponade using optical coherence tomography. Six eyes of six patients with retinal detachment related to choroidal coloboma underwent pars plana vitrectomy with internal tamponade using silicone oil. Pre- and postoperative best-corrected visual acuities, intraocular pressure measurements, and intra- and postoperative complications were obtained. Color fundus photographs and optical coherence tomography images were taken at each follow-up. Patients were observed up to a mean of 14 months (range, 8-18 months). Silicone oil was removed in all eyes. In all patients who had undergone vitrectomy, the retina was completely reattached before and after silicone oil extraction. Postoperatively, best-corrected visual acuities improved in 5 patients and remained unchanged in 1 patient ranging from 20/200 to 20/40 at the last follow-up. Although the retina was reattached in all patients, the optical coherence tomography showed a persistent intercalary membrane detachment in 4 patients (67%). In 1 patient (16%), subclinical retinal detachment that did not increase during the follow-up after silicone oil removal was detected just beyond the margin of the coloboma. After vitrectomy and silicone oil removal, optical coherence tomography showed persistent detachment of the intercalary membrane in most patients. These findings emphasize the importance of sealing the junction between the intercalary membrane and extracolobomatous retina with a laser barrier.


Ultralightweight silver nanowires hybrid polyimide composite foams for high-performance electromagnetic interference shielding.
Ultralightweight silver nanowires (AgNWs) hybrid polyimide (PI) composite foams with microcellular structure and low density of 0.014-0.022 g/cm(3) have been fabricated by a facile and effective one-pot liquid foaming process. The tension flow generated during the cell growth induced the uniform dispersion of AgNWs throughout the cell walls. The interconnected AgNWs network in the cell walls combined with the large 3D AgNWs network caused by 3D structure of foams provided fast electron transport channels inside foams. The electromagnetic interference (EMI) shielding effectiveness (SE) of these foams increased with increasing AgNWs loading as well as the nanowire aspect ratio due to the increasing connections of the conduction AgNWs network. Appropriate surface treatment like etching or spraying facilitated the construction of the seamlessly interconnected 2D AgNWs network on the surface, which could effectively reflect electromagnetic waves. Maximum specific EMI SE of values of 1210 dB·g(-1)·cm(3) at 200 MHz, 957 dB·g(-1)·cm(3) at 600 MHz, and 772 dB·g(-1)·cm(3) at 800-1500 MHz were achieved in sprayed composite foams containing <0.044 vol % AgNWs loading, which far surpasses the best values of other composite materials. The reflections of interconnected AgNWs networks on the surface and inside foams combined with the multiple reflections at interfaces contributed to the shielding effect.


Nano- and microparticles of organic fluorescent dyes: self-organization and optical properties.
Organic nanostructured materials are of increasing interest for applications in the fields of bioanalysis, photocatalysis, photonics, and organic light-emitting diodes. However, their preparation is still difficult to control and their optical properties are inadequately known. A solvent-exchange process called the "reprecipitation method" was used here to prepare nano- and microcrystals from fluorescent dyes belonging, for example, to the coumarin and nitrobenzoxadiazole (NBD) series. Typically, the dyes were dissolved in a hydrophilic organic solvent and then suddenly placed in an aqueous environment, where they spontaneously produce molecular assemblies. According to the self-association properties of the dyes and to the experimental conditions used, the nano- and microcrystals obtained exhibited different sizes and shapes, as observed by fluorescence and electron microscopy. In some cases, the crystal habit was controlled by adding some additives to the reprecipitation medium. The overall optical properties of the free-standing particles in suspension were generally quite close to those of the dissolved dyes. However, strong distortions of the absorption and emission spectra were observed for crystals grown in the presence of ionic additives. Under the fluorescence microscope, individual microcrystals may show peculiar emission characteristics, displaying bright and dark zones, or behaving like tiny optical fibers.


Scaling up private land conservation to meet recovery goals for grassland birds.
Long-term population declines have elevated recovery of grassland avifauna to among the highest conservation priorities in North America. Because most of the Great Plains is privately owned, recovery of grassland bird populations depends on voluntary conservation with strong partnerships between private landowners and resource professionals. Despite large areas enrolled in voluntary practices through U.S. Department of Agriculture's Lesser Prairie-chicken (Tympanuchus pallidicinctus) Initiative (LPCI), the effectiveness of Farm Bill investments for meeting wildlife conservation goals remains an open question. Our objectives were to evaluate extents to which Conservation Reserve Program (CRP) and LPCI-grazing practices influence population densities of grassland birds; estimate relative contributions of practices to regional bird populations; and evaluate percentages of populations conserved relative to vulnerability of species. We designed a large-scale impact-reference study and used the Integrated Monitoring in Bird Conservation Regions program to evaluate bird population targets of the Playa Lakes Joint Venture. We used point transect distance sampling to estimate density and population size for 35 species of grassland birds on private lands enrolled in native or introduced CRP plantings and LPCI-prescribed grazing. Treatment effects indicated CRP plantings increased densities of three grassland obligates vulnerable to habitat loss, and LPCI grazing increased densities of four species requiring heterogeneity in dense, tall-grass structure (α = 0.1). Population estimates in 2016 indicated the practices conserved breeding habitat for 4.5 million birds (90% CI: 4.0-5.1), and increased population sizes of 16 species , totaling 1.8 million birds (CI: 1.4-2.4). Conservation practices on private land benefited the most vulnerable grassland obligate species (AICc weight = 0.53). By addressing habitat loss and degradation in agricultural landscapes, conservation on private land provides a solution to declining avifauna of North America and scales up to meet population recovery goals for the most imperiled grassland birds.


Improving patient safety by using interprofessional simulation training in health professional education.
Modern medicine is complex. Reports and surveys demonstrate that patient safety is a major problem. Health educators focus on professional knowledge and less on how to improve patient care and safety. The ability to act as part of a team, fostering communication, co-operation and leadership is seldom found in health education. This paper reports the findings from pilot testing a simulated training program in interprofessional student teams. Four teams each comprising one medical, nursing, and intensive nursing student (n = 12), were exposed to two simulation scenarios twice. Focus groups were used to evaluate the program. The findings suggest that the students were satisfied with the program, but some of the videos and simulation exercises could be more realistic and more in accordance with each other. Generally they wanted more interprofessional team training, and had learned a lot about their own team performance, personal reactions and lack of certain competencies. Involving students in interprofessional team training seem to be more likely to enhance their learning process. The students' struggles with roles, competence and team skills underline the need for more focus on combining professional knowledge learning with team training.


Cutaneous allergy to human (recombinant DNA) insulin.
p6 report two cases of cutaneous allergy to human (recombinant DNA) insulin. Each patient had a history of systemic allergic reactions to porcine insulin and was at least as reactive to human as to porcine insulin by end-point cutaneous titration. Both patients' insulin allergy was managed with animal insulins and both have done well. Our experience with these two patients indicates that human insulin (rDNA) should not be expected to be efficacious in all patients with systemic allergy to insulin.


Cell wall composition and biomass saccharification potential of Sida hermaphrodita differ between genetically distant accessions.
Due to its ample production of lignocellulosic biomass, Sida hermaphrodita (Sida), a perennial forb, is considered a valuable raw material for biorefinery processes. The recalcitrant nature of Sida lignocellulosic biomass towards pretreatment and fractionation processes has previously been studied. However, Sida is a non-domesticated species and here we aimed at expanding the potential of such plants in terms of their processability for downstream processes by making use of the natural variety of Sida. To achieve this goal, we established a collection comprising 16 different Sida accessions obtained from North America and Europe. First, we asked whether their cell wall characteristics are reflected in genetic distance or geographical distribution, respectively. A genotyping-by-sequencing (GBS) analysis resulting in a phylogenic tree based on 751 Single Nucleotide Polymorphisms (SNPs), revealed a high genetic diversity and a clear separation between accessions collected in North America and Europe. Further, all three North American accessions were separated from each other. Of the eleven European accessions, five form individual groups and six others belong to a single group. Clonal plants of seven selected accessions of American and European origin were produced and cultivated under greenhouse conditions and the resulting plant material was used for in-depth wet-chemical and spectroscopic cell wall characterization. Two accessions with contrasting cell wall characteristics were then selected and processed using the OrganoCat technology. Results of the different product yields and chemical compositions are reported. Overall, cell wall analyses revealed contrasting clusters regarding these main components between the accessions that can be related to genetic and, partly, geographical distance. Phenotypically, the accessions clustered into two groups that are not entirely overlapping with geographical origin. These results can be the basis for a targeted selection or cultivation of Sida accessions for biorefinery approaches.


The first Acanthamoeba keratitis case in the Midwest region of Brazil: diagnosis, genotyping of the parasite and disease outcome.
We report an Acanthamoeba keratitis case associated with the use of contact lens in a 28-year-old female from Brasília, Brazil. Samples from corneal scraping and contact lens case were used for culture establishment, PCR amplification, and partial sequencing (fragments of ~400kb) of small subunit rDNA; both culture and PCR were positive. The sequence analyses of the cornea and of isolates from the contact lens case showed similarity with the T4 genotype. To the best of our knowledge, this is the first report of T4 Acanthamoeba keratitis case from the Midwest region of Brazil.


Leukopenia after postmastectomy irradiation.
Significant peripheral white blood cell depression was noted in 75% of postmastectomy patients receiving chest wall and nodal irradiation and in 50% of patients receiving only peripheral nodal irradiation. Leukopenia was documented for as long as 36 months following therapy. With the current trend to earlier institution of chemotherapy, the routine use of postoperative irradiation must be reevaluated.


[Study on the changing structure of disabled population caused by birth defects in China].
To Compare the differences of classification and grading on disability between the TWO National Sample Surveys on Disability in 1987 and 2006, and to analyze the change of structure on disabled population with birth defects (BD). Quantitative analysis had been carried out based on the investigation of two national sample surveys. (1) Prevalence rates of Disabilities caused by BD of 0 - 14, 15 - 64 and ≥ 65 age groups in 2006 were 0.1%, 0.28% and 1.15% respectively, all higher than those in 1987. There was significant difference among the age group of ≥ 65, between the two standard periods of survey. (2) The difference of prevalence rates on Disabilities caused by BD between males and females in 2006 was 0.03% higher than that of 1987 and the difference of proportion on Disability caused by BD between males and females in 2006 was 0.08%, which was lower than those data from the year 1987 (2006: χ(2) = 66.254, P < 0.001; 1987: χ(2) = 22.895, P < 0.001). (3) Prevalence rate of Disabilities caused by BD in rural area was 0.49% in 1987, and 0.74% in 2006 after standardization, which had an 50% increase during the past 19 years. Prevalence rate of Disabilities caused by BD in urban area was 0.35% in 1987 and 0.50% in 2006, which had an 43%. Increase during the past 19 years. (4) Percentage of grade 1 listen-speech disability caused by BD in 2006 deceased 17.35%, and the intelligent disability caused by BD increased 18.21% in 2006. (5) Compared with 1987, the difference of percentage on primary and higher education among disabled persons with BD disabled population and total population, became smaller in 2006. To carry on a better study on disability, evaluation criteria of disability classification and grading standards should not only be taken into account on the continuity of the investigation, but also be better integrated with the international standards in terms of longitudinal comparison of data. Age structure of total population had a significant effect on the changing of structure on disabled persons caused by BD. Rural area was the high-risk area for disability caused by BD in China while female population should be viewed as the focus group of disability caused by BD.


Assessing ChatGPT Responses to Common Patient Questions Regarding Total Hip Arthroplasty.
The contemporary patient has access to numerous resources on common orthopaedic procedures before ever presenting for a clinical evaluation. Recently, artificial intelligence (AI)-driven chatbots have become mainstream, allowing patients to engage with interfaces that supply convincing, human-like responses to prompts. ChatGPT (OpenAI), a recently developed AI-based chat technology, is one such application that has garnered rapid growth in popularity. Given the likelihood that patients may soon call on this technology for preoperative education, we sought to determine whether ChatGPT could appropriately answer frequently asked questions regarding total hip arthroplasty (THA). Ten frequently asked questions regarding total hip arthroplasty were posed to the chatbot during a conversation thread, with no follow-up questions or repetition. Each response was analyzed for accuracy with use of an evidence-based approach. Responses were rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," "satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification." Of the responses given by the chatbot, only 1 received an "unsatisfactory" rating; 2 did not require any correction, and the majority required either minimal (4 of 10) or moderate (3 of 10) clarification. Although several responses required nuanced clarification, the chatbot's responses were generally unbiased and evidence-based, even for controversial topics. The chatbot effectively provided evidence-based responses to questions commonly asked by patients prior to THA. The chatbot presented information in a way that most patients would be able to understand. This resource may serve as a valuable clinical tool for patient education and understanding prior to orthopaedic consultation in the future.


Incidence and pathology of peptic ulcer disease.
Peptic ulcer disease has undergone a significant change in incidence and modern medical and surgical therapeutical modalities seems to change the history and outcome of the disease. The knowledge of the basic morphological and functional background of the entity is based on studies of ulcer formation and healing and of the influence of the gastroduodenal mucosa. Chronic gastritis is closely associated with peptic ulcer, and type, grade and dispersion of gastric changes are correlated to the activity and nature of the ulcer and the subsequent treatment, i.e. antrectomy. Parietal cell subpopulation shows a nearly unsusceptible numerical density during different phases of ulcer disease, only correlated to acid secretion in duodenal ulcer patients. The changes of gastric endocrine cells and morphological and subcellular changes of the parietal cells after medical and surgical treatment indicates a complex cellular regulation in the gastric mucosa.


Effect of age, sex, and refractive errors on central corneal thickness measured by Oculus Pentacam®.
Central corneal thickness (CCT) can be used to assess the corneal physiological condition as well as the pathological changes associated with ocular diseases. It has an influence on the measurement of intraocular pressure and is being used as a screening tool for refractive surgery candidates. The aim of this study was to determine the median CCT among normal Pakistani population and to correlate CCT with age, sex, and refractive errors. We conducted a retrospective analysis of 5,171 healthy eyes in 2,598 patients who came to Hashmanis Hospital, Karachi, Pakistan. The age of the patients ranged from 6 to 70 years. The refractive error was gauged by an auto-refractometer, and CCT was measured using Oculus Pentacam®. The median CCT of our study was 541.0 μm with an interquartile range (IQR) of 44.0 μm. The median age was 26.0 years (IQR: 8.0). Median spherical equivalent (SE) of the patients was -4.3 D (IQR: 3.3) with the median sphere value as -4.0 D (IQR: 3.8). Lastly, the median cylinder was -1.0 D (IQR: 1.3). Age has a weak negative correlation with CCT (r=-0.058) and shows statistical significance (P<0.001). Additionally, males had thinner CCT readings than females (P=0.001). The cylinder values, on the other hand, had a significant (P=0.004) and positive correlation (r=0.154). Three values showed no significant correlation: sphere (P=0.100), SE (P=0.782), and the left or right eye (P=0.151). Among the Pakistani population, CCT was significantly affected by three variables: sex, age, and cylinder. No relationship of CCT was observed with the left or right eye, sphere, and SE.


Salmonella serovars and their distribution in Nigerian commercial chicken layer farms.
Commercial poultry farms (n° 523), located in all the six regions of Nigeria were sampled with a view to generate baseline information about the distribution of Salmonella serovars in this country. Five different matrices (litter, dust, faeces, feed and water) were collected from each visited farm. Salmonella was isolated from at least one of the five matrices in 228 farms, with a farm prevalence of 43.6% (CI95[39.7-48.3%]). Altogether, 370 of 2615 samples collected (14.1%, CI95[12.8; 15.5%]) contained Salmonella. Considering the number of positive farms and the number of positive samples, it was evident that for the majority of the sampled farms, few samples were positive for Salmonella. With regard to the matrices, there was no difference in Salmonella prevalence among the five matrices considered. Of the 370 isolates serotyped, eighty-two different serotypes were identified and Salmonella Kentucky was identified as having the highest isolation rate in all the matrices sampled (16.2%), followed by S. Poona and S. Elisabethville. S. Kentucky was distributed across the country, whereas the other less frequent serovars had a more circumscribed diffusion. This is one of few comprehensive studies on the occurrence and distribution of Salmonella in commercial chicken layer farms from all the six regions of Nigeria. The relatively high prevalence rate documented in this study may be attributed to the generally poor infrastructure and low biosecurity measures in controlling stray animals, rodents and humans. Data collected could be valuable for instituting effective intervention strategies for Salmonella control in Nigeria and also in other developing countries with a similar poultry industry structure, with the final aim of reducing Salmonella spread in animals and ultimately in humans.


Takotsubo cardiomyopathy secondary to spontaneous right-sided pneumothorax.
Takotsubo cardiomyopathy (TCM) is a unique type of cardiomyopathy characterised by left ventricular systolic dysfunction in association with stressful conditions. Patients with this condition usually present with chest pain and dyspnoea, and the presentation can mimic acute coronary syndrome. We present a case of a woman aged 58 years who presented with progressive dyspnoea and cough. Her initial evaluation was suggestive of acute myocardial infarction with elevated serum troponin T and ST segment elevation. Her chest radiograph showed a large right-sided pneumothorax, which was treated with chest tube insertion. Coronary angiography and echocardiogram did not show any evidence of obstructive coronary artery disease but did show a large area of akinesis consistent with TCM. The patient was managed medically with supportive care. Her pneumothorax resolved, and her follow-up echocardiogram also showed improvement. The association between pneumothorax and TCM is rare, and only four other cases have been reported so far in the English literature.


Deep convolutional generative adversarial network for Alzheimer's disease classification using positron emission tomography (PET) and synthetic data augmentation.
With the evolution of deep learning technologies, computer vision-related tasks achieved tremendous success in the biomedical domain. For supervised deep learning training, we need a large number of labeled datasets. The task of achieving a large number of label dataset is a challenging. The availability of data makes it difficult to achieve and enhance an automated disease diagnosis model's performance. To synthesize data and improve the disease diagnosis model's accuracy, we proposed a novel approach for the generation of images for three different stages of Alzheimer's disease using deep convolutional generative adversarial networks. The proposed model out-perform in synthesis of brain positron emission tomography images for all three stages of Alzheimer disease. The three-stage of Alzheimer's disease is normal control, mild cognitive impairment, and Alzheimer's disease. The model performance is measured using a classification model that achieved an accuracy of 72% against synthetic images. We also experimented with quantitative measures, that is, peak signal-to-noise (PSNR) and structural similarity index measure (SSIM). We achieved average PSNR score values of 82 for AD, 72 for CN, and 73 for MCI and SSIM average score values of 25.6 for AD, 22.6 for CN, and 22.8 for MCI.


Sortase-Mediated Phage Decoration for Analytical Applications.
Phage-borne peptides and antibody fragments isolated from phage display libraries have proven to be versatile and valuable reagents for immunoassay development. Due to the lack of convenient and mild-condition methods for the labeling of the phage particles, isolated peptide/protein affinity ligands are commonly removed from the viral particles and conjugated to protein tracers or nanoparticles for analytical use. This abolishes the advantage of isolating ready-to-use affinity binders and creates the risk of affecting the polypeptide activity. To circumvent this problem, we optimized the phage display system to produce phage particles that express the affinity binder on pIII and a polyglycine short peptide fused to pVIII that allows the covalent attachment of tracer molecules employing sortase A. Using a llama heavy chain only variable domain (VHH) against the herbicide 2,4-D on pIII as the model, we showed that the phage can be extensively decorated with a rhodamine-LPETGG peptide conjugate or the protein nanoluciferase (Nluc) equipped with a C-terminal LPETGG peptide. The maximum labeling amounts of rhodamine-LPETGG and Nluc-LPETGG were 1238 ± 63 and 102 ± 16 per phage, respectively. The Nluc-labeled dual display phage was employed to develop a phage bioluminescent immunoassay (P-BLEIA) for the detection of 2,4-D. The limit of detection and 50% inhibition concentration of P-BLEIA were 0.491 and 2.15 ng mL-1, respectively, which represent 16-fold and 8-fold improvement compared to the phage enzyme-linked immunosorbent assay. In addition, the P-BLEIA showed good accuracy for the detection of 2,4-D in spiked samples.


Abdominopelvic ectopic spleen with a comprehensive imaging examination: a case report.
Ectopic spleen is a rare clinical malformation in which the spleen is relocated from its normal anatomical position to other parts of the abdomen. We report a rare case of abdominopelvic ectopic spleen caused by splenic ligament deficiency. A patient experienced intermittent pain in the left upper abdomen that was progressively aggravated. This was confirmed by comprehensive imaging examinations and postoperative pathology. We also performed a review of the literature on the current state of the field. Our data may help to improve the diagnosis and treatment of ectopic spleen.


Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis.
Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates. A total of 49 epitopes were predicted, which revealed a comprehensive binding affinity to the 40 different MHC class I supertypes. Based on the population coverage and HLA cross presentation, nine highly promiscuous epitopes such as LTYDDVWTV (P1), FLFPQRTAL(P2), FLFSNGAVV (P3), YIYNFGIRV (P4), YMTAAFAAL (P5), KLLRPFAPL (P6), FMLGWIVTI (P7), SLFERNKRV (P8), and SVWNRIFTL (P9) which have either a high or an intermediate TAP binding affinity were selected for further analysis. Theoretical population coverage analysis of polytope vaccine (P1-P9) revealed more than 92% population. Stimulation with the cocktail of peptide revealed a proliferative CD8+ T cell response and increased IFN-γ production. An upregulated NF-κB activity is thought to be play a pivotal role in T cell proliferation against the selected peptide. The Th1-type cytokine profile (presence of IFN-γ and absence of IL-10) suggests the potentiality of the cocktail of epitope as a subunit vaccine against leishmaniasis. However, the efficiency of these epitopes to trigger other Th1 cytokines and chemokines in a humanized mice model could explore its plausibility as a vaccine candidate. J. Cell. Biochem. 119: 378-391, 2018. © 2017 Wiley Periodicals, Inc.


Health effects of tobacco use and exposure.
Tobacco is still widely consumed in a variety of different ways, mainly as smokeless tobacco and cigarette smoking. Four traits characterize tobacco use whatever the way of using it: 1) addiction linked to nicotine is behind all the tobacco hazards; 2) individual variation in tobacco susceptibility; 3) dose-response relationship; 4) time-lag effect. Smokeless tobacco, chewed or snuffed can lead mainly to inflammation of the oral cavity and oral cancers. Cigarette smoking accounts for 65-85% of global tobacco consumption. Active smoking can cause: 1) respiratory disorders culminating in chronic obstructive pulmonary disease (COPD) and emphysema; 2) cardiovascular hazards by way of increased vascular spasm and atherosclerosis leading to acute and chronic myocardial events, cerebral and peripheral vascular diseases; 3) cancers: twelve types are caused or related to cigarette smoking. Lung cancer is still the leading cause of cancer death in most high-income countries where data are available. An excess mortality is associated with smoking, with a 2-fold greater risk in smokers than in nonsmokers throughout middle age. The exposed pregnant woman subjects herself and her pregnancy to risks, and her fetus to growth retardation and perinatal morbidity and mortality. Passive smoking implicates 20-80% of the whole population. It can be nearly as harmful as active smoking depending upon risk factors, and can lead to short as well as to long-term effects. Children are the most vulnerable population particularly during the first years of life. Passive smoking increases risks for higher and lower respiratory tract illness but a smoke-free environment improves all these disorders. Ischemic heart diseases and lung cancer are the main risks for non smoking adults exposed to cigarette smoke. Tobacco use and exposure is the single most important source of preventable morbidity, disability and premature mortality. But giving up smoking helps at any time, the sooner the better. Health professionals should be the key advocates in tobacco prevention.


Down-regulation of insulin binding by human and rat hepatocytes in primary culture: the possible role of insulin internalization and degradation.
Insulin binding and down-regulation were studied in primary cultures of human and rat hepatocytes. Equilibrium binding characteristics were similar in the two species, with a curvilinear Scatchard plot compatible with binding sites of high and low apparent affinities. The dose-response curve for insulin stimulation of glycogen synthesis coincided with the dose-occupancy curve of the low affinity sites; a maximal biological effect was reached at 50% occupancy. Exposure of rat hepatocytes to 2 X 10(-9) M insulin for 24 h produced a 48% decrease in binding capacity due to decreases in both types of binding sites and a 50% decrease in maximal insulin stimulation of glycogen synthesis. After exposure to the same insulin concentration human cells had an 83% decrease in maximum binding capacity, due exclusively to a complete loss of low affinity sites, and a total suppression of insulin stimulation of glycogen synthesis. In both species there was a biphasic relation between degradation and binding: over the range of insulin concentration producing binding mainly to high affinity sites degradation increased slowly as binding increased; with higher insulin concentrations and saturation of high affinity sites degradation increased rapidly as binding to low affinity sites increased. At equal levels of binding, down-regulated cells degraded insulin more rapidly than normal cells. It is concluded that: 1) insulin bound to sites of low apparent affinity is responsible for the hormone's glycogenic effect, 2) down-regulation of human hepatocytes virtually eliminates such binding and the glycogenic response and also increases the rate of degradation of insulin in relation to the amount bound to high affinity sites, 3) human cells are more sensitive than rat cells to down-regulation. It is suggested that in human cells the major effects of exposure to insulin are an inhibition of insulin internalization and an increase in the rate of degradation of that insulin which is internalized; in rat cells the major effects are a decrease in cell surface binding and an increased rate of degradation of internalized insulin.


Automated signal classification in the C-2W fusion experiment.
In TAE Technologies' current experimental fusion device, C-2W (also called "Norman"), record breaking, advanced beam-driven field-reversed configuration plasmas are produced and sustained in steady state utilizing variable-energy neutral beams, expander divertors, end-bias electrodes, and an active plasma control system. With a rapid shot-pace and an extensive number of data channels, the amount of data generated necessitates automated signal processing. To this end, a machine learning algorithm consisting of a multi-layered neural network as well as other data processing software has been designed for signal feature identification, allowing for accurate and fast signal classification, anomalous condition detection, and providing for signal pre-processing. With a small set of training data, the neural network can be "bootstrapped" to provide a robust classification system while minimizing human oversight. An example using data from the theta pinch plasma formation pulsed power system is presented. With an overall accuracy of ∼97%-having classified more than 5 × 106 pulsed power signals-the classification scheme is more than sufficient to fine-tune machine set points. However, this technique can be used for near-real-time preprocessing of any plasma physics signal and has wide ranging application in fusion experiments for the varied data produced by plasma diagnostics.


Occupational factors and renal disease.
The male-to-female ratio of patients requiring dialysis treatment commonly approaches 2:1. It is proposed that environmental factors, particularly occupational exposure to hydrocarbons, may account for the excess number of male patients. The term "hydrocarbon" refers to the aliphatic, alicyclic, aromatic, and halogenated hydrocarbons (carbon tetrachloride, chloroform); glycols (ethylene glycol, diethylene glycol, dioxane, glycerol); and organic solvents. Hydrocarbons commonly find use as solvents in industrial manufacturing practices because of their lipid solubility. Hydrocarbons have long been known to be neurotoxicants, affecting both peripheral and central nervous systems. Although benzene and its derivative have a known association with uroepithelial tumors, there is now a considerable body of evidence suggesting a possible role for hydrocarbon exposure in the development of non-neoplastic renal diseases. This article presents an epidemiological case for such an association and critically reviews the literature.


Influence of mastery and sexual frequency on depression in Korean men after a stroke.
Post-stroke depression has negative impacts on rehabilitation. The physical deficits following stroke have been well studied, but there is little information on sexual behavior, mastery, and depression in stroke patients. The purpose of the study was to investigate the influence of sexual frequency and the sense of control on depression in Korean men after stroke. The sample for this study was a convenience sample of 67 Korean men after stroke visiting the convalescent center for disabled people in Seoul, Korea. Participants completed a Sexual Frequency scale, the mastery scale, and the Center for Epidemiologic Studies Depression (CES-D) test. Seventy-eight percent of the subjects were depressed. Sense of control and sexual frequency contributed to depression. Scores on sense of control and sexual frequency accounted for 39.5% of the variance in the depression score. Results indicate that an intervention for depression management after stroke should take into account sexual relationships with their partners and a sense of control.


Growth of the Czech child population 0-18 years compared to the World Health Organization growth reference.
Nationwide anthropological surveys of 0-18-year-old children were carried out in the Czech Republic (former Czech regions of Czechoslovakia) five times during the last 40 years, at 10-year intervals. The measurements provide reference data for the growth of the Czech child population and at the same time ample material for comparison with other populations. A comparison of the results of such nationwide anthropometric surveys with the World Health Organization (WHO) growth reference implies that the growth trend of Czech children is comparable with the WHO reference. The greatest similarity in the shape of the WHO height curves and the results obtained in Czechoslovakia was in 1971. The results obtained in the nationwide surveys also imply that the secular trend still exerts its effect. In the case of height, this finding is consistent during the whole period of 40 years. Concerning weight in higher age categories, especially in girls, the trend slowed down or stopped. Furthermore, there is no problem of malnutrition in the Czech child population. Similarly, as in any other developed nations, the prevalence of overweight and obesity is the problem that merits attention. Am. J. Hum. Biol. 9:459-468, 1997. © 1997 Wiley-Liss, Inc.


A Scoping Review and Assessing the Evidence for Nutrition Education Delivery Strategies for Refugees in High-Income Countries.
Upon resettlement, refugees face many challenges, including limited knowledge of available food and food insecurity, that increase their risks of diet-related diseases. Nutrition education may help them better navigate the challenges of their new food environments and help them live healthier lives. This review assesses the evidence on nutrition education delivery strategies and outcomes among refugees in the United States and other high-income countries using Levac review guidelines. Multiple electronic databases were searched using combinations of the following terms: nutrition, food, cooking, or gardening; education, workshop, curriculum, class, literacy, or program; and refugee. The quality of the peer-reviewed papers was assessed using the Medical Education Research Study Quality Instrument (MERSQI) scoring method. A total of 1930 studies were identified, and 17 met the inclusion criteria. The mean MERSQI score of the peer-reviewed studies was 9.02 (SD, 3.3; range, 1-14). The key nutrition education delivery strategies included conducting a needs assessment and providing client-centered education, a collaborative approach in program design, and hands-on activities such as cooking and store visits. A refugee's literacy level, cultural, and language barriers are common challenges to nutrition education delivery. Because there is limited evidence regarding the efficacy of programs regarding changes in refugees' nutrition knowledge and diet-related behaviors, future research should include rigorously designed studies and the development and implementation of standardized assessment and training tools. The adoption of a context-specific and flexible model is important for effective nutrition education delivery among the refugee population.


Development of memory for spatial locations and object/place associations in infant rhesus macaques with and without neonatal hippocampal lesions.
This study traces the development of spatial memory abilities in monkeys and reports the effects of selective neonatal hippocampal lesions on performance across development. Two different versions of the visual paired-comparison (VPC) task were used. The VPC-Spatial-Location task tested memory for object-locations that could be solved using an egocentric spatial frame of reference and the VPC-Object-In-Place task taxed memory for spatial relations using an allocentric reference frame. Eleven rhesus macaques (6 neonatal sham-operated controls and 5 with neonatal neurotoxic hippocampal lesions) were tested on both tasks as infants (8 months), juveniles (18 months), and adults (5-6 years). Memory for spatial locations was present by 18 months of age, whereas memory for object-place relations was present only in adulthood. Also, neonatal hippocampal lesions delayed the emergence of memory for spatial locations and abolished memory for object-place associations, particularly in animals that had sustained extensive and bilateral hippocampal lesions. The differential developmental time course of spatial memory functions and of the effects of neonatal hippocampal lesions on these functions are discussed in relation to morphological maturation of the medial temporal lobe structures in monkeys. Implications of the findings for the neural basis of spatial memory development in humans are also considered.


Investigations into the organization of information in sensory cortex.
One might take the exploration of sensory cortex in the first decades of the last century as the opening chapter of modern neuroscience. The combined approaches of (i) measuring effects of restricted ablation on functional capacities, both in the clinic and the laboratory, together with (ii) anatomical investigations of cortical lamination, arealization, and connectivity, and (iii) the early physiological probing of sensory representations, led to a fundamental body of knowledge that remains relevant to this day. In our time, there can be little doubt that its organization as a mosaic of columnar modules is the pervasive functional property of mammalian sensory cortex [Brain 120 (1997) 701]. If one accepts the assertion that columns and maps must improve the functioning of the brain (why else would they be the very hallmark of neocortex?), then the inevitable question is: exactly what advantages do they permit? In this review of our recent presentation at the workshop on Homeostasis, plasticity and learning at the Institut Henri Poincaré, we will outline a systematic approach to investigating the role of modular, map-like cortical organization in the processing of sensory information. We survey current evidence concerning the functional significance of cortical maps and modules, arguing that sensory cortex is involved not solely in the online processing of afferent data, but also in the storage and retrieval of information. We also show that the topographic framework of primary sensory cortex renders the encoding of sensory information efficient, fast and reliable.


Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations.
Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH), and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration. Study objectives were to conduct 1) Time-and-Motion (TM) simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2) a Cost Minimization Analysis (CMA) relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution) via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1) Learning (initial use instructions), 2) Preparation (arrange device for use), 3) Administration (actual simulation manikin injection), and 4) Storage (maintain product viability between doses), in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages), non-drug medical supplies, and drug product costs. Norditropin(R) NordiFlex and Norditropin(R) NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsvaerd, Denmark) took less weekly Total Time (p < 0.05) to use than either of the comparator products, Genotropin(R) Pen (GTP, Pfizer, Inc, New York, New York) or HumatroPen(R) (HTP, Eli Lilly and Company, Indianapolis, Indiana). Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes), NNP (2.48 minutes) GTP (4.11 minutes), HTP (8.64 minutes), p < 0.05)). Administration and Storage times were not statistically different. NNF (15.8 minutes) and NNP (16.2 minutes) also took less time to Learn than HTP (24.0 minutes) and GTP (26.0 minutes), p < 0.05). The number of weekly required administration steps was also least with NNF and NNP. Opportunity cost savings were greater in devices that were easier to prepare for use; GTP represented an 11.8% drug product savings over NNF, NNP and HTP at time of study. Overall supply costs represented <1% of drug costs for all devices. Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.


Evaluation of the Friedmann Visual Field Analyser Mark II. Part 2. Results from a population with induced visual field defects.
The Friedmann Visual Field Analyser Mark II is evaluated with a group of 301 normal eyes, 155 of which had an induced visual field defect. Measures of sensitivity and specificity are calculated from these data by criteria similar to those used by other researchers. The inadequacies of using pass/fail criteria in the clinical situation are discussed, and a solution is proposed in which each field response is scored and the score compared with those from normal and defective populations. An example is given of how this form of analysis could be incorporated into the clinical situation.


Biohumoral and endocrine parameters in assessment of surgical trauma in open and laparoscopic cholecystectomy.
Every surgical procedure causes metabolic, endocrine, and hemodynamic stress in the organism. The aim of this work was to assess the extent of trauma following each of the two types of cholecystectomy (traditional/open and laparoscopic) by measuring palette of biochemical parameters. This prospective, single- center study included 120 patients subjected to elective cholecystectomy during the period of one year. Sixty patients were treated laparoscopically and 60 traditionally. Biohumoral and endocrine parameters were determined from 24-hour urine and blood. We measured adrenaline, noradrenaline, metabolites of corticosteroid hormones (17-hydroxyl and 17-keto steroids), C-reactive protein (CRP), albumin, glycemia, creatine-phosphokinase (CPK), lactate-dehydrogenase (LDH), red blood cells sedimentation and serum concentration of potassium. We observed significantly lower levels of adrenaline (p < 0.01), noradrenaline (p < 0.05), dopamine (p < 01.01), 17-hydroxyl (p < 0.01) and 17-keto steroids (p < 0.01), glycemia (p < 0.01), CPK (p < 0.01), LDH (p < 0.01) and red blood cells sedimentation (p < 0.01) following laparoscopic cholecystectomy compared to traditional one. Significant increase in CRP levels was recorded postoperatively in both groups (p < 0.05), as well as significant decrease in serum albumin values (p < 0.05). Duration of the hospitalization following laparoscopic cholecystectomy was significantly shorter (p < 0.01). The intensity of organism response is proportional to the intensity of surgical trauma. Metabolic, tissue and neuroendocrine response of organism to trauma has lower intensity after laparoscopic cholecystectomy.


Agriculture in Africa: strategies to improve and sustain smallholder production systems.
Agricultural development lies at the heart of poverty reduction and increased food security of most developing nations. Sub-Saharan Africa (hereafter referred to as Africa) is, however, the only region in the world where per capita agricultural productivity has remained stagnant over the past 40 years. In Asia and Latin America, the use of tailored techniques and technologies has transformed agricultural practice and its productivity, leading to what has been called the "green revolution." The dissemination of uniquely African green revolution technologies has not occurred on the continent. This chapter will argue that the same results in increased productivity and food security can be achieved in Africa if the appropriate investments are made in key interventions: soil fertility improvement, improved seeds, water management, market access, extension services, access to credit, and improvements in weather forecasting. Where these have happened, even partially, the outcome has been remarkable. However, bringing them to scale in ways that sustainably increase agricultural productivity and alleviate poverty requires increased investments and innovative institutional arrangements. Fortunately, several research and development projects on the continent, including the Millennium Villages Project, are providing valuable insights. Finally, this chapter outlines the key remaining challenges.


Cloning and expression of phospholipase A2 from guinea pig gastric mucosa, its induction by carbachol and secretion in vivo.
A cDNA encoding phospholipase A2 (PLA2) was cloned from guinea pig gastric mucosa using a rat pancreatic-PLA2-cDNA fragment as a probe. The cDNA contains an open reading frame sufficient to encode the entire amino-acid sequence of a PLA2-precursor protein consisting of 146 amino acids, including a putative 16-residue signal peptide and a 6-residue activation peptide at the NH2-terminus. Its nucleotide sequence exhibits 70% similarity to that of rat pancreatic PLA2 cDNA. The deduced amino-acid sequence has all the typical pancreatic PLA2 characteristics, with the exception of the substitution of Phe for Tyr at position 28 in the calcium-binding loop of the mature enzyme. When an expression vector containing the PLA2 cDNA was transfected into COS-7 cells, a major portion of the proenzyme was secreted into the culture medium. Northern-blot analysis showed the mRNA was present in guinea pig lung and pancreas at much lower levels than in the stomach. The effect of carbachol, a muscarinic acetylcholine agonist, on the secretion of gastric PLA2 and on its mRNA level in the gastric mucosa were examined. PLA2 secretion into the gastric juice was maximal 30 min after the subcutaneous administration of carbachol (0.4 mg/kg). It also increased the PLA2-mRNA level in the tissue, the maximal mRNA level being delayed about 15 min compared with that in PLA2 secretion. These results suggest that vagal stimuli may contribute to PLA2 secretion and its compensatory synthesis, and that the secreted PLA2 may participate in the digestion of dietary and biliary phospholipids in the small intestine of guinea pig.


Convergence Analysis of Online Gradient Method for High-Order Neural Networks and Their Sparse Optimization.
In this article, we investigate the boundedness and convergence of the online gradient method with the smoothing group L1/2 regularization for the sigma-pi-sigma neural network (SPSNN). This enhances the sparseness of the network and improves its generalization ability. For the original group L1/2 regularization, the error function is nonconvex and nonsmooth, which can cause oscillation of the error function. To ameliorate this drawback, we propose a simple and effective smoothing technique, which can effectively eliminate the deficiency of the original group L1/2 regularization. The group L1/2 regularization effectively optimizes the network structure from two aspects redundant hidden nodes tending to zero and redundant weights of surviving hidden nodes in the network tending to zero. This article shows the strong and weak convergence results for the proposed method and proves the boundedness of weights. Experiment results clearly demonstrate the capability of the proposed method and the effectiveness of redundancy control. The simulation results are observed to support the theoretical results.


[Not Available].
Hildegard of Bingen (1098-1179), the famous priestess of South-Germany, wrote an outstanding work including theological books, a composers work, a large correspondence and a medical book named "the book about the subtilities in the different natures of the creatures": "Liber subtilitatum diversarum naturarum creaturarum". This work has later been splitted in two or three books, the "Physica", the "Causae et curae" and the "Berliner Fragmente", perhaps a part of the "Causae et curae". Until today not all handwritings are critically edited. 25 plants can be found in gynecological or obstetrical indication in her writings. Regarded under modern aspects most of them could be used in minor gynecological problems. Some are almost unknown today, others are regarded as too dangerous. Finally the medical work of Hildegard of Bingen can be estimated as a threshhold of experience, but it should not be transferred into the modern medicine without a detailed analysis.


DiNuP: a systematic approach to identify regions of differential nucleosome positioning.
With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. We describe a novel computational approach, DiNuP, that compares nucleosome profiles generated by high-throughput sequencing under various conditions. DiNuP provides a statistical P-value for each identified RDNP based on the difference of read distributions. DiNuP also empirically estimates the false discovery rate as a cutoff when two samples have different sequencing depths and differentiate reliable RDNPs from the background noise. Evaluation of DiNuP showed it to be both sensitive and specific for the detection of changes in nucleosome location, occupancy and fuzziness. RDNPs that were identified using publicly available datasets revealed that nucleosome positioning dynamics are closely related to the epigenetic regulation of transcription. DiNuP is implemented in Python and is freely available at http://www.tongji.edu.cn/~zhanglab/DiNuP. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Optical coherence tomography angiography features of retinitis post-rickettsial fever.
The intraocular manifestations of rickettisial retinitis include retinal vasculitis, maculopathy, optic neuritis, and neurosensory detachment. Extensive leakage of dye on the fundus fluorescein angiography may obscure visualization in eyes with retinitis. We report the vascular changes in eyes with rickettsial retinitis and its response to treatment using optical coherence tomography angiography. The microvascular abnormalities we noted were, capillary drop out areas corresponding to retinitis patches, vascular loops, and pruning of vessels. The choriocapillary slabs showed signal void areas. Post-treatment there was vascular remodeling with decrease in non-perfused area, appearance of new vascular lateral branching, and appearance of collaterals.


Interdisciplinary media management and information skills training.
The rationale for planning, teaching, and subsequent revision of a course in health sciences information skills and media management practices presented as a part of a curriculum in medical illustration training is described. National events influencing the course content are discussed. Effects of the course on student attitudes and perceptions are presented in the conclusions.


Conformation-dependent reaction thermochemistry: study of lactones and lactone enolates in the gas phase.
Gas-phase acidities (Delta H degrees (acid)) of lactones with ring sizes from four to seven have been measured on a Fourier transform ion cyclotron resonance mass spectrometer. Electron affinities (EAs) of the corresponding lactone enolate radicals were measured on a continuous-wave ion cyclotron resonance mass spectrometer, and the bond dissociation energies (BDEs) of the alpha C-H bonds were derived. In order of increasing ring size, Delta H degrees (acid) = 368.7 +/- 2., 369.4 +/- 2.2, 367.3 +/- 2.2, and 368.3 +/- 2.2 kcal/mol and BDE = 99.4 +/- 2.3, 94.8 +/- 2.3, 89.2 +/- 2.3, and 92.8 +/- 2.4 kcal/mol for beta-propiolactone, gamma-butyrolactone, delta-valerolactone, and epsilon-caprolactone, respectively. For their corresponding enolate radicals, EA = 44.1 +/- 0.3, 38.8 +/- 0.3, 35.3 +/- 0.3, and 37.9 +/- 0.6 kcal/mol. All of these lactones are considerably more acidic than methyl acetate, consistent with a dipole repulsion model. Both BDEs and EAs show a strong dependence on ring size, whereas Delta H degrees (acid) does not. These findings are discussed, taking into account differential electronic effects and differential strain between the reactant and product species in each reaction.


Layer-By-Layer Nanoparticle Vaccines Carrying the G Protein CX3C Motif Protect against RSV Infection and Disease.
Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to the RSV G glycoprotein CX3C motif, mediates virus clearance and decreases leukocyte trafficking to the lungs of RSV-infected mice. In this study, we show that vaccination with layer-by-layer nanoparticles (LbL-NP) carrying the G protein CX3C motif induces blocking antibodies that prevent the interaction of the RSV G protein with the fractalkine receptor (CX3CR1) and protect mice against RSV replication and disease pathogenesis. Peptides with mutations in the CX3C motif induced antibodies with diminished capacity to block G protein-CX3CR1 binding. Passive transfer of these anti-G protein antibodies to mice infected with RSV improved virus clearance and decreased immune cell trafficking to the lungs. These data suggest that vaccination with LbL-NP loaded with the CX3C motif of the RSV G protein can prevent manifestations of RSV disease by preventing the interaction between the G protein and CX3CR1 and recruitment of immune cells to the airways.


Extending the scope of NMR spectroscopy with microcoil probes.
Capillary NMR (CapNMR) spectroscopy has emerged as a major breakthrough for increasing the mass-sensitivity of NMR spectroscopic analysis and enabling the combination of NMR spectroscopy with other analytical techniques. Not only is the acquisition of high-sensitivity spectra getting easier but the quality of CapNMR spectra obtained in many small-molecule applications exceeds what can be accomplished with conventional designs. This Minireview discusses current CapNMR technology and its applications for the characterization of mass-limited, small-molecule and protein samples, the rapid screening of small-molecule or protein libraries, as well as hyphenated techniques that combine CapNMR with other analytical methods.


Enhanced biofilm formation and reduced virulence of Actinobacillus pleuropneumoniae luxS mutant.
Actinobacillus pleuropneumoniae is the pathogen of porcine contagious pleuropneumonia causing great economic losses globally. LuxS is known to be involved in the interspecies quorum sensing by mediating the production of AI-2 signal molecule and play important roles in regulating various behaviors of bacteria. In this study, A. pleuropneumoniae was tested to be able to produce AI-2 like molecule. A luxS deletion mutant strain was constructed by homologous replacement, and its growth features, biofilm formation and virulence were characterized. The luxS mutant showed obvious growth deficiency when cultured in the serum-free medium. Biofilm formation of the mutant strain was significantly enhanced. In a mouse infection model, the 50% lethal dose of the mutant strain was increased up to 96-folds, and the ability to colonize in different mouse tissues was significantly decreased. Down-regulation of apxIIA, a major virulence factor of A. pleuropneumoniae, may contribute to the virulence attenuation of the mutant strain. Our data demonstrated that LuxS is functional in the AI-2-mediated quorum sensing in A. pleuropneumoniae and LuxS may regulate different behaviors including biofilm formation and virulence of this important pathogen.


Strategies for MCR image analysis of large hyperspectral data-sets.
Polymer microarrays are a key enabling technology for high throughput materials discovery. In this study, multivariate image analysis, specifically multivariate curve resolution (MCR), is applied to the hyperspectral time of flight secondary ion mass spectroscopy (ToF-SIMS) data from eight individual microarray spots. Rather than analysing the data individually, the data-sets are collated and analysed as a single large data-set. Desktop computing is not a practical method for undertaking MCR analysis of such large data-sets due to the constraints of memory and computational overhead. Here, a distributed memory High-Performance Computing facility (HPC) is used. Similar to what is achieved using MCR analysis of individual samples, the results from this consolidated data-set allow clear identification of the substrate material; furthermore, specific chemistries common to different spots are also identified. The application of the HPC facility to the MCR analysis of ToF-SIMS hyperspectral data-sets demonstrates a potential methodology for the analysis of macro-scale data without compromising spatial resolution (data 'binning'). Copyright © 2012 John Wiley & Sons, Ltd.


Grafting of a high-affinity Zn(II)-binding site on the beta-barrel of retinol-binding protein results in enhanced folding stability and enables simplified purification.
In a rational protein design approach, the His3 Zn(II)-binding site from the active center of human carbonic anhydrase II was transplanted on the beta-barrel of mammalian serum retinol-binding protein (RBP) in a solvent-accessible location on the protein's outer surface. Several mutants of RBP were generated and produced in Escherichia coli, and their Zn(II)-binding properties were investigated in equilibrium dialysis experiments. One mutant, RBP/H3(A), with His residues introduced at the positions 46, 54, and 56 in the polypeptide sequence was shown to bind Zn(II) specifically with a stoichiometry of 1 and a corresponding dissociation constant equal to 36 +/- 10 nM. Binding of Zn(II) had no influence on the binding of retinoic acid, a natural ligand of RBP. In guanidinium chloride-induced unfolding experiments the mutant was found to be significantly stabilized in the presence of small concentrations of ZnSO4. This effect could be quantitatively explained using thermodynamic theory. Furthermore, it was demonstrated that the protein-bound Zn(II) is accessible to iminodiacetic acid as an additional chelating ligand without competition for the metal ion. Thus it was possible to use the grafted metal-binding site for the efficient purification of the engineered, bifunctional RBP via immobilized metal affinity chromatography from the bacterial protein extract.


Decreased risk for myocardial infarction and lower tumor necrosis factor-alpha levels in carriers of variants of the PDCD1 gene.
Increasing interest has been directed toward the inflammatory mechanisms involved in the pathogenesis of myocardial infarction (MI). In the search for genetic mechanisms underlying these inflammatory components, we studied variants of programmed cell death-1 (PDCD1), an immunoinhibitory receptor that inhibits lymphocyte activation and cytokine production, previously shown to be associated with several autoimmune disorders. The PD1.1, PD1.3, and PD1.6 polymorphisms of the PDCD1 gene were typed in the Stockholm Heart Epidemiology Program, a population-based clinical material consisting of 1179 first-time MI case patients and 1528 unaffected control subjects. Individual alleles and haplotypes were studied for association with levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and C-reactive protein and risk for MI. We observed a weak protective effect of PD1.3A allele for MI (odds ratio: 0.78, 95% confidence interval: 0.61-0.98). We also observed decreased levels of TNF-alpha in carriers of the PD1.1A/PD1.3G/PD1.6A haplotype, which is consistent with our previous observation that this haplotype may be protective from autoimmune conditions. Carriers of variants of the PDCD1 gene exhibit a decreased risk for nonfatal myocardial infarction, and PDCD1 mediates variation in TNF-alpha levels.


Deposition of general ellipsoidal particles.
We present a systematic overview of granular deposits composed of ellipsoidal particles with different particle shapes and size polydispersities. We study the density and anisotropy of such deposits as functions of small to moderate size polydispersity and two shape parameters that fully describe the shape of a general ellipsoid. Our results show that, while shape influences significantly the macroscopic properties of the deposits, polydispersity in the studied range plays apparently a secondary role. The density attains a maximum for a particular family of nonsymmetrical ellipsoids, larger than the density observed for prolate or oblate ellipsoids. As for anisotropy measures, the contact forces are increasingly preferred along the vertical direction as the shape of the particles deviates from a sphere. The deposits are constructed by means of a molecular dynamics method, where the contact forces are efficiently and accurately computed. The main results are discussed in the light of applications for porous media models and sedimentation processes.


A systematic review on the effects of resistance and plyometric training on physical fitness in youth- What do comparative studies tell us?
To date, several meta-analyses clearly demonstrated that resistance and plyometric training are effective to improve physical fitness in children and adolescents. However, a methodological limitation of meta-analyses is that they synthesize results from different studies and hence ignore important differences across studies (i.e., mixing apples and oranges). Therefore, we aimed at examining comparative intervention studies that assessed the effects of age, sex, maturation, and resistance or plyometric training descriptors (e.g., training intensity, volume etc.) on measures of physical fitness while holding other variables constant. To identify relevant studies, we systematically searched multiple electronic databases (e.g., PubMed) from inception to March 2018. We included resistance and plyometric training studies in healthy young athletes and non-athletes aged 6 to 18 years that investigated the effects of moderator variables (e.g., age, maturity, sex, etc.) on components of physical fitness (i.e., muscle strength and power). Our systematic literature search revealed a total of 75 eligible resistance and plyometric training studies, including 5,138 participants. Mean duration of resistance and plyometric training programs amounted to 8.9 ± 3.6 weeks and 7.1±1.4 weeks, respectively. Our findings showed that maturation affects plyometric and resistance training outcomes differently, with the former eliciting greater adaptations pre-peak height velocity (PHV) and the latter around- and post-PHV. Sex has no major impact on resistance training related outcomes (e.g., maximal strength, 10 repetition maximum). In terms of plyometric training, around-PHV boys appear to respond with larger performance improvements (e.g., jump height, jump distance) compared with girls. Different types of resistance training (e.g., body weight, free weights) are effective in improving measures of muscle strength (e.g., maximum voluntary contraction) in untrained children and adolescents. Effects of plyometric training in untrained youth primarily follow the principle of training specificity. Despite the fact that only 6 out of 75 comparative studies investigated resistance or plyometric training in trained individuals, positive effects were reported in all 6 studies (e.g., maximum strength and vertical jump height, respectively). The present review article identified research gaps (e.g., training descriptors, modern alternative training modalities) that should be addressed in future comparative studies.


Maxillary sinus augmentation with autogenous tibial bone graft as an in-office procedure.
This retrospective study evaluates the efficacy of maxillary sinus grafting using autologous tibial bone in an outpatient setting. Twenty-seven patients undergoing lateral proximal tibial bone graft with subsequent sinus lifts were involved in this study. All surgeries were performed by the same surgeon in a private practice setting. A total of 28 tibial bone grafts and sinus lifts were performed on 27 patients. All subjects had minimal morbidity without any major complications. At the 1-year follow-up all implants that were placed into the grafted sites maintained stability, and no implants were lost. Two patients complained of hypertrophic scars at the site of bone harvesting (7.4%). One patient complained of leg pain for 10 weeks after the procedure, which resolved completely (2.7%). Overall complication rate was 10.1%. We conclude that the surgical harvesting of proximal tibial bone is associated with a low incidence of overall complications, mild postoperative pain, relative ease of harvest, minimal operative time, immediate ambulation, and rapid recovery, which make it an ideal office procedure when a significant amount of corticocancellous bone is required for maxillary sinus grafting.


Fecal Impairment Framework, A New Conceptual Framework for Assessing Fecal Contamination in Recreational Waters.
Fecal pollution of surface water is a pervasive problem that negatively affects waterbodies concerning both public health and ecological functions. Current assessment methods monitor fecal indicator bacteria (FIB) to identify pollution sources using culture-based quantification and microbial source tracking (MST). These types of information assist stakeholders in identifying likely sources of fecal pollution, prioritizing them for remediation, and choosing appropriate best management practices. While both culture-based quantification and MST are useful, they yield different kinds of information, potentially increasing uncertainty in prioritizing sources for management. This study presents a conceptual framework that takes separate human health risk estimates based on measured MST and E. coli concentrations as inputs and produces an estimate of the overall fecal impairment risk as its output. The proposed framework is intended to serve as a supplemental screening tool for existing monitoring programs to aid in identifying and prioritizing sites for remediation. In this study, we evaluated the framework by applying it to two primarily agricultural watersheds and several freshwater recreational beaches using existing routine monitoring data. Based on a combination of E. coli and MST results, the proposed fecal impairment framework identified four sites in the watersheds as candidates for remediation and identified temporal trends in the beach application. As these case studies demonstrate, the proposed fecal impairment framework is an easy-to-use and cost-effective supplemental screening tool that provides actionable information to managers using existing routine monitoring data, without requiring specialized expertize.


Predicting behavior change from persuasive messages using neural representational similarity and social network analyses.
Neural activity in medial prefrontal cortex (MPFC), identified as engaging in self-related processing, predicts later health behavior change. However, it is unknown to what extent individual differences in neural representation of content and lived experience influence this brain-behavior relationship. We examined whether the strength of content-specific representations during persuasive messaging relates to later behavior change, and whether these relationships change as a function of individuals' social network composition. In our study, smokers viewed anti-smoking messages while undergoing fMRI and we measured changes in their smoking behavior one month later. Using representational similarity analyses, we found that the degree to which message content (i.e. health, social, or valence information) was represented in a self-related processing MPFC region was associated with later smoking behavior, with increased representations of negatively valenced (risk) information corresponding to greater message-consistent behavior change. Furthermore, the relationship between representations and behavior change depended on social network composition: smokers who had proportionally fewer smokers in their network showed increases in smoking behavior when social or health content was strongly represented in MPFC, whereas message-consistent behavior (i.e., less smoking) was more likely for those with proportionally more smokers in their social network who represented social or health consequences more strongly. These results highlight the dynamic relationship between representations in MPFC and key outcomes such as health behavior change; a complete understanding of the role of MPFC in motivation and action should take into account individual differences in neural representation of stimulus attributes and social context variables such as social network composition.


Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.
The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.


[Kidney-sparing surgery for recurrent ureteral and bladder cancers in an aged patient with functionally solitary horseshoe kidney].
A 79-year-old woman was admitted with recurrent ureteral and bladder cancers. She had a horseshoe kidney with a non-functioning right renal unit. Fifteen months earlier, multiple urothelial tumors had first developed in the left upper ureter and bladder. Transurethral resection of bladder tumor (TUR-Bt) and partial ureterectomy (2 cm) had been performed. Presently, the recurrent tumors were located at the left lower ureter and bladder. Considering the high age of the patient, TUR-Bt and partial ureterectomy (5 cm) were performed. Besides urothelial cancers, she had been operated for carcinomas of the colon, uterus and stomach. Kidney-sparing therapy has successfully maintained her quality of life.


An O-glycosyltransferase promotes cell adhesion during development by influencing secretion of an extracellular matrix integrin ligand.
Protein secretion and localization are crucial during eukaryotic development, establishing local cell environments as well as mediating cell interactions, signaling, and adhesion. In this study, we demonstrate that the glycosyltransferase, pgant3, specifically modulates integrin-mediated cell adhesion by influencing the secretion and localization of the integrin ligand, Tiggrin. We demonstrate that Tiggrin is normally O-glycosylated and localized to the basal matrix where the dorsal and ventral cell layers adhere in wild type Drosophila wings. In pgant3 mutants, Tiggrin is no longer O-glycosylated and fails to be properly secreted to this basal cell layer interface, resulting in disruption of integrin-mediated cell adhesion in the wing. pgant3-mediated effects are dependent on enzymatic activity, as mutations that form a stable protein yet abrogate O-glycosyltransferase activity result in Tiggrin accumulation within the dorsal and ventral cells comprising the wing. Our results provide the first in vivo evidence for the role of O-glycosylation in the secretion of specific extracellular matrix proteins, thus altering the composition of the cellular "microenvironment" and thereby modulating developmentally regulated cell adhesion events. As alterations in cell adhesion are a hallmark of cancer progression, this work provides insight into the long-standing association between aberrant O-glycosylation and tumorigenesis.


A hemilabile manganese(I)-phenol complex and its coordination induced O-H bond weakening.
The known compound K[(PO)2Mn(CO)2] (PO = 2-((diphenylphosphino)methyl)-4,6-dimethylphenolate) (K[1]) was protonated to form the new Mn(i) complex (HPO)(PO)Mn(CO)2 (H1) and was determined to have a pKa approximately equal to tetramethylguanidine (TMG). The reduction potential of K[1] was determined to be -0.58 V vs. Fc/Fc+ in MeCN and allowed for an estimation of an experimental O-H bond dissociation free energy (BDFEO-H) of 73 kcal mol-1 according to the Bordwell equation. This value is in good agreement with a corrected DFT computed BDFEO-H of 68.0 kcal mol-1 (70.3 kcal mol-1 for intramolecular H-bonded isomer). The coordination of the protonated O-atom in the solid-state H1 was confirmed using FTIR spectroscopy and X-ray crystallography. The phenol moiety is hemilabile as evident from computation and experimental results. For instance, dissociation of the protonated O-atom in H1 is endergonic by only a few kcal mol-1 (DFT). Furthermore, [1]- and other Mn(i) compounds coordinated to PO and/or HPO do not react with MeCN, but H1 reacts with MeCN to form H1+MeCN. Experimental evidence for the solution-bound O-atoms of H1 was obtained from 1H NMR and UV-vis spectroscopy and by comparing the electronic spectra of bona fide 16-e- Mn(i) complexes such as [{PNP}Mn(CO)2] (PNP = -N{CH2CH2(PiPr2)}2) and [(Me3SiOP)(PO)Mn(CO)2] (Me3Si1). Compound H1 is only meta-stable (t1/2 0.5-1 day) and decomposes into products consistent with homolytic O-H bond cleavage. For instance, treatment of H1 with TEMPO resulted in formation of TEMPOH, free ligand, and [MnII{(PO)2Mn(CO)2}2]. Together with the experimental and calculated weakened BDFEO-H, these data provide strong evidence for the coordination and hemilability of the protonated O-atom in H1 and represents the first example of the phenolic Mn(i)-O linkage and a rare example of a "soft-homolysis" intermediate in the bond-weakening catalysis paradigm.


Written informed consent for participation in a study and reduction in consent rate.
The association between the method of obtaining informed consent and the consent rate in a cohort study, as well as the differences between consenters and non-consenters with regard to blood-sample donation are unclear. We measured the consent rates among 64-year-old residents who underwent medical checkups in a city for a cohort study consisting of a questionnaire survey and blood-sample donation and determined the influence of different approaches to informed consent and the participants' characteristics on the consent rates. Of 3,098 residents who underwent medical checkups over 10 years, 99.2% responded to the questionnaire survey, and 92.5% agreed to blood-sample donation. The consent rate for blood-sample donation after obtaining individual written informed consent was lower than that observed with the general-announcement approach. Differences in the consent rates for participation in the questionnaire study were, however, negligible. A higher percentage of men than women consented to donate blood samples. After adjustments for gender, it was observed that individuals with a history of hypertension and those without depression consented to blood-sample donation significantly more frequently. The consent rate for blood-sample donation to the study decreased when the opt-in approach with written consent was used. This decrease may introduce consent bias, and the method of obtaining informed consent should be revised.


Impacts of one century of wastewater discharge on soil transformation through ferrolysis and related metal pollutant distributions.
Discharge of wastewater leading to notable soil surface contamination is widely reported. But few works highlight the fast dynamics of soils and their morphological transformations that may result from such anthropogenic activities. Near Paris (France), sandy Luvisols were irrigated with urban wastewater since the 1890s. Within and outside the discharge area, the soil cover presents decameter-sized cryogenic structures. We studied macro morphological soil characteristics, soil chemistry and clay mineralogy on selected bulk samples, as well as contemporary pedofeatures and related metal pollutant distribution patterns in soil thin sections from subsurface horizons. Annual repetitive waterlogging and drying cycles initiated a hydromorphic soil forming process: ferrolysis, based on iron reduction producing alkalinity under anaerobic conditions, and iron oxidation producing acidity in aerobic conditions. Its intensity was enhanced at the top of thick clay-rich B-horizons in the center of cryogenic structures. The polygonal soil structure favored the evacuating of soil water and alkalinity. Within one century, such recurrent alternating redox conditions have led to clay destruction, removal of iron, strong bleaching of the E horizon and formation of abiotic Fe-rich pedofeatures at depth. In addition, between anaerobic clay-rich B and aerated E or C horizons, the contrasting hydrodynamic conditions enhanced manganese (Mn) oxidizing fungal activity and the formation of biotic Mn-rich pedofeatures. Both types of pedofeatures trapped metal pollutants in deep soil horizons. In our work, the impacts of centenary anthropogenic activity were amplified by millenary cryogenic structures, acting together to promote fast soil dynamics, within a few decades.


[Enhanced external counterpulsation therapy for patients with angina pectoris].
Enhanced external counterpulsation (EECP) is a noninvasive therapy offered to patients with angina pectoris who have unacceptable chest pain despite medical treatment and who have no operative options. During EECP three sets of pneumatic cuffs wrapped around the lower extremities are inflated to a pressure of 260-300 mmHg in diastole. This creates an augmented diastolic blood pressure and an increase in coronary blood flow. The therapy is usually given for one hour five days a week in seven weeks. EECP is known to reduce the frequency of angina, increase the quality of life and reduce the frequency of hospitalisation.


Direct and latent effects of ocean acidification on the transition of a sea urchin from planktonic larva to benthic juvenile.
Ongoing ocean acidification is expected to affect marine organisms and ecosystems. While sea urchins can tolerate a wide range of pH, this comes at a high energetic cost, and early life stages are particularly vulnerable. Information on how ocean acidification affects transitions between life-history stages is scarce. We evaluated the direct and indirect effects of pH (pHT 8.0, 7.6 and 7.2) on the development and transition between life-history stages of the sea urchin Strongylocentrotus droebachiensis, from fertilization to early juvenile. Continuous exposure to low pH negatively affected larval mortality and growth. At pH 7.2, formation of the rudiment (the primordial juvenile) was delayed by two days. Larvae raised at pH 8.0 and transferred to 7.2 after competency had mortality rates five to six times lower than those kept at 8.0, indicating that pH also has a direct effect on older, competent larvae. Latent effects were visible on the larvae raised at pH 7.6: they were more successful in settling (45% at day 40 post-fertilization) and metamorphosing (30%) than larvae raised at 8.0 (17 and 1% respectively). These direct and indirect effects of ocean acidification on settlement and metamorphosis have important implications for population survival.


Epidermis Microstructure Inspired Graphene Pressure Sensor with Random Distributed Spinosum for High Sensitivity and Large Linearity.
Recently, wearable pressure sensors have attracted tremendous attention because of their potential applications in monitoring physiological signals for human healthcare. Sensitivity and linearity are the two most essential parameters for pressure sensors. Although various designed micro/nanostructure morphologies have been introduced, the trade-off between sensitivity and linearity has not been well balanced. Human skin, which contains force receptors in a reticular layer, has a high sensitivity even for large external stimuli. Herein, inspired by the skin epidermis with high-performance force sensing, we have proposed a special surface morphology with spinosum microstructure of random distribution via the combination of an abrasive paper template and reduced graphene oxide. The sensitivity of the graphene pressure sensor with random distribution spinosum (RDS) microstructure is as high as 25.1 kPa-1 in a wide linearity range of 0-2.6 kPa. Our pressure sensor exhibits superior comprehensive properties compared with previous surface-modified pressure sensors. According to simulation and mechanism analyses, the spinosum microstructure and random distribution contribute to the high sensitivity and large linearity range, respectively. In addition, the pressure sensor shows promising potential in detecting human physiological signals, such as heartbeat, respiration, phonation, and human motions of a pushup, arm bending, and walking. The wearable pressure sensor array was further used to detect gait states of supination, neutral, and pronation. The RDS microstructure provides an alternative strategy to improve the performance of pressure sensors and extend their potential applications in monitoring human activities.


Biological therapies in nonsmall cell lung cancer.
Biological therapies have improved survival outcomes of advanced-stage nonsmall cell lung cancer (NSCLC). Genotype-directed therapies have changed treatment paradigms of patients with EGFR-mutant and ALK/ROS1-rearranged lung adenocarcinomas, and the list of druggable targets with demonstrated clinical actionability (BRAF, MET, RET, NTRK1 and HER2) continues to expand. Furthermore, we have incrementally understood the mechanisms of cancer immune evasion and foresee ways to effectively circumvent them, particularly at the immune checkpoint level. Drugs targeting the tumour immune-evasive PD-1 pathway have demonstrated remarkable treatment benefits in this disease, with a non-negligible fraction of patients potentially receiving long-term survival benefits. Herein, we briefly discuss the role of various medical disciplines in the management of advanced-stage NSCLC and review the most relevant biological therapies for this disease, with particular emphasis in genotype-directed therapies and immune checkpoint inhibitors.


The effects of a combined physical activity, recreation, and art and craft program on ADL, cognition, and depression in the elderly.
[Purpose] To determine the effects of a combined physical activity, arts and crafts, and recreational program on the activities of daily living (ADL), cognitive function, and depression in the elderly. [Subjects and Methods] Twenty-eight elderly persons aged 65 years or older who live in P City, South Korea participated in a program combining arts and crafts and physical and recreational activities, twice weekly for eight weeks (a total of 16 sessions). The subjects' ADL, cognitive function, and depression were measured before and after the program using the following assessment instruments: the FIM, MMSE-K, and BDI, respectively. [Results] The results showed that, after the program intervention, ADL were remarkably improved for both men and women, cognitive function increased considerably, and depression levels significantly decreased, especially for elderly women. [Conclusion] The results of the present study indicate that a program combining physical and recreational activities, as well as arts and crafts, had positive effects on the health of the elderly and provide evidence for managing their health.