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No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target.

No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target.

The topic of combining observations from instruments of different frequencies and sensitivities on remote sensing platforms has been underutilized in undergraduate and graduate atmospheric science curricula, but is vital to obtaining holistic views of the Earth climate system. An online education applet on this topic has been developed for use in radar and remote sensing atmospheric science courses that meets the requirements outlined in Table 1. The developed applet attempts to reduce the curriculum gap by guiding students through atmospheric weather phenomena and allowing them to explore the performance of a variety of radar frequencies and characteristics. This applet leverages a high-resolution cloud-resolving model and satellite radar simulator to provide a synthetic learning laboratory environment. It contains one-to-one comparisons between the simulated environment and approximate observations of that environment through the use of hypothetical remote sensing instruments. A limited set of orbits and planar views are selected to highlight advantages and shortfalls of potential instrument configurations. Future formal assessments of the learning tool will allows its effectiveness to be quantified and guide further improvement of the tool beyond currently planned development activities.

We present a microfluidic lab-on-printed circuit board (PCB) device containing alloy vertical electrodes for sorting microparticles using dielectrophoresis. The device consists of a hydrodynamic prefocuser and an electronic sorting region. Lining the two sidewalls of the electronic sorting region are regularly spaced rectangular metal electrodes reaching from the floor to the ceiling of the flow channel that bridge electric field lines laterally across the channel. The size and distribution of these vertical electrodes are arranged asymmetrically such that the resultant electric field forms sharp electric field gradients across the channel; specific geometries were optimized using finite element methods. Particles entering the device are initially focused on a single stream as they pass through the prefocuser. Subsequently, they are exposed to the lateral electric field gradient and separate into streams based on their size and dielectric properties. Validation was performed by dielectrophoretically separating live cells from dead cells. Importantly, the system presented can be readily integrated with various external sensors and actuators using commercially available components owing to the device's integration into a PCB.

Background: Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory.Methods: Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322) in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC) expression of γ-interferon and T-bet transcription factor (Tbx21) by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF) samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points). Dendritic cells were defined as lineage (-) and MHC class II high (+).Results: 73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02) and ~5x excluding non-responders (3.2% to 14.5%, p < 0.001). This effect was sustained over multiple cycles for approximately half of the responders, but tachyphylaxis over subsequent chemotherapy cycles was noted for the remainder. Treatment also led to a significant reduction in the proportion of circulating regulatory T-cells (Treg; p = 0.0042). PBMC Tbx21 levels declined by 75% following each chemotherapy cycle despite administration of GM-CSF (p = 0.02). PBMC γ-interferon expression, however was unchanged.Conclusions: This clinical trial confirms the suppressive effects of chemotherapy on Th1 cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm of the immune system for cancer patients receiving cytotoxic therapy.Trial Registration: ClinicalTrials.gov: NCT00257322. © 2012 Martinez et al; licensee BioMed Central Ltd.

Chemokines help control normal leukocyte trafficking as well as their infiltration into tissues during acute and chronic inflammation. Matrix metalloproteinases (MMPs) help support the extravasation and infiltration of leukocytes through limited proteolysis of basement membranes and matrix material. The effect of the chemokines RANTES/CCL5, MCP-1/CCL and SDF-1/CXCL12 on secretion of the matrix metalloproteinase B and its endogenous inhibitor TIMP-1 was studied. RANTES/CCL5 and SDF-1/CXCL12 were found to induce MMP-9 secretion in primary human monocytes while TIMP-1 secretion was not affected. RANTES/CCL5 effects were mediated through CCR1 because the CCR1 antagonist BX471 was found to effectively block RANTES/CCL5-induced MMP-9 secretion.

The chemokine RANTES is produced by a variety of tissues, including cells of the monocyte/macrophage lineage. RANTES expression is rapidly and transiently up-regulated in primary monocytes and the monocytic cell line Mono Mac 6 in response to stimulation by the bacterial product lipopolysaccharide (LPS). Transient transfection of Mono Mac 6 cells with RANTES reporter-promoter deletion constructs, in conjunction with DNase I footprinting and heterologous reporter gene assays, allowed identification of an LPS-responsive region within the RANTES promoter. Electrophoretic mobility shift assays (EMSA), methylation interference and EMSA supershift experiments were used to characterize sequences and transcription factors responsible for this LPS inducibility. The region, termed RANTES site G [R(G)], contains consensus sites for Ets and CRE/AP-1-like elements. Site-directed mutagenesis of the Ets site resulted in a loss of only 15 % of promoter activity, while mutation of the CRE/AP-1 site led to a loss of 40 % of LPS-induced promoter activity. The Ets site constitutively binds the Ets family member PU.1. LPS stimulation leads to an induction of ATF-3 and JunD factor binding to the CRE/AP-1 site. Thus, LPS induction of RANTES transcription is mediated, in part, through the activation and selective binding of ATF and Jun nuclear factors to the R(G) promoter module.

Dendritic cells (DCs) are potent antigen presenting cells reported to undergo irreversible functional 'maturation' in response to inflammatory signals such as TNF-alpha. The current paradigm holds that this DC maturation event is required for full functional capacity and represents terminal differentiation of this cell type, culminating in apoptotic cell death. This provides a possible mechanism for avoiding dysregulated immunostimulatory activity, but imposes constraints on the capacity of DCs to influence subsequent immune responses and to participate in immunological memory. We report that the cell surface and functional effects induced by TNF-alpha are reversible and reinducible. These effects are accompanied by a concordant modulation of cytokine mRNA expression that includes the induction of proinflammatory factors (IL-15, IL-12, LT-alpha, LT-beta, TNF-alpha, RANTES) which is coincident with the down-regulation of counter-regulatory cytokines (IL-10, TGF-beta1, TGF-beta2, IL-1 RA, MCP-1). The resultant net effect is a dendritic cell activation state characterized by a transient proinflammatory posture. These results demonstrate that 1) human DCs do not undergo terminal 'maturation' in response to TNF-alpha, 2) DC phenotypes are more pleiotropic than previously thought, and 3) DCs are potential immunoregulatory effector cells with implications for control of immune responses in both in vivo and in vitro systems.

Nesse artigo são observados criticamente os signos de masculinidade utilizados na caracterização de personagens em quatro contos de Os prisioneiros, de Rubem Fonseca: “Fevereiro ou março”, “Duzentos e vinte e cinco gramas”, “Teoria do consumo conspícuo” e “Henri”. Procuramos demonstrar tanto a recorrência de certos signos (virilidade sexual, força física, descontrole, agressividade, refinamento, comando, autocontrole, coragem e intelectualidade) como a complexidade e peculiaridade com que estes aparecem em cada narrativa, reiterando sua compreensão enquanto atos performáticos. Esses, por sua vez, são continuamente exibidos e repetidos, de modo a fazer parecer, para outras personagens, que seriam espontâneos, de modo a atestar sua pertença a um grupo privilegiado. Pudemos atestar, no entanto, que os signos de masculinidade nas obras representam na verdade mais um modo de aprisionamento das personagens, sendo este um tema central que transpassa os diversos contos da coletânea e que apontam para sua retomada nas obras seguintes de Rubem Fonseca.

Igor da Silva Brum,1 Lucio Frigo,2 Paulo Goncalo Pinto dos Santos,1 Carlos Nelson Elias,3 Guilherme Aparecido Monteiro Duque da Fonseca,2 Jorge Jose de Carvalho4 1Implantology Department, School of Dentistry, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; 2Periodontology Department, School of Dentistry, Universidade Guarulhos, São Paulo, Brazil; 3Instituto Militar de Engenharia, Rio de Janeiro, Brazil; 4Biology Department, School of Medicine, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, BrazilCorrespondence: Lucio FrigoPeriodontology Department, School of Dentistry, Universidade Guarulhos, Praça Teresa Cristina, 01, Guarulhos, São Paulo, 07023-070, BrazilTel/Fax +55-11- 2464-1684Email luciofrigo@uol.com.brBackground: Synthetic biomaterials have played an increasingly prominent role in the substitution of naturally derived biomaterials in current surgery practice. In vitro and in vivo characterization studies of new synthetic biomaterials are essential to analyze their physicochemical properties and the underlying mechanisms associated with the modulation of the inflammatory process and bone healing.Purpose: This study compares the in vivo tissue behavior of a synthetic biomaterial nano-hydroxyapatite/beta-tricalcium phosphate (nano-HA/ß-TCP mixture) and deproteinized bovine bone mineral (DBBM) in a rat calvarial defect model. The innovation of this work is in the comparative analysis of the effect of new synthetic and commercially xenogenic biomaterials on the inflammatory response, bone matrix gain, and stimulation of osteoclastogenesis and osteoblastogenesis.Methods: Both biomaterials were inserted in rat defects. The animals were divided into three groups, in which calvarial defects were filled with xenogenic biomaterials (group 1) and synthetic biomaterials (group 2), or left unfilled (group 3, controls). Sixty days after calvarial bone defects filled with biomaterials, periodic acid Schiff (PAS) and Masson’s trichrome staining, immunohistochemistry tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), and electron microscopy analyses were conducted.Results: Histomorphometric analysis revealed powerful effects such as a higher amount of proteinaceous matrix and higher levels of TNF-α and MMP-9 in bone defects treated with alloplastic nano-HA/ß-TCP mixture than xenogenicxenogic biomaterial, as well as collagen-proteinaceous material in association with hydroxyapatite crystalloids.Conclusion: These data indicate that the synthetic nano-HA/ß-TCP mixture enhanced bone formation/remodeling in rat calvarial bone defects. The nano-HA/ß-TCP did not present risks of cross-infection/disease transmission. The synthetic nano-hydroxyapatite/beta-tricalcium phosphate mixture presented adequate properties for guided bone regeneration and guided tissue regeneration for dental surgical procedures.Keywords: biomaterial, hydroxyapatite, beta-tricalcium phosphate, bone healing, histomorphometry

Miracle tales are didactic stories related to Buddhist figures, objects, and places that describe supernormal occurrences brought about by acts of great piety and fervent devotion. They present the audience with concrete examples of the workings of karma, while simultaneously setting verifiable historical precedents in a bid to prove the religious efficacy of Buddhism in China. These were also historiographical works, providing a wealth of detail regarding not only religious life and belief in China, but also local lore, politics, architectural trends, and much more. This paper will focus on a text called the Ji shenzhou sanbao gantong lu 集神州三寶感通錄 (T2106), a collection of miracle tales compiled by the seventh-century scholar-monk, Daoxuan 道宣 (596–667 CE). This text is a collection of narratives drawn from literary and epigraphy sources, as well as orally transmitted stories. As a Buddhist figurehead and as the author of many seminal historiographical works, Daoxuan played a central role in the overall localization of this tradition in China. Bearing this in mind, this paper seeks to interpret the “collective images” presented in Daoxuan’s collection of miracle tales, those representations of the miraculous and the supernormal.

The System of Rice Intensification (SRI) operates under aerobic conditions so that helpful microbes are active and abundant. Effective N-fixing rhizobacteria and indigenous phosphate solubilizers Azotobacter and Pseudomonas grow well in the organic compost Bioorganic because it resembles their natural habitat. The purpose of this research is to find out the right dose of Bioorganic fertilizer and the most N and P doses needed to optimize the SRI method of rice crop production. This research uses a factorial randomized block design. The first factor is Bioorganic fertilizer dosage (1, 3, and 6) t ha-1. The second factor is the dose of N and P fertilizers to use (0, 25, 50, and 75)% of the recommended dosage. The results of this study inform you about Bioorganic fertilizers containing Azotobacter and Pseudomonas fluorescens indigenous. Azotobacter bacteria produce the availability of nutrients N, which functions as Plant Growth Promoting Rhizobacteria (PGPR), these bacteria quickly colonize the root system, regulate hormonal balance, nutrition, and encourage resistance to pathogens. Pseudomonas fluorescens bacteria acts as a provider of phosphorus and nutrients in the generative phase. Both of these microbes have a role in SRI method of rice plant metabolism to increase vegetative and generative growth of rice plants with SRI method with production reaching production of 8.80 t ha-1 in B2 (3 t ha-1) and N2P2 (50%) with the production of 9.21 t ha-1, so the use of inorganic fertilizers is more efficient. Rice soil nutrient status increased pH from slightly acidic to neutral, C-organic increased from 1.27% (low) to 9.30-10.68% (high), N total from 0.13% (low) to 0.45-0.58% (high), P- available from 13.0 ppm reaching 18.0-20.0 ppm (moderate), the Bioorganic application has not been able to increase the C: N, CEC value and base saturation. Nutrient uptake of N and P on the leaves of rice plants is better at dose B2. Bioorganic applications increase the nutrient content of paddy soils planted with the SRI method compared to initial soil nutrient analysis.

Program Kemitraan Masyarakat (PKM) penerapan budidaya padi metode SRI dengan teknologi bioorganik plus dilakukan pada Kelompok Tani (K.T) Sakinah dan Kelompok Tani (K.T) Sejahtera di Jorong Ganting Taram dengan tujuan untuk mengatasi permasalahan petani yang berbudidaya padi dengan sistem konvensional yaitu rendahnya kuantitas produksi dan pendapatan yang disebabkan oleh tingginya pemakaian bibit dan pupuk anorganik, kurangnya pemahaman pemanfaatan kotoran dan urin sapi menjadi kompos biooganik plus dan pupuk cair organik (POC), pertengkaran akibat perebutan air, serangan hama dan penyakit serta pembakaran jerami. Metode pelaksanaan PKM adalah dengan memberikan penyuluhan, pelatihan, pembuatan demplot dan evaluasi pada setiap kegiatan. Materi pada penyuluhan yaitu cara mengatasi masalah budidaya padi dengan sistem konvensional dan beralih ke metode SRI. Kegiatan pelatihan yaitu: perbanyakan massal Trichoderma harzianum dan Pseudomonas fluorescents serta pembuatan pupuk bioorganik plus dan pupuk organik cair. Demplot dilakukan di lahan kedua kelompok tani. Hasil pelatihan diaplikasikan dengan budidaya padi metode SRI. Hasil pengamatan di K.T Sejahtera dan K.T Sakinah dengan budidaya padi metode SRI diperoleh data yaitu : tinggi tanaman 117-128 cm, jumlah anakan 47-50, jumlah malai/rumpun 36-42, jumlah gabah/malai 101-110 butir, bobot 1000 butir 21,0-21,2 gram dan produksi/ha 8,4810,88 ton. Pada sistem konvensional diperoleh data yaitu : tinggi tanaman 90-93 cm, jumlah anakan 30-31, jumlah malai/rumpun 24-27, jumlah gabah/malai 76-80 butir, bobot 1000 butir 19,5-19,8 gram dan produksi/ha 3,95-4,75 ton. Hasil analisa finansial B/C pada metode SRI dan konvensional adalah 2,95-4,45 dan 0,18-0,43. Kesimpulannya pemberian pupuk bioorganik plus pada tanaman padi metode SRI mampu meningkatkan pertumbuhan vegetatif dan generatif tanaman padi.

Orang Minangkabau menyebut diri mereka sebagai orang beradat dan menunjukkan kemuliaan derajat serta martabat memakai kain tenun. Kondisi ini menjadikan kerajinan tenun sebagai industri rumah tangga dan memunculkan kelompok Usaha Kecil dan Menengah (UKM) di Nagari Kubang Kabupaten Lima Puluh Kota. Kelompok Usaha Kecil dan Menengah (UKM) Marni Geneng dan CV Rangkiang adalah mitra dari PPUD Kerajinan Tenun Minangkabau di Nagari Kubang Kabupaten Lima Puluh Kota. Kedua UKM ini sepakat untuk bermitra dalam kegiatan PPUD yang diselenggarakan oleh Tim Pengabdian Politeknik Pertanian Negeri Payakumbuh dalam rangka menuju pasar ekspor luar negeri. Tujuan dalam program PPUD pada kedua UKM ini adalah meningkatkan nilai omset, aset, peningkatan jumlah dan mutu produk serta memperluas pasar produk sehingga peluang untuk ekspor semakin terbuka. Metode pembinaan kepada UKM mitra meliputi ceramah, diskusi, pelatihan, demonstrasi, pendampingan dan evaluasi program. Ceramah, diskusi, demonstrasi dan pelatihan dilakukan untuk diversifikasi produk berbahan dasar tenun. Selanjutnya dilakukan pendampingan untuk semua topik yang sudah diberikan. Keberhasilan program maka tim PPUD melakukan evaluasi. Pendampingan yang dilakukan tim pengabdian PPUD kepada UKM mitra pengrajin tenun Kubang, mampu meningkatkan omset melalui diversifikasi produk yang dihasilkan.

Abstract Purpose: To evaluate the influence tramadol on functional recovery of acute spinal cord injury in rats. Methods: Ten rats were divided into two groups (n = 5). All animals were submitted by a laminectomy and spinal cord injury at eighth thoracic vertebra. In control group, the rats didn’t receive any analgesic. In tramadol group, the rats received tramadol 4mg/Kg at 12/12h until 5 days by subcutaneous. Animals were following by fourteen days. Was evaluated the Basso, Beattie, Bresnahan scale (locomotor evaluation) and Rat Grimace Scale (pain evaluation) at four periods. Results: There no difference between the groups in locomotor evaluation in all periods evaluated (p>0.05) and in both groups there was a partial recover of function. The tramadol group show a lower pain levels at the first, third and seventh postoperatively days when comparing to the control group. Conclusion: The tramadol as an analgesic agent don’t influence on functional recovery of acute spinal cord injury in rats

O artigo propõe uma leitura do romance Barba ensopada de sangue (2012), de Daniel Galera, que parte de sua relação com a tradição realista, que repercute na literatura brasileira contemporânea, para a investigação das marcas do realismo traumático na obra, especialmente as repetições que são estabelecidas entre o protagonista e seu avô. Para tal, foram retomadas reflexões, especialmente de Schøllhammer (2013) sobre as marcas do realismo na prosa brasileira, de Ginzburg (2002) sobre a repercussão da estética do trauma no Brasil e de Foster (2017 e 2020) sobre o realismo traumático como categoria importante para a compreensão das artes na atualidade. Percebe-se na obra a centralidade do tema da perda, posto como trauma simultaneamente repetido e deslocado, e sua relação com um padrão de masculinidade que insiste em ressurgir. Destaca-se também a importância da cadela Beta na narrativa como figura simbólica que tensiona o paralelismo de modo a evitar que o padrão de repetição se torne simples cópia.

Fractures of the distal end of the tibia without joint involvement are usually the result of high-energy trauma. Local anatomic conditions lead to high rates of infection, delayed consolidation, and exposure of fixation hardware. In this setting, minimally invasive techniques are indicated to mitigate the complications of surgical treatment. The aim of this study is to present an alternative for the surgical treatment of distal tibia fractures using a minimally invasive technique and a nonconventional implant. Level of Evidence V; Therapeutic Studies; Expert Opinion.

Esse artigo aborda o protagonista do romance Mãos de Cavalo (2006), de Daniel Galera, tomando como ponto de partida a perspectiva da identidade narrativa, elaborada por Paul Ricoeur (1991, 2010). Tal operação se faz necessária em virtude dos distintos planos temporais da narrativa, os quais apresentam a personagem com características diferentes na juventude e na fase adulta. Os traços em que se percebe maior descontinuidade entre os planos temporais dizem respeito às formas distintas com que o protagonista fantasia e experiencia sua masculinidade, o que requer a retomada de estudos sobre essa temática, tais como o de Baubérot (2013), Connell (2016) e Venayre (2013). Assim, foi possível identificar tanto a importância dos padrões de virilidade para ele como as implicações do fracasso em incorporar essas normas no seu cotidiano. Nesse sentido, as análises apontaram para: i) a centralidade de dois episódios no romance, nos quais a percepção ou a tentativa de superação da covardia provocam mudanças significativas no protagonista; ii) a teatralidade das expressões viris como respostas a padrões normativos de masculinidade; iii) a correlação entre o uso de anacronias e a presença constante da temática da identidade em Mãos de cavalo. Aponta-se, por fim, para a conveniência de estudos dessa natureza em outros romances de Daniel Galera.

Summary: Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

Malaria is a deadly disease caused by a protozoan parasite whose mode of transmission is through a female Anopheles mosquito. It affects persons of all ages; however, pregnant mothers, young children, and the elderly suffer the most due to their dwindled immune state. The currently prescribed antimalarial drugs have been associated with adverse side effects ranging from intolerance to toxicity. Furthermore, the costs associated with conventional approach of managing malaria are arguably high especially for persons living in low-income countries, hence the need for alternative and complementary approaches. Medicinal plants offer a viable alternative because of their few associated side effects, are arguably cheaper, and are easily accessible. Based on the fact that studies involving antimalarial medicinal plants as potential sources of efficacious and cost-effective pharmacotherapies are far between, this research was designed to investigate antiplasmodial and cytotoxic activities of organic and aqueous extracts of selected plants used by Embu traditional medicine practitioners to treat malaria. The studied plants included Erythrina abyssinica (stem bark), Schkuhria pinnata (whole plant), Sterculia africana (stem bark), Terminalia brownii (leaves), Zanthoxylum chalybeum (leaves), Leonotis mollissima (leaves), Carissa edulis (leaves), Tithonia diversifolia (leaves and flowers), and Senna didymobotrya (leaves and pods). In vitro antiplasmodial activity studies of organic and water extracts were carried out against chloroquine-sensitive (D6) and chloroquine-resistance (W2) strains of Plasmodium falciparum. In vivo antiplasmodial studies were done by Peter’s four-day suppression test to test for their in vivo antimalarial activity against P. berghei. Finally, cytotoxic effects and safety of the studied plant extracts were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) rapid calorimetric assay technique. The water and methanolic extracts of T. brownii and S. africana and dichloromethane extracts of E. abyssinica, S. pinnata, and T. diversifolia leaves revealed high in vitro antiplasmodial activities (IC50≤10 μg/ml). Further, moderate in vivo antimalarial activities were observed for water and methanolic extracts of L. mollissima and S. africana and for dichloromethane extracts of E. abyssinica and T. diversifolia leaves. In this study, aqueous extracts of T. brownii and S. africana demonstrated high antiplasmodial activity and high selectivity indices values (SI≥10) and were found to be safe. It was concluded that T. brownii and S. africana aqueous extracts were potent antiplasmodial agents. Further focused studies geared towards isolation of active constituents and determination of in vivo toxicities to ascertain their safety are warranted.

It has been known to us that solar radiation contributes to photoaging. Until recently, it was thought to be due to ultraviolet rays alone. However, a growing number of evidence confirms that visible and infrared (IR) rays also contribute to extrinsic aging. Visible and IR rays account for 50% and 45% of the solar radiation reaching the earth. Ultraviolet A induces retrograde mitochondrial signal, thus leading to induction of matrix metalloproteinase. Ultraviolet B and IRC cause heat-related generation of free radicals and destruction of collagen and elastin. Exposure to visible light induces cytokines, free-radical formation, and pigmentary changes in human skin. The end result of solar radiation is generation of free radicals and ultimately oxidative damage, photoaging, and photocarcinogenesis. The present broad spectrum sunscreen does not provide complete protection of the human skin from oxidative insult. So, a combination of a sun protection factor active component along with an antioxidant is the ideal way of photoprotection. Till date, a number of antioxidants have been tried in human and animals which have shown to be an effective photoprotective agent, though few studies have failed to prove the same. Even with conflicting reports, effect of antioxidants on human skin needs to be explored more. A good study design with a large sample size in humans must be conducted as visible light and IR rays contribute significantly to photodamage.

OBJECTIVE: This study's purpose was to adapt the Roter Interaction Analysis System (RIAS) for telemedicine clinics and to investigate the adapted measure's reliability. The study also sought to better understand the volume of technology-related utterance in established telemedicine clinics and the feasibility of using the measure within the telemedicine setting. This initial evaluation is a first step before broadly using the adapted measure across technologies and raters. METHODS: An expert panel adapted the RIAS for the telemedicine context. This involved accounting for all consultation participants (patient, provider, presenter, family) and adding technology-specific subcategories. Ten new and 36 follow-up telemedicine encounters were videotaped and double coded using the adapted RIAS. These consisted primarily of follow-up visits (78.0%) involving patients, providers, presenters, and other parties. Reliability was calculated for those categories with 15 or more utterances. RESULTS: Traditional RIAS categories related to socioemotional and task-focused clusters had fair to excellent levels of reliability in the telemedicine setting. Although there were too few utterances to calculate the reliability of the specific technology-related subcategories, the summary technology-related category proved reliable for patients, providers, and presenters. Overall patterns seen in traditional patient-provider interactions were observed, with the number of provider utterances far exceeding patient, presenter, and family utterances, and few technology-specific utterances. CONCLUSION: The traditional RIAS is reliable when applied across multiple participants in the telemedicine context. Reliability of technology-related subcategories could not be evaluated; however, the aggregate technology-related cluster was found to be reliable and may be especially relevant in understanding communication patterns with patients new to the telemedicine setting. Use of the RIAS instrument is encouraged to facilitate comparison between traditional, face-to-face clinics and telemedicine; among diverse consultation mediums and technologies; and across different specialties. Future research is necessary to further investigate the reliability and validity of adding technology-related subcategories to the RIAS. The limited number of technology-related utterances, however, implies a certain degree of comfort with two-way interactive video consultation among study participants. PRACTICE IMPLICATIONS: Telemedicine continues to increase access to healthcare. The technology-related categories of the adapted RIAS were reliable when aggregated, thereby providing a tool to better understand how telemedicine affects provider-patient communication and outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To identify the patient profile that obtains better clinical and quality of life improvement after lumbar spinal stenosis surgery, comparing the results in the pre and postoperative periods. Methods: Thirty-seven patients with lumbar spine stenosis submitted to surgery were prospectively evaluated. Through the 36-Item Short Form General Health Survey (SF-36) questionnaire we performed a preoperative analysis to identify morbidities and social security benefit earning. The SF-36 is a subjective postoperative questionnaire to assess surgical success six months after the surgery. Results: There were unfavorable outcomes in patients who received social security benefits and in those who had morbidities. According to the SF-36 score, the surgical result is better when the patient is non-smoker (p=0.05), non-hypertense (p=0.040), non-diabetic (p =0.010) or non sedentary (p=0.019), respectively on mental health, pain, social aspects and general health domains. Conclusion: The patient profiles that best benefit from the surgery are those who do not have morbidities and had no social security benefit. Evidence Level II, Prospective Study.

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p

OBJETIVO: avaliar a associação entre hipotireoidismo e a ocorrência de sintomas depressivos e ansiosos. MÉTODOS: foi realizado um estudo do tipo caso-controle, no período de julho de 2006 a março de 2008, no qual foram incluídas 100 mulheres (50 pacientes com hipotireoidismo primário e 50 controles eutireoidianas) com idade entre 18 e 65 anos. Foram avaliados idade, raça/cor da pele, estado civil, nível educacional, consumo de álcool, situação de trabalho, índice de massa corpórea e estado menopausal. Foram realizadas dosagens de TSH e utilizadas as escalas de ansiedade e de depressão de Beck em todos os casos e controles. O programa utilizado para a análise estatística foi o SPSS, versão 14. O nível de significância adotado foi pPURPOSE: to study the association between hypothyroidism and depression and anxiety symptoms. METHODS: a case-control study was carried out from July 2006 to March 2008 on 100 patients (50 patients with primary hypothyroidism and 50 euthyroid controls) aged 18 to 65 years. Age, race/skin color, marital status, education level, alcohol use, working status, body mass index and menopausal status were evaluated. TSH levels were determined and the Beck Depression and Beck Anxiety Scales were applied to all cases and controls. Statistical analysis was performed using the SPSS software version 14.0. The level of significance was set at p

FUNDAMENTO: A insuficiência aórtica crônica importante sintomática (IAo) leva a grande remodelamento ventricular esquerdo, à custa de hipertrofia de mióciotos e remodelamento da matriz extracelular. A relevância da concentração de fibrose intersticial nos pacientes acometidos é desconhecida. Analisamos o grau de fibrose no ventrículo esquerdo (VE) em pacientes sintomáticos com IAo submetidos a tratamento cirúrgico e sua relação com características funcionais e anatômicas. OBJETIVO: Avaliar a fibrose miocárdica na insuficiência aórtica crônica importante. MÉTODOS: Selecionaram-se 28 pacientes com IAo (16 com função VE normal e 12 com disfunção do VE), os quais foram analisados no pré e pós-operatório por ecodopplercardiografia. A capacidade funcional foi medida pelo teste de esforço cardiopulmonar. Para comparação dos resultados histopatológicos, um grupo-controle de 9 pacientes foi constituído. RESULTADOS: A média etária foi de 39 ± 12 anos, 75% do sexo masculino com 84% de etiologia reumática. Vinte e cinco pacientes permaneceram em classes funcionais I e II ao fim do estudo e apresentaram redução significativa dos diâmetros do VE entre os momentos pré e pós-operatórios. Houve três óbitos não relacionados à disfunção VE. Os parâmetros do teste cardiopulmonar não se modificaram entre o pré e o pós-operatório. O volume de fibrose intersticial em pacientes com IAo foi significativamente quando maior comparado ao grupo controle (3,47 ± 1,9% vs 0,82 ± 0,96%, respectivamente, p = 0,001). Não houve correlação entre o grau de fibrose do VE, parâmetros ecocardiográficos e funcionais. CONCLUSÃO: Em pacientes com IAo, a presença de fibrose miocárdica não se associou às alterações clínicas, ecocardiográficas ou funcionais.FUNDAMENTO: La insuficiencia aórtica crónica severa sintomática (IAo crónica severa) ocasiona una gran remodelación ventricular izquierda, por cuenta de hipertrofia de miociotos y remodelación de la matriz extracelular. Se desconoce la relevancia de la concentración de fibrosis intersticial en los pacientes acometidos. Analizamos el grado de fibrosis en el ventrículo izquierdo (VI) en pacientes sintomáticos con IAo crónica severa sometidos a tratamiento quirúrgico y su relación con características funcionales y anatómicas. OBJETIVO: Evaluar la fibrosis miocárdica en la insuficiencia aórtica crónica severa. MÉTODOS: Se seleccionaron a 28 pacientes con IAo crónica severa (16 con función VI normal y 12 con disfunción del VI), los que se analizaron en el pre y el postoperatorio por ecocardiografía Doppler. Se midió la capacidad funcional por la prueba de esfuerzo cardiopulmonar. Para comparación de los resultados histopatológicos, se constituyó a un Grupo Control de 9 pacientes. RESULTADOS: El promedio de edad fue de 39±12 años, el 75% del sexo masculino con el 84% de etiología reumática. El total de 25 pacientes permanecieron en clases funcionales I e II al fin del estudio y presentaron reducción significativa de los diámetros del VI entre los momentos pre y postoperatorios. Hubo tres óbitos no relacionados a la disfunción VI. Los parámetros de la prueba cardiopulmonar no se modificaron entre el pre y el postoperatorio. El volumen de fibrosis intersticial en pacientes con IAo crónica severa fue significativo cuando mayor, comparado al Grupo control (3,47 ± 1,9% vs. 0,82 ±0,96%, respectivamente, p = 0,001). No hubo correlación entre el grado de fibrosis del VI, parámetros ecocardiográficos y funcionales. CONCLUSIÓN: En pacientes con IAo crónica severa, la presencia de fibrosis miocárdica no se asoció a las alteraciones clínicas, ecocardiográficas o funcionales.BACKGROUND: Significant symptomatic chronic aortic regurgitation (AR) leads to considerable left ventricular remodeling at the expense of myocyte hypertrophy and extracellular matrix remodeling. The relevance of interstitial fibrosis concentration in these patients is unknown. We analyzed the degree of fibrosis in the left ventricle (LV) in symptomatic patients with AR submitted to surgical treatment, and its relationship with functional and anatomical characteristics. OBJECTIVE: To evaluate myocardical fibrosis in chronic severe aortic regurgitation. METHODS: Twenty-eight patients with chronic symptomatic AR (16 with normal LV function and 12 with LV dysfunction) were selected and assessed pre- and postoperatively by echocardiography. Functional capacity was measured using maximal oxygen consumption (VO2max) through the cardiopulmonary test. Myocardial fibrosis volume fraction (MFV) was quantified through endomyocardial biopsy performed in all patients during surgery. We compared the histopathologic results with a nine-patient control group. RESULTS: The mean age was 39 ± 12 years, 75% of the patients were male, and the rheumatic etiology accounted for 84% of the cases. Twenty-five patients remained in FC l and ll at the end of the study, and there was a significant reduction of the LV diameters between the preoperative and late postoperative timepoints. Three deaths occurred but they were not related to postoperative ventricular dysfunction. The parameters of the cardiopulmonary test were similar between pre- and postoperative timepoints. MFV in patients with AR was significantly higher than in the control group (3.47 ± 1.9% vs 0.82 ± 0.96%, respectively, p=0.001). There was no statistical correlation among LV fibrosis and LV diameters, LVEF and MVO2. CONCLUSION: In patients with significant symptomatic AR, the presence of limited myocardial fibrosis was not associated with clinical, echocardiographic or functional complications.

BACKGROUND AND AIMS: Although there is much known about liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases observed in newborn infants and those in adults. For example, how do newborns respond to duct epithelial cell injury? Do the stellate cells in newborns respond similarly to those in adults during biliary obstruction? METHODS: Ninety newborn Wistar rats aged six days, weighing 8.0 - 13.9 g each, and 90 adult rats weighing 199.7 - 357.0 g each, were submitted to bile duct ligation. After surgery, they were randomly divided and sacrificed on the 3rd, 5th, 7th, 14th, 21st or 28th day post-bile duct ligation. Hepatic biopsies were obtained and immunohistochemical semi-quantification of desmin and α-SMA expression was performed in hepatic stellate cells and in myofibroblasts in the portal space, and between the portal space and the liver lobule. RESULTS: Desmin expression in the myofibroblast cells post-bile duct ligation was higher in young rats, reaching its peak level in a shorter time when compared to the adult animals. The differences between the groups for α-SMA expression were less significant than for desmin. CONCLUSIONS: These findings indicate that there is an increase in the number of collagen-producing myofibroblast cells in young animals, suggesting that there is more intense fibrosis in this population. This finding may explain why young animals with bile duct obstruction experience more intense portal fibrosis that is similar to the pathology observed in the livers of newborns with biliary atresia.

Ocean acidification and hypoxic events are an increasing worldwide problem, but the synergetic effects of these factors are seldom explored. However, this synergetic occurrence of stressors is prevalent. The coastline of Chile not only suffers from coastal hypoxia but the cold, oxygen-poor waters in upwelling events are also supersaturated in CO2, a study site to explore the combined effect of ocean acidification and hypoxia. We experimentally evaluated the metabolic response of different invertebrate species (2 anthozoans, 9 molluscs, 4 crustaceans, 2 echinoderms) of the coastline of central Chile (33°30’S, 71°37’W) to hypoxia and ocean acidification within predicted levels and in a full factorial design. Organisms were exposed to 4 different treatments (ambient, low oxygen, high CO2, and the combination of low oxygen and high CO2) and metabolism was measured after 3 and 6 days. We show that the combination of hypoxia and increased pCO2 reduces the respiration significantly, compared to a single stressor. The evaluation of synergistic pressures, a more realistic scenario than single stressors, is crucial to evaluate the effect of future changes for coastal species and our results provide the first insight on what might happen in the next 100 years.