Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24 injection in the diagnosis of adrenal insufficiency

BACKGROUND: In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT. METHODS: Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l. RESULTS: There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficient cortisol response result after 60 minutes also had an insufficient result after 30 minutes. The cortisol value taken after 30 minutes did not add incremental diagnostic value in any of the cases under investigation compared with the 60 minutes' sample. CONCLUSIONS: Based on the findings of the present analysis the utility of a cortisol measurement 30 minutes after high dose ACTH injection was low and did not add incremental diagnostic value to a single measurement after 60 minutes.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations

PURPOSE A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

Antiseptic solutions modulate the paracrine-like activity of bone chips: differential impact of chlorhexidine and sodium hypochlorite

AIM: Chemical decontamination increases the availability of bone grafts; however, it is unclear whether antiseptic processing changes the biological activity of bone. MATERIALS AND METHODS: Bone chips were incubated with 4 different antiseptic solutions including (1) povidone-iodine (0.5%), (2) chlorhexidine diguluconate (0.2%), (3) hydrogen peroxide (1%) and (4) sodium hypochlorite (0.25%). After 10 minutes of incubation, changes in the capacity of the bone-conditioned medium to modulate gene expression of gingival fibroblasts was investigated. RESULTS: Conditioned medium obtained from freshly prepared bone chips increased the expression of TGF-β target genes interleukin 11 (IL11), proteoglycan4 (PRG4), NADPH oxidase 4 (NOX4), and decreased the expression of adrenomedullin (ADM), and pentraxin 3 (PTX3) in gingival fibroblasts. Incubation of bone chips with 0.2% chlorhexidine, followed by vigorously washing resulted in a bone-conditioned medium with even higher expression of IL11, PRG4, and NOX4. These findings were also found with a decrease in cell viability and an activation of apoptosis signaling. Chlorhexidine alone, at low concentrations, increased IL11, PRG4 and NOX4 expression, independent of the TGF-β receptor I kinase activity. In contrast, 0.25% sodium hypochlorite almost entirely abolished the activity of bone-conditioned medium, while the other two antiseptic solutions, 1% hydrogen peroxide and 0.5% povidone-iodine, had relatively no impact, respectively. CONCLUSION: These in vitro findings demonstrate that incubation of bone chips with chlorhexidine differentially affects the activity of the respective bone-conditioned medium compared to the other antiseptic solutions. The data further suggest that the main effects are caused by chlorhexidine remaining in the bone-conditioned medium after repeated washing of the bone chips. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. KEYWORDS: Autografts; TGF-β; antiseptic solution; bone; bone conditioned medium; bone supernatant; chlorhexidine; hydrogen peroxide; povidone-iodine; sodium hypochlorite

Bone Conditioned Medium: Preparation and Bioassay.

Autologous bone grafts are widely used in oral and maxillofacial surgery, orthopedics, and traumatology. Autologous bone grafts not only replace missing bone, they also support the complex process of bone regeneration. This favorable behavior of autografts is attributed to the three characteristics: osteoconductivity, osteogenicity, and osteoinductivity. However, there is another aspect: Bone grafts release a myriad of molecules, including growth factors, which can target mesenchymal cells involved in bone regeneration. The paracrine properties of bone grafts can be studied in vitro by the use of bone-conditioned medium (BCM). Here we present a protocol on how to prepare bone-conditioned medium from native pig cortical bone, and bone that underwent thermal processing or demineralization. Cells can be directly exposed to BCM or seeded onto biomaterials, such as collagen membranes, previously soaked with BCM. We give examples for in vitro bioassays with mesenchymal cells on the expression of TGF-β regulated genes. The presented protocols should encourage to further reveal the paracrine effects of bone grafts during bone regeneration and open a path for translational research in the broad field of reconstructive surgery.

Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.

Conditioned medium from fresh and demineralized bone enhances osteoclastogenesis in murine bone marrow cultures

OBJECTIVES Osteoclasts rapidly form on the surface of bone chips at augmentation sites. The underlying molecular mechanism, however, is unclear. Soluble factors released from bone chips in vitro have a robust impact on mesenchymal cell differentiation. Whether these soluble factors change the differentiation of hematopoietic cells into osteoclasts remains unknown. METHODS Osteoclastogenesis, the formation of tartrate-resistant acid phosphatase-positive multinucleated cells, was studied with murine bone marrow cultures exposed to RANKL and M-CSF, and conditioned medium from fresh (BCM) and demineralized bone matrix (DCM). Histochemical staining, gene and protein expression, as well as viability assays were performed. RESULTS This study shows that BCM had no impact on osteoclastogenesis. However, when BCM was heated to 85°C (BCMh), the number of tartrate-resistant acid phosphatase-positive multinucleated cells that developed in the presence of RANKL and M-CSF approximately doubled. In line with the histochemical observations, there was a trend that BCMh increased expression of osteoclast marker genes, in particular the transcription factor c-fos. The expression of c-fos was significantly reduced by the TGF-β receptor I antagonist SB431542. DCM significantly stimulated osteoclastogenesis, independent of thermal processing. CONCLUSIONS These data demonstrate that activated BCM by heat and DBM are able to stimulate osteoclastogenesis in vitro. These in vitro results support the notion that the resorption of autografts may be supported by as yet less defined paracrine mechanisms.

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Function and regulation of the Pem homeobox gene in vivo

Pem, a member of the PEPP homeobox family, is expressed in somatic cells in male and female reproductive tissues. In the adult murine testis, Pem is specifically expressed in Sertoli cells, where it is restricted to stages IV–VIII of the seminiferous epithelial cycle. To identify Pem's function in Sertoli cells, transgenic mice were generated that express Pem in Sertoli cells during all stages of the seminiferous epithelial cycle. This resulted in an increase in double-strand DNA breaks in preleptotene spermatocytes and single-strand DNA breaks in elongating spermatids. My results suggest that Pem regulates Sertoli-cell genes that encode secreted or cell-surface proteins that serve to control premeiotic DNA replication, DNA repair, and/or chromatin remodeling in the adjacent germ cells. Three additional transgenic mouse containing varying lengths of the Pem male-specific promoter (Pp) were generated to identify the sequences responsible for regulating Pem expression in the testis and epididymis. My analysis suggests that there are at least two regulatory regions in the Pem Pp. In the testis, region II directs androgen-dependent expression specifically in Sertoli cells whereas region I fine-tunes stage-specific expression by acting as a negative regulator. In the epididymis, region II confers androgen-dependent, developmentally-regulated expression in the caput whereas region I prevents inappropriate expression in the corpus. I also report the identification and characterization of two human PEPP family members related to Pem that I have named hPEPP1 and hPEPP2. The hPEPP1 and hPEPP2 homeodomains are more closely related to PEPP subfamily homeodomains than to any other homeodomain subfamily. Both genes are localized to the specific region of the human X chromosome that shares synteny with the region on the murine X chromosome containing three PEPP homeobox genes, Pem, Psx-1, and Psx-2. hPEPP1 and hPEPP2 mRNA expression is restricted to the testis but is aberrantly expressed in tumor cells of different origins, analogous to the expression pattern of Pem but not of Psx-1 or Psx-2. Unlike all known PEPP members, neither hPEPP1 nor hPEPP2 are expressed in placenta, which suggests that the regulation of the PEPP family has undergone significant alteration since the split between hominids and rodents. ^

XCO2 and XCH4 total column measurement during POLARSTERN cruise PS83 (ANT-XXIX/10), north-south gradient

A portable Fourier transform spectrometer (FTS), model EM27/SUN, was deployed onboard the research vessel Polarstern to measure the column-average dry air mole fractions of carbon dioxide (XCO2) and methane (XCH4) by means of direct sunlight absorption spectrometry. We report on technical developments as well as data calibration and reduction measures required to achieve the targeted accuracy of fractions of a percent in retrieved XCO2 and XCH4 while operating the instrument under field conditions onboard the moving platform during a 6-week cruise on the Atlantic from Cape Town (South Africa, 34° S, 18° E; 5 March 2014) to Bremerhaven (Germany, 54° N, 19° E; 14 April 2014). We demonstrate that our solar tracker typically achieved a tracking precision of better than 0.05° toward the center of the sun throughout the ship cruise which facilitates accurate XCO2 and XCH4 retrievals even under harsh ambient wind conditions. We define several quality filters that screen spectra, e.g., when the field of view was partially obstructed by ship structures or when the lines-of-sight crossed the ship exhaust plume. The measurements in clean oceanic air, can be used to characterize a spurious air-mass dependency. After the campaign, deployment of the spectrometer alongside the TCCON (Total Carbon Column Observing Network) instrument at Karlsruhe, Germany, allowed for determining a calibration factor that makes the entire campaign record traceable to World Meteorological Organization (WMO) standards. Comparisons to observations of the GOSAT satellite and concentration fields modeled by the European Centre for Medium-Range Weather Forecasts (ECMWF) Copernicus Atmosphere Monitoring Service (CAMS) demonstrate that the observational setup is well suited to provide validation opportunities above the ocean and along interhemispheric transects.

La herencia de una guerra perdida : La memoria multidireccional en Los rojos de ultramar de Jordi Soler

Los rojos de Ultramar (2004) del mexicano Jordi Soler es una novela que sondea la memoria de la guerra civil española y la dictadura franquista, indagando en sus consecuencias a nivel individual y colectivo a partir de la experiencia de los exiliados. El narrador de la novela, trasunto del propio autor, es nieto de un republicano exiliado que se propone investigar a fondo la accidentada biografía de su abuelo. La obra comparte muchos rasgos formales y temáticos con varias novelas de la memoria recientes de autores españoles, tales como Soldados de Salamina de Javier Cercas y Mala gente que camina de Benjamín Prado, en las que la investigación histórica de un narrador-personaje funciona como motor narrativo. Sin embargo, la obra aporta al debate español en torno a la memoria histórica una novedosa visión desde fuera de las fronteras nacionales. Por medio de la voz del narrador, portador de dos culturas (la mexicana y la catalana) y dos lenguas (el castellano y el catalán), la novela de Soler proporciona una perspectiva transnacional y multicultural, que se aproxima a lo que Michael Rothberg ha denominado memoria multidireccional. El objetivo de este artículo es, por un lado, identificar y discutir las características narrativas que Los rojos de ultramar comparte con las novelas-investigación de autores españoles y, por otro lado, profundizar en la aportación particular de esta obra, que reivindica la hibridez cultural y utiliza la memoria de una comunidad cultural específica (la de los republicanos exiliados) de modo ejemplar para crear solidaridad entre diferentes grupos culturales.

Jordi Arbonès en Argentina : Un traductor del inglés al catalán

Desde su radicación en Argentina en 1956, Jordi Arbonès, nacido en Cataluña, comienza a traducir obras del inglés al catalán. A medida que avanza en el conocimiento de la lengua y cultura de ambas sociedades, recibe pedidos de importantes editoriales para publicar en catalán las obras de autores reconocidos universalmente, permitiendo así la introducción de los mismos en el ámbito catalán, especialmente en el posfranquismo. A su muerte en 2001, tiene unas 150 obras traducidas. En base a su legado, se crea la 'Càtedra Jordi Arbonès' en la Facultat de Traducció i d'Interpretació de la Universitat Autònoma de Barcelona

La herencia de una guerra perdida : La memoria multidireccional en Los rojos de ultramar de Jordi Soler

Los rojos de Ultramar (2004) del mexicano Jordi Soler es una novela que sondea la memoria de la guerra civil española y la dictadura franquista, indagando en sus consecuencias a nivel individual y colectivo a partir de la experiencia de los exiliados. El narrador de la novela, trasunto del propio autor, es nieto de un republicano exiliado que se propone investigar a fondo la accidentada biografía de su abuelo. La obra comparte muchos rasgos formales y temáticos con varias novelas de la memoria recientes de autores españoles, tales como Soldados de Salamina de Javier Cercas y Mala gente que camina de Benjamín Prado, en las que la investigación histórica de un narrador-personaje funciona como motor narrativo. Sin embargo, la obra aporta al debate español en torno a la memoria histórica una novedosa visión desde fuera de las fronteras nacionales. Por medio de la voz del narrador, portador de dos culturas (la mexicana y la catalana) y dos lenguas (el castellano y el catalán), la novela de Soler proporciona una perspectiva transnacional y multicultural, que se aproxima a lo que Michael Rothberg ha denominado memoria multidireccional. El objetivo de este artículo es, por un lado, identificar y discutir las características narrativas que Los rojos de ultramar comparte con las novelas-investigación de autores españoles y, por otro lado, profundizar en la aportación particular de esta obra, que reivindica la hibridez cultural y utiliza la memoria de una comunidad cultural específica (la de los republicanos exiliados) de modo ejemplar para crear solidaridad entre diferentes grupos culturales.

La herencia de una guerra perdida : La memoria multidireccional en Los rojos de ultramar de Jordi Soler

Los rojos de Ultramar (2004) del mexicano Jordi Soler es una novela que sondea la memoria de la guerra civil española y la dictadura franquista, indagando en sus consecuencias a nivel individual y colectivo a partir de la experiencia de los exiliados. El narrador de la novela, trasunto del propio autor, es nieto de un republicano exiliado que se propone investigar a fondo la accidentada biografía de su abuelo. La obra comparte muchos rasgos formales y temáticos con varias novelas de la memoria recientes de autores españoles, tales como Soldados de Salamina de Javier Cercas y Mala gente que camina de Benjamín Prado, en las que la investigación histórica de un narrador-personaje funciona como motor narrativo. Sin embargo, la obra aporta al debate español en torno a la memoria histórica una novedosa visión desde fuera de las fronteras nacionales. Por medio de la voz del narrador, portador de dos culturas (la mexicana y la catalana) y dos lenguas (el castellano y el catalán), la novela de Soler proporciona una perspectiva transnacional y multicultural, que se aproxima a lo que Michael Rothberg ha denominado memoria multidireccional. El objetivo de este artículo es, por un lado, identificar y discutir las características narrativas que Los rojos de ultramar comparte con las novelas-investigación de autores españoles y, por otro lado, profundizar en la aportación particular de esta obra, que reivindica la hibridez cultural y utiliza la memoria de una comunidad cultural específica (la de los republicanos exiliados) de modo ejemplar para crear solidaridad entre diferentes grupos culturales.

Jordi Arbonès en Argentina : Un traductor del inglés al catalán

Desde su radicación en Argentina en 1956, Jordi Arbonès, nacido en Cataluña, comienza a traducir obras del inglés al catalán. A medida que avanza en el conocimiento de la lengua y cultura de ambas sociedades, recibe pedidos de importantes editoriales para publicar en catalán las obras de autores reconocidos universalmente, permitiendo así la introducción de los mismos en el ámbito catalán, especialmente en el posfranquismo. A su muerte en 2001, tiene unas 150 obras traducidas. En base a su legado, se crea la 'Càtedra Jordi Arbonès' en la Facultat de Traducció i d'Interpretació de la Universitat Autònoma de Barcelona