bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male hypogonadism: an extended classification based on a developmental, endocrine physiology‐based approach
Authors: Rey R. A. , Grinspon R. P. , Gottlieb S. , Pasqualini T. , Knoblovits P. , Aszpis S. , Pacenza N. , Stewart Usher J. , Bergadá I. , Campo S. M. 
Published: October 2012

SummaryNormal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin‐like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti‐Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic‐pituitary‐testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic‐pituitary‐testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic‐pituitary‐testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal‐onset or postnatal‐onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving the gonads and the hypothalamic‐pituitary axis.
Ventricular Fibrillation Induced by Spontaneous Hypothermia in a Patient with Early Repolarization Syndrome
Authors: FEDERMAN NICHOLAS J. , MECHULAN ALEXIS , KLEIN GEORGE J. , KRAHN ANDREW D. 
Published: October 2012

Hypothermia and Early Repolarization SyndromeIntroductionThe early repolarization (ER) pattern on ECG was originally described in the context of hypothermia.Case SummaryWe present the case of a 34‐year‐old male with cardiac arrest in the context of spontaneous hypothalamic mediated thermal dysregulation after intracranial hemorrhage. Ventricular fibrillation with a marked ER pattern recurred with therapeutic hypothermia. Spontaneous hypothermia due to hypothalamic dysregulation was observed to enhance the amplitude of the ER pattern and was contemporaneous with recurrent ventricular fibrillation during follow‐up.ConclusionsHypothermia is an important trigger of VF in the setting of early repolarization syndrome, and warrants assessment as an environmental trigger of spontaneous events. (J Cardiovasc Electrophysiol, Vol. 24, pp. 586–588, May 2013)
Immune‐Induced Expression of Lipocalin‐2 in Brain Endothelial Cells: Relationship with Interleukin‐6, Cyclooxygenase‐2 and the Febrile Response
Authors: Hamzic N. , Blomqvist A. , Nilsberth C. 
Published: October 2012

Interleukin (IL)‐6 is critical for the febrile response to peripheral immune challenge. However, the mechanism by which IL‐6 enables fever is still unknown. To characterise the IL‐6‐dependent fever generating pathway, we used microarray analysis to identify differentially expressed genes in the brain of lipopolysaccharide (LPS)‐treated IL‐6 wild‐type and knockout mice. Mice lacking IL‐6 displayed a two‐fold lower expression of the lipocalin‐2 gene (lcn2), and this difference was confirmed by real‐time reverse transcriptase‐polymerase chain reaction. Conversely, the induction of lipocalin‐2 protein was observed in brain vascular cells following i.p. administration of recombinant IL‐6, suggesting a direct relationship between IL‐6 and lipocalin‐2. Immunohistochemical analysis also revealed that LPS‐induced lipocalin‐2 is expressed by brain endothelial cells and is partly co‐localised with cyclooxygenase‐2 (Cox‐2), the rate‐limiting enzyme for the production of inflammatory induced prostaglandin E2 (PGE2), which is the key mediator of fever. The direct role of lipocalin‐2 in fever was examined in LPS‐challenged lipocalin‐2 knockout mice. In both male and female mice, normal fever responses were observed at near‐thermoneutral conditions (29–30 °C) but when recorded at normal room temperature (19–20 °C), the body temperature of lipocalin‐2 knockout female mice displayed an attenuated fever response compared to their wild‐type littermates. This difference was reflected in significantly attenuated mRNA expression of Cox‐2 in the brain of lipocalin‐2 knockout female mice, but not of male mice, following challenge with peripheral LPS. Our findings suggest that IL‐6 influences the expression of lipocalin‐2, which in turn may be involved in the control of the formation of Cox‐2, and hence central PGE2‐production. We have thus identified lipocalin‐2 as a new factor in the pathway of inflammatory IL‐6 signalling. However, the effect of lipocalin‐2 on fever is small, being sex‐dependent and ambient temperature‐specific, and thus lipocalin‐2 cannot be considered as a major mediator of the IL‐6‐dependent fever generating pathway.
MSX1 gene polymorphisms in non‐syndromic cleft lip and/or palate
Authors: Cardoso ML , Bezerra JF , Oliveira GHM , Soares CD , Oliveira SR , de Souza KSC , da Silva HPV , Silbiger VN , Luchessi AD , Fajardo CM , Hirata RDC , Almeida MG , Hirata MH , Rezende AA 
Published: October 2012

ObjectiveThe aim of this study was to investigate the contribution of 6 polymorphic variants of the MSX1 gene in non‐syndromic cleft lip and/or palate (NSCL/P).MethodsThree hundred and fifty‐eight individuals (158 NSCL/P cases and 200 controls) were genotyped by TaqMan allelic discrimination using predesigned SNP assays. Statistical analyses were conducted using the software spss 15.0 and the r statistical suite. Haplotype block structure and haplotype frequencies were determined using the Haploview. A P‐value of 0.05 and confidence interval of 95% were used for all of statistical tests.ResultsThe patients with non‐syndromic cleft lip and/or palate were characterized by similar distribution of MSX1 genotypes and allele in comparison to subjects without oral clefts (P > 0.05). Two haplotype blocks were constructed with polymorphisms of MSX1 gene and haplotypes formed showed a similar frequency in patients with and without oral clefts.ConclusionsThe present study provides no evidence that MSX1 polymorphisms (rs3775261, rs1042484, rs12532, rs6446693, rs4464513 and rs1907998) play a major role in NSCL/P.
Anesthetic implications of infants with mandibular hypoplasia treated with mandibular distraction osteogenesis
Authors: Frawley Geoff , Espenell Ainsley , Howe Peter , Shand Jocelyn , Heggie Andrew 
Published: October 2012

SummaryObjectivesTo document the incidence of difficult intubation following mandibular distraction osteogenesis (MDO) in children with severe mandibular hypoplasia.BackgroundSyndromes associated with significant mandibular hypoplasia, especially Pierre Robin sequence, provide a challenge in airway management both in and out of the operating room. Mandibular advancement using mandibular distraction osteogenesis devices has been used in infants in an attempt to reduce the incidence of acute life‐threatening airway obstruction. Whether MDO also reduces the incidence of difficult intubation has not been adequately described.MethodsA retrospective chart review of 51 infants with upper airway obstruction secondary to mandibular hypoplasia who required MDO between January 2002 and 2012. The primary outcome was the incidence of difficult or failed intubation. Secondary outcomes were the relationship between syndrome type and the incidence of difficult intubation.ResultsFifty‐one PRS infants were identified. Twenty‐eight patients had isolated PRS, six had syndromic PRS, seven had Treacher Collins syndrome, and 10 had another coexisting syndrome. Prior to mandibular distraction osteogenesis (MDO), the incidence of difficult intubation was 71%, with the highest incidence in patients with Treacher Collins syndrome (100%), sPRS syndrome (100%), and PRS (65%). Following MDO, the incidence of difficult intubation was 8.3%. The difference was statistically significant for all patients (Kruskal–Wallis rank test P = 0.0001) those with isolated PRS (P = 0.0001), syndromic PRS (P = 0.0023), and other syndromes (P = 0.0002), but not for Treacher Collins syndrome (P = 0.21). Three patients had pre existing tracheostomies.ConclusionsIn a select group of infants with severe upper airway obstruction who have failed nonsurgical airway interventions, mandibular distraction osteogenesis reduces the incidence of difficult mask ventilation and difficult intubation. We were not able to compare the improvement in airway management to a comparable group of PRS infants who did not undergo surgical intervention. The improvement in laryngeal view was most marked for infants with isolated PRS but no significant benefit was demonstrated in infants with TCS.
Calcium‐ and potassium‐permeable plasma membrane transporters are activated by copper in Arabidopsis root tips: linking copper transport with cytosolic hydroxyl radical production
Authors: RODRIGO‐MORENO ANA , ANDRÉS‐COLÁS NURIA , POSCHENRIEDER CHARLOTTE , GUNSÉ BENET , PEÑARRUBIA LOLA , SHABALA SERGEY 
Published: October 2012

ABSTRACTTransition metals such as copper can interact with ascorbate or hydrogen peroxide to form highly reactive hydroxyl radicals (OH•), with numerous implications to membrane transport activity and cell metabolism. So far, such interaction was described for extracellular (apoplastic) space but not cytosol. Here, a range of advanced electrophysiological and imaging techniques were applied to Arabidopsis thaliana plants differing in their copper‐transport activity: Col‐0, high‐affinity copper transporter COPT1‐overexpressing (C1OE) seedlings, and T‐DNA COPT1 insertion mutant (copt1). Low Cu concentrations (10 µm) stimulated a dose‐dependent Gd3+ and verapamil sensitive net Ca2+ influx in the root apex but not in mature zone. C1OE also showed a fivefold higher Cu‐induced K+ efflux at the root tip level compared with Col‐0, and a reduction in basal peroxide accumulation at the root tip after copper exposure. Copper caused membrane disruptions of the root apex in C1OE seedlings but not in copt1 plants; this damage was prevented by pretreatment with Gd3+. Our results suggest that copper transport into cytosol in root apex results in hydroxyl radical generation at the cytosolic side, with a consequent regulation of plasma membrane OH•‐sensitive Ca2+ and K+ transport systems.
Tetraploid Rangpur lime rootstock increases drought tolerance via enhanced constitutive root abscisic acid production
Authors: ALLARIO THIERRY , BRUMOS JAVIER , COLMENERO‐FLORES JOSE M. , IGLESIAS DOMINGO J. , PINA JOSE A. , NAVARRO LUIS , TALON MANUEL , OLLITRAULT PATRICK , MORILLON RAPHAËL 
Published: October 2012

ABSTRACTWhole‐genome duplication, or polyploidy, is common in many plant species and often leads to better adaptation to adverse environmental condition. However, little is known about the physiological and molecular determinants underlying adaptation. We examined the drought tolerance in diploid (2x) and autotetraploid (4x) clones of Rangpur lime (Citrus limonia) rootstocks grafted with 2x Valencia Delta sweet orange (Citrus sinensis) scions, named V/2xRL and V/4xRL, respectively. Physiological experiments to study root–shoot communication associated with gene expression studies in roots and leaves were performed. V/4xRL was much more tolerant to water deficit than V/2xRL. Gene expression analysis in leaves and roots showed that more genes related to the response to water stress were differentially expressed in V/2xRL than in V/4xRL. Prior to the stress, when comparing V/4xRL to V/2xRL, V/4xRL leaves had lower stomatal conductance and greater abscisic acid (ABA) content. In roots, ABA content was higher in V/4xRL and was associated to a greater expression of drought responsive genes, including CsNCED1, a pivotal regulatory gene of ABA biosynthesis. We conclude that tetraploidy modifies the expression of genes in Rangpur lime citrus roots to regulate long‐distance ABA signalling and adaptation to stress.
Vitamin D and overall mortality
Authors: Guerrieri‐Gonzaga Aliana , Gandini Sara 
Published: October 2012

SummaryVitamin D is a steroid molecule, mainly produced in the skin that regulates the expression of a large number of genes. Several meta‐analyses of epidemiological studies support the evidence that low vitamin D serum level, which is highly prevalent worldwide, could be a ‘new’ risk factor for many chronic diseases including cancer, and for all‐cause mortality. A meta‐analysis in healthy subjects suggested that current doses of vitamin D supplements could be associated with decrease in total mortality rates. However, these associations are insufficient to establish causality between vitamin D and all‐cause mortality. Furthermore, long‐term health effects of high doses of vitamin D, that is, prolonged supplementation and association with different baseline vitamin D levels, remain to be investigated. Several trials are ongoing but population‐based, placebo‐controlled randomized trials with total mortality as the main endpoint should be planned to confirm a real beneficial effect of vitamin D for non‐skeletal diseases and to prove causality.
Linear Atrophoderma of Moulin: A Distinct Entity?
Authors: de Golian Emily , Echols Kathryn , Pearl Henna , Davis Loretta 
Published: October 2012

AbstractLinear atrophoderma of Moulin (LAM) is a rare dermatologic disorder characterized by a hyperpigmented atrophoderma that consistently follows the lines of Blaschko. There are many clinical and histologic similarities between LAM, atrophoderma of Pasini and Pierini (APP), and morphea, and whether LAM represents part of a disease spectrum or its own distinct entity is debated. This case of a 16‐year‐old boy with LAM supports the hypothesis that LAM, APP, and morphea are a spectrum of disorders rather than unique entities. Although the patient's overall clinical picture supports a diagnosis of LAM with hyperpigmented, depressed lesions following the lines of Blaschko and perivascular lymphocytic infiltrate on biopsy, the bilateral presentation typical of APP, collagen entrapment of eccrine ducts typical of morphea, and changes in dermal collagen illustrate features spanning all three disorders, suggesting a relationship between these conditions that represents a spectrum of disease. Furthermore, a review of all reported cases of LAM in the literature suggests an evolving definition beyond what Moulin and colleagues originally described, including features related to those of APP and morphea.
White Epidermal Nevi at Birth in a Patient with Tuberous Sclerosis
Authors: Elam Capt. Amanda L. , McCleskey Maj. Patrick E. 
Published: October 2012

AbstractWe report a neonate who presented at birth with multiple, scattered, white macerated plaques. Punch biopsy confirmed epidermal nevi. At 3 months of age the patient presented with infantile spasms and, after full evaluation, was diagnosed with tuberous sclerosis complex (TSC). We suggest that physicians consider TSC in a neonate with epidermal nevi inconsistent with any described epidermal nevus syndrome.
Expression of Inhibin/Activin Subunits in the Equine Uteri during the Early Pregnancy
Authors: Zhang H , Nagaoka K , Imakawa K , Nambo Y , Watanabe G , Taya K , Weng Q 
Published: October 2012

ContentsThe establishment of equine pregnancy is a unique and long process during which a series of physical and possibly biochemical interactions are required between the conceptus and uterus. In this study, we investigated the expression pattern of inhibin/activin subunits in the uterus during early pregnancy. The uteri from four adult mares on cyclic day 13 or pregnancy day 25 were obtained. Immunohistochemical experiments suggested that inhibin/activin subunits were immunolocalized in the luminal and glandular epithelium on pregnancy day 25. In addition, the inhibin α and inhibin/activin βBsubunits were not detected, and inhibin/activin βAsubunit was detected, in the luminal and glandular epithelium on cyclic day 13. Real‐time polymerase chain reaction and Western blotting results for the inhibin/activin subunits suggested a significant increase in the expression of inhibin/activin subunit βBand a significant decrease in the expression of inhibin/activin subunit βAon pregnancy day 25 compared with those on cyclic day 13. Enzyme‐linked immunosorbent assays suggested a significant decrease in the concentration of activinAin endometrium extracts from cyclic day 13 to pregnancy day 25. These results suggest that inhibins or activins synthesized in the uterus, as endocrine factors and necessary nutriments, have different expression patterns and may play different, important roles during early embryonic development of the equine.
Post‐Islamism, the Failure of an Idea: Regards on Islam and Nationalism from Khomeini’s Death to the Arab Revolts
Authors: García Luz Gómez 
Published: October 2012

Abstract«Post‐Islamism» remains a controversial concept in Western academia. Both the definition itself and its applicability have led to an intellectual debate that may be partially deemed a failure. Such a failure relates not only to the difficulty implicit in establishing its theoretical boundaries (which has in turn led to an internal response within academia itself),1but also to the rather limited effect and repercussions that the notion itself has had in the Arab‐Islamic world.2Twenty years into the development of a post‐Islamist theoretical framework, the prevalence of post‐Islamism as a useful analytical tool in sociopolitical terms now faces the challenge of having to confront the 2011 Arab revolts. The revolts have challenged the theoretical underpinnings that served as a basis for the post‐Islamist discourse, which argued for the decline of Islamism as a valid political alternative. Post‐Islamist theoreticians had argued that Islamism would eventually be replaced by an individualistic experience of Islam based on the vindication of civil rights and the separation of the realms of political and religious legitimacy. The latest election results in North Africa show the strength and diversity of political Islam (under permanent questioning and re‐elaboration) as well as the appropriateness of the «post‐» categories of analysis («post‐Islamism, post‐modernity, post‐nationalism»).
Laminated carbonate deposits in Roman aqueducts: Origin, processes and implications
Authors: Sürmelihindi Gül , Passchier Cees W. , Spötl Christoph , Kessener Paul , Bestmann Michel , Jacob Dorrit E. , Baykan Orhan N. 
Published: October 2012

AbstractCarbonate deposits in Roman aqueducts of Patara and Aspendos (southern Turkey) were studied to analyse the nature of their regular layering. Optical microscopy and electron‐backscattered diffraction results show an alternation of dense, coarsely crystalline, translucent laminae composed of bundles and fans of elongate calcite crystals with their c‐axes parallel to the long axis, and porous, fine‐grained laminae with crystals at near‐random orientation. The δ18O and δ13C data show a strong cyclicity and anti‐correlation, whereby high and low δ18O values correspond to dense columnar and porous fine‐grained laminae, respectively. Geochemical analyses show similar cyclic changes in carbonate composition. Electron microprobe and laser ablation inductively coupled mass spectrometry analyses show that porous fine‐grained laminae are enriched in elements associated with detrital material (Fe, Mg, K, Al and Si), whereas the dense columnar laminae are nearly pure calcite. The gradient in major and trace‐element distribution, regular changes in crystal type and in oxygen and carbon‐isotope composition from porous fine‐grained to dense columnar laminae reflect changes in water chemistry, discharge, temperature and biological activity. Because of the strong bimodal cyclicity of the Mediterranean climate in southern Turkey, the observed laminae can be attributed to calcite deposition during the dry (porous fine‐grained) and wet season (dense columnar), respectively. This observation implies that, with proper geochemical and microstructural control, lamination in carbonate deposits in Roman aqueducts can be used for relative dating of aqueduct construction and maintenance and to obtain data on external factors that influenced the aqueducts, such as palaeoclimate and natural hazards. Carbonate deposits in Roman aqueducts show properties of both flowstone speleothems and riverine fresh water tufa. As many aqueducts of nearly identical channel geometry are present in different climate zones and with different source water characteristics, they can be used as natural experiment setups to test and improve existing models of how laminated fresh water carbonates record climate on time scales ranging from seasonal to millennial.
Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A
Authors: Marchand‐Pauvert Véronique , Aymard Claire , Giboin Louis‐Solal , Dominici Federica , Rossi Alessandro , Mazzocchio Riccardo 
Published: October 2012

Key points
Botulinum neurototoxin type A (BoNT‐A) is known to block central synapses after muscular injection due to retrograde transport in animal models.
BoNT‐A‐induced changes in the human CNS activity have been attributed so far to indirect mechanisms involving peripheral afferent inputs modified after muscular injection.
The question of a possible direct central action of BoNT‐A in humans was further addressed by investigating the modification of spinal recurrent inhibition in stroke patients after BoNT‐A muscular injection.
Recurrent inhibition from soleus motor axons to motoneurones supplying quadriceps was depressed after BoNT‐A injection in ankle plantarflexors.
BoNT‐A, through retrograde transport, affects spinal synaptic transmission in humans.
Abstract  The natural target of the botulinum neurototoxin type A (BoNT‐A) is the neuromuscular junction. When injected into a muscle, BoNT‐A is internalized by motoneurone terminals where it functions as an endopeptidase, cleaving protein components of the synaptic machinery responsible for vesicle docking and exocytosis. As a result, BoNT‐A induces a characteristic flaccid paralysis of the affected muscle. In animal models, BoNT‐A applied in the periphery can also influence central activity via retrograde transport and transcytosis. An analogous direct central effect in humans is still debated. The present study was designed to address whether BoNT‐A modifies the activity of the spinal recurrent inhibitory pathways, when injected at muscular level, in humans. To avoid methodological bias, the recurrent inhibition from an injected muscle (soleus) was investigated on an untreated muscle (quadriceps), and stimulation parameters (producing recurrent inhibition) were monitored on a third non‐injected muscle but innervated by the same nerve as the soleus (flexor digitorum brevis). The experiments were performed on 14 post‐stroke patients exhibiting spasticity in ankle plantarflexors, candidates for BoNT‐A. One month after BoNT‐A, the level of recurrent inhibition was depressed. It is suggested that the depression of recurrent inhibition was induced by BoNT‐A, injected peripherally, through axonal transport and blockade of the cholinergic synapse between motoneurone recurrent collaterals and Renshaw cells.