Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach.

OBJECTIVE: To determine the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders (25-35 follicles with a diameter of ≥12 mm on day of triggering) who received a gonadotropin-releasing hormone (GnRH) agonist to trigger final follicular maturation. METHODS: We used individual data from women who participated in four different clinical trials and were high responders to ovarian stimulation in a GnRH antagonist protocol in this retrospective combined analysis. All women were evaluated for signs and symptoms of OHSS using identical criteria based on Golan's system (1989). RESULTS: High responders (n = 77) were of different ethnicities. There were no differences in baseline characteristics between women with or without signs and symptoms of OHSS. Mean ± standard deviation baseline data were: age, 32.3 ± 3.5 years; anti-Müllerian hormone, 42.4 ± 20.7 pmol/L; antral follicle count, 21.5 ± 9.2. Before triggering, duration of stimulation was 9.5 ± 1.6 days and the mean number of follicles with a diameter of ≥12 mm and ≥17 mm was 26.5 ± 4.4 and 8.8 ± 4.7, respectively. Mean serum estradiol (17,159 pmol/l) and progesterone (5.1 nmol/l) levels were high at 36 h after triggering. Overall, 17/77 high responders (22%) developed signs and symptoms of mild OHSS which lasted 6-21 days. The most frequently prescribed medication was cabergoline to prevent worsening of OHSS. No severe OHSS occurred and no OHSS cases were reported as serious adverse events. CONCLUSIONS: High responders receiving GnRH agonist for triggering should be informed that they may experience signs and symptoms of mild OHSS.

Certification of protein biomarker standards using element MS and generic standards: Application to human cytokines.

The availability of protein standards and methods for their characterization, quantification, and purity assessment are currently a bottleneck in absolute quantitative proteomics. In this work, we introduce an absolute quantitative analytical strategy based on ICP-MS sulfur detection that uses sulfate as generic standard to quantify and certify the mass purity of protein standards. The methodology combines capillary chromatographic separation with parallel detection with ICP-MS and ESI-MS to determine proteoforms concentration and identity, respectively. The workability of the methodology was demonstrated using recombinant human cytokine standards IP-10 and Flt3L (2 batches), which are relevant biomarkers for carcinoma or inflammatory diseases. Every key factor (transport efficiency, column recovery, signal stability and internal standard suitability) was taken into account and certified BSA standard was used as quality control for validation purposes. Protein quantification values and resulting mass purity certification of IP-10 and one batch of Flt3L were very high (100 and 86%, respectively). Lower mass purity obtained for another batch of Flt3L (<70%) concurred with the finding of significant proteoforms resulted from oxidation processes as observed by parallel ESI-MS.

Frailty as a predictor of clinical problems and events that require elderly patients with heart failure to use health resources.

BACKGROUND: The clinical management of elderly patients with heart failure (HF) is not firmly established. Decision-making should be individualized depending on the biological deterioration of each patient, from aggressive management to a palliative approach. Frailty can serve as the basis for this comprehensive individualized management. Our objective was to evaluate the importance of the main clinical problems, as well as the events that required the use of health resources, based the degree of frailty, in elderly patients with HF. METHODS AND RESULTS: Retrospective observational cohort study. Frailty was defined according to the deficit accumulation construct. A total of 546 patients hospitalized for acute HF were included. The median age (Q1-Q3) was 82 (78-86) years. A total of 454 patients (83%) showed some degree of frailty: 221 (48.7%) mild, 207 (45.6%) moderate and 26 (5.7%) advanced. There was a significant tendency towards polypharmacy from no to severe frailty. Hospital events were recorded for 4 (1-6) patients with mild frailty, 4 (2-6) patients with moderate frailty and 2 ((1-4) patients with advanced frailty (p = 0.045). A total of 204 patients (37.4%) died during follow-up. The median time to death was 11.4 (4-16.8), 6.7 (3.3-11.6), 6.5 (3.4-12.2) and 4.1 (0.8-7.7) months for patients with no, mild, moderate, or advanced frailty, respectively (p = 0.006). CONCLUSIONS: Frailty due to deficit accumulation is a good predictor of clinical problems and events that require the use of health resources; therefore, it can serve as a basis for the management of HF in the elderly.

[Models of public care for the population with acquired brain injury in Spain: a study of the situation by Spanish autonomous communities]. / Modelos de atención pública a la población con daño cerebral adquirido en España: un estudio de la situación por comunidades autónomas.

INTRODUCTION: Rehabilitation after Acquired Brain Injury (ABI) is a dynamic, progressive process aimed at functional improvement of the affected person and their family. There is an international consensus on how the model that guides this process should be; however, in our country there are numerous territorial discrepancies regarding its application. Therefore, the objective of this work is to analyze and update the knowledge about the practices developed in the field of rehabilitation and the regulations available in each autonomous community. SUBJECTS AND METHODS: 62 participants (71.7% women), including both direct care professionals and public administration positions from the 17 Spanish Autonomous Communities and the autonomous cities of Ceuta and Melilla. A questionnaire composed of 31 questions on the functioning of rehabilitation throughout the three phases of care that often follow ABI was developed. This questionnaire was applied to these professionals in each of the Autonomous Communities, through semi-structured interviews. RESULTS: The results show the great territorial inequality existing in the functioning of rehabilitation during the recovery process of a person with ABI and the significant deficiencies of specific resources, specialized professionals such as neuropsychologists and necessary aspects such as socio-sanitary coordination. CONCLUSIONS: It is necessary to develop state regulations that guarantee the minimum basic aspects of the rehabilitation process in the DCA, in its different phases and in all the Autonomous Communities.

TITLE: Modelos de atención pública a la población con daño cerebral adquirido en España: un estudio de la situación por comunidades autónomas.Introducción. La rehabilitación tras el daño cerebral adquirido (DCA) es un proceso dinámico, progresivo y orientado a la mejora funcional de la persona afectada y de su núcleo familiar. Existe un consenso internacional sobre cómo debe ser el modelo que guíe dicho proceso; sin embargo, en nuestro país, se producen numerosas discrepancias territoriales en lo que respecta a su aplicación. Por ello, el objetivo del presente trabajo es analizar y actualizar el conocimiento sobre las prácticas desarrolladas en materia de rehabilitación y la normativa disponible en cada comunidad autónoma. Sujetos y métodos. Los participantes fueron 62 personas (71,7% mujeres), entre las cuales se encontraban tanto profesionales de atención directa como cargos de la administración pública de las 17 comunidades autónomas españolas y de las ciudades autónomas de Ceuta y Melilla. Se elaboró un cuestionario compuesto de 31 preguntas sobre el funcionamiento de la rehabilitación a lo largo de las tres fases asistenciales que suceden al DCA y que fue respondido por dichos profesionales en cada una de las comunidades autónomas a través de entrevistas semiestructuradas. La información obtenida se sintetizó por medio de análisis descriptivos. Resultados. Los resultados ponen de manifiesto la gran desigualdad territorial existente en el funcionamiento de la rehabilitación durante el proceso de recuperación tras un DCA y las carencias significativas de recursos específicos, profesionales especializados, como los neuropsicólogos, y aspectos necesarios, como la coordinación sociosanitaria. Conclusiones. Resulta necesario elaborar una normativa estatal que garantice los aspectos básicos mínimos sobre el proceso rehabilitador en el DCA, en sus distintas fases y en todas las comunidades autónomas.

Modelos de atención pública a la población con daño cerebral adquirido en España: un estudio de la situación por comunidades autónomas / Models of public care for the population with acquired brain injury in Spain: a study of the situation by Spanish autonomous communities

Introducción: La rehabilitación tras el daño cerebral adquirido (DCA) es un proceso dinámico, progresivo y orientado a la mejora funcional de la persona afectada y de su núcleo familiar. Existe un consenso internacional sobre cómo debe ser el modelo que guíe dicho proceso; sin embargo, en nuestro país, se producen numerosas discrepancias territoriales en lo que respecta a su aplicación. Por ello, el objetivo del presente trabajo es analizar y actualizar el conocimiento sobre las prácticas desarrolladas en materia de rehabilitación y la normativa disponible en cada comunidad autónoma. Sujetos y métodos: Los participantes fueron 62 personas (71,7% mujeres), entre las cuales se encontraban tanto profesionales de atención directa como cargos de la administración pública de las 17 comunidades autónomas españolas y de las ciudades autónomas de Ceuta y Melilla. Se elaboró un cuestionario compuesto de 31 preguntas sobre el funcionamiento de la rehabilitación a lo largo de las tres fases asistenciales que suceden al DCA y que fue respondido por dichos profesionales en cada una de las comunidades autónomas a través de entrevistas semiestructuradas. La información obtenida se sintetizó por medio de análisis descriptivos. Resultados: Los resultados ponen de manifiesto la gran desigualdad territorial existente en el funcionamiento de la rehabilitación durante el proceso de recuperación tras un DCA y las carencias significativas de recursos específicos, profesionales especializados, como los neuropsicólogos, y aspectos necesarios, como la coordinación sociosanitaria. Conclusiones: Resulta necesario elaborar una normativa estatal que garantice los aspectos básicos mínimos sobre el proceso rehabilitador en el DCA, en sus distintas fases y en todas las comunidades autónomas.(AU)

Introduction: Rehabilitation after Acquired Brain Injury (ABI) is a dynamic, progressive process aimed at functional improvement of the affected person and their family. There is an international consensus on how the model that guides this process should be; however, in our country there are numerous territorial discrepancies regarding its application. Therefore, the objective of this work is to analyze and update the knowledge about the practices developed in the field of rehabilitation and the regulations available in each autonomous community. Subjects and methods: 62 participants (71.7% women), including both direct care professionals and public administration positions from the 17 Spanish Autonomous Communities and the autonomous cities of Ceuta and Melilla. A questionnaire composed of 31 questions on the functioning of rehabilitation throughout the three phases of care that often follow ABI was developed. This questionnaire was applied to these professionals in each of the Autonomous Communities, through semi-structured interviews. Results: The results show the great territorial inequality existing in the functioning of rehabilitation during the recovery process of a person with ABI and the significant deficiencies of specific resources, specialized professionals such as neuropsychologists and necessary aspects such as socio-sanitary coordination.Conclusions: It is necessary to develop state regulations that guarantee the minimum basic aspects of the rehabilitation process in the DCA, in its different phases and in all the Autonomous Communities.(AU)

Early prediction of developing spontaneous activity in cultured neuronal networks.

Synchronization and bursting activity are intrinsic electrophysiological properties of in vivo and in vitro neural networks. During early development, cortical cultures exhibit a wide repertoire of synchronous bursting dynamics whose characterization may help to understand the parameters governing the transition from immature to mature networks. Here we used machine learning techniques to characterize and predict the developing spontaneous activity in mouse cortical neurons on microelectrode arrays (MEAs) during the first three weeks in vitro. Network activity at three stages of early development was defined by 18 electrophysiological features of spikes, bursts, synchrony, and connectivity. The variability of neuronal network activity during early development was investigated by applying k-means and self-organizing map (SOM) clustering analysis to features of bursts and synchrony. These electrophysiological features were predicted at the third week in vitro with high accuracy from those at earlier times using three machine learning models: Multivariate Adaptive Regression Splines, Support Vector Machines, and Random Forest. Our results indicate that initial patterns of electrical activity during the first week in vitro may already predetermine the final development of the neuronal network activity. The methodological approach used here may be applied to explore the biological mechanisms underlying the complex dynamics of spontaneous activity in developing neuronal cultures.

Prorocentroic Acid, a Neuroactive Super-Carbon-Chain Compound from the Dinoflagellate Prorocentrum hoffmannianum.

Prorocentroic acid (PA) was isolated from the dinoflagellate Prorocentrum hoffmannianum. Relative configurations for its 35 asymmetric centers were determined by analysis of NMR data including heteronuclear couplings and quantum mechanical calculations. PA was tested by using murine cortical neurons grown on microelectrode arrays. Long-term exposure to subtoxic concentrations induced a significant reorganization of neuronal signaling, mainly by changes in the bursting activity. The observed effects could be due to the activation of a plasticity process.

Does the pectoralis minor length influence acromiohumeral distance, shoulder pain-function, and range of movement?

OBJECTIVE: To determine the association between pectoralis minor length (PML) and the acromiohumeral distance (AHD) in the symptomatic (S) and the asymptomatic (A) shoulder of subjects with chronic shoulder pain, and in shoulder free of pain controls (C). Furthermore, to analyze the relationship between PML and shoulder pain-function and range of movement (ROM) free of pain. DESIGN: A cross sectional study. SETTING: Primary care centres. PARTICIPANTS: A sample of fifty-four participants with chronic shoulder pain in their dominant arm was recruited, as well as fifty-four participants with shoulder free of pain. MAIN OUTCOME MEASURES: PML test and AHD measured by ultrasound. RESULTS: There was a non statistical significant correlation between PML and AHD for all the groups at both 0° (S = 0.03, p = 0.29; A = 0.06, p = 0.66; C = -0.17, p = 0.29) and 60° (S = -0.10, p = 0.84; A = -0.18, p = 0.19; C = -0.03, p = 0.84) of shoulder elevation. Likewise, there was a non statistical significant correlation between PML and shoulder pain-function (0.09, p = 0.52), and ROM (-0.13, p = 0.35). CONCLUSIONS: PML is poorly associated with AHD, as well as with shoulder pain and mobility, in people with chronic shoulder pain. Other biomechanics alterations, as well as the presence of central/peripheral sensitization should be considered.

Veratridine-sensitive Na+ channels regulate human sperm fertilization capacity.

AIMS: The sperm plasma membrane contains specific ion channels and transporters that initiate changes in Ca2+, Na+, K+ and H+ ions in the sperm cytoplasm. Ion channels are key regulators of the sperm membrane potential, cytoplasmic Ca2+ and intracellular pH (pHi), which leads to regulate motility, capacitation, acrosome reaction and other physiological processes crucial for successful fertilization. Expression of epithelial sodium channels (ENaC) and voltage-gated sodium channels (Nav) in human spermatozoa has been reported, but the role of Na+ fluxes sodium channels in the regulation of sperm cell function remains poorly understood. In this context, we aimed to analyze the physiological role of Nav channels in human sperm. MAIN METHODS: Motility and hyperactivation analysis was conducted by CASA analysis. Flow cytometry and spectrophotometry approaches were carried out to measure Capacitation, Acrosome reaction, immunohistochemistry for Tyr-residues phosporylation, [Ca2+]i levels and membrane potential. KEY FINDINGS: Functional studies showed that veratridine, a voltage-gated sodium channel activator, increased sperm progressive motility without producing hyperactivation while the Nav antagonist lidocaine did induce hyperactivated motility. Veratridine increased protein tyrosine phosphorylation, an event occurring during capacitation, and its effects were inhibited in the presence of lidocaine and tetrodotoxin. Veratridine had no effect on the acrosome reaction by itself, but was able to block the progesterone-induced acrosome reaction. Moreover, veratridine caused a membrane depolarization and modified the effect of progesterone on [Ca2+]i and sperm membrane potential. SIGNIFICANCE: Our results suggest that veratridine-sensitive Nav channels are involved on human sperm fertility acquisition regulating motility, capacitation and the progesterone-induced acrosome reaction in human sperm.

Is coracohumeral distance associated with pain-function, and shoulder range of movement, in chronic anterior shoulder pain?

BACKGROUND: The aim of this study was twofold: (i) to assess the intrarater reliability of coracohumeral distance; (ii) to investigate the level of association between coracohumeral distance measured by ultrasonography, and pain-disability and shoulder range of movement, in patients suffering from chronic anterior shoulder pain. METHODS: An observational, cross sectional study was carried out. A convenience sample comprised of 87 patients with chronic anterior shoulder pain was assessed from 3 primary care centres. Main outcomes as pain and function were measured through the shoulder pain and disability index. Furthermore, shoulder range of movement-free of pain in shoulder elevation, as well as coracohumeral distance at both 0 and 60 degrees, were collected. RESULTS: Absence of any correlation was found between coracohumeral distance and shoulder pain and disability index at both 0 and 60 degrees of shoulder elevation. Furthermore, absence of any correlation was found between coracohumeral distance measurements and active shoulder range of movement -free of pain. CONCLUSIONS: There was poor association between coracohumeral distance and shoulder pain and function, as well as with shoulder range of movement, in patients with chronic anterior shoulder pain. Hence, clinicians should consider, not only increasing this space, but also other possibilities in their therapies, when patients with anterior shoulder pain are treated. TRIAL REGISTRATION: ACTRN12614000144617 . Registered: 1st March 2014.

Emotional well-being amongst female inmates in prisons: the relevance of their addictive history and their country of origin.

OBJECTIVE: To know more about the emotional well-being of women held in prisons in Spain by analyzing the state of mental health they present and investigating the factors that affect them. MATERIAL AND METHODS: A sample of 434 inmates in Spanish penitentiary centers was studied. An ad hoc designed questionnaire was used and a logistic regression analysis was conducted to determine the variables and to what extent they influence emotional well-being. RESULTS: The existence of a statistically significant relationship between the well-being stages and the origin variables (region of origin of the women) and the history of substance addiction were confirmed. No significant relationship has been found for well-being levels from other variables (maternity, social or family support, gender violence or having or not having a partner). CONCLUSIONS: Having a problematic history of drug use negatively affects the levels of emotional well-being of women detained in prisons. The low levels of substance use in women of Latin American origin is related to their more positive levels of emotional well-being.

Increased Expression of Aquaporin 9 in Trophoblast From Gestational Diabetic Patients.

Gestational diabetes mellitus is the most frequent pathophysiological alteration in pregnancy, increasing the incidence of complications in both mother and fetus. The macrosomia that occurs in these fetuses may be related with some changes in nutrient transport mechanism in placenta. The presence of aquaporin 9, an aquaglyceroporin, has previously been demonstrated in placenta. We raised the question whether aquaporin 9 expression may be upregulated in placenta from gestational diabetes, thus providing a faster transport of glycerol and water through placenta. We studied 21 placentas (13 controls and 8 gestational diabetes) from cesarean delivery at term. The expression of aquaporin 9 was analyzed by quantitative PCR, immunoblot, and immunohistochemistry. The median values from quantitative PCR were compared by nonparametric tests for independent samples (Mann-Whitney U-test). We have found that trophoblast from gestational diabetes express higher amount of aquaporin 9, which was found statistically significant (p<0.05). The increase in aquaporin 9 expression was confirmed by immunoblot, and localization in the syncytiotrophoblast was checked by immunohistochemistry. The increase in aquaporin 9 expression in placenta from gestational diabetes may contribute to the higher transport rate in this pathology of pregnancy.

Insulin and Leptin Signaling in Placenta from Gestational Diabetic Subjects.

Insulin and leptin receptors are known to share signaling pathways, such as JAK2/STAT-3 (Janus kinase2/signal transduction and activator of transcription3), MAPK (Mitogen activated protein kinase), and PI3K (phosphoinositide 3-kinase). Both positive and negative cross-talk have been previously found in different cellular systems. Gestational diabetes (GDM) is a pathophysiological state with high circulating levels of both insulin and leptin. We have previously found that these 3 signaling pathways are activated in placenta from GDM patients to promote translation, involving the activation of leptin receptor. Now, we have tested the hypothesis that both leptin and insulin receptors might contribute to this activation in a positive way that may become negative when the system is overactivated. We studied the activation of leptin and insulin receptors in placenta from GDM and healthy pregnancies. We have also performed in vitro studies with insulin and leptin stimulation of trophoblast explants from healthy placenta. We have found that both leptin and insulin receptors are activated in placenta from GDM. In vitro stimulation of trophoblast explants with both leptin and insulin at submaximal doses (0.1 nM) potentiated the activation of signaling, whereas preincubation with maximal concentrations of insulin (10 nM) and further stimulation with leptin showed negative effect. Trophoblastic explants from GDM placenta, which presented high signaling levels, had a negative signaling effect when further incubated in vitro with leptin. In conclusion, insulin and leptin receptors have positive effects on signaling, contributing to high signaling levels in GDM placenta, but insulin and leptin have negative effects upon overstimulation.

Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells.

STUDY QUESTION: Are neurokinin B (NKB), NK3 receptor (NK3R), kisspeptin (KISS1) and kisspeptin receptor (KISS1R) expressed in human ovarian granulosa cells? SUMMARY ANSWER: The NKB/NK3R and kisspeptin/KISS1R systems are co-expressed and functionally active in ovarian granulosa cells. WHAT IS KNOWN ALREADY: The NKB/NK3R and KISS1/KISS1R systems are essential for reproduction. In addition to their well-recognized role in hypothalamic neurons, these peptide systems may contribute to the control of fertility by acting directly on the gonads, but such a direct gonadal role remains largely unknown. STUDY DESIGN, SIZE, DURATION: This study analyzed matched mural granulosa cells (MGCs) and cumulus cells (CCs) collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: The samples were provided by 56 oocyte donor women undergoing ovarian stimulation treatment. Follicular fluid samples containing MGCs and cumulus-oocyte complexes were collected after transvaginal ultrasound-guided oocyte retrieval. RT-PCR, quantitative real-time PCR, immunocytochemistry and western blot were used to investigate the pattern of expression of the NKB/NK3R and KISS/KISS1R systems in MGCs and CCs. Intracellular free Ca(2+) levels, [Ca(2+)]i, in MGCs after exposure to NKB or KISS1, in the presence or not of tachykinin receptor antagonists, were also measured. MAIN OUTCOME AND THE ROLE OF CHANCE: NKB/NK3R and KISS1/KISS1R systems were expressed, at the mRNA and protein levels, in MGCs and CCs, with significantly higher expression in CCs. Kisspeptin increased the [Ca(2+)]i in the cytosol of human MGCs while exposure to NKB failed to induce any change in [Ca(2+)]i. However, the [Ca(2+)]i response to kisspeptin was reduced in the presence of NKB. The inhibitory effect of NKB was only partially mimicked by the NK3R agonist, senktide and marginally suppressed by the NK3R-selective antagonist SB 222200. Yet, a cocktail of antagonists selective for the NK1, NK2 and NK3 receptors blocked the effect of NKB. LIMITATIONS, REASONS FOR CAUTION: The granulosa and cumulus cells were obtained from oocyte donors undergoing ovarian stimulation, which in comparison with natural cycles, may have affected gene and protein expression in granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS: Our data demonstrate that, in addition to their indispensable effects at the central nervous system, the NKB/NK3R and kisspeptin/KISS1R systems are co-expressed and are functionally active in non-neuronal reproductive cells of the female gonads, the ovarian granulosa cells. STUDY FUNDING/ COMPETING INTERESTS: This work was supported by grants from Ministerio de Economía y Competitividad (CTQ2011-25564 and BFI2011-25021) and Junta de Andalucía (P08-CVI-04185), Spain. J.G.-O., F.M.P., M.F.-S., N.P., A.C.-R., T.A.A., M.H., M.R., M.T.-S. and L.C. have nothing to declare.

Belizentrin, a highly bioactive macrocycle from the dinoflagellate Prorocentrum belizeanum.

Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.

Camouflage therapy workshop for pediatric dermatology patients: a review of 6 cases.

Certain skin conditions, such as vitiligo, acne, vascular malformations, and surgical scars, can impair the quality of life of pediatric patients, especially adolescents-even to the point of hindering psychosocial development. We review the cases of 6 patients with discoloration or scarring, predominantly of the face, who attended our cosmetic camouflage workshops from January through December 2012. The quality-of-life impact of their skin disorder was assessed before and after workshop attendance. Cosmetic camouflage is an easily replicated, cheap, and noninvasive adjunctive treatment of great potential value in managing skin conditions that impair the physical and emotional well-being of pediatric patients.

Impact of assisted reproduction treatments on Spanish newborns: report of 14,119 pregnancies.

PURPOSE: To investigate neonatal malformation, prematurity, and stillbirth in singleton and multiple pregnancies derived from different Assisted Reproductive Techniques (ART). METHODS: In this prospective cohort study data were collected, from private and public Spanish IVF units, during the years 2008 and 2009. During this period, 8,682 pregnancies were analysed from the initial 14,119 pregnancies reported. Pregnancies included in the study derived from IUI (n = 1,065), IVF (n = 838), ICSI (n = 5,080), FET (n = 1,404) and PGD (n = 295). This first analysis focuses primarily on neonatal malformation, prematurity, and stillbirth both in singleton and multiple pregnancies derived from different ART. Malformations were classified according to the WHO ICD 10 code. RESULTS: Malformations were found in 0.83 % of our newborns. No differences in malformations were observed between singletons or multiples independently of the ART used. There was a significant difference in prematurity rate among singletons depending on treatment but this association was not observed in multiple pregnancies. Stillbirth was significantly lower in singleton (0.72 %) than in multiple pregnancies (1.82 %). CONCLUSIONS: The percentage of malformations observed in ART newborns was similar to the rate observed in the normally-conceived Spanish population. Multiplicity seems to be the most important factor associated with an increased incidence of newborn complications such as prematurity or stillbirth.

Surgical treatment of giant anal condyloma in HIV patients: unanswered questions.

We are writing to comment on the article by Uribe et al., "Management on giant anal condyloma by wide local excision and anoplasty". [1] Anogenital warts are among the most common sexually transmitted diseases seen in surgical practice, they are found in up to 1.7% of the general population, but in HIV population, they range from 3 to 24.9%. It is important to realise that 78% of patients with external anogenital warts have internal lesions as well although they are unlikely to be proximal to the dentate line. [2] This article is protected by copyright. All rights reserved.

Characterization of the kisspeptin system in human spermatozoa.

Kisspeptin, the product of the KISS1 gene, plays an essential role in the regulation of spermatogenesis acting primarily at the hypothalamic level of the gonadotropic axis. However, the presence of kisspeptin and its canonical receptor, KISS1R, in spermatozoa has not been explored nor the direct effects of kisspeptin on sperm function have been studied so far. In the present study, we analysed the expression of kisspeptin and its receptor in sperm cells by western blot and immunocytochemistry assays and evaluated the effects of exposure to kisspeptin on sperm intracellular Ca(2+) concentration, [Ca(2+)]i, sperm motility, sperm hyperactivation and the acrosome reaction. Changes in [Ca(2+)]i were monitored using Fura-2, sperm kinematic parameters were measured using computer-assisted sperm analysis (CASA), and the acrosome reaction was measured using fluorescein isothiocyanate-coupled Pisum sativum agglutinin lectin (FITC-PSA method). We found that kisspeptin and its receptor are present in sperm cells, where both are mainly localized in the sperm head, around the neck and in the flagellum midpiece. Exposure to kisspeptin caused a slow, progressive increase in [Ca(2+)]i, which reached a plateau about 3-6 min after kisspeptin exposure. In addition, kisspeptin modulated sperm progressive motility causing a biphasic (stimulatory and inhibitory) response and also induced transient sperm hyperactivation. The effects of kisspeptin on sperm motility and hyperactivation were inhibited by the antagonist of KISS1R, peptide 234. Kisspeptin did not induce the acrosome reaction in human spermatozoa. These data show for the first time that kisspeptin and its receptor are present in human spermatozoa and modulate key parameters of sperm function. This may represent an additional mechanism for their crucial function in the control of male fertility.