Perinatal outcomes in lesbian couples employing shared motherhood IVF compared with those performing artificial insemination with donor sperm.

STUDY QUESTION: In lesbian couples, is shared motherhood IVF (SMI) associated with an increase in perinatal complications compared with artificial insemination with donor sperm (AID)? SUMMARY ANSWER: Singleton pregnancies in SMI and AID had very similar outcomes, except for a non-significant increase in the rate of preeclampsia/hypertension (PE/HT) in SMI (recipient's age-adjusted odds ratio (OR) = 1.9, 95% CI = 0.7-5.2; P = 0.19), but twin SMI pregnancies had a much higher frequency of PE/HT than AID twins (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4; P = 0.01). WHAT IS KNOWN ALREADY: Oocyte donation (OD) pregnancies are associated with an increase in perinatal complications, in particular, preterm delivery and low birth weight, and PE/HT. However, it is unclear to what extent these complications are due to OD process or to the conditions why OD was performed, such as advanced age and underlying health conditions. Unfortunately, the literature concerning perinatal outcomes in SMI is scarce. STUDY DESIGN, SIZE, DURATION: Retrospective study involving 660 SMI cycles (299 pregnancies) and 4349 AID cycles (949 pregnancies) assisted over a 10-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: All cycles fulfilling the inclusion criteria performed in lesbian couples seeking fertility treatment in 17 Spanish clinics of the same group. Pregnancy rates of SMI and AID cycles were compared. Perinatal outcomes were compared: gestational length, newborn weight, preterm and low birth rates, PE/HT rates, cesarean section rates, perinatal mortality, and newborn malformations. MAIN RESULTS AND THE ROLE OF CHANCE: Pregnancy rates were higher in SMI than in AID (45.3% versus 21.8%, P < 0.001). There was a non-significant trend to higher multiple rate in AID (4.7% versus 8.5%, P = 0.08). In single pregnancies, there were no differences between SMI and AID in gestational age (278 days (268-285) versus 279 (272-284), P = 0.24), preterm rate (8.3% versus 7.3%, P = 0.80), preterm <28 weeks (0.6% versus 0.4%, P = 1.00), newborn weight (3195 g (2915-3620) versus 3270 g (2980-3600), P = 0.296), low birth rate (6.4% versus 6.4%, P = 1.00), extremely low birth weight (0.6% versus 0.5%, P = 1.00), and the distribution of newborns by weight groups. Cesarean section rate, newborn malformation rate, and perinatal mortality were also similar in SMI and AID. Additionally, there was non-significant trend in hypertensive disorders to an increase in PE/HT among SMI (recipient's age-adjusted OR = 1.9, 95% CI = 0.7-5.2). Overall, perinatal data are consistent with what is reported in the general population. In twin pregnancies, the aforementioned perinatal parameters were also very similar in SMI and AID. However, SMI twin pregnancies had a very high risk of PE/HT when compared with AID (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our data regarding the pregnancy course were obtained from information registered in the delivery report as well as from what was reported by the patients themselves, so a certain degree of inaccuracy cannot be ruled out. Additionally, in some parameters, there was up to 10% of data missing. However, since the methodology of reporting was the same in SMI and AID groups, one should not expect a differential reporting bias. It cannot be ruled out that the risk of PE/HT in simple gestations would be significant in a larger study. Additionally, in the SMI group allocation to the transfer of 2 embryos was not randomized so some bias is possible. WIDER IMPLICATIONS OF THE FINDINGS: SMI, if single embryo transfer is performed, seems to be is a safe procedure. Double embryo transfer should not be performed in SMI. Our data suggest that the majority of complications in OD could be related more with recipient status than with OD itself, since with SMI (performed in women without fertility problems) the perinatal complications were much lower than usually described in OD. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Prevalence of Neospora caninum, Toxoplasma gondii and Brucella abortus in water buffalo (Bubalus bubalis): Climatic and environmental risk factors in eastern and southeast Mexico.

A total of 600 serum samples from five farms were collected and the geographic coordinates of each farm were georeferenced to establish two Köppen climate classes (wet tropical and tropical rainforest). Serum samples were examined by commercially available enzyme-linked immunosorbent assay (ELISA) kits to detect antibodies against N. caninum and T. gondii, while anti-B. abortus antibodies were analysed using the Rose Bengal test and ELISA kit. The overall estimated prevalence of N. caninum, T. gondii and B. abortus was 41.2%, 30.7% and 0.5%, respectively. The highest percentages of positive buffaloes with neosporosis and toxoplasmosis were found in the states of Tabasco (46.7%, wet tropical climate) and Veracruz (32.7%, tropical rainforest climate), respectively. Multivariate logistic regression showed that N. caninum seropositivity in buffalos was associated with the normalized difference vegetation index (NDVI) (OR: 1.068; 95% CI: 1.026-1.112; P = 0.001) and tropical climate regions (OR: 1.737; 95% CI: 1.112-2.712; P = 0.015). In addition, statistical analysis revealed that sex (OR: 1.737, 95% CI: 1.685-9.737; P = 0.002), NDVI (OR: 1.382; 95% CI: 1.095-1.746; P = 0.007) and rainfall (OR: 1.478; 95% CI: 1.110-1.967; P = 0.007) were significant risk factors for T. gondii infections. These results indicate that the potential impact of the risk factors was different for each disease in buffaloes, which may be useful for developing regionally adapted control strategies and preventive measures.

From initial segment to cauda: a regional characterization of mouse epididymal CD11c+ mononuclear phagocytes based on immune phenotype and function.

Successful sperm maturation and storage rely on a unique immunological balance that protects the male reproductive organs from invading pathogens and spermatozoa from a destructive autoimmune response. We previously characterized one subset of mononuclear phagocytes (MPs) in the murine epididymis, CX3CR1+ cells, emphasizing their different functional properties. This population partially overlaps with another subset of understudied heterogeneous MPs, the CD11c+ cells. In the present study, we analyzed the CD11c+ MPs for their immune phenotype, morphology, and antigen capturing and presenting abilities. Epididymides from CD11c-EYFP mice, which express enhanced yellow fluorescent protein (EYFP) in CD11c+ MPs, were divided into initial segment (IS), caput/corpus, and cauda regions. Flow cytometry analysis showed that CD11c+ MPs with a macrophage phenotype (CD64+ and F4/80+) were the most abundant in the IS, whereas those with a dendritic cell signature [CD64- major histocompatibility complex class II (MHCII)+] were more frequent in the cauda. Immunofluorescence revealed morphological and phenotypic differences between CD11c+ MPs in the regions examined. To assess the ability of CD11c+ cells to take up antigens, CD11c-EYFP mice were injected intravenously with ovalbumin. In the IS, MPs expressing macrophage markers were most active in taking up the antigens. A functional antigen-presenting coculture study was performed, whereby CD4+ T cells were activated after ovalbumin presentation by CD11c+ epididymal MPs. The results demonstrated that CD11c+ MPs in all regions were capable of capturing and presenting antigens. Together, this study defines a marked regional variation in epididymal antigen-presenting cells that could help us understand fertility and contraception but also has larger implications in inflammation and disease pathology.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Leptin deficiency modulates allograft survival by favoring a Th2 and a regulatory immune profile. [corrected].

Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice. Leptin deficiency results in an increased frequency of Treg and Th2 cells and a prolonged graft survival. These effects of leptin deficiency indicate the importance of leptin and obesity in modulating the allograft immune responses. Our data suggest a possible explanation for the increased susceptibility of hyperleptinemic obese patients to acute and chronic graft rejection.

Immunological biomarkers: catalysts for translational advances in autoimmune diabetes.

In a recent workshop organized by the JDRF focused on the 'Identification and Utilization of Robust Biomarkers in Type1 Diabetes', leaders in the field of type 1 diabetes (T1D)/autoimmunity and assay technology came together from academia, government and industry to assess the current state of the field, evaluate available resources/technologies and identify gaps that need to be filled for moving the field of T1D research forward. The highlights of this workshop are discussed in this paper, as well as the proposal for a larger, planned consortium effort, incorporating a JDRF Biomarker Core, to foster collaboration and accelerate progress in this critically needed area of T1D research.

Borrowing strength with nonexchangeable priors over subpopulations.

We introduce a nonparametric Bayesian model for a phase II clinical trial with patients presenting different subtypes of the disease under study. The objective is to estimate the success probability of an experimental therapy for each subtype. We consider the case when small sample sizes require extensive borrowing of information across subtypes, but the subtypes are not a priori exchangeable. The lack of a priori exchangeability hinders the straightforward use of traditional hierarchical models to implement borrowing of strength across disease subtypes. We introduce instead a random partition model for the set of disease subtypes. This is a variation of the product partition model that allows us to model a nonexchangeable prior structure. Like a hierarchical model, the proposed clustering approach considers all observations, across all disease subtypes, to estimate individual success probabilities. But in contrast to standard hierarchical models, the model considers disease subtypes a priori nonexchangeable. This implies that when assessing the success probability for a particular type our model borrows more information from the outcome of the patients sharing the same prognosis than from the others. Our data arise from a phase II clinical trial of patients with sarcoma, a rare type of cancer affecting connective or supportive tissues and soft tissue (e.g., cartilage and fat). Each patient presents one subtype of the disease and subtypes are grouped by good, intermediate, and poor prognosis. The prior model should respect the varying prognosis across disease subtypes. The practical motivation for the proposed approach is that the number of accrued patients within each disease subtype is small. Thus it is not possible to carry out a clinical study of possible new therapies for rare conditions, because it would be impossible to plan for sufficiently large sample size to achieve the desired power. We carry out a simulation study to compare the proposed model with a model that assumes similar success probabilities for all subtypes with the same prognosis, i.e., a fixed partition of subtypes by prognosis. When the assumption is satisfied the two models perform comparably. But the proposed model outperforms the competing model when the assumption is incorrect.

Speciation and phylogeography of giant petrels Macronectes.

We examine global phylogeography of the two forms of giant petrel Macronectes spp. Although previously considered to be a single taxon, and despite debate over the status of some populations and the existence of minimal genetic data (one mitochondrial cytochrome b sequence per form), the current consensus based on morphology is that there are two species, Northern Giant Petrel M. halli and Southern Giant Petrel M. giganteus. This study examined genetic variation at cytochrome b as well as six microsatellite loci in giant petrels from 22 islands, representing most island groups at which the two species breed. Both markers support separate species status, although sequence divergence in cytochrome b was only 0.42% (corrected). Divergence was estimated to have occurred approximately 0.2mya, but with some colonies apparently separated for longer (up to 0.5 my). Three clades were found within giant petrels, which separated approximately 0.7mya, with the Southern Giant Petrel paraphyletic to a monophyletic Northern Giant Petrel. There was evidence of past fragmentation during the Pleistocene, with subsequent secondary contact within Southern Giant Petrels. The analysis also suggested a period of past population expansion that corresponded roughly to the timing of speciation and the separation of an ancestral giant petrel population from the fulmar Fulmarus clade.

The relationship between oxygen consumption and body acceleration in a range of species.

The ability to measure the energy expenditure of free-ranging animals is of great importance but the techniques available each have their limitations. Recently, as an alternative to more established techniques, an integrated measure of body acceleration termed overall dynamic body acceleration (ODBA) has been used as a calibrated proxy for rate of oxygen consumption (V(O(2))) and hence metabolic rate. The present study tested the potential of this technique, firstly by expanding the range of species for which the V(O(2))-ODBA relationship has been defined and secondly by undertaking a validation exercise to explore the accuracy of predictions made using ODBA. V(O(2))-ODBA relationships during terrestrial locomotion were established for several bipedal and quadrupedal endotherms and compiled with similar relationships previously determined in other species. A model incorporating all of these species showed that ODBA is an excellent predictor of V(O(2)) but there is variation in the V(O(2))-ODBA relationship between species, and further variation within some species. Including measurements such as body mass and structural size in prediction equations might further improve the predictive power of the 'ODBA technique' and eliminate species-specific differences. In the validation exercise, estimate errors were calculated for the species-specific predictive equations. The use of ODBA to estimate V(O(2)) was valid across all species examined and may show a greater potential for estimating energy expenditure for individual animals than other techniques.

[Terminal illness. Death... in the words of professionals. A qualitative study based on in-depth interviews with health professionals]. / Enfermedad terminal, muerte... en palabras de los profesionales (y II). Un estudio cualitativo de entrevistas en profundidad a profesionales de la salud.

This article is the second part of an interesting qualitative research project which presents and interprets opinions made by diverse medical and nursing professionals regarding care provided to terminal patients and relationships with patients' relatives.

[Perceptions of health care professionals about end-of-life care, obstacles and ethical dilemmas in hospitals, primary care and nursing homes.] / Percepciones de los profesionales sobre la atención prestada, obstáculos y dilemas éticos relacionados con el final de la vida en hospitales, centros de Atención Primaria y residencias de ancianos.

BACKGROUND: This study compares the perceptions of physicians and nurses regarding professional practice, perceived obstacles and ethical dilemmas in end-of-life care in primary care (PC), hospitals and nursing homes (NH). METHODS: Descriptive, cross-sectional and multicentre study. Intentional sampling of physicians and nurses with more than four months professional practice from four hospitals, five PC centres and twenty-nine NH in Granada was carried out. An ad hoc questionnaire was developed to assess perception of professional practice in eight dimensions (structure and processes of care, physical, psychological, social, spiritual, cultural, ethical aspects and care for the dying), frequency of ethical dilemmas, and obstacles to optimum care. Scores of different settings were compared using the ANOVA test and post hoc analysis. RESULTS: A total of 378 professionals participated, 215 (56.9%) from hospitals, 97 (25.7%) from PC and 66 (17.5%) from NH. NH professionals were older and had more professional experience than those from PC and hospitals, and they also rated both the institution and their own professional practice significantly better (p<0.01) than other professionals with respect to the dimensions of structure and processes of care, physical, psychological, social, spiritual, cultural aspects and care for the dying. Psychological and ethical aspects were the worst valued in all settings, with no differences regarding ethical aspects. Fewer ethical dilemmas were identified by PC professionals, while NH professionals perceived greater obstacles to end-of-life care in relation to other settings. CONCLUSION: Primary care and hospitalization presented similar results on the perception of end-of-life care, and lower results than those of nursing homes, although in these centres more ethical dilemmas and more obstacles were identified.

Tropomyosin-induced arthritis in rats.

OBJECTIVE: Immunization of rats with alpha-tropomyosin (TPM) led to arthritis, uveitis and dermatitis, typical features of Behçet's disease (BD). The present study characterizes the arthritic features of this animal model, not previously described. METHODS: Lewis rats were immunized with bovine alpha-TPM and another group of rats was treated with neutralizing anti- tumor necrosis factor-alpha (TNF-alpha) antibodies. RESULTS: Clinically more than 90% of the immunized rats developed severe acute arthritis 12 days after vaccination. Rats that were followed-up for 6 months had persistent inflammation of the leg joints. Histologic studies demonstrated predominant mononuclear infiltrations in the acute phase of arthritis; the chronic arthritic process resulted in cartilage and bone damage and abundant fibrosis which led to joint deformations. Male and female rats had a similar clinical course. Analysis of the splenocyte cytokine profile kinetics revealed a persistently high level of interferon-gamma (INF-gamma) and an increase in TNF-alpha secretion during the acute phase. Increasing levels of interleukin (IL)-10 heralded the decline in clinical arthritis. No IL-4 was detected. No arthritis was detected in the rats treated with anti-TNF-alpha antibodies. CONCLUSION: The data indicates that alpha-TPM serves as an autoantigen to induce acute and chronic destructive arthritis in rats. This model is a TNF-alpha dependent autoimmune disease, with a Th1 cytokine profile.

Role and therapeutic value of dendritic cells in central nervous system autoimmunity.

Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis.

Occipitoatlantal instability and vertebrobasilar ischemia: case report.

A 37-year-old woman had occipitoatlantal instability due to hypoplasia of the occipital condyles. Neck pain and transient ischemic attacks in the vertebrobasilar territory occurred with extension of the neck, which also caused convergence spasm. Angiography demonstrated that these manifestations were due to compression of the vertebral arteries during neck extension. Immobilization of the neck in a Minerva cast resulted in complete relief of symptoms.

Immunization with recombinant Trypanosoma cruzi ribosomal P2beta protein induces changes in the electrocardiogram of immunized mice.

Molecular expression cloning techniques revealed that patients with severe chronic Chagas heart disease showed a strong humoral response against the cloned C-terminal portion of the Trypanosoma cruzi ribosomal P2beta protein, previously named JL5. The main linear epitope of this polypeptide was mapped to the 13 C-terminal amino acid sequence EEEDDDMGFGLFD (named R13), which is almost identical to the mammalian ribosomal P consensus sequence EESDDDMGFGLFD (named H13). Enzyme-linked immunosorbent assay measurements demonstrated that sera from patients with chronic Chagas heart disease presented a very specific anti-P humoral response with high anti-R13, but low H13 antibody levels. We attempted to develop an animal model that would reproduce, at least partially, two features of the human infection: (1) the serological pattern of the anti-P response, and (2) specific cardiac symptoms. To this effect, mice were immunized with T. cruzi P2beta recombinant protein. Immunization reproduced the typical anti-P antibody profile defined for chronic infections, but did not induce cardiac inflammatory lesions. However, it altered significantly the electrocardiograms of immunized mice. It is suggested that this assay represents a functional test for assessing the biological activity of antibodies against T. cruzi ribosomal P protein on cardiac muscle.

CT findings in spinocerebellar degeneration.

Thirty-five CT scans were studied from patients with several forms of spinocerebellar degeneration. Atrophy was determined by objective measurements of the number and width of cerebellar sulci, transverse diameter and surface area of the fourth ventricle, brainstem ratio, cerebellopontine angle cistern, and Evans' index. Two-thirds of the patients with Friedreich's ataxia showed moderate cerebellar atrophy and an increase in the surface area of the fourth ventricle. Severe cerebellar atrophy and enlargement of the cerebellopontine angle cistern was seen in patients with olivopontocerebellar (OPC) atrophy and idiopathic cortical cerebellar atrophy. In the OPC atrophy group there was also prominent atrophy of the brainstem and an increase in the fourth ventricle parameters. Alcoholic cerebellar degeneration showed a specific pattern of cerebellar atrophy most prominent in the superior vermis, together with a slight increase in the fourth ventricle surface, a reduction in the size of the brainstem, and an enlargement of the cerebellopontine angle cistern. Supratentorial atrophy was present only in the OPC and alcoholic atrophy groups. In one patient with spastic ataxia, CT was normal but MR imaging revealed prominent atrophy of the spinal cord. These CT patterns appear to be distinctive enough to permit the diagnosis and classification of the various forms of spinocerebellar degeneration.