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BACKGROUND: Per federal law, "988" became the new three-digit dialing code for the National Suicide & Crisis Lifeline on July 16, 2022 (previously reached by dialing "1-800-283-TALK"). AIMS OF THE STUDY: This study aimed to produce state-level estimates of: (i) annual increases in 988 Lifeline call volume following 988 implementation, (ii) the cost of these increases, and (iii) the extent to which state and federal funding earmarked for increases in 988 Lifeline call volume are sufficient to meet call demand. METHOD: A 50 state pre-post policy implementation design was used. State-level Lifeline call volume data were obtained. For each state, we calculated the absolute difference in number of Lifeline calls in the four-month periods between August-November 2021 (pre-988 implementation) and August-November 2022 (post-988 implementation), and also expressed this difference as percent change and rate per 100,000 population. The difference call volume was multiplied by a published estimate of the cost of a single 988 Lifeline call (USD 82), and then by multiplied by three to produce annual, 12-month state-level cost increase estimates. These figures were then divided by each state's population size to generate cost estimates per state resident. State-level information on the amount of state (FY 2023) and federal SAMHSA (FY 2022) funding earmarked for 988 Lifeline centers in response to 988 implementation were obtained from legal databases and government websites and expressed as dollars per state resident. State-level differences between per state resident estimates of increased cost and funding were calculated to assess the extent to which state and federal funding earmarked for increases in 988 Lifeline call volume were sufficient to meet call demand. RESULTS: 988 Lifeline call volume increased in all states post-988 implementation (within-state mean percent change = +32.8%, SD = +20.5%). The total estimated cost needed annually to accommodate increases in 988 Lifeline call volume nationally was approximately USD 46 million. The within-state mean estimate of additional cost per state resident was +USD 0.16 (SD = +USD 0.11). The additional annual cost per state resident exceeded USD 0.40 in three states, was between USD 0.40- USD 0.30 in three states, and between USD 0.30 - USD 0.20 in seven states. Twenty-two states earmarked FY 2023 appropriations for 988 Lifeline centers in response to 988 (within-state mean per state resident = USD 1.51, SD = USD 1.52) and 49 states received SAMHSA 988 capacity building grants (within-state mean per state resident = USD 0.36, SD = USD 0.39). State funding increases exceeded the estimated cost increases in about half of states. CONCLUSIONS: The Lifeline's transition to 988 increased 988 Lifeline call volume in all states, but the magnitude of the increase and associated cost was heterogenous across states. State funding earmarked for increases in 988 Lifeline center costs is sufficient in about half of states. Sustained federal funding, and/or increases in state funding, earmarked for 988 Lifeline centers is likely important to ensuring that 988 Lifeline centers have the capacity to meet call demand in the post-988 implementation environment.

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Sexual size dimorphism (SSD) is widespread and variable in nature. Although female-biased SSD predominates among insects, the proximate ecological and evolutionary factors promoting this phenomenon remain largely unstudied. Here, we employ modern phylogenetic comparative methods on eight subfamilies of Iberian grasshoppers (85 species) to examine the validity of different models of evolution of body size and SSD and explore how they are shaped by a suite of ecological variables (habitat specialization, substrate use, altitude) and/or constrained by different evolutionary pressures (female fecundity, strength of sexual selection, length of the breeding season). Body size disparity primarily accumulated late in the history of the group and did not follow a Brownian motion pattern, indicating the existence of directional evolution for this trait. We found support for the converse of Rensch's rule (i.e. females are proportionally bigger than males in large species) across all taxa but not within the two most speciose subfamilies (Gomphocerinae and Oedipodinae), which showed an isometric pattern. Our results do not provide support for the fecundity or sexual selection hypotheses, and we did not find evidence for significant effects of habitat use. Contrary to that expected, we found that species with narrower reproductive window are less dimorphic in size than those that exhibit a longer breeding cycle, suggesting that male protandry cannot solely account for the evolution of female-biased SSD in Orthoptera. Our study highlights the need to consider alternatives to the classical evolutionary hypotheses when trying to explain why in certain insect groups males remain small.

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The integration of genetic information with ecological and phenotypic data constitutes an effective approach to gain insight into the mechanisms determining interpopulation variability and the evolutionary processes underlying local adaptation and incipient speciation. Here, we use the Pyrenean Morales grasshopper (Chorthippus saulcyi moralesi) as study system to (i) analyse the relative role of genetic drift and selection in range-wide patterns of phenotypic differentiation and (ii) identify the potential selective agents (environment, elevation) responsible for variation. We also test the hypothesis that (iii) the development of dispersal-related traits is associated with different parameters related to population persistence/turnover, including habitat suitability stability over the last 120 000 years, distance to the species distribution core and population genetic variability. Our results indicate that selection shaped phenotypic differentiation across all the studied morphological traits (body size, forewing length and shape). Subsequent analyses revealed that among-population differentiation in forewing length was significantly explained by a temperature gradient, suggesting an adaptive response to thermoregulation or flight performance under contrasting temperature regimes. We found support for our hypothesis predicting a positive association between the distance to the species distribution core and the development of dispersal-related morphology, which suggests an increased dispersal capability in populations located at range edges that, in turn, exhibit lower levels of genetic variability. Overall, our results indicate that range-wide patterns of phenotypic variation are partially explained by adaptation in response to local environmental conditions and differences in habitat persistence between core and peripheral populations.

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The study of the factors structuring genetic variation can help to infer the neutral and adaptive processes shaping the demographic and evolutionary trajectories of natural populations. Here, we analyse the role of isolation by distance (IBD), isolation by resistance (IBR, defined by landscape composition) and isolation by environment (IBE, estimated as habitat and elevation dissimilarity) in structuring genetic variation in 25 blue tit (Cyanistes caeruleus) populations. We typed 1385 individuals at 26 microsatellite loci classified into two groups by considering whether they are located into genomic regions that are actively (TL; 12 loci) or not (NTL; 14 loci) transcribed to RNA. Population genetic differentiation was mostly detected using the panel of NTL. Landscape genetic analyses showed a pattern of IBD for all loci and the panel of NTL, but genetic differentiation estimated at TL was only explained by IBR models considering high resistance for natural vegetation and low resistance for agricultural lands. Finally, the absence for IBE suggests a lack of divergent selection pressures associated with differences in habitat and elevation. Overall, our study shows that markers located in different genomic regions can yield contrasting inferences on landscape-level patterns of realized gene flow in natural populations.

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Bluetongue virus (BTV), the causative agent of bluetongue disease (BT) in domestic and wild ruminants, is worldwide distributed. A total of 27 serotypes have been described so far, and several outbreaks have been reported. Vaccination is critical for controlling the spread of BTV. In the last years, subunit vaccines, viral vector vaccines and reverse genetic-based vaccines have emerged as new alternatives to conventional ones. In this study, we developed an experimental subunit vaccine against BTV4, with the benefit of targeting the recombinant protein to antigen-presenting cells. The VP2 protein from an Argentine BTV4 isolate was expressed alone or fused to the antigen presenting cell homing (APCH) molecule, in the baculovirus insect cell expression system. The immunogenicity of both proteins was evaluated in guinea pigs and cattle. Titers of specific neutralizing antibodies in guinea pigs and cattle immunized with VP2 or APCH-VP2 were high and similar to those induced by a conventional inactivated vaccine. The immunogenicity of recombinant proteins was further studied in the IFNAR(-/-) mouse model where the fusion of VP2 to APCH enhanced the cellular immune response and the neutralizing activity induced by VP2.

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UNLABELLED: Ankylosing spondylitis (AS) leads to osteopenia/osteoporosis and spine rigidity. We conducted a case-control study and found that AS-affected patients have a 5-fold and 50% increased risk of clinical spine and all clinical fractures, respectively. Excess risk of both is highest in the first years and warrants an early bone health assessment after diagnosis. INTRODUCTION: Ankylosing spondylitis (AS) is related to spine rigidity and reduced bone mass, but data on its impact on fracture risk are scarce. We aimed to study the association between AS and clinical fractures using a case-control design. METHODS: From the Danish Health Registries, we identified all subjects who sustained a fracture in the year 2000 (cases) and matched up to three controls by year of birth, gender and region. Clinically diagnosed AS was identified using International Classification of Diseases, 8th revision (ICD-8; 71249), and International Classification of Diseases, 10th revision (ICD-10; M45) codes. We also studied the impact of AS duration. Conditional logistic regression was used to estimate crude and adjusted odds ratios (ORs) for non-traumatic fractures (any site, clinical spine and non-vertebral) according to AS status and time since AS diagnosis. Multivariate models were adjusted for fracture history, socio-economic status, previous medical consultations, alcoholism and use of oral glucocorticoids. RESULTS: We identified 139/124,655 (0.11%) AS fracture cases, compared to 271/373,962 (0.07%) AS controls. Unadjusted (age- and gender-matched) odds ratio (OR) were 1.54 [95% confidence interval (95%CI) 1.26-1.89] for any fracture, 5.42 [2.50-11.70] for spine and 1.39 [1.12-1.73] for non-vertebral fracture. The risk peaked in the first 2.5 years following AS diagnosis: OR 2.69 [1.84-3.92] for any fracture. CONCLUSIONS: Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35% increased risk of non-vertebral fracture. This excess risk peaks early, in the first 2.5 years of AS disease. Patients should be assessed for fracture risk early after AS diagnosis.

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Understanding the factors determining genetic diversity and structure in peripheral populations is a long-standing goal of evolutionary biogeography, yet little empirical information is available for tropical species. In this study, we combine information from nuclear microsatellite markers and niche modelling to analyse the factors structuring genetic variation across the southernmost populations of the tropical oak Quercus segoviensis. First, we tested the hypothesis that genetic variability decreases with population isolation and increases with local habitat suitability and stability since the Last Glacial Maximum (LGM). Second, we employed a recently developed multiple matrix regression with randomisation (MMRR) approach to study the factors associated with genetic divergence among the studied populations and test the relative contribution of environmental and geographic isolation to contemporary patterns of genetic differentiation. We found that genetic diversity was negatively correlated with average genetic differentiation with other populations, indicating that isolation and limited gene flow have contributed to erode genetic variability in some populations. Considering the relatively small size of the study area (<120 km), analyses of genetic structure indicate a remarkable inter-population genetic differentiation. Environmental dissimilarity and differences in current and past climate niche suitability and their additive effects were not associated with genetic differentiation after controlling for geographic distance, indicating that local climate does not contribute to explain spatial patterns of genetic structure. Overall, our data indicate that geographic isolation, but not current or past climate, is the main factor determining contemporary patterns of genetic diversity and structure within the southernmost peripheral populations of this tropical oak.

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In natural populations, mating between relatives can have important fitness consequences due to the negative effects of reduced heterozygosity. Parental level of inbreeding or heterozygosity has been also found to influence the performance of offspring, via direct and indirect parental effects that are independent of the progeny own level of genetic diversity. In this study, we first analysed the effects of parental heterozygosity and relatedness (i.e. an estimate of offspring genetic diversity) on four traits related to offspring viability in great tits (Parus major) using 15 microsatellite markers. Second, we tested whether significant heterozygosity-fitness correlations (HFCs) were due to 'local' (i.e. linkage to genes influencing fitness) and/or 'general' (genome-wide heterozygosity) effects. We found a significant negative relationship between parental genetic relatedness and hatching success, and maternal heterozygosity was positively associated with offspring body size. The characteristics of the studied populations (recent admixture, polygynous matings) together with the fact that we found evidence for identity disequilibrium across our set of neutral markers suggest that HFCs may have resulted from genome-wide inbreeding depression. However, one locus (Ase18) had disproportionately large effects on the observed HFCs: heterozygosity at this locus had significant positive effects on hatching success and offspring size. It suggests that this marker may lie near to a functional locus under selection (i.e. a local effect) or, alternatively, heterozygosity at this locus might be correlated to heterozygosity across the genome due to the extensive ID found in our populations (i.e. a general effect). Collectively, our results lend support to both the general and local effect hypotheses and reinforce the view that HFCs lie on a continuum from inbreeding depression to those strictly due to linkage between marker loci and genes under selection.

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Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations.

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Dispersal and local patterns of adaptation play a major role on the ecological and evolutionary trajectory of natural populations. In this study, we employ a combination of genetic (25 microsatellite markers) and field-based information (seven study years) to analyse the impact of immigration and local patterns of adaptation in two nearby (<7 km) blue tit (Cyanistes caeruleus) populations. We used genetic assignment analyses to identify immigrant individuals and found that dispersal rate is female-biased (72%). Data on lifetime reproductive success indicated that immigrant females produced fewer local recruits than their philopatric counterparts whereas immigrant males recruited more offspring than those that remained in their natal location. In spite of the considerably higher immigration rates of females, our results indicate that, in absolute terms, their demographic and genetic impact in the receiving populations is lower than that in immigrant males. Immigrants often brought novel alleles into the studied populations and a high proportion of them were transmitted to their recruits, indicating that the genetic impact of immigrants is not ephemeral. Although only a few kilometres apart, the two study populations were genetically differentiated and showed strong divergence in different phenotypic and life-history traits. An almost absent inter-population dispersal, together with the fact that both populations receive immigrants from different source populations, is probably the main cause of the observed pattern of genetic differentiation. However, phenotypic differentiation (PST) for all the studied traits greatly exceeded neutral genetic differentiation (FST), indicating that divergent natural selection is the prevailing factor determining the evolutionary trajectory of these populations. Our study highlights the importance of integrating individual- and population-based approaches to obtain a comprehensive view about the role of dispersal and natural selection on structuring the genotypic and phenotypic characteristics of natural populations.

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Aphids harbor a variety of bacterial endosymbionts, including the obligate symbiont Buchnera aphidicola and diverse facultative symbionts. The former supplies its host with essential amino acids. The latter are not indispensable for insect survival, but often improve their host's fitness. To date, the study of such associations was restricted to aphids of Holarctic origin. The bacterial microbiota of seven Aphis species from Argentina was investigated. The presence of B. aphidicola was assessed by specific PCR. Additional symbionts were identified through PCR with eubacterial universal primers, cloning, and sequencing of nearly complete 16S rRNA gene, intergenic spacer region, and partial 23S rRNA gene and subjected to phylogenetic analysis. Infection with B. aphidicola was confirmed in every species analyzed. The facultative symbiont Serratia symbiotica was detected in Aphis malalhuina Mier Durante, Nieto Nafría & Ortego, 2003, Aphis senecionicoides Blanchard, 1944, and Aphis schinifoliae Blanchard, 1939, while Hamiltonella defensa was identified in Aphis mendocina Mier Durante, Ortego & Nieto Nafría, 2006. Arsenophonus sp. was found infecting Aphis melosae Mier Durante & Ortego, 1999, and a new, undescribed Aphis sp. In Aphis danielae Remaudière, 1994, no facultative symbionts could be recorded. When analyzing the highly conserved 16S rRNA gene, the phylogenetic tree grouped the S. symbiotica, H. defensa, and Arsenophonus isolates into three well-defined clusters showing little variability among clones corresponding to the same aphid host species. This article reports for the first time the endosymbionts associated with aphids native to South America. Despite their geographic origin, the qualitative composition of their microbiota revealed no evident differences from that described for aphids in the Northern Hemisphere.

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OBJECTIVES: Over the past few years researchers have suggested that vitamin D plays a diverse role in autoimmune diseases such as systemic lupus erythematosus (SLE). We sought to determine the prevalence and predictors of vitamin D deficiency in a cohort of non-supplemented female SLE patients from the Mediterranean region. METHODS: We carried out a prospective cohort study on all SLE patients who had visited the Department of Rheumatology at the Parc de Salut MAR (Barcelona, Spain) between June 2007 and December 2008, excluding those who had been taking vitamin D supplements (total: 73 patients, all female). For each patient, demographic information was collected; scores were measured for disease severity [SLE Disease Activity Index (SLEDAI)] and structural damage [Systemic Lupus International Collaborating Clinic/American College of Rheumatology, (SLICC/ACR) Damage Index]; pharmacological treatment was recorded; analytical variables were analysed; and plasma levels of 25-hydroxy vitamin D [25(OH)D] were quantified. RESULTS: Among the patients in our cohort, 68.5% [95% confidence interval (CI) 60.3-79.2] exhibited vitamin D deficiency [plasma level of 25(OH)D < 30 ng/mL]. The predictors for vitamin D deficiency were daily sunscreen use [odds ratio (OR) 1.67, p = 0.02] and high body mass index (BMI) (OR 1.32 when adjusted for seasons and patient age, p = 0.04). We did not find any correlation between vitamin D deficiency and SLEDAI score (p = 0.31), SLICC/ACR score (p = 0.82), or any other of the variables. CONCLUSIONS: Vitamin D insufficiency is highly prevalent among SLE patients, even in southern regions. Sunscreen use and obesity increase the risk. Clinicians should be aware of these factors and supplement SLE patients at risk of vitamin D deficiency accordingly.

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UNLABELLED: Accumulating evidence indicates that the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a key role in esophageal carcinogenesis. A better understanding of the pathway downstream of COX-2 may reveal novel targets for the prevention of esophageal adenocarcinoma (EAC). The objective of this study was to characterize the profile of genes involved in PGE2 metabolism and signaling in an experimental model of EAC. Esophagojejunostomy with gastric preservation was performed in wistar rats to induce gastroduodenal reflux. Rats were sacrificed 2 or 4 months after surgery. Nine non-operated rats were used to obtain normal (control) esophageal tissues. RESULTS: All rats that underwent esophagojejunostomy developed inflammation. In addition, 90% of the animals showed intestinal metaplasia; of those, 40% progressed to AC. This process was accompanied by a significant increase in esophageal PGE2 levels and the induction of both mRNA and protein levels of COX-2, COX-1, prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, and PGE2 receptors EP3, EP4 and especially EP2, which rose to particularly high levels in experimental rats. In addition, exposure to a selective COX-2 inhibitor (SC58125) or an EP1/EP2 antagonist (AH6809), but not an EP4 antagonist (AH23848B), significantly reduced cell proliferation of esophageal explants in 24 hour-organ culture experiments. Our data suggest that, in addition to COX-2, other components of the PGE2 pathway, including COX-1, may play important roles in the development of EAC induced by gastroduodenal reflux in the rat. Although it must be confirmed in vivo, the EP2 receptor may represent a promising selective target in the prevention of Barrett's associated AC.

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BACKGROUND: 30% of patients with colorectal cancer (CRC) in Dukes stages A and B (T1-T4, N0, M0) present tumor recurrence and die after 5 years follow up. This unexpectedly poor evolution might be attributable to the presence of lymph node micrometastasis undetected in routine examination with haematoxilin-eosine (H&E). OBJECTIVE: To assess the presence of undetected micrometastasis. PATIENTS AND METHODS: we conducted a retrospective study of the locoregional lymph nodes in 85 patients operated for CRC in Dukes stages A and B (T1-T4, N0, M0), using immunohistochemistry with anticytokeratin antibodies AE1/AE3. In this descriptive, inferential bivariant and survival study, we analyzed different risk factors, including local infiltration T1/T4, Dukes A/B, number of dissected lymph nodes, vascular invasion, micrometastasis, tumor recurrence and death in the context of the presence or absence of micrometastases. RESULTS: Dukes stage and neoplastic angioinvasion are influential in patient prognosis; however, lymph node micrometastases were not associated with a poorer outcome of CRC. CONCLUSIONS: Locorregional lymph node micrometastases detected with anticytokeratine antibodies AE1/AE3 in Dukes A and B CRC patients are not associated with reduced survival.

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Introducción: un 30% de los pacientes con cáncer colorrectal(CCR) en estadios A y B de Dukes (T1-T4, N0, M0) presentan recidivatumoral y/o fallecen a los 5 años. Esta inesperada malaevolución, en casos presumiblemente curados podría deberse, entreotras causas, a la presencia de micrometástasis linfoganglionaresno detectadas en el estudio de rutina: hematoxilina-eosina(H&E).Objetivo: determinar si la presencia de micrometástasis linfoganglionaresdetectadas mediante inmunohistoquímica con anticuerposanticitoqueratina AE1/AE3, influyen en la evolución delCCR.Pacientes y métodos: se han estudiado los ganglios linfáticoslocorregionales de 85 pacientes con CCR en estadios A y Bde Dukes (T1-T4, N0, M0), mediante técnicas de inmunohistoquímicacon anticuerpos anticitoqueratinas AE1/AE3, para poner demanifiesto la presencia de micrometástasis. Se ha realizado un estudiodescriptivo, inferencial bivariante y de supervivencia, segúndistintos factores de riesgo, centrado en la presencia o no de micrometástasis.Resultados: hemos observado que el estadio de Dukes y laangioinvasión neoplásica son factores que influyen en el pronósticode estos pacientes. Sin embargo, no se ha demostrado que lapresencia de micrometástasis linfoganglionares se asocie a unapeor evolución en el CCR.Conclusiones: las micrometástasis linfoganglionares locorregionalesdetectadas mediante anticuerpos anticitoqueratinaAE1/AE3, en pacientes con CCR en estadios A y B de Dukes, nose asocian a una menor supervivencia(au9

Background: 30% of patients with colorectal cancer (CRC) inDukes stages A and B (T1-T4, N0, M0) present tumor recurrenceand die after 5 years follow up. This unexpectedly poor evolutionmight be attributable to the presence of lymph node micrometastasisundetected in routine examination with haematoxilin-eosine(H&E).Objective: to assess the presence of undetected micrometastasis.Patients and methods: we conducted a retrospective studyof the locoregional lymph nodes in 85 patients operated for CRCin Dukes stages A and B (T1-T4, N0, M0), using immunohistochemistrywith anticytokeratin antibodies AE1/AE3. In this descriptive,inferential bivariant and survival study, we analyzed differentrisk factors, including local infiltration T1/T4, Dukes A/B,number of dissected lymph nodes, vascular invasion, micrometastasis,tumor recurrence and death in the context of the presenceor absence of micrometastases.Results: Dukes stage and neoplastic angioinvasion are influentialin patient prognosis; however, lymph node micrometastaseswere not associated with a poorer outcome of CRC.Conclusions: locorregional lymph node micrometastases detectedwith anticytokeratine antibodies AE1/AE3 in Dukes A andB CRC patients are not associated with reduced survival(AU)

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Objetivo: Evaluar la prevalencia de enfermedad tiroidea autoinmune (ETA) enpacientes con diabetes tipo 1 (DM1) y su relación con variables clínicas y analíticas.Material y métodos: Estudio observacional descriptivo en pacientescon DM1 en el que se analiza la prevalencia de ETA y los factores relacionados.Resultados: Se estudiaron 507 pacientes con DM1 (50,4% mujeres)de 33,5 ± 11,8 años de edad y 16,1 ± 9,5 años de evolución de la DM1, ycon un nivel medio de HbA1c del 7,8 ± 1,4%. El 17,8% de los pacientes presentabaETA (9,9% hipotiroidismo primario, 7,1% hipotiroidismo subclínico y0,8% enfermedad de Graves). Los pacientes DM1 y ETA eran, con mayor frecuencia,mujeres (24,6 frente a 10,8%; p <0,001) y fumadores (15,6 frentea 2,2%; p= 0,039) y presentaban niveles séricos de colesterol LDL (c-LDL)más elevados (110,1 ± 31,4 frente a 102,9 ± 28,8 mg/dL; p <0,043).Conclusión: Observamos una elevada prevalencia de ETA en pacientes conDM1, asociándose a sexo femenino, tabaquismo activo y niveles elevados dec-LDL. Recomendamos el cribado sistemático de ETA en pacientes con DM1,que permita un precoz diagnóstico y tratamiento(AU)

Objective: To evaluate the prevalence of autoimmune thyroid disease in type1 diabetes patients and their association to clinical and analytical parameters.Methodology: A retrospective observational study of type 1 diabetes patientswas designed to analyze the prevalence of autoimmune thyroid disease andrelated factors. Results: The study included 507 patients with type 1 diabetes(50.4% women), aged 33.5 ± 11.8 years with an average duration of diabetesof 16.1 ± 9.5 years. The average level of HbA1c was 7.8 ± 1.4%.Theprevalence of autoimmune thyroid function disorder was 17.8% (9.9% primaryhypothyroidism, 7.1% subclinical hypothyroidism, and 0.8% Graves disease).There was a positive association between thyroid disease and femalegender (24.6% versus 10.8% in men, p <0.001), smoking (15.6% versus2.2%, p= 0.039) and serum LDL levels (110.1 ± 31.4 mg/dL versus 102.9± 28.8 mg/dL; p <0.043). Conclusion: Prevalence of autoimmune thyroiddisease in type 1 diabetes patients is high and it is associated with femalegender, smoking and increased LDL levels. We suggest a systematic screeningfor autoimmune thyroid disease in type 1 diabetes to establish an early diagnoseand treatment(AU)

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BACKGROUND: Accumulating evidence suggests that cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2 exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and EP4). AIM: To investigate which PGE2 receptor subtypes regulate PGE2 signals in the oesophageal adenocarcinoma sequence. METHODS: Expression was determined in oesophageal biopsies from 85 patients with oesophagitis, Barrett's metaplasia, intraepithelial neoplasia, oesophageal adenocarcinoma and normal oesophagus. Levels of mRNA and protein expression were determined by quantitative PCR, immunohistochemistry and western-blot. Expression of EP receptors was also determined in response to acid and bile exposure in the Barrett's adenocarcinoma cell line OE33. RESULTS: All four EP receptors subtypes were expressed in human oesophageal tissues. COX-2 and, especially, EP2 were increased in the Barrett's metaplasia-intraepithelial neoplasia-adenocarcinoma sequence. Expression of the EP4 receptor protein was increased in oesophageal adenocarcinoma. In contrast, expression levels of COX-1 and EP3 receptor were decreased along the sequence. No differences in EP1 expression were found. Treatment with the bile acid deoxycholate increased COX-2, EP1, EP2 and EP4 expression in OE33 cells. CONCLUSIONS: Our data suggest that in addition to COX-2, EP2 and EP4 receptors could be a selective target in the prevention and/or treatment of the Barrett's-associated adenocarcinoma.

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Some alleles are inherited more frequently than expected from Mendel's rule. This phenomenon, known as transmission ratio distortion (TRD), is found in a broad variety of taxa, but it is thought to be unusual and occurs at a low frequency in any particular population. Here, we used seven microsatellite markers to search for possible TRD in a wild lesser kestrel (Falco naumanni) population. Among the nine alleles analysed with at least 200 known meioses for each sex, we found that two of them (156-AG5 in males and 362-FN1.11 in females) presented subtle (k=0.6) but significant departures from Mendelian segregation. Moreover, in a sample of 53 alleles with at least 15 known meioses, we found a positive correlation between their transmission rates and their frequencies in the population. To estimate the transmission scores for the loci and individuals, we developed a method that allowed us to discover that another locus, FP-46, showed significant TRD, despite the lack of a significant deviation from parity for the alleles considered individually. Finally, we found a consistent transmission bias both within loci and within individuals across loci. Inter-individual differences in TRD support the idea that distorters act over several loci that are evenly distributed across the whole genome, particularly in individuals bearing the distorter alleles. Overall, these findings suggest that TRD might be a more widespread phenomenon than previously revealed by analyses at the allele level.

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Numerical models were developed to simulate temperature profiles in Newtonian fluids during continuous flow microwave heating by one way coupling electromagnetism, fluid flow, and heat transport in ANSYS 8.0 and COMSOL Multiphysics v3.4. Comparison of the results from the COMSOL model with the results from a pre-developed and validated ANSYS model ensured accuracy of the COMSOL model. Prediction of power Loss by both models was in close agreement (5-13% variation) and the predicted temperature profiles were similar. COMSOL provided a flexible model setup whereas ANSYS required coupling incompatible elements to transfer load between electromagnetic, fluid flow, and heat transport modules. Overall, both software packages provided the ability to solve multiphysics phenomena accurately.

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Heterozygosity as a target of mate choice has received much attention in recent years and there is growing evidence supporting its role in the evolution of mate preferences. In this study we analyse mating patterns in relation to heterozygosity in a lesser kestrel (Falco naumanni) population intensively monitored over six study years (2002-2007). The magnitude of heterozygosity-based assortative mating varied over time, being particularly patent in the last study years (2006, 2007). We have found evidence that this mating pattern entails both direct and indirect-genetic benefits. Clutch size increased with female heterozygosity and more heterozygous males raised a higher number of fledglings particularly in those years when the strength of the heterozygosity-based assortative mating was markedly higher. In the last study year, parent-offspring correlation of heterozygosity was stronger and higher than the expected if individuals would have randomly mated with respect to heterozygosity. Overall, our results offer empirical support to the heterozygous mate hypothesis of sexual selection but suggest that genetic diversity may act as a temporally variable target for mate choice.

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