FNDC5/Irisin polymorphisms are associated with osteopenia in postmenopausal Mayan-Mestizo women.

OBJECTIVE: This study aimed to analyze the association between rs3480 and rs16835198 of FNDC5/Irisin and their haplotypes with variations in bone mineral density (BMD) and osteopenia/osteoporosis in postmenopausal Mayan-Mestizo women. METHODS: We studied 547 postmenopausal women of Maya-Mestizo origin. BMD was measured in the lumbar spine and total hip by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time PCR allelic discrimination. Differences between the means of BMD according to genotype were analyzed with covariance. Allele frequency differences were assessed by χ2 and logistic regression was used to test for associations. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. RESULTS: Under a recessive model, we observed a significant association of rs3480 with the presence of osteopenia at the total hip and femoral neck (p = 0.008 and p = 0.003, respectively). For rs16835198, we found an association with osteopenia at the total hip and femoral neck in a dominant model (p = 0.043 and p = 0.009, respectively). CONCLUSIONS: We found an association of rs3480 with risk to present osteopenia at the total hip and femoral neck, while rs16835198 was associated as a protector for presence of osteopenia only at the femoral neck.

(-)-Epicatechin inhibits development of dilated cardiomyopathy in δ sarcoglycan null mouse.

BACKGROUND AND AIMS: Several studies propose that (-)-epicatechin, a flavonol present in high concentration in the cocoa, has cardioprotective effects. This study aimed to evaluate the impact of (-)-epicatechin on the development of dilated cardiomyopathy in a δ sarcoglycan null mouse model. METHODS AND RESULTS: δ Sarcoglycan null mice were treated for 15 days with (-)-epicatechin. Histological and morphometric analysis of the hearts treated mutant mice showed significant reduction of the vasoconstrictions in the coronary arteries as well as fewer areas with fibrosis and a reduction in the loss of the ventricular wall. On the contrary, it was observed a thickening of this region. By Western blot analysis, it was shown, and increment in the phosphorylation level of eNOS and PI3K/AKT/mTOR/p70S6K proteins in the heart of the (-)-epicatechin treated animals. On the other hand, we observed a significantly decreased level of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) heart failure markers. CONCLUSION: All the results indicate that (-)-epicatechin has the potential to prevent the development of dilated cardiomyopathy of genetic origin and encourages the use of this flavonol as a pharmacological therapy for dilated cardiomyopathy and heart failure diseases.

The TGFß pathway is a key player for the endothelial-to-hematopoietic transition in the embryonic aorta.

The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor ß (TGFß) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGFß signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGFß pathway is preferentially balanced with a prominent role of Alk1/TgfßR2/Smad1 and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acvrl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGFß through the Alk1/TgfßR2 receptor axis is acting on endothelial cells to produce hematopoiesis.

Polymer waveguide couplers based on metal nanoparticle-polymer nanocomposites.

In this work Au nanoparticles (AuNPs) are incorporated into poly(methyl methacrylate) (PMMA) waveguides to develop optical couplers that are compatible with planar organic polymer photonics. A method for growing AuNPs (of 10 to 100 nm in size) inside the commercially available Novolak resist is proposed with the intention of tuning the plasmon resonance and the absorption/scattering efficiencies inside the patterned structures. The refractive index of the MNP-Novolak nanocomposite (MNPs: noble metal nanoparticles) is carefully analysed both experimentally and numerically in order to find the appropriate fabrication conditions (filling factor and growth time) to optimize the scattering cross section at a desired wavelength. Then the nanocomposite is patterned inside a PMMA waveguide to exploit its scattering properties to couple and guide a normal incident laser light beam along the polymer. In this way, light coupling is experimentally demonstrated in a broad wavelength range (404-780 nm). Due to the elliptical shape of the MNPs the nanocomposite demonstrates a birefringence, which enhances the coupling to the TE mode up to efficiencies of around 1%.

Association of the rs1801133 variant in the MTHFR gene and sporadic Parkinson's disease.

The MTHFR gene has been reported as a susceptibility locus for sporadic Parkinson's disease (sPD). The functional variant rs1801133 has been linked to hyperhomocysteinemia and dopaminergic cell death. Among different populations, Mexican-Mestizos (most present-day Mexicans) have the highest frequency of this variant. Therefore, we sought to determine a possible association of rs1801133 with SPD. In total, 356 individuals were included: 140 patients with PD, diagnosed according to the Queen Square Brain Bank criteria, and 216 neurologically healthy controls. Genotyping was performed using TaqMan probes for rs1801133 and real-time PCR. Logistic regression analysis with adjustment for smoking and gender was used to test for an association between genotype and SPD. The CC genotype was associated with SPD; exp() = 2.06; 95% CI: 1.101-3.873, p = 0.024. No association with age at onset, cognitive impairment or gender was found in our study group. Our data suggest an important role of MTHFR gene variants in SPD.

Efficient excitation of photoluminescence in a two-dimensional waveguide consisting of a quantum dot-polymer sandwich-type structure.

In this Letter, we study a new kind of organic polymer waveguide numerically and experimentally by combining an ultrathin (10-50 nm) layer of compactly packed CdSe/ZnS core/shell colloidal quantum dots (QDs) sandwiched between two cladding poly(methyl methacrylate) (PMMA) layers. When a pumping laser beam is coupled into the waveguide edge, light is mostly confined around the QD layer, improving the efficiency of excitation. Moreover, the absence of losses in the claddings allows the propagation of the pumping laser beam along the entire waveguide length; hence, a high-intensity photoluminescence (PL) is produced. Furthermore, a novel fabrication technology is developed to pattern the PMMA into ridge structures by UV lithography in order to provide additional light confinement. The sandwich-type waveguide is analyzed in comparison to a similar one formed by a PMMA film homogeneously doped by the same QDs. A 100-fold enhancement in the waveguided PL is found for the sandwich-type case due to the higher concentration of QDs inside the waveguide.

Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

Trombo mural en endoprótesis aórticas abdominales: factores predictivos y evolución clínica / Mural thrombus in abdominal aortic endograft: Predictive factors and clinical progress

INTRODUCCIÓN: El incremento del tratamiento endovascular en aneurismas de aorta abdominal ha dado lugar a nuevas complicaciones, como la formación de trombo intraprótesis, cuya aparición no está exenta de riesgos. OBJETIVOS: Conocer la incidencia de trombo mural, su evolución clínica y determinar qué factores pueden influir directamente en su desarrollo. MATERIAL Y MÉTODOS: Revisamos retrospectivamente (julio 2006-octubre 2011) pacientes con reparación endovascular de aneurismas de aorta abdominal y seguimiento por angiografía tomográfica computarizada superior a 6 meses. Estudiamos la aparición de trombo mural en relación con características de la endoprótesis (tipo, material, longitud, ratio [R2 / (r12 + r22)] y permeabilidad de las arterias iliacas internas) mediante tablas de contingencia, ANOVA de un factor y regresión logística. RESULTADOS: Recogimos 63 casos con seguimiento medio de 17,43 meses. La incidencia de trombo mural fue de 22,2% (14), de los cuales el 78,6% (11) se desarrollaron durante el primer mes y el 21,4% (3) en los 6 siguientes. Observamos mayor incidencia para Excluder(R) (7 de 18 [28%]) y Zenith(R) (5 de 8 [62,5%]) (p = 0,010), siendo la ratio el único factor predictivo de formación de trombo, tanto en el análisis bivariante (p = 0,001; intervalo de confianza del 95% 0,392-1,453) como en la regresión logística (p = 0,021; odds ratio 3,424; intervalo de confianza del 95% [1,205-9,727]). En ningún caso hubo regresión de trombo. Solamente uno evolucionó a trombosis de rama a 17 meses de seguimiento, no precisando intervención adicional. CONCLUSIONES: El trombo mural intraprotésico es un hallazgo frecuente tras reparación endovascular en aneurismas de aorta abdominal, asociándose más a algunos tipos de endoprótesis. Hallar una discordancia importante de áreas puede ser útil como factor predictivo. En caso de detección precoz de trombo, recomendamos seguimiento más exhaustivo mediante angiografía tomográfica computarizada

INTRODUCTION: The increase in endovascular treatment of abdominal aortic aneurysms has led to seeing more complications, such as intraprosthesis thrombus formation, which is not without risk. OBJECTIVES: To determine the incidence of mural thrombus and the clinical course, and the factors that can directly influence its development. MATERIAL AND METHODS: A retrospective review (July 2006-October 2011) was conducted on patients with endovascular repair of abdominal aortic aneurysms, who were monitored with computed tomographic angiography for more than 6 months. A study was made of the appearance of mural thrombus in relation to the endograft characteristics (type, material, length, ratio [R2 / (r12 + r22)] and internal iliac artery patency) using contingency tables, ANOVA test, and logistic regression. RESULTS: A total of 63 cases were found, with an average follow-up of 17.43 months. The incidence of mural thrombus recorded was 22.2% (14), of which 78.6% (11) developed in the first month, and 21.4% (3) in the following 6 months. There was a higher incidence with Excluder(R) (7 of 18 [28%]) and Zenith(R) (5 of 8 [62.5%]) (P = 0.010), being the ratio the only predictor of thrombus formation, in both bivariate analysis (P =0.001; 95% confidence interval from 0.392 to 1.453) and logistic regression (P = 0.021; odds ratio 3.424; 95% CI 1.205 to 9.727). There were no cases of thrombus recurrence. Only one case progressed to branch thrombosis in 17 months of follow-up, which did not require additional intervention. CONCLUSIONS: Intra-prosthetic mural thrombus is commonly found after endovascular abdominal aortic aneurysms repair, being more associated to other types of endografts. Finding a major discrepancy area may be useful as a predictor. For early detection of thrombus, we recommend a closer monitoring with computed tomographic angiography

Demonstration of near infrared gas sensing using gold nanodisks on functionalized silicon.

In this work, we demonstrate experimentally the use of an array of gold nanodisks on functionalized silicon for chemosensing purposes. The metallic nanostructures are designed to display a very strong plasmonic resonance in the infrared regime, which results in highly sensitive sensing. Unlike usual experiments which are based on the functionalization of the metal surface, we functionalized here the silicon substrate. This silicon surface was modified chemically by buildup of an organosilane self-assembled monolayer (SAM) containing isocyanate as functional group. These groups allow for an easy surface regeneration by simple heating, thanks to the thermally reversible interaction isocyanate-analyte, which allows the cyclic use of the sensor. The technique showed a high sensitivity to surface binding events in gas and allowed the surface regeneration by heating of the sensor at 150 °C. A relative wavelength shift ∆λ(max)λ(0)=0.027 was obtained when the saturation level was reached.

Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1.

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. To date, 4 different genes have been identified as responsible for the presence of KS; however, in many cases no mutations have been found in any of these genes. Herein, we report the molecular findings regarding the analysis of fibroblast growth factor receptor 1 (FGFR1), prokineticin receptor 2 (PROKR2), and prokineticin (PROK2) in patients with KS. Twenty-four patients with KS were studied in whom mutations in KAL1 had been investigated previously. Polymerase chain reaction products from FGFR1, PROKR2, and PROK2 were sequenced and mutations were sought in the open reading frame of the 3 genes. Two patients presented a heterozygous T-to-G transversion in exon 2 (c.518T>G) of the PROKR2, which results in a leucine-to-arginine substitution at codon 173. Our results strengthen the hypothesis of possible digenic inheritance in some patients with KS. Likewise, our data extend previous reports demonstrating that PROKR2 plays a role in the etiology of this syndrome.

Full-length SRY protein is essential for DNA binding.

SRY directs testicular development. It has been suggested that the only high-mobility group (HMG) box of the SRY is important for the function of this protein; however, other studies have suggested that the N- and C-terminal regions are also involved in this process. Herein, we analysed and compared in vitro the DNA-binding activity of the full-length SRY and three mutants (HMG box alone, N-terminal less and C-terminal less SRY proteins). DNA-binding capability was analysed by mobility shift assays, optical density and dissociation constant by using pure non-fusion SRY proteins. The structure of the full-length SRY was carried out using a protein molecular model. The HMG box SRY alone and C-terminal less SRY proteins had a statistically diminished DNA binding in comparison with the full-length SRY. In contrast, the affinity for DNA of the N-terminal less SRY was relatively similar to the full-length SRY. Likewise, three-dimensional structure of the full-length SRY suggested that some residues of the C-terminal region of the SRY interact with DNA. We demonstrate the importance that full-length SRY has, particularly the C-terminal region of the protein, in DNA binding in vitro. Likewise, the affinity of the HMG box alone is clearly reduced when compared with the full-length SRY.

Charge dissipation in e-beam lithography with Novolak-based conducting polymer films.

Charging of common resist materials during electron beam (e-beam) writing leads to deflection of the electron beam path, which can result in significant pattern displacement. Here we report a new conducting polymer to eliminate charging. A common approach is to place the conducting layer underneath the e-beam resist layer. Conductivity equal or greater than 10(-4) S cm(-1) has been reported to prevent pattern displacement. Some other properties such as a flat surface layer, chemical inertness and insolubility in both the top resist solvent and the developer are also necessary. The way to achieve all these properties consisted in synthesizing a conducting polymer inside an insulating polymer to form an interpenetrating polymer network (IPN) which could combine their properties. Novolak was used as the host polymer and terthiophene (3T) as the monomer to polymerize. Cu(ClO(4))(2) initiates simultaneously the oxidative polymerization of the 3T and its subsequent doping inside Novolak during the bake step in a one-step reaction. Solvent-resistant and homogeneous conducting films with smooth surfaces were achieved. The conductivity was of the order of 10(-2) S cm(-1). Patterning of the top resist was carried out without disturbing its lithographic performance.

Evaluación de la calidad y suficiencia de la alimentación de un grupo de mujeres de la Región Metropolitana de Chile / Assessment of quality and adequacy of the diet of women from the Metropolitan Region of Chile

El propósito de este estudio fue aportar nuevos antecedentes acerca de la suficiencia y calidad de la alimentación de mujeres adultas chilenas. Se determinó en 54 mujeres el Índice de Masa Corporal (IMC) y la calidad de la alimentación mediante su adecuación a las recomendaciones de energía y nutrientes, porciones de alimentos recomendadas por las Guías de Alimentación Chilenas y al Índice de Alimentación Saludable (ISA) adaptado. Se observó un 55 por ciento de exceso de peso, una buena adecuación del consumo de vitamina C y ácido Fólico y baja de energía, hierro, calcio, fibra. Para verduras, frutas y lácteos el consumo promedio fue menos del 50 por ciento de las porciones recomendadas. El G por ciento fue de 32.6 por ciento con un aporte de grasas saturadas menor del 10 por ciento y de colesterol menor al máximo sugerido. Sólo el 20.4 por ciento consumía una alimentación saludable. No se encontró una asociación entre IMC y consumo de energía e ISA. Se concluye que una importante proporción del grupo de mujeres estudiadas presenta una alimentación poco saludable, con un inadecuado consumo de alimentos y desequilibrios en el aporte de nutrientes.

The purpose of this study was to provide new data on the quality and adequacy of the diet of Chilean women. Body mass index (BMI) and the quality of the diet in terms of adequacy of nutrient intakes, food portions as suggested to the Chilean nutrient pyramid, and an adaptation of the healthy food index (HFI) were evaluated in a group of 54 women. Fifty-five percent of subjects had excess body weight. Adequate intakes of vitamin C and folic acid but not energy, iron, calcium, fiber were observed. Mean intakes of vegetables, fruits and dairy products were less than 50 percent of the recommended portions. F percent was 32.6 percent. Saturated fat was less than 10 percent and cholesterol intake less than maximum suggested. Appropriate values of HFI were obtained in 20.4 percent of individuals. No associations were found among BMI and energy intake and HFI. It is concluded that a high proportion of women presents less-than-adequate diets.

No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome.

BACKGROUND: Etiology and inheritance pattern in polycystic ovary syndrome (PCOS) remain uncertain. Granulosa cells from follicles of women with PCOS have little, if any, aromatase (encoded by the CYP19 gene) activity; follicles contain low levels of estradiol, P450arom mRNA and aromatase stimulating bioactivity. Mice with targeted disruption of the CYP19 gene present cystic follicles. It has been proposed that chronic exposure to high levels of LH, because of aromatase deficiency, determines the development of ovarian cysts. Herein, we investigated if mutations in the CYP19 gene and/or its ovary promoter are causal in patients with PCOS. METHODS: Twenty-five patients with PCOS and 50 control women were studied. PCR analysis of genomic DNA and complete sequence of all exons of the aromatase gene and its ovary promoter were performed. RESULTS: No heterozygous or homozygous mutant alleles were present in any of the patients studied. CONCLUSIONS: In the population studied, mutations of the P450arom gene or its promoter are not the cause of PCOS. However, these findings do not preclude the possible importance of an aromatase disorder in PCOS etiology. Variations in aromatase complex function could play a role in PCOS etiology, but the determinants of such variations might be located in other genes.

A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis.

Aetiology of mixed gonadal dysgenesis (MGD) has not been completely elucidated. Molecular analyses have failed to demonstrate the presence of mutations in sex-determining region on Y chromosome (SRY); it has been suggested that these individuals may bear mutations in other genes involved in the testis-determining pathway. Desert hedgehog's (DHH) importance regarding male sex differentiation has been demonstrated in various studies we describe here, for the first time, two cases of MGD in which a monoallelic single base deletion in DHH is associated with the disorder. Genomic DNA was isolated from paraffin-embedded gonad tissue from 10 unrelated patients with MGD and three controls; in addition to, DNA from peripheral blood leukocytes in 100 controls. Coding sequence abnormalities in DHH were assessed by exon-specific PCR, single-stranded conformation polymorphism (SSCP) and direct sequencing. In two patients, a heterozygous 1086delG in exon 3 was found. Comparing previously described mutations in DHH to the one observed in this study, we can affirm that the phenotypic spectrum of patients with gonadal dysgenesis due to mutations in DHH is variable. This study continues to demonstrate the importance that DHH has in mammalian male sexual differentiation, providing extended evidence that DHH constitutes a key gene in gonadal differentiation.

Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis.

Mutations of SRY are the cause of complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. We describe the first report in which three cases of 46,XY complete PGD are attributed to mutations of the Desert hedgehog (DHH) gene. DHH was sequenced using genomic DNA from paraffin-embedded gonadal tissue from six patients with complete 46,XY PGD. Mutations were found in three patients: a homozygous mutation in exon 2, responsible for a L162P, and a homozygous 1086delG in exon 3. Mutated individuals displayed 46,XY complete PGD, differentiating from the only previously described patient with a homozygous DHH mutation, who exhibited a partial form of PGD with polyneuropathy, suggesting that localization of mutations influence phenotypic expression. This constitutes the first report where mutations of DHH are associated with the presence of 46,XY complete PGD, demonstrating that the genetic origin of this entity is heterogeneous and that disorders in other genes, different from SRY, involved in the testis-determining pathway are implicated in abnormal testicular differentiation in humans. These data extend previous reports demonstrating DHH is a key gene in gonadal differentiation.

Identification of three novel mutations in the KAL1 gene in patients with Kallmann syndrome.

Kallmann's syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. Genetic defects have been observed throughout the KAL1 gene, located on the Xp22.3 region, in less than 50% of the patients. We report the molecular study of the KAL1 gene in 12 males with KS. PCR of the 14 exons of the KAL1 gene was performed on genomic DNA. PCR products of all exons were purified and sequenced. Three novel genetic defects were found. One patient exhibited a complete deletion of exon 5. The second presented a duplication of nucleotides 158-168; this insertion causes a termination codon (TGA) within the same exon. The third presented a mutation in exon 6, in which codon 262 changes from arginine to a stop codon. In the remaining nine individuals, no mutations were found. Three previously reported polymorphic changes were also documented. The deletion of exon 5 occurs within the region encoding the first fibronectin type III-like repeat of the KAL1 protein, this being the first KS patient who exhibits a complete deletion of a single exon of the KAL1 gene. The duplication of nucleotides in exon 1 is located in the conserved cysteine-rich N-terminal region that corresponds to the whey acidic protein motif, affecting the KAL1 protein either by interrupting the normal transcription or stopping the translation at the stop codon. The last novel mutation, a stop codon in exon 6, is located within the region encoding the first fibronectin type III-like repeat of the KAL1 protein. The absence of mutations in the majority of patients suggests the possibility of the existence of other genes involved or that in certain individuals the presence of various polymorphisms within the KAL1 gene could predispose to disease, as has been demonstrated in other pathological entities.

Effect of counseling to improve compliance in Mexican women receiving depot-medroxyprogesterone acetate.

This study purported to determine the effect of pretreatment counseling upon discontinuation of 150 mg depot-medroxyprogesterone acetate (Depo-Provera) given for contraception. A total of 350 Mexican women participated: 175 received detailed structured pretreatment counseling about the hormonal effects of the injectable vs. routine counseling upon duration of use and efficacy of the method. Study termination rates were significantly lower in the structured counseling group than in the control group. Cumulative life table discontinuation rates were 17% (30/175) and 43.4% (76/175), respectively (p <0.05). The most common reasons for terminating DMPA were menstrual changes (8.6 and 32% for counseling and control group, respectively). The findings suggest that pretreatment counseling on expected side effects increases the continuation rates of DMPA users.

A comparison of marital interaction patterns between couples in which the husband does or does not have Alzheimer's disease.

UNLABELLED: Objectives. Our main purpose was to examine similarities and differences in patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for moderately impaired husbands with probable AD and 27 noncaregiving wives from comparable sociodemographic backgrounds were videotaped in their homes during both mealtime and a future event planning task. In addition, they completed self-report questionnaires to assess depression, stress, relationship mutuality, and perceived hope. Results. Compared with their counterparts, caregiving wives reported higher levels of depression and stress, but similar shared values and closeness. For the three factors developed from the Marital Interaction Coding System (MICS, version IV; Supportive Facilitative, and Rapport Building), a complex pattern of results was found in which disease status, type of task, and gender interacted significantly. Noncaregiving couples were more interactive overall and expressed more support to each other. Caregiving wives were found to be most facilitative during the planning task, whereas AD husbands were highest on interactions that built rapport (e.g., smiling) during that same task. Caregiving wives actually increased their facilitative behavior from the mealtime to planning task, probably reflecting the increased demand characteristics of the latter. DISCUSSION: This study is one of a small body of literature to describe the negative impact of AD on spousal communication as observed and coded in two videotaped interaction situations in the home. Suggestions are made for future research, including the inclusion of longitudinal designs and non-Caucasian couples.

A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene.

BACKGROUND AND OBJECTIVE: Mutations in the GnRH receptor (GnRH-R) gene cause hypogonadotrophic hypogonadism. Here, we present the molecular studies of the GnRH-R gene in three families with isolated hypogonadotrophic hypogonadism. PATIENTS: Three unrelated families, with at least two members diagnosed with isolated hypogonadotrophic hypogonadism were included. MEASUREMENTS: DNA sequencing was performed after polymerase chain reaction amplification of each of the three exons of the gene. RESULTS: A novel homozygous missense mutation, at nucleotide 268, turning glutamic acid into lysine, located at the second transmembrane domain of the GnRH-R gene was found in two patients pertaining to one of the families studied. Both parents and an unaffected brother were heterozygous carriers of one mutant allele, an unaffected sister was homozygote wild type. In the other two affected families no mutations were found in the GnRH-R gene. CONCLUSIONS: This constitutes the first description of an spontaneous mutation located at the second transmembrane domain (Glu90Lys) of the GnRH-R, indicating that the integrity of glutamic acid at this position is crucial for receptor function. Also this report, complementing others, demonstrates that mutations are distributed throughout the GnRH-R gene and that as in the only other homozygous mutation previously described, affected patients present a complete form of hypogonadotrophic hypogonadism. Due to the fact that apparently consanguinity was present in our affected family, we presume that the mutation derived from a common ancestor, by a founder gene effect.