12-item version of Boston Naming Test: usefulness in the diagnosis of primary progressive aphasia, frontotemporal dementia, and Alzheimer's disease.

The 12-item version of the Boston Naming Test (BNT) was adapted to Argentina for the detection of dementia due to Alzheimer's disease (AD), with scores similar to the original 60-item version (sensitivity and specificity of 85 and 94%, respectively) without demographic influence (age and educational level). To date, no publications on the use of abbreviated BNT in other degenerative pathologies with language impairment have been reported. Objective: The objective of this study was to evaluate the usefulness of 12-item BNT in primary progressive aphasia (PPA), the behavioral variant of frontotemporal dementia (FTDbv), and AD. Methods: Notably, 47 patients with probable AD (NIA-AA 2011) - clinical dementia rating (CDR) 0.5-1, 55 with FTDbv, 17 with PPA, and 46 controls were evaluated and matched for age and education. Exclusion criteria were as follows: alcoholism, other previous neurological or psychiatric illnesses, and education <4 years. All were assessed with a full neuropsychological battery and a 12-item version of BNT. Results: Median scores of 12-item BNT were as follows: PPA: 3.87 (SD=2.99), AD: 6.13 (SD=3.03); FTDbv: 8.41 (SD=2.53); and controls: 10.22 (SD=1.82). Receiver Operating Characteristic (ROC) curves were plotted. Conclusions: The 12-item version of BNT can be useful, simple, and fast to identify and differentiate PPA, FTDbv, and AD from controls while retaining the discriminative ability of the original version.

A versão de 12 itens do Teste de Nomeação de Boston (TNB) foi adaptada para a Argentina para a detecção de demência por doença de Alzheimer (DA), com escores semelhantes à versão original de 60 itens (sensibilidade e especificidade de 85 e 94%, respectivamente) sem influência demográfica (idade e escolaridade). Até o momento, não foram relatadas publicações sobre o uso do TNB abreviado em outras patologias degenerativas com comprometimento da linguagem. Objetivo: avaliar a utilidade do TNB de 12 itens na afasia progressiva primária (APP), na variante comportamental da demência frontotemporal (DFT) e na doença de Alzheimer (DA). Métodos: 47 prováveis DA (NIA-AA 2011) ­ CDR 0,5­1, 55 DFT, 17 APP e 46 controles foram avaliados e pareados por idade e escolaridade. Critérios de exclusão: alcoolismo, outras doenças neurológicas ou psiquiátricas prévias e escolaridade <4 anos. Todos foram avaliados com uma bateria neuropsicológica completa e versão de 12 itens do TNB. Resultados: medianas das pontuações de 12 itens TNB: APP: 3,87 (DP=2,99), DA: 6,13 (DP=3,03); DFT: 8,41 (DP=2,53) e Controles: 10,22 (DP=1,82). As curvas ROC foram traçadas. Conclusões: O TNB de 12 itens pode ser útil, simples e rápido para identificar e diferenciar APP, DFT e DA nos controles, mantendo a capacidade discriminativa da versão original.

12-item version of Boston Naming Test: usefulness in the diagnosis of primary progressive aphasia, frontotemporal dementia, and Alzheimer's disease / Teste de nomeação de boston de 12 itens: utilidade no diagnóstico de afasia progressiva primária, demência frontotemporal e doença de alzheimer

ABSTRACT. The 12-item version of the Boston Naming Test (BNT) was adapted to Argentina for the detection of dementia due to Alzheimer's disease (AD), with scores similar to the original 60-item version (sensitivity and specificity of 85 and 94%, respectively) without demographic influence (age and educational level). To date, no publications on the use of abbreviated BNT in other degenerative pathologies with language impairment have been reported. Objective: The objective of this study was to evaluate the usefulness of 12-item BNT in primary progressive aphasia (PPA), the behavioral variant of frontotemporal dementia (FTDbv), and AD. Methods: Notably, 47 patients with probable AD (NIA-AA 2011) — clinical dementia rating (CDR) 0.5-1, 55 with FTDbv, 17 with PPA, and 46 controls were evaluated and matched for age and education. Exclusion criteria were as follows: alcoholism, other previous neurological or psychiatric illnesses, and education <4 years. All were assessed with a full neuropsychological battery and a 12-item version of BNT. Results: Median scores of 12-item BNT were as follows: PPA: 3.87 (SD=2.99), AD: 6.13 (SD=3.03); FTDbv: 8.41 (SD=2.53); and controls: 10.22 (SD=1.82). Receiver Operating Characteristic (ROC) curves were plotted. Conclusions: The 12-item version of BNT can be useful, simple, and fast to identify and differentiate PPA, FTDbv, and AD from controls while retaining the discriminative ability of the original version.

RESUMO. A versão de 12 itens do Teste de Nomeação de Boston (TNB) foi adaptada para a Argentina para a detecção de demência por doença de Alzheimer (DA), com escores semelhantes à versão original de 60 itens (sensibilidade e especificidade de 85 e 94%, respectivamente) sem influência demográfica (idade e escolaridade). Até o momento, não foram relatadas publicações sobre o uso do TNB abreviado em outras patologias degenerativas com comprometimento da linguagem. Objetivo: avaliar a utilidade do TNB de 12 itens na afasia progressiva primária (APP), na variante comportamental da demência frontotemporal (DFT) e na doença de Alzheimer (DA). Métodos: 47 prováveis DA (NIA-AA 2011) — CDR 0,5-1, 55 DFT, 17 APP e 46 controles foram avaliados e pareados por idade e escolaridade. Critérios de exclusão: alcoolismo, outras doenças neurológicas ou psiquiátricas prévias e escolaridade <4 anos. Todos foram avaliados com uma bateria neuropsicológica completa e versão de 12 itens do TNB. Resultados: medianas das pontuações de 12 itens TNB: APP: 3,87 (DP=2,99), DA: 6,13 (DP=3,03); DFT: 8,41 (DP=2,53) e Controles: 10,22 (DP=1,82). As curvas ROC foram traçadas. Conclusões: O TNB de 12 itens pode ser útil, simples e rápido para identificar e diferenciar APP, DFT e DA nos controles, mantendo a capacidade discriminativa da versão original.

Genetic dissection of the BRCA2 promoter and transcriptional impact of DNA variants.

PURPOSE: Promoter mutations may affect transcription and can be associated with human diseases. However, the promoters of the breast cancer (BC) genes are not regularly screened. Our goal was to investigate the BRCA2 promoter in order to study a possible correlation between impaired transcription and disease. METHODS: The proximal and core promoter of the BRCA2 gene was sequenced in 95 high-risk BC patients. A BRCA2-promoter insert [- 938 to + 312 from the transcription start site (TSS)] was generated and cloned into the firefly luciferase vector pGL4.10. Promoter variants and deletions were introduced by site-directed mutagenesis and quantified by Dual-Luciferase assays and semi-quantitative RT-PCR. RESULTS: Three different variants were detected in high-risk BC patients: rs3092989, rs206118, and rs563971900. Functional mapping of 13 overlapping deletions revealed four down-regulating segments (TSS positions): -59_-10del/µdel3 (16% of activity of the wild-type construct), -104_-55del/µdel4 (62%), -239_-190del/µdel7 (39%), -464_-415/µdel12 (78%), suggesting the presence therein of putative transcriptional activator motifs. Additionally, six microdeletions rendered luciferase overexpression: +32_+81del/µdel1 (356%), -14_+36del/µdel2 (180%), -194_-145del/µdel6 (154%), -284_-235del/µdel8 (168%), -329_-280del/µdel9 (111%), and -509_-460del/µdel13 (139%), which is indicative of repressor elements. Functional assays of 15 promoter variants (including those detected in patients) showed that ten of them significantly altered expression with seven up-regulating (113-163%) and three down-regulating (rs551887850_G, rs570548398_T, rs55880202_T; 72-83%) SNPs. Eight of them were located in an ENCODE-DNase Hypersensitive Cluster (TSS - 185 to + 105) where most active transcriptional motifs are known to be placed. CONCLUSIONS: BRCA2 expression is highly sensitive to promoter variations as most of them induced relevant changes. Moreover, we mapped critical regions of the BRCA2 promoter that may constitute potential targets for regulatory variants. Three SNPs moderately decreased luciferase activity, but confirmation of its potential pathogenicity requires further analysis. These data reinforce the need to screen the promoter regions of breast cancer genes with a view to discovering novel deleterious mutations.

Alterations in bone morphogenetic protein 15, growth differentiation factor 9, and gene expression in granulosa cells in preovulatory follicles of dairy cows given porcine LH.

In a previous work, using porcine LH (pLH) in lieu of GnRH for synchronizing ovulation in dairy cows improved pregnancy rates without increasing plasma progesterone concentrations after ovulation. The LH profile is known to remain elevated above basal concentrations (≥1 ng/mL) for up to 20 hours in pLH-treated cows compared to less than 6 hours in GnRH-treated cows. Because LH triggers a cascade of signaling networks in the preovulatory follicle to promote final maturation and support oocyte competence, we hypothesized that dissimilar LH profiles will differentially regulate the intrafollicular factors and expression of downstream genes associated with improved oocyte competence. Specific objectives were to determine differences in the abundance of oocyte-secreted factors in the preovulatory follicular fluid and target genes in granulosa cells associated with oocyte competence, in response to exogenous porcine LH or GnRH-induced endogenous bovine LH exposure, in dairy cows. Follicular contents were aspirated by a transvaginal ultrasound-guided procedure from the preovulatory follicle of cyclic, nonlactating Holstein cows 21 ± 1 hour after administration of either pLH (25-mg) or GnRH (100-µg). Mature forms of bone morphogenetic protein 15, growth differentiation factor 9, and transforming growth factorß1 were approximately 2-fold more abundant in pLH-treated cows which were exposed to an extended, low LH profile, than in GnRH-treated cows that had a short, high LH profile. The relative abundance of messenger RNA for cyclooxygenase-2, LH receptor, and progesterone receptor in granulosa cells, was about two-, eight-, and two-fold higher, respectively, in cows subjected to pLH than GnRH treatment. We infer that the improved pregnancy rate after pLH-induced ovulation reported previously, occurred through greater activation of intrafollicular transforming growth factor-ß1 superfamily members, as these proteins promote cumulus expansion and oocyte competence.

Fecal and urinary lignans, intrafollicular estradiol, and endometrial receptors in lactating dairy cows fed diets supplemented with hydrogenated animal fat, flaxseed or sunflower seed.

We hypothesized that the inclusion of flaxseed in the diets of lactating dairy cows will increase urinary and fecal concentrations of the lignans, secoisolariciresinol diglycoside (SDG), enterolactone and enterodiol, reduce intrafollicular concentrations of IGF-I and estradiol, and subsequently reduce estradiol and oxytocin receptor expression in the endometrium. To test this hypothesis, 27 cycling, lactating Holstein cows were assigned to 1 of 3 diets supplemented with saturated fatty acids (SAT), flax (FLX), or sunflower (SUN) seed. Rations were formulated to provide 750 g supplemental fat/cow/d in all dietary groups. Ovulation (Day 0) was synchronized, and 5 d later, follicles>8 mm were ablated by an ultrasound-guided procedure in all cows. Samples of blood (Days 0 to 14), follicular fluid (Day 5 and 15), endometrium (Day 15), as well as urine and feces were collected in a subset of the animals. The fecal concentrations of SDG and enterodiol were higher (P<0.05) in cows fed FLX than in those fed SAT or SUN. Enterodiol increased (P<0.05) in urine samples of cows fed FLX, compared to those of cows fed SUN. However, follicular estradiol concentrations on Day 5 and 15 and endometrial concentrations of estradiol and oxytocin receptors on Day 15 did not differ among the dietary groups. Mean plasma progesterone concentrations were higher (P<0.05) in cows fed FLX and SUN than in those fed SAT. In summary, a diet supplemented with flaxseed increased the concentrations of SDG and enterodiol in feces, as hypothesized, but did not alter intrafollicular concentrations of IGF-I or estradiol, or endometrial populations of oxytocin or estrogen receptors in lactating dairy cows.

Effects of estradiol cypionate (ECP) on ovarian follicular dynamics, synchrony of ovulation, and fertility in CIDR-based, fixed-time AI programs in beef heifers.

Estradiol cypionate (ECP) was used in beef heifers receiving a controlled internal drug release (CIDR; insertion = Day 0) device for fixed-time AI (FTAI) in four experiments. In Experiment 1, heifers (n = 24) received 1mg ECP or 1mg ECP plus 50mg commercial progesterone (CP) preparation i.m. on Day 0. Eight or 9 days later, CIDR were removed, PGF was administered and heifers were allocated to receive 0.5mg ECP i.m. concurrently (ECP0) or 24h later (ECP24). There was no effect of treatment (P = 0.6) on mean (+/-S.E.M.) day of follicular wave emergence (3.9+/-0.4 days). Interval from CIDR removal to ovulation was affected (P<0.05) only by duration of CIDR treatment (88.3+/-3.8h versus 76.4+/-4.1h; 8 days versus 9 days, respectively). In Experiment 2, 58 heifers received 100mg progesterone and either 5mg estradiol-17beta or 1mg ECP i.m. (E-17beta and ECP groups, respectively) on Day 0. Seven (E-17beta group) or 9 days (ECP group) later, CIDR were removed, PGF was administered and heifers received ECP (as in Experiment 1) or 1mg EB 24h after CIDR removal, with FTAI 58-60h after CIDR removal. Follicular wave emergence was later (P<0.02) and more variable (P<0.002) in heifers given ECP than in those given E-17beta (4.1+/-0.4 days versus 3.3+/-0.1 days), but pregnancy rate was unaffected (overall, 69%; P = 0.2). In Experiment 3, 30 heifers received a CIDR device and 5mg E-17beta, with or without 100mg progesterone (P) i.m. on Day 0. On Day 7, CIDR were removed and heifers received ECP as described in Experiment 1 or no estradiol (Control). Intervals from CIDR removal to ovulation were shorter (P<0.05) in ECP0 (81.6+/-5.0h) and ECP24 (86.4+/-3.5h) groups than in the Control group (98.4+/-5.6h). In Experiment 4, heifers (n = 300) received a CIDR device, E-17beta, P, and PGF (as in Experiment 3) and after CIDR removal were allocated to three groups (as in Experiment 2), with FTAI 54-56h (ECP0) or 56-58h (ECP24 and EB24) after CIDR removal. Pregnancy rate did not differ among groups (overall, 63.6%, P = 0.96). In summary, although 1mg ECP (with or without progesterone) was less efficacious than 5mg E-17beta plus 100mg progesterone for synchronizing follicular wave emergence, 0.5mg ECP (at CIDR removal or 24h later) induced a synchronous ovulation with an acceptable pregnancy rate to fixed-time AI.

Effects of dose and route of administration of cloprostenol on luteolysis, estrus and ovulation in beef heifers.

Four experiments were conducted (with crossbred beef heifers) to determine the effects of dose and route of administration of cloprostenol on luteolysis, estrus and ovulation. In Experiment 1, 19 heifers with a CL > or = 17 mm in diameter were randomly allocated to receive cloprostenol as follows: 100 microg s.c., 250 microg s.c., or 500 microg i.m. Heifers given 100 microg s.c. had a longer (P<0.03) interval (120.0 h+/-10.7 h; mean+/-S.E.M.) from treatment to ovulation than those given either 250 microg s.c. or 500 microg i.m. (92.0 h+/-7.4 h and 84.0 h+/-8.2 h, respectively). In Experiment 2, 28 heifers were given porcine LH (pLH), followed in 7 days by cloprostenol (same doses and routes as in Experiment 1), and a second dose of pLH 48 h after cloprostenol. Luteolysis occurred in all heifers, and no difference was detected among treatment groups in the interval from cloprostenol treatment to ovulation (mean, 101 h; P<0.9). In Experiment 3, 38 heifers at random stages of the estrous cycle (but with plasma progesterone concentrations > or =1.0 ng/ml) received 500 or 125 microg cloprostenol by either i.m. or s.c. injection (2/2 factorial design). There was no difference (P<0.4) among groups in the proportions of heifers that were detected in estrus or that ovulated. However, the interval from cloprostenol treatment to estrus was shorter (P<0.02) in the group that received 500 microg i.m. (58.5h) than in the other three groups (500 microg s.c., 75.0 h; 125 microg i.m., 78.0 h; and 125 microg s.c., 82.3h). In Experiment 4, 36 heifers were treated (as in Experiment 3) on Day 7 after ovulation. The proportions of heifers detected in estrus and ovulating after 125 microg s.c. (33 and 44%, respectively) or 125 microg i.m. (55 and 55%) were lower (P<0.05) than in those that received 500 microg s.c. (100 and 100%), but not different from those receiving 500 microg i.m. (78 and 89%, respectively). Overall, ovulation was detected in 9/18 heifers given 125 microg and 17/18 heifers given 500 microg of cloprostenol, on Day 7 (P<0.01) and was detected in 17/20 heifers given 125 microg and 18/18 heifers given 500 microg of cloprostenol, at random stages of the estrous cycle (P>0.05). Although there was no significant difference in luteolytic efficacy between i.m. and s.c. injections of the recommended dose (500 microg) of cloprostenol, variability in responsiveness to a reduced dose depended upon CL sensitivity, therefore, reduced doses cannot be recommended for routine use.