Progesterone concentrations, exogenous equine chorionic gonadotropin, and timing of prostaglandin F-2 alpha treatment affect fertility in postpuberal Nelore heifers

Two experiments were performed to test the hypothesis that elevated progesterone concentrations impair pregnancy rate to timed artificial insemination (TAI) in postpuberal Nelore heifers. In Experiment 1, postpuberal Nelore heifers (n = 398) received 2 mg estradiol benzoate (EB) and either a new progesterone-releasing intravaginal device containing 1.9 g of progesterone (CIDR) (first use) or a CIDR previously used for 9 d (second use) or for 18 d (third use) on Day 0, 12.5 mg prostaglandin F-2 alpha (PGF(2 alpha)) on Day 7, 0.5 mg estradiol cypionate (ECP) and CIDR withdrawal on Day 9, and TAI on Day 11. Largest ovarian follicle diameter was determined on Day 11. The third-use CIDR treatment increased largest ovarian follicle diameter and pregnancy rate. Conception to TAI was reduced in heifers with smaller follicles in the first- and second-use CIDR treatments, but not in the third-use CID treatment. In Experiment 2, postpuberal Nelore heifers received the synchronization treatment described in Experiment 1 or received 12.5 mg PGF2. on Day 9 rather than Day 7. In addition, 50% of heifers received 300 IU equine chorionic gonadotropin (eCG) on Day 9. Heifers were either TAI (Experiment 2a; n = 199) or Al after detection of estrus (Experiment 2b; n = 125 of 202). In Experiment 2a, treatment with cCG increased pregnancy rate to TAI in heifers that received PGF2. on Day 9 but not on Day 7 and in heifers that received a first-use CIDR but not in heifers that received a third-use CIDR. Treatments did not influence reproductive performance in Experiment 2b. In summary, pregnancy rate to TAI in postpuberal Nelore heifers was optimized when lower concentrations of cxogcnous progesterone were administered, and eCG treatment was beneficial in heifers expected to have greater progesterone concentrations. (C) 2009 Elsevier B.V. All rights reserved.

Comparison of progesterone-based protocols with gonadotropin-releasing hormone or estradiol benzoate for timed artificial insemination or embryo transfer in lactating dairy cows

The objective was to compare two protocols for synchronizing ovulation in lactating Holstein cows submitted to timed AI (TAI) or timed ET (TET). Within each farm (n = 8), cows (n = 883; mean +/- SEM 166.24 +/- 3.27 d postpartum, yielding 36.8 +/- 0.34 kg of milk/d) were randomly assigned to receive either: 1) an intravaginal progesterone insert (CIDR (R)) with 1.9 g of progesterone + GnRH on Day -10, CIDR (R) withdrawal + PGF2 alpha on Day -3, and 1 mg estradiol cypionate on Day -2 (treatment GP-P-E; n(TAI) = 180; n(TET) = 260); or 2) a CIDR (R) insert + 2 mg estradiol benzoate on Day -10, PGF2 alpha on Day -3, CIDR (R) withdrawal + 1 mg estradiol cypionate on Day -2 (treatment EP-P-E; n(TAI) = 174; n(TET) = 269). Cows were subsequently randomly assigned to receive either TAT on Day 0 or TET on Day 7. Serum progesterone concentration on Day -3 was greater in GP-P-E than in EP-P-E (2.89 +/- 0.15 vs 2.29 +/- 0.15 ng/mL; P < 0.01), with no significant effect of group on serum progesterone on Day 7. Compared to cows submitted to TAI, those submitted to TET had greater pregnancy rates on Day 28 (44.0% [233/5291 vs 29.7% [105/354]; p < 0.001) and on Day 60 (37.6% [199/529] vs 26.5 [94/354]; P < 0.001). However, there were no effects of treatments (GP-P-E vs EP-P-E; P > 0.10) on synchronization (87.0% [383/440] vs 85.3% [378/443]), conception (TAI: 35.3% [55/156] vs 33.8% [50/148]; TET: 50.7% [115/227] vs 51.3% [118/230]) and pregnancy rates on Days 28 (TAT: 30.5% [55/180] vs 28.7% 150/174]; TET: 44.2% [115/260] vs 43.9% [118/2691) and 60 (TAI: 27.2% [49/80] vs 25.9% [45/174]; TET: 38.8% [101/260] vs 36.4% [98/269]). In conclusion, GP-P-E increased serum progesterone concentrations on Day -3, but rates of synchronization, conception, and pregnancy were not significantly different between cows submitted to GP-P-E and EP-P-E protocols, regardless of whether they were inseminated or received an embryo. (c) 2011 Elsevier B.V. All rights reserved.

Strategies to improve fertility in postpartum multiparous Bos indicus cows submitted to a fixed-time insemination protocol with gonadotropin-releasing hormone and prostaglandin F-2 alpha

In Exp. 1, we evaluated the effects of 2 lengths of progesterone exposure [CIDR (controlled intravaginal drug release); 7 vs. 14 d] before a modified CO-Synch protocol [50.0-mu g injection of GnRH 6.5 d before a 25.0-mg injection of PGF(2 alpha) followed by another injection of GnRH and fixed-time AI (TAI) 2 d after PGF(2 alpha)], with or without temporary weaning (TW) before GnRH treatments, on fertility of suckled multiparous Bos indicus cows (n = 283) and on calf performance. Timed AI pregnancy rates for cows receiving 7 d CIDR + TW, 7 d CIDR, 14 d CIDR + TW, and 14 d CIDR were 53, 47, 46, and 41%, respectively (P > 0.10). Calves submitted to two 48-h TW 6 d apart had decreased mean BW at 240 d (187.9 +/- 2.7 vs. 195.5 +/- 2.7 kg; P < 0.05), but BW at 420 d was not affected by TW (240.1 +/- 5.1 kg). In Exp. 2, we evaluated the effect of no treatment and treatment with or without a CIDR insert between GnRH and PGF(2 alpha) treatments of a modified CO-Synch protocol on pregnancy rate to TAI, and throughout a 90-d breeding season in suckled multiparous Bos indicus cows (n = 453). The inclusion of a CIDR between first GnRH and PGF(2 alpha) treatments of a modified CO-Synch protocol did not improve pregnancy rate (29 and 33% for cows receiving CO-Synch + CIDR and CO-Synch protocol, respectively), and cycling cows had poorer TAI pregnancy rates than anestrous cows treated with either synchronization protocol (21.7 vs. 40.7%; P < 0.05). However, regardless of treatment with CIDR, cows submitted to TAI protocol had greater (P < 0.05) pregnancy rates at 30 (54.8 vs. 11.2%), 60 (72.1 vs. 38.8%), and 90 d (82.0 vs. 57.9%) of breeding season than untreated cows.

Effects of temperament on pregnancy rates to fixed-timed AI in Bos indicus beef cows

The objective of the present experiment was to assess the effects of temperament on pregnancy rates to fixed-time AI (FTAI) in Bos indicus beef cows. A total of 761 multiparous lactating Nelore cows, originated from 4 different commercial cow-calf ranches, were evaluated for BCS and temperament at the time of FTAI (day 0). Temperament was assessed by chute score and exit velocity. Further, individual exit score was calculated by dividing exit velocity results into quintiles and assigning cows with a score from 1 to 5 (exit score: 1 = slowest cows; 5 = fastest cow). Temperament scores were calculated by averaging cow chute score and exit score. Cows were also classified for temperament type according to temperament score (<= 3 = adequate temperament, >3 = excitable temperament). Pregnancy status was verified by detecting a viable conceptus with rectal ultrasonography approximately 40 days after FTAI. Chute score, exit velocity, and temperament score were not correlated to BCS (P>0.31). Hence, BCS did not differ (P=0.30) according to temperament type (4.13 vs. 4.09 for cows with excitable and adequate temperament, respectively; SEM = 0.070). Pregnancy rates to FTAI tended to be negatively affected by temperament score (P=0.08), whereas the probability of cows becoming pregnant to FTAI was negatively associated with temperament score (linear effect, P<0.01). Accordingly, pregnancy rates were reduced (P=0.05) in cows with excitable temperament compared to cows with adequate temperament (35.3 vs. 42.8% of pregnant cows/total cows, respectively; SEM = 2.85). Pregnancy rates to FTAI were not affected by chute score (P=0.25), although the probability of cows becoming pregnant to FTAI tended to be negatively associated with chute score (linear effect, P=0.07). Pregnancy rates to FTAI were negatively affected by exit score (P=0.05), and the probability of cows becoming pregnant to FTAI was negatively associated with exit score and with actual exit velocity (linear effects, P<0.01). Results from this experiment indicate that excitable temperament is detrimental to pregnancy rates of B. indicus cows assigned to an estrus synchronization + FTAI protocol. Published by Elsevier B.V.

Effects of postbreeding gonadotropin treatments on conception rates of lactating dairy cows subjected to timed artificial insemination or embryo transfer in a tropical environment

The objective of experiment 1 was to evaluate the effects of treatments with human chorionic gonadotropin (hCG) or GnRH 7 d after induced ovulation on reproductive performance of lactating dairy cows submitted to timed artificial insemination (TAI) or timed embryo transfer (TET). A total of 834 potential breedings were used from 661 lactating Holstein cows (37.3 +/- 0.3 kg of milk/d). Cows had ovulation synchronized and were assigned randomly to receive TAI on d 0 or TET on d 7. Within each group, cows were assigned randomly to receive on d 7 no additional treatment (control; n(TAI) = 156; n(TET) = 126), a 100 mu g i.m. injection of GnRH (n(TAI) = 155; n(TET) = 124), or a 2,500 TU i.m. injection of hCG (ITA = 151; n(TET) = 122). Postbreeding treatment affected the percentages of pregnant cows at TET on d 28 (control: 38.1%; GnRH: 52.4%; hCG: 45.1%) and on d 60 (control: 32.5%; GnRH: 41.1%; hCG: 38.5%), but postbreeding treatment did not affect percentages of pregnant cows at TAT on d 28 (control: 30.1%; GnRH: 32.2%; hCG: 32.4%) or on d 60 (control: 25.6%; GnRH: 27.1%; hCG: 29.8%). The objective of experiment 2 was to evaluate the effect of a treatment with GnRH 7 d after TET on reproductive performance of lactating dairy cows that received a previous GnRH treatment at TET. A total of 285 potential breedings were used from 257 lactating Holstein cows (35.1 +/- 0.8 kg of milk/d). Cows had ovulation synchronized and were assigned for TET on d 7. Immediately after TET, all cows were treated with a 100 mu g i.m. injection of GnRH. on d 14, cows were assigned randomly to receive (G7-14; n = 147) or not (G7; n = 138) an additional injection of GnRH. Pregnancy diagnosis were performed on d 28 and 60. The additional treatment with GnRH on d 14 did not affect the percentages of pregnant cows on d 28 (G7: 48.5%; G7-14: 42.9%) or on d 60 (G7: 39.8%; G7-14: 37.4%). In conclusion, treatment with GnRH or hCG 7 d after induced ovulation increased conception rates in lactating dairy cows submitted to TET, but not in cows submitted to TAI. Moreover, treatment with GnRH 7 d after TET did not enhance reproductive performance of lactating dairy cows that received a previous GnRH treatment at TET.

Neighborhood Interactions and Larval Dispersal Behavior in Blowflies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Synchronization of ovulation in beef cows (Bos indicus) using GnRH, PGF2 alpha and estradiol benzoate

The objective of this study was to evaluate protocols for synchronizing ovulation in beef cattle. In Experiment 1, Nelore cows (Bos indicus) at random stages of the estrous cycle were assigned to 1 of the following treatments: Group GP controls (nonlactating, n=7) received GnRH agonist (Day 0) and PGF2 alpha (Day 7); while Groups GPG (nonlactating, n=8) and GPG-L (lactating, n=9) cows were given GnRH (Day 0), PGF2a (Day 7) and GnRH again (Day 8, 30 h after PGF2 alpha). A new follicular wave was observed 1.79+/-0.34 d after GnRH in 19/24 cows. After PGF2a, ovulation occurred in 19/24 cows (6/7 GP, 6/8 GPG, 7/9 GPG-L). Most cows (83.3%) exhibited a dominant follicle just before PGF2a, and 17/19 ovulatory follicles were from a new follicular wave. There was a more precise synchrony of ovulation (within 12 h) in cows that received a second dose of GnRH (GPG and GPG-L) than controls (GP, ovulation within 48 h; P<0.01). In Experiment 2, lactating Nelore cows with a visible corpus luteum (CL) by ultrasonography were allocated to 2 treatments: Group GPE (n=10) received GnRH agonist (Day 0), PGF2a (Day 7) and estradiol benzoate (EB; Day 8, 24 h after PGF2 alpha); while Group EPE (n=11), received EB (Day 0), PGF2a (Day 9) and EB (Day 10, 24 h after PGF2a). Emergence of a new follicular wave was observed 1.6+/-0.31 d after GnRH (Group GPE). After EB injection (Day 8) ovulation was observed at 45.38+/-2.03 h in 7/10 cows within 12 h. In Group EPE the emergence of a new follicular wave was observed later (4.36+/-0.31 d) than in Group GEP (1.6+/-0.31 d; P<0.001). After the second EB injection (Day 10) ovulation was observed at 44.16+/-2.21 h within 12 (7/11 cows) or 18 h (8/11 cows). All 3 treatments were effective in synchronizing ovulation in beef cows. However, GPE and, particularly EPE treatments offer a promising alternative to the GPG protocol in timed artificial insemination of beef cattle, due to the low cost of EB compared with GnRH agonists. (C) 2000 by Elsevier B.V.

Synchronization of ovulation in crossbred dairy heifers using gonadotrophin-releasing hormone agonist, prostaglandin F2a and human chorionic gonadotrophin or estradiol benzoate

Girolando (Gir x Holstein) is a very common dairy breed in Brazil because it combines the rusticity of Gir (Bos indicus) with the high milk yield of Holstein (Bos taurus). The ovarian follicular dynamics and hormonal treatments for synchronization of ovulation and timed artificial insemination were studied in Girolando heifers. The injection of a gonadotrophin-releasing hormone (GnRH) agonist was followed 6 or 7 days (d) later by prostaglandin F2a (PGF2a). Twenty-four hours after PGF2a injection either human chorionic gonadotropin (hCG, GPh-d6 and GPh-d7 groups) or estradiol benzoate (EB, GPE-d6 and GPE-d7 groups) was administered to synchronize ovulation and consequently allow timed artificial insemination (AI) 24 and 30 h after hCG and EB injection, respectively. Follicular dynamics in Girolando heifers was characterized by the predominance of three follicular waves (71.4%) with sizes of dominant follicles (10-13 mm) and corpus luteum (approximately 20 mm) similar to those for Bos indicus cattle. In the GnRH-PGF-hCG protocol, hCG administration induced earlier ovulation (67.4 h, P<0.01) compared to the control group (GnRH-PGF) and a better synchronization of ovulation, since most of it occurred within a period of 12 to 17 h. Pregnancy rate after timed AI was 42.8 (3/7, GPh-d6) to 50% (7/14, GPh-d7). In contrast, estradiol benzoate (GnRH-PGF-EB protocol) synchronized ovulation of only 5 of 11 heifers from the GPE-d7 group and of none (0/7) from the GPE-d6 group, which led to low pregnancy rates after timed AI (27.3 and 0%, respectively). However, since a small number of Girolando heifers was used to determine pregnancy rates in the present study, pregnancy rates should be confirmed with a larger number of animals.

Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle

Extracellular matrix remodeling occurs during ovarian follicular development, mediated by plasminogen activators (PAs) and PA inhibitors including protease nexin-1 (PN-1). In the present study we measured expression/activity of the PA system in bovine follicles at different stages of development by timed collection of ovaries during the first follicular wave and during the periovulatory period, and in follicles collected from an abattoir. The abundance of mRNA encoding PN-1, tissue-type PA (tPA), urokinase (uPA) and PA inhibitor-1 (PAI-1) were initially upregulated by human chorionic gonadotropin (hCG) in bovine preovulatory follicular wall homogenates. PN-1, PAI-1 and tPA mRNA expression then decreased near the expected time of ovulation, whereas uPA mRNA levels remained high. PN-1 concentration in follicular fluid (FF) decreased and reached the lowest level at the time of ovulation, whereas plasmin activity in FF increased significantly after hCG. Follicles collected from the abattoir were classified as non-atretic, early-atretic or atretic based on FF estradiol and progesterone content: PN-1 protein levels in FF were significantly higher in non-atretic than in atretic follicles, and plasmin activity was correspondingly higher in the atretic follicles. No changes in PN-1 levels in FF were observed during the growth of pre-deviation follicles early in a follicular wave. These results indicate that PN-1 may be involved in the process of atresia in non-ovulatory dominant follicles and the prevention of precocious proteolysis in periovulatory follicles.

Relationship between lower-limb muscle strength and frailty among elderly people

CONTEXTO E OBJETIVO: A sarcopenia é o principal fator envolvido no desenvolvimento da síndrome de fragilidade. O objetivo foi investigar a relação entre força muscular de membros inferiores e as variáveis sexo, idade e critérios de fragilidade; comparar a força muscular de membros inferiores com cada critério de fragilidade e verificar seu poder de estimativa do risco para fragilidade em idosos ambulatoriais. TIPO DE ESTUDO E LOCAL: Estudo transversal no Ambulatório de Geriatria de um hospital universitário de Campinas. MÉTODO: Foi avaliada uma amostra de conveniência não-probabilística de 150 idosos de ambos os sexos em acompanhamento ambulatorial, com coleta de dados sócio-demográficos (sexo e idade) e de saúde física (critérios de fragilidade e teste de levantar e sentar da cadeira cinco vezes consecutivamente). Foram realizadas análises descritivas, de comparação e de regressão logística multivariada. RESULTADOS: A maioria dos idosos (77,3%) apresentou idade igual ou superior a 70 anos, com predomínio do sexo feminino (64,0%) e baixo escore no teste de levantar e sentar da cadeira cinco vezes consecutivas (81,4% escore 0 ou 1), 55,3% dos idosos apresentaram três ou mais critérios de fragilidade. Verificou-se associação significativa entre a força muscular de membros inferiores e as variáveis idade e número de critérios de fragilidade. CONCLUSÕES: Menores níveis de força muscular de membros inferiores estão associados a idade avançada e maior presença de sinais de fragilidade. Além disso, a força muscular de membros inferiores também está associada com os critérios redução da velocidade de marcha e da força de preensão palmar.

A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia

Purpose: To analyse the effects of two interventions on the cognition and balance of institutionalized elderly people with mixed dementia.Methods: Fifty-four participants were allocated into three groups. Group 1 was assisted by an interdisciplinary programme comprising physiotherapy, occupational therapy and physical education. A physiotherapist alone carried out the intervention in group 2. Group 3 was considered as control. Assessors were blinded to guarantee the absence of bias. Cognitive functions were analysed with the Mini-Mental State Examination and the Brief Cognitive Screening Battery. Balance was assessed with the Berg Balance Scale and the Timed Get-Up-and-Go Test. Multiple analysis of variance (MANOVA) was used to test possible main effects of the interventions.Results: The results showed benefits on the balance of subjects in both groups 1 (F=3.9, P < 0.05) and 2 (F= 3.1, P < 0.05), compared with group 3. MANOVA did not indicate benefits on the cognitive functions between groups 1 and 3 (F= 1.1, P > 0.05) and groups 2 and 3 (F= 1.6, P > 0.05). However, univariate analysis indicated some benefits of the interdisciplinary intervention on two specific domains measured by the Brief Cognitive Screening Battery (F=26.5, P < 0.05; F= 4.4, P < 0.05).Conclusion: Six months of multidisciplinary or physiotherapeutic intervention were able to improve a person's balance. Although global cognition did not improve through treatment, when the intervention was carried out on a multidisciplinary basis we observed an attenuation in the decline of global cognition on two specific cognitive domains. Exercises applied in different contexts may have positive outcomes for people with dementia.

Balance, executive functions and falls in elderly with Alzheimer's disease (AD): A longitudinal study

Elderly individuals with AD are more susceptible to falls, which might be associated with decrements in their executive functions and balance, among other things. We aimed to analyze the effects of a program of dual task physical activity on falls, executive functions and balance of elderly individuals with AD. We studied 21 elderly with probable AD, allocated to two groups: the training group (TG), with 10 elderly who participated in a program of dual task physical activity; and the control group (CG), with 11 elderly who were not engaged in regular practice of physical activity. The Clock Drawing Test (CDT) and the Frontal Assessment Battery (FAB) were used in the assessment of the executive functions, while the Berg Balance Scale (BBS) and the Timed Up-and-Go (TUG)-test evaluated balance. The number of falls was obtained by means of a questionnaire. We observed a better performance of the TG as regards balance and executive functions. Moreover, the lower the number of steps in the TUG scale, the higher the scores in the CDT, and in the FAB. The practice of regular physical activity with dual task seems to have contributed to the maintenance and improvement of the motor and cognitive functions of the elderly with AD. (C) 2011 Elsevier B.V. All rights reserved.

Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer's disease

The decline in frontal cognitive functions contributes to alterations of gait and increases the risk of falls in patients with dementia, a category which included Alzheimer's disease (AD). The objective of the present study was to compare the gait parameters and the risk of falls among patients at different stages of AD, and to relate these variables with cognitive functions. This is a cross-sectional study with 23 patients with mild and moderate AD. The Clinical Dementia Rating was used to classify the dementia severity. The kinematic parameters of gait (cadence, stride length, and stride speed) were analyzed under two conditions: (a) single task (free gait) and (b) dual task (walking and counting down). The risk of falls was evaluated using the Timed Up-and-Go test. The frontal cognitive functions were evaluated using the Frontal Assessment Battery (FAB), the Clock Drawing Test (CDT) and the Symbol Search Subtest. The patients who were at the moderate stage suffered reduced performance in their stride length and stride speed in the single task and had made more counting errors in the dual task and still had a higher fall risk. Both the mild and the moderate patients exhibited significant decreases in stride length, stride speed and cadence in the dual task. Was detected a significant correlation between CDT, FAB, and stride speed in the dual task condition. We also found a significant correlation between subtest Similarities, FAB and cadence in the dual task condition. The dual task produced changes in the kinematic parameters of gait for the mild and moderate AD patients and the gait alterations are related to frontal cognitive functions, particularly executive functions.

Muscle strength assessment among children and adolescents with growing pains and joint hypermobility

OBJETIVO: Avaliar, por meio de teste quantitativo, a força muscular em crianças e adolescentes com dores de crescimento, associada ou não com hipermobilidade articular e comparadas com controles saudáveis. MÉTODO: Quarenta e sete casos de crianças e adolescentes acompanhados por dores de crescimento, sendo 24 com hipermobilidade articular (DC-HA), 23 sem hipermobilidade articular (DC) e 47 controles saudáveis pareados por idade e gênero foram submetidos a dois testes quantitativos para a avaliação da força muscular, o Childhood Myositis Assessment Scale (CMAS) e o Manual Muscle Strength Test (MMT). Os dados antropométricos como altura, peso, índice de massa corporal, prega cutânea tricipital, circunferência média do braço e a área muscular do braço foram comparados entre os três grupos. RESULTADOS: Os três grupos não apresentaram diferença estatística entre as medidas antropométricas. Houve diferença significante entre a mediana da pontuação do CMAS, sendo menores no grupo DC (47, mínimo e máximo 39-52) e DC-HA (46, mínimo e máximo 40-51), comparados com controles (50, mínimo e máximo 45-52; p<0,0001). Dois dos exercícios cronometrados do CMAS, a elevação da cabeça e a duração da elevação das pernas, tiveram menor pontuação nos pacientes comparados aos controles (p<0.0001). A pontuação mediana do MMT no grupo DC (79, mínimo e máximo 73-80) e DC-HA (78, mínimo e máximo 32-80) também apresentou diferença significante, sendo menor nos pacientes que nos controles (80, mínimo e máximo 78-80; p<0,0001). A melhor correlação entre a pontuação do CMAS e MMT foi no grupo DC-HA (Spearman r=0,65; p=0,0007). A aplicação do CMAS e MMT em duas ocasiões apresentou boa concordância e coeficiente de correlação intraclasse de 0,87 (IC 95% 0,64-0,96; p<0,0001) e 0,92 (IC 95% 0,76-0,97; p<0,0001), respectivamente. CONCLUSÃO: Os pacientes com dores de crescimento com ou sem hipermobilidade articular apresentaram fraqueza muscular de leve a moderada quando comparados com controles saudáveis.

Dental caries and the nutritional status of preschool children: a spatial analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)