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INTRODUCTION: The study reported the time (from the initial submission to the final decision) to evaluate a clinical research project by one of the 39 French national ethics committees. The times from this final decision to the first participant inclusion and study achievement (first patient inclusion to the end of the last patient's follow-up) were also reported. METHODS: Clinical research projects submitted between January 1st 2019 and June 30th 2023 were analyzed according to their type (research on drugs, clinical investigations, performance studies, research implying human person), and the promotor (industry, university hospital, general hospital, private medical institution, others). The times of assessment of the project by the ethic committee (from the initial submission to the final decision), of the first participant inclusion (from the approval of the project) and of study achievement (first patient inclusion to the end of the last patient's follow-up) were calculated. RESULTS: Among 467 submitted clinical research projects, 424 were approved (90.8 %). The median time [Q1-Q3] to evaluate a project was 73 days [51-98] whatever the types of projects and promotors. In 307 accepted projects, the first patient inclusion occurred after 134 days [61-237] and was being waited for 347 days [306-510] in 39 other ones. In 122 projects, the time for study achievement was 446 days [230-731]. In 185 other projects, the inclusions were still in progress for 699 days [397-1098]. CONCLUSION: In this concerned ethic committee, a final decision was edited after a median assessment time of 73 days (with >90 % approvals), shorter than the times to include the first patient and for achieving the study.
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Our objectives were to compare the proportion of lactating dairy cows diagnosed with health disorders (HD) and herd performance when using a health monitoring program designed to rely primarily but not exclusively on alerts from automated health monitoring (AHM) systems or a health monitoring program based primarily on systematic clinical examinations, milk yield monitoring, and visual observation of cows. In a clinical trial, at â¼30 d before expected parturition, nulliparous and parous Holstein cows, stratified by parity and days in gestation, were randomly assigned to the high-intensity clinical monitoring (HIC-M; n = 625) or automated monitoring (AUT-M; n = 624) treatment. Cows were fitted with a neck-attached rumination and physical activity monitoring tag, and individual daily milk yield data were collected from parlor milk meters. For cows in HIC-M, clinical examination was conducted daily until 10 d in milk (DIM) and then in response to milk yield reduction alerts or visual observation of clinical signs of HD over the course of 21 DIM. For cows in AUT-M, clinical examination until 21 DIM was because of health index (HI) score alerts and reduced milk yield alerts. The HI score alerts used were generated based on the manufacturer's settings for the system for the last 2-h period before cows were selected for examination. Visual observation of clinical signs of HD was used for identifying cows potentially missed by automated alerts. Binomial and quantitative data were analyzed by logistic regression and ANOVA with repeated measures, respectively. The percentage of cows diagnosed with at least 1 HD during the experimental treatments risk period tended to be greater and the incidence rate ratio of HD diagnosed was greater in the HIC-M than in the AUT-M treatment. We found no difference between treatments for cows that exited the herd up to 60 or 150 DIM, but more cows tended to exit the herd from 61 to 150 DIM in the HIC-M than in the AUT-M treatment. No differences were detectable between treatments in daily or total milk yield to 21 DIM or in weekly mean milk yield and total milk yield to 150 DIM. More cows were inseminated in estrus for first service if in the HIC-M treatment and had no HD diagnosed than if in the HIC-M treatment but with HD diagnosed, or in the AUT-M treatment and had no HD diagnosed. Cows in the AUT-M treatment with HD diagnosed did not differ from other groups. No differences between treatments were observed in pregnancies per artificial insemination or pregnancy loss for first service. Despite a reduction in the risk of diagnosis of HD, no evidence indicated that a health monitoring program that relied on AHM system alerts to select cows for clinical examination reduced herd performance compared with a more intensive program that included systematic clinical examinations of all cows for the first 10 DIM, reduced milk yield alerts, and visual observation. However, to obtain the same herd performance as with the HIC-M treatment, the AUT-M treatment required use of visual observation. In conclusion, a health monitoring program designed to rely primarily on targeted clinical examination based on alerts from automated health monitoring systems might be a feasible alternative to programs that rely more on clinical examination, provided that visual observation is used to identify cows not detected by automated alerts.
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Lactancia , Condicionamiento Físico Animal , Embarazo , Femenino , Bovinos , Animales , Lactancia/fisiología , Paridad , Leche , Estro , Inseminación Artificial/veterinariaRESUMEN
Our objective was to compare reproductive outcomes of primiparous lactating Holstein cows of different genetic merit for fertility submitted for insemination with management programs that prioritized artificial insemination (AI) at detected estrus (AIE) or timed AI (TAI). Moreover, we aimed to determine whether subgroups of cows with different fertility potential would present a distinct response to the reproductive management strategies compared. Lactating primiparous Holstein cows (n = 6 commercial farms) were stratified into high (Hi-Fert), medium (Med-Fert), and low (Lo-Fert) genetic fertility groups (FG) based on a Reproduction Index value calculated from multiple genomic-enhanced predicted transmitting abilities. Within herd and FG, cows were randomly assigned either to a program that prioritized TAI and had an extended voluntary waiting period (P-TAI; n = 1,338) or another that prioritized AIE (P-AIE; n = 1,416) and used TAI for cows, not AIE. Cows in P-TAI received first service by TAI at 84 ± 3 d in milk (DIM) after a Double-Ovsynch protocol, were AIE if detected in estrus after a previous AI, and received TAI after an Ovsynch-56 protocol at 35 ± 3 d after a previous AI if a corpus luteum (CL) was visualized at nonpregnancy diagnosis (NPD) 32 ± 3 d after AI. Cows with no CL visualized at NPD received TAI at 42 ± 3 d after AI after an Ovsynch-56 protocol with progesterone supplementation (P4-Ovsynch). Cows in P-AIE were eligible for AIE after a PGF2α treatment at 53 ± 3 DIM and after a previous AI. Cows not AIE by 74 ± 3 DIM or by NPD 32 ± 3 d after AI received P4-Ovsynch for TAI at 74 ± 3 DIM or 42 ± 3 d after AI. Binary data were analyzed with logistic regression, count data with Poisson regression, continuous data by ANOVA, and time to event data by Cox's proportional hazard regression. Pregnancy per AI (P/AI) to first service was greater for cows in the Hi-Fert (59.8%) than the Med-Fert (53.6%) and Lo-Fert (47.7%) groups, and for the P-TAI (58.7%) than the P-AIE (48.7%) treatment. Overall, P/AI for all second and subsequent AI combined did not differ by treatment (P-TAI = 45.2%; P-AIE = 44.5%) or FG (Hi-Fert = 46.1%; Med-Fert = 46.0%; Lo-Fert = 42.4%). The hazard of pregnancy after calving was greater for the P-AIE than the P-TAI treatment [hazard ratio (HR) = 1.27, 95% CI: 1.17 to 1.37)], and for the Hi-Fert than the Med-Fert (HR = 1.16, 95% CI: 1.05 to 1.28) and Lo-Fert (HR = 1.34, 95% CI: 1.20 to 1.49) groups. More cows in the Hi-Fert (91.2%) than the Med-Fert (88.4%) and Lo-Fert (85.8%) groups were pregnant at 200 DIM. Within FG, the hazard of pregnancy was greater for the P-AIE than the P-TAI treatment for the Hi-Fert (HR = 1.41, 95% CI: 1.22 to 1.64) and Med-Fert (HR = 1.28, 95% CI: 1.12 to 1.46) groups but not for the Lo-Fert group (HR = 1.13, 95% CI: 0.98 to 1.31). We conclude that primiparous Holstein cows of superior genetic merit for fertility had better reproductive performance than cows of inferior genetic merit for fertility, regardless of the type of reproductive management used. In addition, the effect of programs that prioritized AIE or TAI on reproductive performance for cows of superior or inferior genetic merit for fertility depended on the outcomes evaluated. Thus, programs that prioritize AIE or TAI could be used to affect certain outcomes of reproductive performance or management.
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Sincronización del Estro , Lactancia , Embarazo , Femenino , Bovinos , Animales , Lactancia/fisiología , Sincronización del Estro/métodos , Hormona Liberadora de Gonadotropina , Dinoprost , Reproducción/fisiología , Fertilidad/fisiología , Estro , Progesterona , Inseminación Artificial/veterinaria , Inseminación Artificial/métodosRESUMEN
Our objective was to evaluate reproductive management programs for submission of Holstein heifers for first insemination with conventional or sexed semen. In experiment 1, nulliparous Holstein heifers (n = 462) were submitted to a 5-d progesterone-releasing intravaginal device (PRID)-Synch protocol [d 0, GnRH + PRID; d 5, PGF2α - PRID; d 6, PGF2α; d 8, GnRH + TAI] and were randomly assigned for PRID removal on d 5 or 6 of the protocol followed by timed artificial insemination (TAI) with conventional semen. Delaying PRID removal decreased early expression of estrus before scheduled TAI (0.9 vs. 12.2%), and pregnancies per AI (P/AI) did not differ between treatments. In experiment 2, nulliparous Holstein heifers (n = 736) from 3 commercial farms were randomized within farm to 1 of 3 treatments for first AI with sexed semen: (1) CIDR5 [d -6, GnRH + controlled internal drug release (CIDR); d -1, PGF2α - CIDR; d 0, PGF2α; d 2, GnRH + TAI]; (2) CIDR6 (d -6, GnRH + CIDR; d -1, PGF2α; d 0, PGF2α - CIDR; d 2, GnRH + TAI); and (3) EDAI (PGF2α on d 0 followed by once-daily estrous detection and AI). Delaying CIDR removal decreased early expression of estrus before scheduled TAI (0.004 vs. 27.8%); however, CIDR5 heifers tended to have more P/AI at 35 (53 vs. 45 vs. 46%) and 64 (52 vs. 45 vs. 45%) days after AI than CIDR6 and EDAI heifers, respectively. Overall, CIDR5 and CIDR6 heifers had fewer days to first AI and pregnancy than EDAI heifers which resulted in less feed costs than EDAI heifers due to fewer days on feed until pregnancy. Despite greater hormonal treatment costs for CIDR5 heifers, costs per pregnancy were $16.66 less for CIDR5 than for EDAI heifers. In conclusion, delaying PRID removal by 24 h within a 5-d PRID-Synch protocol in experiment 1 suppressed early expression of estrus before TAI, and P/AI for heifers inseminated with conventional semen did not differ between treatments. By contrast, although delaying CIDR removal by 24 h within a 5-CIDR-Synch protocol in experiment 2 suppressed early expression of estrus before TAI, delaying CIDR removal by 24 h tended to decrease P/AI for heifers inseminated with sexed semen. Further, submission of heifers to a 5-d CIDR-Synch protocol for first AI tended to increase P/AI and decrease the cost per pregnancy compared with EDAI heifers.
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Detección del Estro , Sincronización del Estro , Animales , Bovinos , Dinoprost , Estro , Femenino , Hormona Liberadora de Gonadotropina , Inseminación Artificial/veterinaria , Embarazo , Resultado del Embarazo , Progesterona , SemenRESUMEN
This study aimed to determine the in vivo effectiveness of the ethanolic extract of Piper betle L. leaves against Staphylococcus aureus-infected wounds in mice and its antimicrobial properties on clinical isolates of multiple drug-resistant bacterial pathogens. Twenty mice were divided into four groups. Wounds were created in all mice under anesthesia by excision from the dorsal skin down to the subcutaneous fat and inoculating with S. aureus. After 24 h, the wound of each mouse was treated once daily by application of the respective cream. Group I was treated with mupirocin antibacterial cream; Group II received a cream base containing no active ingredient; Groups III and IV were treated with 2.5% and 5.0% concentrations of P. betle cream, respectively. Further, an in vitro study was performed by adding undiluted, 1:50 and 1:100 dilutions of the four studied creams in normal saline containing 1.5 × 108 CFU/mL of the following bacteria: antimicrobial-susceptible S. aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant S. aureus, extended-spectrum ß-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus, metallo-ßlactamase-producing P. aeruginosa and carbapenem-resistant Klebsiella pneumoniae. The mice in Groups III and IV had significantly faster wound contraction and significantly shorter reepithelialization time than Group II (p < 0.05), which were not significantly different from Group I (p > 0.05). P. betle creams inhibited all studied bacterial strains at full concentration and at a dilution of 1:50. The inhibitory effect was more significant than Groups I and II (p < 0.05), except on S. aureus. Specifically, S. aureus inhibition was not significantly different for Groups III and IV (p > 0.05) when compared with Group I. Cream formulations derived from P. betle ethanolic extract have great potential as antimicrobial agents for the treatment of wound infection. Further clinical tests are recommended to determine the safety and efficacy of these formulations in other mammalian species.
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Antibacterianos , Piper betle , Extractos Vegetales , Infecciones Estafilocócicas , Infección de Heridas , Animales , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Piper betle/química , Extractos Vegetales/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Infección de Heridas/tratamiento farmacológicoRESUMEN
Our objective was to compare the effect of treatment with GnRH at the first treatment (G1) of the Breeding-Ovsynch portion of a Double-Ovsynch (DO) protocol with human chorionic gonadotropin (hCG) on pregnancies per artificial insemination (P/AI) in lactating dairy cows. In experiment 1, lactating dairy cows (n = 1,932) submitted to a DO protocol for first timed artificial insemination (TAI) on 2 commercial dairy farms were blocked by parity (primiparous vs. multiparous) and were randomly assigned to receive 100 µg of GnRH versus 2,500 IU of hCG at G1. Overall, P/AI 39 d after TAI for cows inseminated with sexed dairy semen was greater for cows treated with GnRH than for cows treated with hCG within each parity (primiparous: 42.6% vs. 38.2%; multiparous: 39.4% vs. 30.3%). Similarly, P/AI 39 d after TAI for multiparous cows inseminated with conventional beef semen tended to be greater for cows treated with GnRH than for cows treated with hCG (41.1% vs. 34.3%). In experiment 2, lactating Holstein cows (n = 43) were blocked by parity and were randomly assigned to the treatment protocols described for experiment 1. Ovaries were evaluated with transrectal ultrasonography immediately before treatment and 24, 28, 32, 36, and 40 h after treatment to assess time from treatment to ovulation, and blood samples were collected immediately before G1, at the first PGF2α treatment, 8 and 16 h later, at the second PGF2α treatment, 8 and 16 h later, at the second GnRH (G2) treatment, and at TAI to compare luteolysis based on serum progesterone (P4) concentrations. Although mean (± standard error of the mean) time from treatment to ovulation was approximately 2 h greater for cows treated with hCG than for cows treated with GnRH (33.7 ± 0.6 vs. 31.5 ± 0.6 h), P4 concentrations during luteolysis and the proportion of cows with complete luteolysis (P4 <0.4 ng/mL at G2) did not differ between treatments. We conclude that replacing 100 µg of GnRH with 2,500 IU of hCG at G1 of a DO protocol decreased fertility to TAI in lactating dairy cows but did not affect the rate or completeness of luteolysis despite the increased interval from treatment to ovulation.
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Sincronización del Estro , Hormona Liberadora de Gonadotropina , Animales , Bovinos , Gonadotropina Coriónica , Ensayos Clínicos Veterinarios como Asunto , Dinoprost , Femenino , Fertilidad , Inseminación Artificial/veterinaria , Lactancia , Ovulación , ProgesteronaRESUMEN
The objective of this study was to evaluate the effect of two prostaglandin F2α (PGF) treatments 24 h apart (500 µg of cloprostenol) and treatment with a double PGF dose on d 7 (1000 µg of cloprostenol) during a 7-d Ovsynch protocol on progesterone (P4) concentration and pregnancy per artificial insemination (P/AI) in lactating Holstein cows. We hypothesized that treatment leads to a decreased P4 concentration at the second GnRH treatment (G2) and an increase in P/AI compared to the traditional 7-d Ovsynch protocol. A secondary hypothesis was that the treatment effect is influenced by the presence of a corpus luteum (CL) at the first GnRH treatment (G1). Two experiments were conducted on 8 commercial dairy farms in Germany. Once a week, cows from both experiments were assigned in a consecutive manner to receive: (1) Ovsynch (control: GnRH; 7 d, PGF; 9 d, GnRH), (2) Ovsynch with a double PGF dose (GDPG: GnRH; 7 d, 2xPGF; 9 d, GnRH), or (3) Ovsynch with a second PGF treatment 24 h later (GPPG: GnRH; 7 d, PGF; 8 d, PGF; 32 h, GnRH). All cows received timed AI (TAI) approximately 16 h after G2. Pregnancy diagnosis was performed by transrectal palpation (38 ± 3 d after TAI, experiment 1) or transrectal ultrasonography (35 ± 7 d after TAI, experiment 2). Whereas farms from experiment 1 used a Presynch-Ovsynch protocol (PGF, 14 d later PGF, 12 d later GnRH, 7 d later PGF, 2 d later GnRH, and 16-18 h later TAI) to facilitate first postpartum TAI, no presynchronization protocol was used on farms from experiment 2. In experiment 1, we enrolled 1581 lactating dairy cows (60 experimental units) from 2 dairy farms. At G2, blood samples were collected from a subsample of cows (n = 491; 16 experimental units) to determine P4 concentration at G2. In experiment 2, we enrolled 1979 lactating dairy cows (252 experimental units) from 6 dairy farms. Transrectal ultrasonography was performed to determine the presence or absence of a CL at G1. In experiment 1, treatment affected P/AI (P = 0.01) and P/AI was greater for GDPG (38.2%) and GPPG (38.9%) than for control cows (29.8%). Both, GDPG and GPPG cows had decreased P4 concentration at G2 compared with control cows (P < 0.01). Whereas both treatments increased the percentage of cows with very low P4 concentration (0.00-0.09 ng/mL) at G2, only the GPPG treatment decreased the percentage of cows with high P4 concentration (≥0.6 ng/mL) at G2 compared to the control group. In experiment 2, P/AI was greater for GPPG (37.4%) than for control cows (31.0%; P = 0.03) and tended to be greater than for GDPG cows (31.8%; P = 0.05). Cows from the GDPG group had similar (P = 0.77) P/AI compared to the control group. Pregnancy per AI did not differ between cows with a CL at G1 and cows without a CL at G1 (34.1% vs. 32.6%; P = 0.50). There was no interaction between treatment and presence of a CL at G1 on P/AI (P = 0.61). Combining data from the 2 experiments but excluding cows from experiment 1 receiving presynchronization before first TAI (n = 2573; 312 experimental units), P/AI was greater for GPPG (40.3%; P < 0.01) than for control (31.8%) and GDPG cows (33.4%). Between GDPG and control cows, P/AI did not differ (P = 0.46). We conclude that overall the addition of a second PGF treatment on d 8 during a 7-d Ovsynch protocol increased P/AI compared to the traditional 7-d Ovsynch including a single PGF dose on d 7 and to a double PGF dose on d 7. Doubling the PGF dose on d 7 in a 7-d Ovsynch protocol did not affect P/AI. Use of a presynchronization protocol, however, seems to influence the effect of a dose frequency modification of PGF treatment in an Ovsynch protocol. Presynchronized cows receiving first postpartum TAI had similarly increased P/AI treated with a double PGF dose compared with treatment with a second PGF dose. Future studies need to elucidate whether the treatment effect is modified by presynchronization of the first postpartum TAI.
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Sincronización del Estro , Progesterona , Animales , Bovinos , Dinoprost/farmacología , Femenino , Fertilidad , Hormona Liberadora de Gonadotropina/farmacología , Inseminación Artificial/veterinaria , Lactancia , Embarazo , Resultado del Embarazo , Prostaglandinas FRESUMEN
Lutalyse HighCon (dinoprost tromethamine; Zoetis) has been approved for use both intramuscularly and subcutaneously in lactating dairy cows, although the effect of route of administration on circulating 13,14-dihydro-15-keto-prostaglandin F2α (PGFM), the metabolite of PGF2α, has not been evaluated. Multiparous, lactating Holstein cows were submitted to an Ovsynch protocol in which the last GnRH treatment (G2) was designated as d 0. Cows were fitted with indwelling jugular catheters on d 6 and administered 25 mg of dinoprost tromethamine (2 mL of Lutalyse HighCon) on d 7 either subcutaneously in the neck (SC; n = 6) or intramuscularly in the semitendinosus muscle (IM; n = 6). Blood samples were collected every 15 min after treatment for 1.75 h, then every 2 h for 48 h, and at 60 and 72 h, with the last time point corresponding to when cows would have received timed AI at 72 h within an Ovsynch protocol. Circulating PGFM concentrations were greater for SC than for IM cows from 15 to 90 min after treatment, which resulted in a greater area under the PGFM curve during the first 90 min after treatment (means ± SEM; 1,664 ± 129 pg·h/mL vs. 1,146 ± 177 pg·h/mL for SC vs. IM cows, respectively). This resulted in complete luteolysis in all but one cow in the SC treatment at 56 h, when GnRH would have been administered if dinoprost tromethamine had been administered as part of an Ovsynch protocol for timed AI. For cows that underwent complete luteal regression, circulating P4 did not differ between treatments at any time point. Thus, although SC cows had increased circulating PGFM 15 to 90 min after treatment, there was no difference in circulating P4 during induced luteolysis based on route of dinoprost tromethamine administration.
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Our objective was to assess the effect of treatment with GnRH or 4 increasing doses of human chorionic gonadotropin (hCG) on the ovulatory response of a first-wave dominant follicle and subsequent plasma progesterone (P4) concentrations. Lactating Holstein cows were blocked by parity (primiparous vs. multiparous) and randomly assigned to receive no treatment (control, CON; n = 147), 100 µg of GnRH (n = 144), or 1,000 (n = 138), 2,000 (n = 144), 2,500 (n = 142), or 3,300 (n = 139) IU of hCG 7 d after the last GnRH treatment (G2) of a Double-Ovsynch (DO) or Resynch protocol. Blood samples were collected and ovaries were evaluated with transrectal ultrasonography immediately before treatment and 7 d later to assess serum P4 concentrations and ovulatory response to treatment. Data were analyzed using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc., Cary, NC). Overall, ovulatory response differed and was 4.8, 79.0, 77.4, 88.9, 92.9, and 95.6% for CON, GnRH, 1,000-, 2,000-, 2,500-, and 3,300-IU hCG treatments, respectively. The increase in plasma P4 concentrations from 7 to 14 d after G2 differed among treatments and was 3.5, 5.9, 5.7, 6.6, 7.0, and 6.5 ng/mL for CON, GnRH, 1,000-, 2,000-, 2,500-, and 3,300-IU hCG treatments, respectively. In conclusion, lactating Holstein cows treated 7 d after G2 with 100 µg of GnRH or 1,000 IU of hCG had similar ovulatory responses (~78%), whereas cows treated with 2,000, 2,500, or 3,300 IU of hCG had increased ovulatory responses (~92%). Ovulatory response of cows treated with 2,000 or 2,500 IU of hCG did not differ, whereas the ovulatory response after 3,300 IU was greater than that after 2,000 IU of hCG. Plasma P4 concentrations and luteal volume 7 d after treatment were increased compared with those of untreated control cows.
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@#This study aimed to determine the in vivo effectiveness of the ethanolic extract of Piper betle L. leaves against Staphylococcus aureus-infected wounds in mice and its antimicrobial properties on clinical isolates of multiple drug-resistant bacterial pathogens. Twenty mice were divided into four groups. Wounds were created in all mice under anesthesia by excision from the dorsal skin down to the subcutaneous fat and inoculating with S. aureus. After 24 h, the wound of each mouse was treated once daily by application of the respective cream. Group I was treated with mupirocin antibacterial cream; Group II received a cream base containing no active ingredient; Groups III and IV were treated with 2.5% and 5.0% concentrations of P. betle cream, respectively. Further, an in vitro study was performed by adding undiluted, 1:50 and 1:100 dilutions of the four studied creams in normal saline containing 1.5 × 108 CFU/mL of the following bacteria: antimicrobial-susceptible S. aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus, metallo-βlactamase-producing P. aeruginosa and carbapenem-resistant Klebsiella pneumoniae. The mice in Groups III and IV had significantly faster wound contraction and significantly shorter reepithelialization time than Group II (p < 0.05), which were not significantly different from Group I (p > 0.05). P. betle creams inhibited all studied bacterial strains at full concentration and at a dilution of 1:50. The inhibitory effect was more significant than Groups I and II (p < 0.05), except on S. aureus. Specifically, S. aureus inhibition was not significantly different for Groups III and IV (p > 0.05) when compared with Group I. Cream formulations derived from P. betle ethanolic extract have great potential as antimicrobial agents for the treatment of wound infection. Further clinical tests are recommended to determine the safety and efficacy of these formulations in other mammalian species.
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Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.
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Adamantano/análogos & derivados , Artritis Reumatoide/tratamiento farmacológico , Niacinamida/análogos & derivados , Adamantano/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Quinasas Janus/antagonistas & inhibidores , Niacinamida/uso terapéutico , Resultado del TratamientoRESUMEN
The aim of this work was to gain a more comprehensive and perspicacious view of the endophytic diazotrophic community (EDC) of tomato plant bacteria and assess the effects of chemical fertilization and the plant phenologic stage on the status of those microbes. When the EDC of stem and roots from tomato plants grown in a greenhouse with and without exogenous chemical fertilization was examined by pyrosequencing the nifH gene during the growth cycle, a high taxonomic and phylogenetic diversity was observed. The abundant taxa were related to ubiquitous endophytes such as Rhizobium or Burkholderia but also involved anaerobic members usually restricted to flooded plant tissues, such as Clostridium, Geobacter, and Desulfovibrio. The EDC composition appeared to be dynamic during the growth phase of the tomato, with the structure of the community at the early stages of growth displaying major differences from the late stages. Inorganic fertilization negatively affected the diversity and modified the profile of the predominant components of the EDC in the different growth stages. Populations such as Burkholderia and Geobacter plus the Cyanobacteria appeared particularly affected by fertilization.Our work demonstrates an extensive endophytic diazotrophic diversity, suggesting a high potential for nitrogen fixation. The effect of the phenologic stage and inorganic-chemical soil fertilization on the community structure indicated a dynamic community that responded to environmental changes. These findings contribute to a better understanding of endophytic associations that could be helpful in assisting to shape the endomicrobiome that provides essential benefits to crops.
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Endófitos/clasificación , Endófitos/efectos de los fármacos , Fertilizantes , Fijación del Nitrógeno , Solanum lycopersicum/crecimiento & desarrollo , Variación Genética , Solanum lycopersicum/microbiología , Filogenia , Raíces de Plantas/microbiología , Microbiología del SueloRESUMEN
The objective of this randomized controlled experiment was to evaluate reproductive performance and reproductive physiological outcomes of lactating Holstein cows managed for second and greater artificial insemination (AI) services with the Short-Resynch or Day 25 Resynch program. Cows from 2 commercial farms were randomly assigned after first service to the Short-Resynch (SR; n = 870) or Day 25 Resynch (D25R; n = 917) program in which they remained until 210 d after first service or left the herd. Cows in D25R received GnRH 25 ± 3 d after AI, whereas cows in SR did not. Cows not reinseminated at detected estrus (AIE) by 32 ± 3 d after AI underwent nonpregnancy diagnosis (NPD) through transrectal ultrasonography (TUS). Nonpregnant cows from both treatments with a corpus luteum (CL) ≥15 mm and an ovarian follicle ≥10 mm (hereafter, CL cows) received 2 PGF2α treatments 24 h apart, GnRH 32 h after the second PGF2α, and timed AI 16 to 18 h later. Cows that did not meet the criteria to be included in the CL group (NoCL cows) received a modified Ovsynch protocol with progesterone (P4) supplementation [P4-Ovsynch; GnRH and controlled internal drug-release device (CIDR) in, 7 d later CIDR removal and PGF2α, 24 h later PGF2α, 32 h later GnRH, and 16 to 18 h later timed AI]. In a subgroup of cows, blood samples were collected and TUS conducted at each treatment to evaluate ovarian responses to resynchronization. Binary data were analyzed with logistic regression, continuous data by ANOVA, and time-to-event data by Cox's proportional hazard regression. A greater proportion (mean; 95% CI) of cows were AIE before NPD in the SR (60.5%; 57.0-63.8; n = 3,416) than the D25R (50.1%; 46.5-53.7; n = 3,177) treatment, whereas pregnancy per AI (P/AI) at 32 d for AIE services before NPD was greater for the D25R (41.3%; 38.8-43.8; n = 1,560) than the SR (37.6%; 35.5-39.8; n = 1,961) treatment. At NPD, a greater proportion of cows in the D25R (84.3%; 82.2-86.2) than the SR (77.0%; 74.4-79.4) treatment were considered CL cows. Pregnancy per AI at 32 d was greater for the D25R than the SR treatment for all timed AI services (D25R = 43.0%; 40.2-45.9 vs. SR = 36.8%; 33.8-39.8) and for CL cows (D25R = 42.8%; 39.7-45.9 vs. SR = 33.8%; 30.6-37.2) but did not differ for NoCL cows (D25R = 39.4%; 32.1-47.3 vs. SR = 44.0%; 36.8-51.4). The hazard ratio for time to pregnancy (1.03; 0.93-1.14) and the proportion of cows not pregnant at the end of the observation period (D25R = 5.9%; 4.4-7.8 vs. SR = 6.7%; 5.0-8.7) did not differ between SR and D25R treatments. The GnRH treatment 25 d after AI resulted in more cows with P4 >1 ng/mL (D25R = 80.5%; 75.3-84.9 vs. SR = 63.6%; 57.3-69.4) and smaller follicle diameter at NPD 32 ± 3 d after AI for D25R (16.2 ± 0.4 mm) than for SR (17.5 ± 0.4 mm); however, it did not affect follicle diameter and luteal regression risk (CL cows only) before TAI. We concluded that the use of reproductive management programs including SR and D25R for CL cows and the P4-Ovsynch protocol for NoCL cows resulted in similar hazard of pregnancy and proportion of nonpregnant cows for up to 210 d after first service.
Asunto(s)
Bovinos/fisiología , Dinoprost/farmacología , Sincronización del Estro/métodos , Hormona Liberadora de Gonadotropina/farmacología , Inseminación Artificial/veterinaria , Lactancia/fisiología , Animales , Dinoprost/administración & dosificación , Esquema de Medicación , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Inseminación Artificial/métodos , Embarazo , Reproducción/fisiologíaRESUMEN
Our objectives were to test the efficacy of intravaginal (IVG) administration of PGF2α to induce corpus luteum (CL) regression, compare circulating progesterone (P4) profiles in cows receiving IVG versus intramuscular (IM) treatment with PGF2α, and evaluate reproductive outcomes. Lactating Holstein cows were synchronized using a Double-Ovsynch protocol [GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 1 d later PGF2α, 32 h later GnRH, 16 to 20 h timed artificial insemination (TAI)] to receive TAI at 67 ± 3 d in milk. Seven days after the first GnRH treatment (time 0), cows with at least 1 visible CL ≥15 mm were blocked by parity and randomly assigned to a treatment that consisted of IM injection (IM-PGF; n = 201) or IVG instillation (IVG-PGF; n = 201) of PGF2α. Cows in IM-PGF received a single 25-mg dose of PGF2α (dinoprost tromethamine) intramuscularly. Cows in IVG-PGF received two 25-mg doses of PGF2α 12 h apart delivered through a catheter in the cranial portion of the vagina. Blood samples were collected at 0, 12, 48, and 72 h after treatment. Ovulation to the first GnRH of Double-Ovsynch was determined through transrectal ultrasonography. Only cows with P4 ≥1 ng/mL (functional CL) at time 0 (IM-PGF = 169; IVG-PGF = 179) were included in the analyses. Binary and quantitative data were analyzed by logistic regression and ANOVA with repeated measures, respectively. Results are presented as least squares means. Concentrations of P4 and the proportion of cows with a new CL at time 0 did not differ. Overall, the proportion of cows with CL regression using 1 ng of P4/mL (IM-PGF = 89.0%; IVG-PGF = 86.7%) or 0.5 ng of P4/mL (IM-PGF = 82.2%; IVG-PGF = 82.1%) as the cutoff did not differ. Concentrations of P4 were affected by treatment, time, and treatment × time interaction. Cows in IVG-PGF had greater mean P4 at 12 h than cows in IM-PGF. Mean P4 did not differ at 48 or 72 h after treatment. The proportion of cows with estrus recorded within 3 d of treatment (IM-PGF = 45.4%; IVG-PGF = 48.9%), ovulation risk after treatment (IM-PGF = 88.5%; IVG-PGF = 85.1%), and pregnancies per artificial insemination after TAI (IM-PGF = 51.5%; IVG-PGF = 57.8%) did not differ. We concluded that 2 IVG doses of 25 mg of PGF2α 12 h apart were as effective as a single 25-mg IM dose of PGF2α for inducing luteal regression in lactating dairy cattle.
Asunto(s)
Bovinos/fisiología , Dinoprost/análogos & derivados , Luteólisis/efectos de los fármacos , Oxitócicos/administración & dosificación , Reproducción , Administración Intravaginal , Animales , Dinoprost/administración & dosificación , Estro/efectos de los fármacos , Sincronización del Estro , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Inyecciones Intramusculares/veterinaria , Inseminación Artificial/veterinaria , Lactancia , Ovulación/efectos de los fármacos , Paridad , Embarazo , Progesterona/sangre , Distribución AleatoriaRESUMEN
BACKGROUND: Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations. METHODS: A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines. RESULTS: Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes. CONCLUSIONS: Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
Asunto(s)
Enfermedades Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Grasas de la Dieta/administración & dosificación , Epigénesis Genética , Metabolismo de los Lípidos/genética , Obesidad/genética , Animales , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/prevención & control , Enfermedad Crónica , Metilación de ADN , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/prevención & control , Modelos Animales de Enfermedad , Ácidos Grasos/administración & dosificación , Ácidos Grasos/efectos adversos , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Interacción Gen-Ambiente , Humanos , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/metabolismo , Obesidad/patología , Obesidad/prevención & control , Ácidos Grasos trans/administración & dosificación , Ácidos Grasos trans/efectos adversosRESUMEN
The final sentence of the Acknowledgements should be as follows: This work was supported by grants from Instituto de Salud Carlos III (BA15/00092), Spanish Ministry of Economy and Competitiveness/EU-ERDF (SAF2016-80626-R, SAF2013-49149-R, BFU2014-51672-REDC), Fundación CajaCanarias (AP2015/008) to RF, and the Australian National Health and Medical Research (NHMRC program grant to SRL and KKK (APP1017028).
RESUMEN
Persistent organic pollutants (POPs) were assessed for the first time in blue whales from the South Pacific Ocean. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane and its main metabolites (DDTs), were determined in 40 blubber samples from 36 free-ranging individuals and one stranded, dead animal along the coast of southern Chile between 2011 and 2013. PCBs were the most abundant pollutants (2.97-975â¯ng/g l.w.), followed by DDTs (3.50-537â¯ng/g l.w.), HCB (nd-77.5â¯ng/g l.w.) and PBDEs (nd-33.4â¯ng/g l.w). There was evidence of differences between sexes, with lower loads in females potentially due to pollutants passing to calves. POP concentrations were higher in specimens sampled in 2013; yet, between-year differences were only statistically significant for HCB and PBDEs. Lower chlorinated (pentaâ¯>â¯tetraâ¯>â¯tri) and brominated (tetraâ¯>â¯tri) congeners were the most prevalent among PCBs and PBDEs, respectively, mostly in agreement with findings previously reported in blue and other baleen whales. The present study provides evidence of lower levels of contamination by POPs in eastern South Pacific blue whales in comparison to those reported for the Northern Hemisphere.
Asunto(s)
Tejido Adiposo/metabolismo , Balaenoptera/metabolismo , Monitoreo del Ambiente , Contaminantes Químicos del Agua/metabolismo , Animales , Chile , DDT/metabolismo , Femenino , Éteres Difenilos Halogenados/metabolismo , Hexaclorobenceno/metabolismo , Hidrocarburos Clorados/metabolismo , Masculino , Océano Pacífico , Bifenilos Policlorados/metabolismoRESUMEN
OBJECTIVES: Decide how prison infrastructure guarantees health's right a suitable environment of Establecimiento Penitenciario Anexo de Mujeres de Chorrillos (EPAMCh) prisoners. MATERIAL AND METHOD: For the materials was used an interview guide addressed to 10 specialist and interview guide addressed to 30 prisoners. About the method, it was selected the qualitative approach, the applied type with the phenomenological design. RESULTS: The interview experts said that Establecimiento Penitenciario Anexo de Mujeres de Chorrillos current infrastructure and don´t give minima sanitary services. In the polls, the prisoners unanimously answered that conditions were precarious, but mostly said that they were willing to incorporate to a health education program and bet for a preventive medicine without forget the curative. DISCUSSION: Is Important foment the preventive medicine in order to get a strong health education in jails. To reverse this reality would mean change a guarantee in their health rights and a suitable environment.
Asunto(s)
Actitud Frente a la Salud , Servicios Preventivos de Salud , Prisioneros/psicología , Prisiones/organización & administración , Derecho a la Salud , Salud de la Mujer , Femenino , Encuestas de Atención de la Salud , Humanos , Entrevistas como Asunto , Perú , Investigación Cualitativa , Ajuste SocialRESUMEN
Objetivos: Determinar cómo la infraestructura penitenciaria garantiza los derechos a la salud y a un ambiente adecuado de las internas del Establecimiento Penitenciario Anexo de Mujeres de Chorrillos (EPAMCh). Material y método: En cuanto a los materiales, se empleó una guía de entrevista dirigida a 10 especialistas en la materia y una guía de encuesta destinada a 30 internas. Por lo que se refiere al método, se seleccionó el enfoque cualitativo de tipo aplicado y un diseño fenomenológico. Resultados: Los expertos en la entrevista afirmaron en su mayoría que la infraestructura actual en el Establecimiento Penitenciario Anexo de Mujeres de Chorrillos no permite prestar los servicios sanitarios mínimos. Por otro lado, en la encuesta, de modo unánime, las internas respondieron que las condiciones son precarias, pero mayoritariamente manifestaron su disposición a incorporarse a un programa educativo sanitario y a apostar por la medicina preventiva sin prescindir de la curativa. Discusión: Es importante fomentar la medicina preventiva. Para ello, es necesario nivelar el grado de instrucción de las internas y conseguir una sólida educación sanitaria. Revertir esta realidad significaría un cambio en la garantía de sus derechos a la salud y de sus derechos a un ambiente adecuado
Objective: To determine how the prison infrastructure can guarantee health rights and an adequate environment for inmates at the Women's Annex of Chorrillos Prison (EPAMCh. Material and method: The materials consisted of a guided interview conducted with 10 specialists on the subject and a guided survey completed by 30 inmates. The method consisted of an applied qualitative approach with a phenomenological design. Results: The experts interviewed said that the current infrastructure of the Women's Annex of Chorrillos Prison is in a state of crisis and does not provide even minimal healthcare services. The surveys completed by the prisoners gave the unanimous response that conditions were precarious, but the majority said that they were willing to form part of a health education program and to commit to preventive medicine without forgetting curative methods. Discussion: Preventive medicine must be promoted. To do this, prisoners' educational levels need to be improved and solid health education systems in prisons should be provided. Changes would need to be made in the guarantees of their rights to health and to adequate surroundings to bring about the necessary changes
Asunto(s)
Humanos , Femenino , Prisioneros/estadística & datos numéricos , Derechos de los Prisioneros , Infraestructura , 17627 , Prevención de Enfermedades , Perú/epidemiología , Prisiones/estadística & datos numéricos , Ajuste Social , Adaptación Psicológica/clasificación , Educación en Salud/tendenciasRESUMEN
En los estudios de casos y controles anidados, el muestreo de los controles se hace habitualmente por densidad de incidencia y mediante emparejamiento. Con respecto a los casos control clásicos, son más eficientes, permiten el cálculo de la incidencia de la enfermedad y cuentan con más validez interna por la menor presencia de sesgo. Las técnicas de riesgos competitivos pueden usarse si se estudian diferentes tipos de eventos y nos centramos en el tiempo y el tipo del primer evento. El particionamiento recursivo es un tipo de análisis multivariante cuyo propósito es la construcción de algoritmos de clasificación, especialmente útiles cuando hay un gran número de variables predictoras con relaciones complejas con el evento objeto de estudio
In nested case-control studies, sampling of controls is usually done by density of incidence and pairing. With regard to the classic control cases studies, nested ones are more efficient, allow the calculation of the incidence of the disease and they have more internal validity due to the lower presence of bias. Competitive risks techniques can be used if we study different types of events and focus on the time and type of the first event. Recursive partitioning is a type of multivariate analysis whose purpose is the construction of classification algorithms, and it is especially useful when there are a large number of predictive variables with complex relationships with the event