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1.
Nat Cell Biol ; 24(1): 51-61, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35027730

RESUMEN

The efficacy of poly(ADP)-ribose polymerase 1 inhibition (PARPi) in BRCA1-deficient cells depends on 53BP1 and shieldin, which have been proposed to limit single-stranded DNA at double-strand breaks (DSBs) by blocking resection and/or through CST-Polα-primase-mediated fill-in. We show that primase (like 53BP1-shieldin and CST-Polα) promotes radial chromosome formation in PARPi-treated BRCA1-deficient cells and demonstrate shieldin-CST-Polα-primase-dependent incorporation of BrdU at DSBs. In the absence of 53BP1 or shieldin, radial formation in BRCA1-deficient cells was restored by the tethering of CST near DSBs, arguing that in this context, shieldin acts primarily by recruiting CST. Furthermore, a SHLD1 mutant defective in CST binding (SHLD1Δ) was non-functional in BRCA1-deficient cells and its function was restored after reconnecting SHLD1Δ to CST. Interestingly, at dysfunctional telomeres and at DNA breaks in class switch recombination where CST has been implicated, SHLD1Δ was fully functional, perhaps because these DNA ends carry CST recognition sites that afford SHLD1-independent binding of CST. These data establish that in BRCA1-deficient cells, CST-Polα-primase is the major effector of shieldin-dependent DSB processing.


Asunto(s)
Proteína BRCA1/genética , Roturas del ADN de Doble Cadena , ADN Polimerasa I/metabolismo , Reparación del ADN/genética , Complejo Shelterina/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Animales , Sitios de Unión/genética , Sistemas CRISPR-Cas/genética , Línea Celular Tumoral , ADN/genética , ADN Primasa/genética , ADN Primasa/metabolismo , Técnicas de Inactivación de Genes , Humanos , Ratones , Inhibidores de Poli(ADP-Ribosa) Polimerasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Recombinasa Rad51/metabolismo , Proteínas de Unión a Telómeros/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética
3.
BMC Public Health ; 21(1): 1733, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34556068

RESUMEN

BACKGROUND: Intimate partner violence (IPV) is a major public health problem with harmful consequences. In Australia, there is no national standard screening tool and screening practice is variable across states. The objectives of this study were to assess in the antenatal healthcare setting: i) the validity of a new IPV brief screening tool and ii) women's preference for screening response format, screening frequency and comfort level. METHODS: One thousand sixty-seven antenatal patients in a major metropolitan Victorian hospital in Australia completed a paper-based, self-administered survey. The survey included four screening items about whether they were Afraid/Controlled/Threatened/Slapped or physically hurt (ACTS) by a partner or ex-partner in the last 12 months; and the Composite Abuse Scale (reference standard). The ACTS screen was presented firstly with a binary yes/no response format and then with a five-point ordinal frequency format from 'never' (0) to 'very frequently' (4). The main outcome measures were test statistics of the four-item ACTS screening tool (sensitivity, specificity, predictive values, and area under the curve) against the reference standard and women's screening preferences. RESULTS: Twelve-month IPV prevalence varied depending on the ACTS response format with 8% (83) positive on ACTS yes/no format, 12.8% (133) positive on ACTS ordinal frequency format and 10.5% (108) on the reference Composite Abuse Scale. Overall, the ACTS screening tool demonstrated clinical utility for the ordinal frequency format (AUC, 0.80; 95% CI = 0.76 to 0.85) and the binary yes/no format (AUC, 0.74, 95% CI = 0.69 to 0.79). The frequency scale (66%) had greater sensitivity than the yes/no scale (51%). The positive and negative predictive values were 56 and 96% for the frequency scale and 68 and 95% for the yes/no scale. Specificity was high regardless of screening question response options. Half (53%) of the women categorised as abused preferred the yes/no scale. Around half of the women (48%, 472) thought health care providers should ask pregnant women about IPV at every visit. CONCLUSIONS: The four-item ACTS tool (using the frequency scale and a cut-off of one on any item) is recommended for written self-administered screening of women to identify those experiencing IPV to enable first-line response and follow-up.


Asunto(s)
Violencia de Pareja , Maltrato Conyugal , Estudios Transversales , Atención a la Salud , Femenino , Humanos , Embarazo , Atención Prenatal
4.
J Dairy Sci ; 104(11): 11580-11592, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34454748

RESUMEN

The continuous trend for a narrowing margin between feed cost and milk prices across dairy farms in the United States highlights the need to improve and maintain feed efficiency. Yeast culture products are alternative supplements that have been evaluated in terms of milk performance and feed efficiency; however, less is known about their potential effects on altering rumen microbial populations and consequently rumen fermentation. Therefore, the objective of this study was to evaluate the effect of yeast culture supplementation on lactation performance, rumen fermentation profile, and abundance of major species of ruminal bacteria in lactating dairy cows. Forty mid-lactation Holstein dairy cows (121 ± 43 days in milk; mean ± standard deviation; 32 multiparous and 8 primiparous) were used in a randomized complete block design with a 7-d adaptation period followed by a 60-d treatment period. Cows were blocked by parity, days in milk, and previous lactation milk yield and assigned to a basal total mixed ration (TMR; 1.6 Mcal/kg of dry matter, 14.6% crude protein, 21.5% starch, and 38.4% neutral detergent fiber) plus 114 g/d of ground corn (CON; n = 20) or basal TMR plus 100 g/d of ground corn and 14 g/d of yeast culture (YC; n = 20; Culture Classic HD, Cellerate Yeast Solutions, Phibro Animal Health Corp.). Treatments were top-dressed over the TMR once a day. Cows were individually fed 1 × /d throughout the trial. Blood and rumen fluid samples were collected in a subset of cows (n = 10/treatment) at 0, 30, and 60 d of the treatment period. Rumen fluid sampled via esophageal tubing was analyzed for ammonia-N, volatile fatty acids (VFA), and ruminal bacteria populations via quantitative PCR amplification of 16S ribosomal DNA genes. Milk yield was not affected by treatment effects. Energy balance was lower in YC cows than CON, which was partially explain by the trend for lower dry matter intake as % body weight in YC cows than CON. Cows fed YC had greater overall ruminal pH and greater total VFA (mM) at 60 d of treatment period. There was a contrasting greater molar proportion of isovalerate and lower acetate proportion in YC-fed cows compared with CON cows. Although the ruminal abundance of specific fiber-digesting bacteria, including Eubacterium ruminantium and Ruminococcus flavefaciens, was increased in YC cows, others such as Fibrobacter succinogenes were decreased. The abundance of amylolytic bacteria such as Ruminobacter amylophilus and Succinimonas amylolytica were decreased in YC cows than CON. Our results indicate that the yeast culture supplementation seems to promote some specific fiber-digesting bacteria while decreasing amylolytic bacteria, which might have partially promoted more neutral rumen pH, greater total VFA, and isovalerate.


Asunto(s)
Lactancia , Rumen , Alimentación Animal/análisis , Animales , Bovinos , Dieta/veterinaria , Suplementos Dietéticos , Digestión , Eubacterium , Femenino , Fermentación , Fibrobacter , Leche , Embarazo , Rumen/metabolismo , Ruminococcus , Saccharomyces cerevisiae , Succinivibrionaceae
6.
J Dairy Sci ; 104(10): 10727-10743, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34253357

RESUMEN

Feeding yeast culture fermentation products has been associated with improved feed intake and milk yield in transition dairy cows. These improvements in performance have been further described in terms of rumen characteristics, metabolic profile, and immune response. The objective of this study was to evaluate the effects of a commercial yeast culture product (YC; Culture Classic HD, Phibro Animal Health) on performance, blood biomarkers, rumen fermentation, and rumen bacterial population in dairy cows from -30 to 50 d in milk (DIM). Forty Holstein dairy cows were enrolled in a randomized complete block design from -30 to 50 DIM and blocked according to expected calving day, parity, previous milk yield, and genetic merit. At -30 DIM, cows were assigned to either a basal diet plus 114 g/d of ground corn (control; n = 20) or a basal diet plus 100 g/d of ground corn and 14 g/d of YC (n = 20), fed as a top-dress. Cows received the same close-up diet from 30 d prepartum until calving [1.39 Mcal/kg of dry matter (DM) and 12.3% crude protein (CP)] and lactation diet from calving to 50 DIM (1.60 Mcal/kg of DM and 15.6% CP). Blood samples and rumen fluid were collected at various time points from -30 to 50 d relative to calving. Cows fed YC compared with control showed a trend for increased energy-corrected milk (+3.2 kg/d). Lower somatic cell counts were observed in YC cows than in control. We detected a treatment × time interaction in nonesterified fatty acids (NEFA) that could be attributed to a trend for greater NEFA in YC cows than control at 7 DIM, followed by lower NEFA in YC cows than control at 14 and 30 DIM. In the rumen, YC contributed to mild changes in rumen fermentation, mainly increasing postpartal valerate while decreasing prepartal isovalerate. This was accompanied by alterations in rumen microbiota, including a greater abundance of cellulolytic (Fibrobacter succinogenes) and lactate-utilizing bacteria (Megasphaera elsdenii). These results describe the potential benefits of supplementing yeast culture during the late pregnancy through early lactation, at least in terms of rumen environment and performance.


Asunto(s)
Rumen , Saccharomyces cerevisiae , Animales , Biomarcadores/metabolismo , Bovinos , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Fermentación , Fibrobacter , Lactancia , Leche , Embarazo , Rumen/metabolismo
8.
Nature ; 596(7872): 433-437, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34321663

RESUMEN

Protein ubiquitination at sites of DNA double-strand breaks (DSBs) by RNF168 recruits BRCA1 and 53BP11,2, which are mediators of the homologous recombination and non-homologous end joining DSB repair pathways, respectively3. Non-homologous end joining relies on 53BP1 binding directly to ubiquitinated lysine 15 on H2A-type histones (H2AK15ub)4,5 (which is an RNF168-dependent modification6), but how RNF168 promotes BRCA1 recruitment and function remains unclear. Here we identify a tandem BRCT-domain-associated ubiquitin-dependent recruitment motif (BUDR) in BRCA1-associated RING domain protein 1 (BARD1) (the obligate partner protein of BRCA1) that, by engaging H2AK15ub, recruits BRCA1 to DSBs. Disruption of the BUDR of BARD1 compromises homologous recombination and renders cells hypersensitive to PARP inhibition and cisplatin. We further show that BARD1 binds nucleosomes through multivalent interactions: coordinated binding of H2AK15ub and unmethylated H4 lysine 20 by its adjacent BUDR and ankyrin repeat domains, respectively, provides high-affinity recognition of DNA lesions in replicated chromatin and promotes the homologous recombination activities of the BRCA1-BARD1 complex. Finally, our genetic epistasis experiments confirm that the need for BARD1 chromatin-binding activities can be entirely relieved upon deletion of RNF168 or 53BP1. Thus, our results demonstrate that by sensing DNA-damage-dependent and post-replication histone post-translation modification states, BRCA1-BARD1 complexes coordinate the antagonization of the 53BP1 pathway with promotion of homologous recombination, establishing a simple paradigm for the governance of the choice of DSB repair pathway.


Asunto(s)
Recombinación Homóloga , Lisina/química , Lisina/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Adulto , Secuencias de Aminoácidos , Proteína BRCA1/química , Proteína BRCA1/metabolismo , Cromatina/metabolismo , Cisplatino/farmacología , Roturas del ADN de Doble Cadena , Daño del ADN/efectos de los fármacos , Femenino , Células HCT116 , Células HEK293 , Histonas/química , Histonas/metabolismo , Humanos , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Dominios Proteicos , Reparación del ADN por Recombinación , Proteínas Supresoras de Tumor/química , Proteína 1 de Unión al Supresor Tumoral P53/deficiencia , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/deficiencia
9.
Anaesth Rep ; 9(1): 86-89, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33982000

RESUMEN

We describe the novel use of the TriTube® and Evone® ventilator (Ventinova, Eindhoven, Netherlands) to facilitate curative resection of a transglottic squamous cell carcinoma. A 43-year-old man presented with acute laryngeal and subglottic airway obstruction secondary to a stage 4 transglottic squamous cell carcinoma. The patient underwent magnetic resonance imaging followed by a diagnostic panendoscopy. It was decided that tumour resection was appropriate and a management plan was established by a multi disciplinary team. A total laryngectomy was performed. It was determined that failure of translaryngeal tracheal intubation could be rescued with emergency surgical front-of-neck airway. General anaesthesia was induced using a total intravenous anaesthesia technique, oxygenation was achieved with high-flow nasal oxygen and the airway was secured using the TriTube and flow-controlled ventilation was delivered throughout the procedure using the Evone ventilator. This avoided an awake or emergency tracheostomy, with the associated theoretical risk of tumour seeding, allowed for excellent gas exchange throughout and permitted the surgeons to maintain a closed system during much of the procedure, including during fashioning of the stoma. When traditional laryngectomy tubes are used, this process ordinarily involves multiple extubations and apnoeic periods. Furthermore, the small subglottic tube allowed intra-operative assessment of the extent of the subglottic tumour, facilitating curative en bloc resection.

10.
Arthroscopy ; 37(4): 1115-1116, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33812516

RESUMEN

The creation of pain as the fifth vital sign in 2001 led to an unforeseen and dramatic increase in postoperative narcotic use. It became clear that chronic opioid use was associated with overdoses and deaths, and state medical licensing boards began to require completion of narcotic Continuing Medical Education courses to maintain licensure. Despite the overwhelming evidence of adverse effects of narcotic usage in both the pre- and postoperative periods, this continues to be a persistent problem in all areas of orthopaedic surgery. The magnitude of the problem is significant and now opioid-specific training is a mandated component of the American Board of Orthopaedic Surgery Maintenance of Certification for their Web-based Longitudinal Assessment of continuing medical education. Large database studies are helpful in identifying trends and factors that influence outcomes, potentially cut cost of care, and hopefully help us find a way out of this ongoing dilemma. This dilemma has taken a long time to create and will require a concerted disciplined effort to eliminate.


Asunto(s)
Trastornos Relacionados con Opioides , Lesiones del Manguito de los Rotadores , Analgésicos Opioides/uso terapéutico , Artroscopía , Humanos , Manguito de los Rotadores , Lesiones del Manguito de los Rotadores/tratamiento farmacológico
11.
Mol Cell ; 81(4): 767-783.e11, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33333017

RESUMEN

Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD cancers.


Asunto(s)
Ensamble y Desensamble de Cromatina , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentales/metabolismo , Nucleosomas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Animales , ADN Helicasas/genética , Replicación del ADN/efectos de los fármacos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Proteínas de Unión al ADN/genética , Recombinación Homóloga/efectos de los fármacos , Ratones , Ratones Noqueados , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Neoplasias Experimentales/genética , Nucleosomas/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/genética
12.
Food Chem (Oxf) ; 3: 100033, 2021 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-35415666

RESUMEN

The last three decades have demonstrated the ability of combining data analytics (e.g. big data, machine learning) with modern analytical instrumental techniques such as vibrational spectroscopy (VIBSPEC) (e.g. NIR, Raman, MIR) and sensing technologies (e.g. electronic noses and tongues, colorimetric sensors) to analyse, measure and monitor a wide range of properties and samples. Developments in instrumentation, hardware and software have placed VIBSPEC as a useful tool to quantify several bioactive compounds and metabolites in a wide range of fruit and plant samples. With the incorporation of hand-held and portable instrumentation, these techniques have been valuable for the development of in-field and high throughput applications, opened new frontiers of analysis in fruits and plants. This review will present and discuss some of the current applications on the use of VIBSPEC techniques combined with data analytics on the measurement bioactive compounds and plant metabolites in different fruit samples.

13.
Nature ; 585(7825): 447-452, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32908313

RESUMEN

Genomic instability is a hallmark of cancer, and has a central role in the initiation and development of breast cancer1,2. The success of poly-ADP ribose polymerase inhibitors in the treatment of breast cancers that are deficient in homologous recombination exemplifies the utility of synthetically lethal genetic interactions in the treatment of breast cancers that are driven by genomic instability3. Given that defects in homologous recombination are present in only a subset of breast cancers, there is a need to identify additional driver mechanisms for genomic instability and targeted strategies to exploit these defects in the treatment of cancer. Here we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q23 amplicon, a recurrent copy number aberration that defines about 9% of all primary breast cancer tumours and is associated with high levels of genomic instability4-6. Specifically, inhibition of polo-like kinase 4 (PLK4) using small molecules leads to centrosome depletion, which triggers mitotic catastrophe in cells that exhibit amplicon-directed overexpression of TRIM37. To explain this effect, we identify TRIM37 as a negative regulator of centrosomal pericentriolar material. In 17q23-amplified cells that lack centrosomes, increased levels of TRIM37 block the formation of foci that comprise pericentriolar material-these foci are structures with a microtubule-nucleating capacity that are required for successful cell division in the absence of centrosomes. Finally, we find that the overexpression of TRIM37 causes genomic instability by delaying centrosome maturation and separation at mitotic entry, and thereby increases the frequency of mitotic errors. Collectively, these findings highlight TRIM37-dependent genomic instability as a putative driver event in 17q23-amplified breast cancer and provide a rationale for the use of centrosome-targeting therapeutic agents in treating these cancers.


Asunto(s)
Neoplasias de la Mama/genética , Centrosoma/metabolismo , Centrosoma/patología , Cromosomas Humanos Par 17/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Centrosoma/efectos de los fármacos , Femenino , Fase G2 , Inestabilidad Genómica , Humanos , Mitosis/genética , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética
14.
Cell Rep ; 32(8): 108068, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32846126

RESUMEN

Using genome-wide radiogenetic profiling, we functionally dissect vulnerabilities of cancer cells to ionizing radiation (IR). We identify ERCC6L2 as a major determinant of IR response, together with classical DNA damage response genes and members of the recently identified shieldin and CTC1-STN1-TEN1 (CST) complexes. We show that ERCC6L2 contributes to non-homologous end joining (NHEJ), and it may exert this function through interactions with SFPQ. In addition to causing radiosensitivity, ERCC6L2 loss restores DNA end resection and partially rescues homologous recombination (HR) in BRCA1-deficient cells. As a consequence, ERCC6L2 deficiency confers resistance to poly (ADP-ribose) polymerase (PARP) inhibition in tumors deficient for both BRCA1 and p53. Moreover, we show that ERCC6L2 mutations are found in human tumors and correlate with a better overall survival in patients treated with radiotherapy (RT); this finding suggests that ERCC6L2 is a predictive biomarker of RT response.


Asunto(s)
Reparación del ADN por Unión de Extremidades/efectos de la radiación , ADN Helicasas/metabolismo , Animales , Humanos , Ratones
15.
Conserv Physiol ; 8(1): coaa033, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32440351

RESUMEN

For Pacific salmon captured and released by fisheries, post-release behaviour and survival may be influenced by their health and condition at time of capture. We sought to characterize the interactions between infectious agent burden, fish immune and stress physiology and fisheries stressors to investigate the potential for capture-mediated pathogen-induced mortality in adult coho salmon Oncorhynchus kisutch. We used radio-telemetry paired with high-throughput qPCR of non-lethal gill biopsies for infectious agents and host biomarkers from 200 tagged fish experimentally displaced and exposed to various experimental fisheries treatments (gill net entanglement, recreational angling and recreational angling with air exposure vs. non-sampled control). We characterized relationships among post-release behaviour and survival, infectious agent presence and loads, physiological parameters and transcription profiles of stress and immune genes. All infectious agents detected were endemic and in loads consistent with previous adult Pacific salmon monitoring. Individuals exposed to fisheries treatments were less likely to reach spawning habitat compared to controls, and handling duration independent of fisheries gear had a negative effect on survival. High infectious agent burden was associated with accelerated migration initiation post-release, revealing behavioural plasticity in response to deteriorating condition in this semelparous species. Prevalence and load of infectious agents increased post-migration as well as transcription signatures reflected changes in immune and stress profiles consistent with senescence. Results from this study further our understanding of factors associated with fisheries that increase risk of post-release mortality and characterize some physiological mechanisms that underpin migratory behaviour.

17.
Eur J Neurol ; 27(8): 1604-1611, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32335972

RESUMEN

BACKGROUND AND PURPOSE: Myeloperoxidase (MPO) is an important oxidative enzyme participating in different stages of cardiovascular disease and predicts prognosis. Little is known about its role in acute cerebrovascular events and carotid plaque vulnerability. In this study, the aim was to assess plasma MPO levels in acute stroke patients and their correlation to stroke severity and stroke outcome. METHODS: Plasma MPO levels were assessed in patients presenting with acute brain ischaemia within 36 h of symptom onset (n = 144, mean age 64.7 ± 11.6 years, 67% men) and in patients with moderate-to-severe carotid stenosis undergoing carotid artery stenting (n = 51, mean age 66.3 ± 8.4 years, 75% men). Patients presenting with acute brain ischaemia were assessed serially for stroke severity and disability. RESULTS: Plasma MPO concentrations (ng/ml) were associated with interleukin-6 (r = 0.38, P < 0.0001) and gender (median interquartile range) of 68.6 (49.8-107.0) vs. 59.7 (42.7-85.5) in women vs. men (P = 0.02). In acute brain ischaemia, MPO concentrations were associated with non-lacunar subtype (bottom, middle and top tertiles 37.5%, 71.7% and 71.7% respectively; P = 0.001), with stroke severity (baseline National Institutes of Health Stroke Scale score > 10, bottom, middle and top tertiles 6.3%, vs. 41.7% and 31.3%, respectively; P < 0.006) as well as with stroke severity at days 1-2, days 4-5 and at discharge (P < 0.05 for all), but less with disability at discharge (modified Rankin Scale score ≥ 2, 41.7% vs. 60.4% and 58.7% for the bottom, middle and top tertiles, respectively; P = 0.096). CONCLUSIONS: Amongst patients with acute brain ischaemia, plasma MPO concentrations were associated with stroke severity and non-lacunar subtype, but not with long-term functional disability.


Asunto(s)
Isquemia Encefálica , Estenosis Carotídea , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peroxidasa , Plasma , Resultado del Tratamiento
18.
J Dairy Sci ; 103(7): 6612-6626, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32307158

RESUMEN

Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.


Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Bovinos/fisiología , Hormona Liberadora de Corticotropina/farmacología , Suplementos Dietéticos/análisis , Leche/metabolismo , Vasopresinas/farmacología , Animales , Dieta/veterinaria , Femenino , Respuesta al Choque Térmico , Humedad , Hidrocortisona/sangre , Lactancia , Paridad , Embarazo , Progesterona/sangre
19.
BMC Psychiatry ; 20(1): 108, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-32143714

RESUMEN

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.


Asunto(s)
Ejercicio Físico , Trastornos Mentales , Conducta Sedentaria , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto Joven
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