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The present experiment aimed at determining whether the timing of the maternal recognition of pregnancy (MRP) was specific to individual mares by determining when luteostasis, a failure to return to oestrus, reliably occurred in individuals following embryo reduction. Singleton (n = 150) and synchronous twin pregnancies (n = 9) were reduced in 10 individuals (5–29 reductions/mare) at pre-determined time points within days 10 (n = 20), 11 (n = 65), 12 (n = 47), 13 (n = 12) or 14 (n = 15) of pregnancy. Prior to embryo reduction, the vesicle diameter was measured in 71% (106/150) of the singleton pregnancies. The interovulatory interval (IOI) was recorded on 78 occasions in seven of the mares in either non-pregnant cycles (n = 37) or those in which luteolysis followed embryo reduction (n = 41). The earliest time post-ovulation at which the embryo reduction resulted in luteostasis in an individual was 252 h (mid-Day 10). Consistency in luteostasis following embryo reduction showed individual variation between mares (272–344 h). Binary logistic regression analysis showed an individual mare effect (p < 0.001) and an effect of the interval post-ovulation at which embryo reduction was undertaken (p < 0.001). However, there was no significant effect of vesicle diameter at the time of embryo reduction (p = 0.099), nor a singleton or twin pregnancy (p = 0.993), on the dependent of luteolysis or luteostasis. The median IOI between individual mares varied significantly (p < 0.05) but was not correlated to the timing of MRP. The timing of MRP varied between the mares but was repeatable in each individual. The factors and mechanisms underlying the individuality in the timing of MRP were not determined and warrant further study.

Oestrogens treatment is often used to induce oestrus behaviour in anoestrous mares to aid in the collection of stallion semen and as recipient mares to receive embryos when combined with progesterone. However, there are no studies to describe the effect of dose and individual mare on the intensity and duration of the response, in both anoestrous and cyclic mares. In Experiment 1, 13 anoestrous mares were treated with one of five doses of oestradiol benzoate (OB) (1, 1.5, 2, 3 and 4 mg) per mare in five consecutive treatment periods (n = 65), to determine the response in terms of endometrial oedema and oestrous behaviour. Experiment 2 and 3 used 3 mg of OB in cyclic mares to confirm or deny the presence of an active corpus luteum (CL). There was a dose rate of OB and individual mare effect (p < 0.05) on the intensity and persistence of endometrial oedema and oestrous behaviour. A total of 2 mg OB was enough to induce endometrial oedema and oestrous behaviour within 48 h in most mares. Mares with an active CL did not show endometrial oedema following treatment of 3 mg OB.

BackgroundThere is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting.MethodsAdult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI); GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed.ResultsAmong 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls.ConclusionsS100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.

InTBIR studies have shown that measurement of blood-based biomarkers adds value to previously proposed clinical decision rules, holding the potential to improve efficiency while reducing radiation exposure. Advanced MRI, including diffusion tensor imaging and volumetric analyses, can identify additional injuries not detectable by visual inspection of standard clinical MR images. [...]the absence of CT abnormalities does not exclude structural damage—an observation relevant to litigation procedures, to management of mild TBI, and when CT scans are insufficient to explain the severity of the clinical condition. In the intensive care setting, automated analysis of blood pressure and intracranial pressure with calculation of derived parameters can help individualise management of TBI. TBI affects multiple domains of functioning, and outcomes are affected by personal characteristics and life-course events, consistent with a multifactorial bio-psycho-socio-ecological model of TBI, as presented in the US National Academies of Sciences, Engineering, and Medicine (NASEM) 2022 report.

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

The clinical severity of traumatic brain injury (TBI) is commonly classified according to the Glasgow Coma Scale (GCS) sum score as mild (13–15), moderate (9–12), or severe (3–8). A new approach is needed for characterising TBI more accurately. In 2022, the US National Institutes of Health–National Institute of Neurological Disorders and Stroke launched an international initiative to address this need, with a focus on the acute phase of injury. Six working groups of TBI experts, implementation scientists, people with lived experience, and federal partners were established, involving 94 participants from 14 countries. The proposed new framework for the characterisation of acute TBI incorporates four pillars: a clinical pillar (full GCS and pupillary reactivity); a biomarker pillar (blood-based measures); an imaging pillar (pathoanatomical measures); and a modifier pillar (features influencing clinical presentation and outcome; CBI-M). The CBI-M framework provides a multidimensional characterisation of TBI to inform individualised clinical management and to improve scientific rigor. Research priorities include validation of the CBI-M framework, evaluation of its applicability beyond the acute phase of TBI, and strategies for clinical implementation.

Most patients with ulcerative colitis are nonsmokers, and patients with a history of smoking usually acquire their disease within a few years after they have stopped smoking 1 – 4 . Among patients who continue to smoke, symptoms may improve, suggesting that smoking may have a beneficial effect 5 , 6 . Given the possibility that nicotine is the ingredient of tobacco smoke responsible for improvement, we treated 16 patients with active ulcerative colitis in an uncontrolled fashion with transdermal nicotine patches, and symptoms improved in 12 7 . We report here the results of a randomized, double-blind, controlled trial of transdermal nicotine in patients . . .

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies. A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Ulcerative colitis is largely a disease of nonsmokers, and patients with ulcerative colitis who are exsmokers have usually acquired the disease within a few years after they stopped smoking. 1 – 5 Patients who smoke intermittently often experience improvement in their colitis symptoms during the periods when they are smoking. 6 , 7 Treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis. 8 , 9 In a randomized, controlled trial, we studied the effect of transdermal nicotine, without mesalamine, on the maintenance of remission in patients with ulcerative colitis. Methods Patients Two hundred fifty patients with ulcerative colitis (age, . . .

Recent theoretical models suggest that the central executive may not be a unified structure. The present study explored the nature of central executive deficits in ecstasy users. In study 1, 27 ecstasy users and 34 non-users were assessed using tasks to tap memory updating (computation span; letter updating) and access to long-term memory (a semantic fluency test and the Chicago Word Fluency Test). In study 2, 51 ecstasy users and 42 non-users completed tasks that assess mental set switching (number/letter and plus/minus) and inhibition (random letter generation). MANOVA revealed that ecstasy users performed worse on both tasks used to assess memory updating and on tasks to assess access to long-term memory (C- and S-letter fluency). However, notwithstanding the significant ecstasy group-related effects, indices of cocaine and cannabis use were also significantly correlated with most of the executive measures. Unexpectedly, in study 2, ecstasy users performed significantly better on the inhibition task, producing more letters than non-users. No group differences were observed on the switching tasks. Correlations between indices of ecstasy use and number of letters produced were significant. The present study provides further support for ecstasy/polydrug-related deficits in memory updating and in access to long-term memory. The surplus evident on the inhibition task should be treated with some caution, as this was limited to a single measure and has not been supported by our previous work.