•The relationship between sex steroids and temperature variation was non-linear.•Testosterone change pattern with temperature was opposite to that for Estradiol.•A pronounced increase in Testosterone ...occurred when temperature surpassed 17 °C.•Peak of Testosterone was associated with parturition, just prior to ovulation.•Progesterone increased after Testosterone peak, associated with ovulation.
The knowledge of how temperature influences elasmobranchs reproductive physiology allows a better understanding of their reproductive patterns. This study describes the relationship between temperature fluctuations and the plasmatic changes of the sex steroids related to reproduction: testosterone (T), estradiol (E2) and progesterone (P4), throughout the female reproductive cycle of the shark Mustelus schmitti. A total of 123 adult females were bi-monthly sampled in Buenos Aires, Argentina, coastal waters. Bottom temperatures were recorded at each sampling point and blood samples were taken from each female for plasma sex steroids measurement. Sex steroid plasma levels were analyzed in relation with maximum follicular diameter (MFD), uterosomatic index (USI, as indicator of pregnancy) and temperature using Generalized Additive Models. Plasmatic E2 and T increased during follicular growth until MFD reached 1.34 and 1.46 cm, respectively. Peak of T occurred at the follicular stage associated with parturition (MFD, 1.4–1.6 cm), just prior to final maturation and ovulation (MFD, 1.6–2.0 cm). Progesterone significantly increased at this last ovarian phase, while T and E2 decreased. The increase of USI with pregnancy was associated to a decrease in T and mainly E2 levels, while P4 remained unaffected. Prior to ovulation, T plasma levels decreased with temperature below to 13 °C and then increased progressively with a pronounced elevation above 17 °C, while E2 presented an opposite pattern. Progesterone plasma levels changed with temperature showing a similar pattern to that observed for T. Using M. schmitti shark as model species, this study shows a clear picture of how seawater temperature variations can affect the reproductive physiology in elasmobranch females. A hypothetical mechanism (based on T elevation driven by temperature increase and its connection by feedback with a P4 rise and parturition/ovulation induction) is proposed as evidence to support that the increase in temperature can trigger reproductive events in elasmobranchs. In addition to its ecological scope, this work contributes to reinforce the relatively scarce general knowledge of elasmobranchs reproductive physiology.
We present a set of ground motion prediction equations (GMPEs) derived for the geometrical mean of the horizontal components and the vertical, considering the latest release of the strong motion ...database for Italy. The regressions are performed over the magnitude range 4–6.9 and considering distances up to 200 km. The equations are derived for peak ground acceleration (PGA), peak ground velocity (PGV) and 5%-damped spectral acceleration at periods between 0.04 and 2 s. The total standard deviation (sigma) varies between 0.34 and 0.38 log
10
unit, confirming the large variability of ground shaking parameters when regional data sets containing small to moderate magnitude events (M < 6) are used. The between-stations variability provides the largest values for periods shorter than 0.2 s while, for longer periods, the between-events and between-stations distributions of error provide similar contribution to the total variability.
The lack of effective therapies for spinal cord injury points to the need for identifying novel targets for therapeutic intervention. Here we report that a small molecule, LM11A-31, developed to ...block proNGF-p75 interaction and p75-mediated cell death crosses the blood-brain barrier efficiently when delivered orally. Administered starting 4 h postinjury, LM11A-31 promotes functional recovery without causing any toxicity or increased pain in a mouse model of spinal contusion injury. In both weight-bearing open-field tests and nonweight-bearing swim tests, LM11A-31 was effective in improving motor function and coordination. Such functional improvement correlated with a >50% increase in the number of surviving oligodendrocytes and myelinated axons. We also demonstrate that LM11A-31 indeed inhibits proNGF-p75 interaction in vivo, thereby curtailing the JNK3-mediated apoptotic cascade. These results thus highlight p75 as a novel therapeutic target for an orally delivered treatment for spinal cord injury.
This article presents a set of Ground-Motion Prediction Equations (GMPEs) for Europe and the Middle East, derived from the RESORCE strong motion data bank, following a standard regression approach. ...The parametric GMPEs are derived for the peak ground acceleration, peak ground velocity, and 5 %-damped pseudo-absolute acceleration response spectra computed over 23 periods between 0.02 and 3 s, considering the average horizontal-component ground-motions. The GMPEs are valid for distances less than 300 km, hypocentral depth up to 35 km and over the magnitude range 4–7.6. Two metrics for the source-to-station distance (i.e. Joyner-Boore and hypocentral) are considered. The selected dataset is composed by 2,126 recordings (at a period of 0.1 s) related to 365 earthquakes, that includes strong-motion data from 697 stations.The EC8 soil classification (four classes from A to D) discriminates recording sites and four classes (normal, reverse, strike-slip, and unspecified) describe the style of faulting. A subset which contains only stations with measured Vs30 and earthquakes with specified focal mechanism (1,224 records from 345 stations and 255 earthquakes) is used to test of the accuracy of the median prediction and the variability associated to the broader data set. A random effect regression scheme is applied and bootstrap analyses are performed to estimate the 95 % confidence levels for the parameters. The total standard deviation sigma is decomposed into between-events and within-event components, and the site-to-site component is evaluated as well. The results show that the largest contribution to the total sigma is coming from the within-event component. When analyzing the residual distributions, no significant trends are observed that can be ascribed to the earthquake type (mainshock-aftershock classification) or to the non-linear site effects. The proposed GMPEs have lower median values than global models at short periods and large distances, while are consistent with global models at long periods
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T
>
1
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s. Consistency is found with two regional models developed for Turkey and Italy, as the considered dataset is dominated by waveforms recorded in these regions.
Innate Immunity in the Middle Ear Mucosa Massa, Helen M.; Spann, Kirsten M.; Cripps, Allan W.
Frontiers in cellular and infection microbiology,
10/2021, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with ...effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.
As several studies demonstrate, good sleep quality is essential for individuals’ well-being, as a lack of restoring sleep may disrupt different physical, mental, and social dimensions of health. For ...this reason, there is increasing interest in tools for the monitoring of sleep based on personal sensors. However, there are currently few context-aware methods to help individuals to improve their sleep quality through behavior change tips. In order to tackle this challenge, in this paper, we propose a system that couples machine learning algorithms and large language models to forecast the next night’s sleep quality, and to provide context-aware behavior change tips to improve sleep. In order to encourage adherence and to increase trust, our system includes the use of large language models to describe the conditions that the machine learning algorithm finds harmful to sleep health, and to explain why the behavior change tips are generated as a consequence. We develop a prototype of our system, including a smartphone application, and perform experiments with a set of users. Results show that our system’s forecast is correlated to the actual sleep quality. Moreover, a preliminary user study suggests that the use of large language models in our system is useful in increasing trust and engagement.
Purpose
Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids ...(LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice.
Methods
Wild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size.
Results
LCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA.
Conclusions
GPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.
Abstract
Background
Atrial fibrillation (AF) has a higher prevalence in men than in women and is associated with measures of adiposity and lean mass (LM). However, it remains uncertain whether the ...risks of AF associated with these measures vary by sex.
Methods
Among 477 904 UK Biobank participants aged 40–69 without prior AF, 23 134 incident AF cases were identified (14 400 men, 8734 women; median follow-up 11.1 years). Cox proportional hazards models were used to estimate the covariate adjusted hazard ratios (HRs) describing the association of AF with weight, measures of adiposity fat mass (FM), waist circumference (WC) and LM, and their independent relevance, by sex.
Results
Weight and WC were independently associated with risk of AF HR: 1.25 (1.23–1.27) per 10 kg, HR: 1.11 (1.09–1.14) per 10 cm, respectively, with comparable effects in both sexes. The association with weight was principally driven by LM, which, per 5 kg, conferred double the risk of AF compared with FM when mutually adjusted HR: 1.20 (1.19–1.21), HR: 1.10 (1.09–1.11), respectively; however, the effect of LM was weaker in men than in women (p-interaction = 4.3 x 10−9). Comparing the relative effects of LM, FM and WC identified different patterns within each sex; LM was the strongest predictor for both, whereas WC was stronger than FM in men but not in women.
Conclusions
LM and FM (as constituents of weight) and WC are risk factors for AF. However, the independent relevance of general adiposity for AF was more limited in men than in women. The relevance of both WC and LM suggests a potentially important role for visceral adiposity and muscle mass in AF development.
ObjectiveThe Anti-Freaze-F (AFF) trial assessed the feasibility of conducting a definitive trial to determine whether intra-articular injection of adalimumab can reduce pain and improve function in ...people with pain-predominant early-stage frozen shoulder.DesignMulticentre, randomised feasibility trial, with embedded qualitative study.SettingFour UK National Health Service (NHS) musculoskeletal and related physiotherapy services.ParticipantsAdults ≥18 years with new episode of shoulder pain attributable to early-stage frozen shoulder.InterventionsParticipants were randomised (centralised computer generated 1:1 allocation) to either ultrasound-guided intra-articular injection of: (1) adalimumab (160 mg) or (2) placebo (saline (0.9% sodium chloride)). Participants and outcome assessors were blinded to treatment allocation. Second injection of allocated treatment (adalimumab 80 mg) or equivalent placebo was administered 2–3 weeks later.Primary feasibility objectives(1) Ability to screen and identify participants; (2) willingness of eligible participants to consent and be randomised; (3) practicalities of delivering the intervention; (4) SD of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months.ResultsBetween 31 May 2022 and 7 February 2023, 156 patients were screened of whom 39 (25%) were eligible. The main reasons for ineligibility were other shoulder disorder (38.5%; n=45/117) or no longer in pain-predominant frozen shoulder (33.3%; n=39/117). Of the 39 eligible patients, nine (23.1%) consented to be randomised (adalimumab n=4; placebo n=5). The main reason patients declined was because they preferred receiving steroid injection (n=13). All participants received treatment as allocated. The mean time from randomisation to first injection was 12.3 (adalimumab) and 7.2 days (placebo). Completion rates for patient-reported and clinician-assessed outcomes were 100%.ConclusionThis study demonstrated that current NHS musculoskeletal physiotherapy settings yielded only small numbers of participants, too few to make a trial viable. This was because many patients had passed the early stage of frozen shoulder or had already formulated a preference for treatment.Trial registration numberISRCTN 27075727, EudraCT 2021-03509-23, ClinicalTrials.gov NCT05299242 (REC 21/NE/0214).
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