Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training

Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.     

Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy: A Systematic Review and Meta-Analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.     

High-intensity interval training can improve hand grip strength,inspiratory muscle,and quality of life in systemic sclerosis subjects

IntroductionSystemic sclerosis/scleroderma (SSc) is a chronic autoimmune disease with connective tissue, multi-organ, and multisystem involvement. The disease has three main characteristics, namely vasculopathy, fibrosis, and autoimmunity. The effect of high-intensity interval training (HIIT) in aerobic exercise on other rheumatic diseases has been studied, for example in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The purpose of this work is to investigate the effectiveness of HIIT of aerobics exercise on improving the inspiratory muscle, quality of life and functional ability for systemic sclerosis subjects.Material and methodsThe study was conducted on patients with confirmed systemic sclerosis who met the inclusion criteria. The research was carried out for 12 months in the outpatient clinic and gait laboratory of the Department of Physical Medicine and Rehabilitation.ResultsAfter HIIT in aerobic exercise, we found significant changes in inspiratory muscle (SNIP values 45.67 [30.92] vs. 54.25 [22.71]), handgrip (13.14 [4.42] vs. 15.63 [4.08]), walking speed (184.70 [26.86] vs. 246.6 [12.30]), metabolic equivalent (3.53 [0.30] vs. 4.21 [1.25]) and Scleroderma-Specific Health Assessment Questionnaire Disability Index for all visual analog scale (VAS) domains except Disability Index. Exercise approaches are characterized by repeated cycles of exercise interrupted by rest. For a range of clinical conditions, HIIT in aerobic exercise is known to remedy blood vessel function.ConclusionsOur results suggest that HIIT in aerobic exercise has improved functional ability, respiratory muscle strength, and quality of life in SSc subjects. Training twice a week in a 12-week HIIT program is considered to be safe for this population. We have to consider internal and external factors that influenced the result. A larger sample and further exploration of the feasibility of combined exercise in SSc patients should be the focus for future research.     

Dissecting the mammalian synaptonemal complex using targeted mutations

In many organisms completion of the first meiotic cell division depends on the correct assembly and disassembly of the synaptonemal complex (SC). This is a structure discovered a little over 50 years ago, which is formed by the close association of axes of homologous sister chromatid pairs. Its structure varies between organisms, although it retains a common tripartite organization in species as evolutionarily distant as budding yeast and humans. In mammals it is essential for crossover formation and completion of meiosis. Components of the mammalian SC have been identified only in the last 15 years, and mouse genetic approaches have started revealing the importance for this structure only in the past 5 years. Here we discuss the progress that has been made in the field of the mammalian SC and what approaches could be considered for its further study.     

Mother and clinician experiences of a trial of a video feedback parent–infant intervention for mothers experiencing difficulties consistent with ‘personality disorder’: A qualitative interview study

Objectives

We explored mothers' and clinicians' experiences of a video feedback intervention adapted for perinatal ‘personality disorder’ (VIPP-PMH) and the acceptability of a randomised controlled trial (RCT) examining its effectiveness.

Design

In-depth qualitative interviews with participants from a two-phase feasibility study of the VIPP-PMH intervention. Participants were mothers experiencing enduring difficulties in managing emotions and relationships, consistent with a ‘personality disorder’, and their 6- to 36-month-old children.

Methods

Forty-four qualitative interviews were conducted, including all nine mothers receiving VIPP-PMH during the pilot phase, 25 of the 34 mothers participating in the RCT (14 allocated to the VIPP-PMH arm and 9 from the control arm), 11 of the 12 clinicians delivering VIPP-PMH and one researcher. Interview data were thematically analysed.

Results

Mothers described feeling motivated to take part in the research and understood the need for randomisation. Research visits were largely experienced positively, with some suggestions for improvement in questionnaire timing and accessibility. Almost all mothers initially felt anxious about being filmed, but reported positive experiences of the intervention, particularly valuing its non-judgemental, positive and child-focussed nature, their supportive relationship with the therapist and the insights they gained on their child.

Conclusions

The findings indicate the likely feasibility and acceptability of undertaking a future definitive RCT of the VIPP-PMH intervention in this population. In designing a future trial, a positive and non-judgemental therapeutic relationship will be important to allay mothers' anxieties about being filmed, and careful consideration should be given to the timing and accessibility of questionnaires used.     

An analysis of the outcome of microsurgical and laparoscopic adhesiolysis for infertility

We evaluated 81 women with adnexal adhesions and no male factorwho underwent microsurgical (n = 59) and laparoscopic (n = 22)adhesiolysis for infertility. The cumulative conception ratesfor all 81 patients at 12 and 24 months were 41 and 44% respectively.The impact of the following variables on cumulative conceptionrates for all patients was examined: age, duration of infertility,type of infertility, ovulatory status, presence and stage ofendometriosis, adhesion grade, adnexal status (bilateral orunilateral disease, unilateral tubal absence), history of previoussurgery, history of pelvic inflammatory disease and treatmentmodality (microsurgical versus laparoscopic). The results ofindependent comparisons of subgroups within each of these variablesmay be biased because of the interrelationships between thevariables. To overcome this problem, a stepwise Cox's proportionalhazards regression analysis was employed. Our analysis showedthat the single most significant variable influencing the cumulativeconception rates was the duration of infertility (P < 0.005).For every additional year of infertility, the probability ofpregnancy after adhesiolysis (microsurgical or laparoscopic)was reduced by 20%. Cumulative conception rates at 12 and 24months after microsurgical adhesiolysis were 36 and 40% respectively,while after laparoscopic adhesiolysis they were 57% at 12 and24 months. When imbalances were adjusted between the two treatmentgroups, there was no statistically significant difference betweenthe cumulative conception rates for microsurgical and laparoscopicadhesiolysis.     

Changes in mean trabecular orientation in the medial condyle of the proximal tibia in osteoarthritis

In osteoarthritis of the knee, degenerative changes occur in the articular cartilage and underlying subchondral bone, particularly of the medial tibial condyle. Cancellous bone sclerosis that accompanies osteoarthritis is not only the result of an increase in bone volume fraction but also a change in trabecular structure. In a comparison with agematched controls (n=4), osteoarthritis (n=11) demonstrated a significant (P0.05) increase in bone volume fraction and trabecular thickness. Overal trabecular orientation in the osteoarthritic group was more vertical or perpendicular to the articular surface than the control group (P0.05) especially in the trabeculae of the cancellous bone layer closest to the articular surface. These alterations in trabecular bone structure could have significant consequences for the mechanical properties of osteoarthritic bone.