Prevalence of reducing carbohydrate intake and fasted training in elite endurance athletes and association with bone injury.

There are conflicting reports both within the lay media and scientific literature regarding the use and benefit of dietary practices that aim to reduce CHO intake in endurance athletes. This study aimed to determine the prevalence of intentional reduction of CHO intake and fasted training in elite endurance-based athletes using a semi-quantitative questionnaire. Bone is a nutritionally modulated tissue; therefore, this study also aimed to explore if these dietary practices are potentially associated with bone injury incidence. The reported reduction of CHO intake was prevalent (28%) with the primary motivation being maintenance or manipulation of body composition. However, discrepancies in athletes' awareness of CHO intake were identified providing a potential avenue of intervention especially within applied practice. The use of fasted training was more prevalent (38%) with athletes using this practice for both body composition manipulation and promoting a desired adaptive response. Forty-four per cent of participants had suffered a radiographically confirmed bone injury at some point in their career. There was no association between reduction in CHO intake and bone injury incidence; however, the incidence of bone injury was 1.61 times higher in those who currently use fasted training compared to those who have never used it or who have used it in the past. Although a direct causal link between these dietary practices and the incidence of bone injury cannot be drawn, it provides robust justification for future investigations of the potential mechanisms that could explain this finding.

Diet and physical activity interventions to improve cardiovascular disease risk factors in liver transplant recipients: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions. METHODS: We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis. RESULTS: Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low. CONCLUSION: Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care.

Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling.

Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity. Yet, the degree to which these cells communicate to coordinate this process remains an open question. Here, we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex. We show that astrocytes do not engulf synapses in this paradigm. Instead, astrocytes reduce their contact with synapses prior to microglia-mediated synapse engulfment. We further show that reduced astrocyte-contact with synapses is dependent on microglial CX3CL1-CX3CR1 signaling and release of Wnts from microglia following whisker removal. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, which then provides a permissive environment for microglia to remove synapses. We further show that this mechanism is critical to remodel synapses in a changing sensory environment and this signaling is upregulated in several disease contexts.

A comparative analysis of microglial inducible Cre lines.

Cre/loxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. Microglial biology has particularly benefited because microglia historically have been difficult to transduce with virus or electroporation methods for gene delivery. Here, we investigate five of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency, cell-type specificity, and spontaneous recombination, depending on the Cre line and inter-loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency, particularly in microglia. There is increasing evidence that microglia are key regulators of neural circuits and major drivers of a broad range of neurological diseases. Reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field and the development of microglia-based therapeutics.

A comparative analysis of microglial inducible Cre lines.

Cre/LoxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. The field of microglial biology has particularly benefited from this technology as microglia have historically been difficult to transduce with virus or electroporation methods for gene delivery. Here, we interrogate four of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency and spontaneous recombination, depending on the Cre line and loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency in microglia, which could be extended to other cell types. There is increasing evidence that microglia are key regulators of neural circuit structure and function. Microglia are also major drivers of a broad range of neurological diseases. Thus, reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field of microglial biology and the development of microglia-based therapeutics.

Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18-102 years.

BACKGROUND: The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. OBJECTIVE: To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. METHODS: Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples). Plasma PLP and erythrocyte glutathione reductase activation coefficient (EGRac), as a functional indicator of riboflavin, were determined. RESULTS: Older (≥65 y) compared with younger (<65 y) adults had significantly lower PLP concentrations (P < 0.001). A stepwise decrease in plasma PLP was observed across riboflavin categories, from optimal (EGRac ≤1.26), to suboptimal (EGRac: 1.27-1.39), to deficient (EGRac ≥1.40) status, an effect most pronounced in older adults (mean ± SEM: 76.4 ± 0.9 vs 65.0 ± 1.1 vs 55.4 ± 1.2 nmol/L; P < 0.001). In individuals with the variant MTHFR 677TT genotype combined with riboflavin deficiency, compared with non-TT (CC/CT) genotype participants with sufficient riboflavin, we observed PLP concentrations of 52.1 ± 2.9 compared with 76.8 ±0.7 nmol/L (P < 0.001). In participants with available dietary data (i.e., NANS cohort, n = 936), PLP was associated with vitamin B-6 intake (nonstandardized regression coefficient ß: 2.49; 95% CI 1.75, 3.24; P < 0.001), supplement use (ß: 81.72; 95% CI: 66.01, 97.43; P < 0.001), fortified food (ß: 12.49; 95% CI: 2.08, 22.91; P = 0.019), and EGRac (ß: -65.81; 95% CI: -99.08, -32.54; P < 0.001), along with BMI (ß: -1.81; 95% CI: -3.31, -0.30; P = 0.019). CONCLUSIONS: These results are consistent with the known metabolic dependency of PLP on flavin mononucleotide (FMN) and suggest that riboflavin may be the limiting nutrient for maintaining vitamin B-6 status, particularly in individuals with the MTHFR 677TT genotype. Randomized trials are necessary to investigate the PLP response to riboflavin intervention within the dietary range. The TUDA study and the NANS are registered at www.ClinicalTrials.gov as NCT02664584 (27 January 2016) and NCT03374748 (15 December 2017), respectively.Clinical Trial Registry details: Trinity-Ulster-Department of Agriculture (TUDA) study, ClinicalTrials.gov no. NCT02664584 (January 27th 2016); National Adult Nutrition Survey (NANS), ClinicalTrials.gov no. NCT03374748 (December 15th 2017).

Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial.

More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen's d effect size for full treatment period per arm and outcome measure ranged from - 0.7 to - 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.

Validity of Session-Rate of Perceived Exertion to Quantify Training Loads in Paralympic Swimmers.

ABSTRACT: Sinnott-O'Connor, C, Comyns, TM, and Warrington, GD. Validity of session-RPE to quantify training loads in Paralympic swimmers. J Strength Cond Res 35(9): 2611-2615, 2021-Multiple measures may be used by coaches to quantify training load (TL). The application of heart rate (HR) has limitations in swimming and in Paralympic swimmers, and it may not always be a suitable measure. Therefore, the aim of this study was to determine the validity and reliability of the session-rate of perceived exertion (sRPE) method for quantifying internal TL in Paralympic swimmers. A further aim was to examine the relationship between athlete and coach perceptions of sRPE TL. Four international Paralympic swimmers selected to compete in Rio 2016 Paralympic Games participated in this study. Heart rate, RPE, and session duration were recorded for 30 training sessions of varied intensities across a 6-week home training period to quantify TL. Significant high to very high positive correlations were observed between sRPE and 3 HR-based measures-Banister's, Edwards, and Lucia's TRIMP (r = 0.68, 0.66, 0.74, p < 0.01, respectively). Moderate correlations were observed between sRPE and distance measures (r = 0.53, p < 0.05) but were lower than those observed with HR-based measures. A 2-way analysis of variance identified significant differences in the sRPE ratings between coaches and athletes (F(2, 108) = 170.4, p < 0.01, η2 = 0.75). The results of this study suggest that the sRPE method may be an appropriate monitoring tool for quantifying TL during water-based training using a single measure in Paralympic swimmers.

A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis.

BACKGROUND: Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality. CASE PRESENTATION: We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation. CONCLUSIONS: Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.

A retrospective study (2001-2017) of acute and chronic morbidity and mortality associated with Staphylococcus aureus bacteraemia in a tertiary neonatal intensive care unit.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) in NICU patients can cause significant morbidity and mortality. AIMS: To review early and late neonatal SAB with regard to risk factors, treatment, acute complications and long-term outcomes. METHODS: A retrospective study of laboratory confirmed SAB over a 16-year period (November 2001-January 2017) in a tertiary neonatal unit in Ireland. FINDINGS: A total of 74 neonates (MSSA n = 72, MRSA n = 2) were identified; 8.1% (n = 6) early sepsis, 91.8% (n = 68) late sepsis. Low birth weight neonates (born weighing less than 2500 g) 80% (n = 59). Median age to bacteraemia 11 days post-delivery (range = 0-100 days); median onset early sepsis 1.5 days versus late sepsis 12 days. Complications of SAB; cellulitis n = 17, pneumonia n = 12, necrotising enterocolitis n = 7, thromobophlebitis n = 5, skin abscess formation n = 4, osteomyelitis n = 3, endocarditis n = 1. Late SAB mortality 6.4% (n = 3). CONCLUSIONS: Preterm and low birth weight infants were at highest risk of SAB. Only a small proportion of affected children had long-term clinical sequelae on follow-up. The high rate of recurrence and breakthrough bacteraemia suggests that early implementation of a targeted anti-staphylococcal antimicrobial regimen may be of particular benefit.

Near-fatal mucormycosis post-double lung transplant presenting as uncontrolled upper gastrointestinal haemorrhage.

Invasive fungal infections in immunosuppressed transplant patients are associated with significant morbidity and mortality. We present a case of splenic mucormycosis post-double lung transplant, presenting as uncontrolled near-fatal upper gastrointestinal haemorrhage, to remind clinicians of the need to consider pre-transplant invasive fungal infection risk factors if an unexpected fungal infection arises in the post-transplant period. This case also highlights the valuable contribution of molecular technology for fungal identification but also the need for clinical correlation.

Epidemiological changes in rubella IgG antibody levels detected in antenatal women from a retrospective rubella seroprevalence study.

BACKGROUND: Rubella is caused by the rubella virus, a single-stranded RNA virus of the Togaviridae family. The most severe complications of rubella in adult women occur during pregnancy when infection can lead to miscarriage, stillbirth or congenital rubella syndrome. Antenatal rubella susceptibility screening is no longer performed in England, Scotland or Wales but continues in Northern Ireland. AIM: The aims of this seroprevalence study were to (1) determine amongst women presenting for antenatal care the percentage of women who are rubella susceptible, rubella immune and those with equivocal rubella antibody levels by year of birth and (2) to consider how rubella vaccination resources can best be utilised. METHODS: A retrospective study was performed analysing all antenatal rubella IgG antibody tests performed between January 2015 and June 2017 inclusive (n = 19,000; excluding duplicate tests). All antenatal women were included regardless of the country of origin and age. RESULTS: From our analysis, 88.7% (n = 16,868) women had plasma concentrations of anti-rubella IgG > 10 IU/ml. 7.3% of women (n = 1403) had rubella IgG levels between 5 and 9.99 IU/ml, and 2.8% (n = 729) had IgG levels < 5 IU/ml. A decline in rubella immunity in younger women was evident. CONCLUSIONS: This study has identified an increase in women who are rubella susceptible and women with equivocal rubella antibody levels. International evidence suggests that rubella serology is unreliable and antenatal screening does not confer any benefit to women during their current pregnancy. Consideration should be given to re-direct resources currently utilised for antenatal screening to facilitate the vaccination of pre-pregnancy and postpartum women and also to opportunistically offer vaccination to all women of childbearing age.

Salivary Biomarkers and Training Load During Training and Competition in Paralympic Swimmers.

CONTEXT: Stress responses in athletes can be attributed to training and competition, where increased physiological and psychological stress may negatively affect performance and recovery. PURPOSE: To examine the relationship between training load (TL) and salivary biomarkers immunoglobulin A (IgA), alpha-amylase (AA), and cortisol across a 16-wk preparation phase and 10-d competition phase in Paralympic swimmers. METHODS: Four Paralympic swimmers provided biweekly saliva samples during 3 training phases-(1) normal training, (2) intensified training, and (3) taper-as well as daily saliva samples in the 10-d Paralympic competition (2016 Paralympic Games). TL was measured using session rating of perceived exertion. RESULTS: Multilevel analysis identified a significant increase in salivary immunoglobulin A (sIgA: 94.98 [27.69] µg·mL-1), salivary alpha-amylase (sAA: 45.78 [19.07] µg·mL-1), and salivary cortisol (7.92 [2.17] nM) during intensified training concurrent with a 38.3% increase in TL. During the taper phase, a 49.5% decrease in TL from the intensified training phase resulted in a decrease in sIgA, sAA, and salivary cortisol; however, all 3 remained higher than baseline levels. A further significant increase was observed during competition in sIgA (168.69 [24.19] µg·mL-1), sAA (35.86 [16.67] µg·mL-1), and salivary cortisol (10.49 [1.89] nM) despite a continued decrease (77.8%) in TL from the taper phase. CONCLUSIONS: Results demonstrate that performance in major competition such as Paralympic games, despite a noticeable reduction in TL, induces a stress response in athletes. Because of the elevated stress response observed, modifications to individual postrace recovery protocols may be required to enable athletes to maximize performance across all 10 d of competition.

The first occurrence of a CTX-M ESBL-producing Escherichia coli outbreak mediated by mother to neonate transmission in an Irish neonatal intensive care unit.

BACKGROUND: Escherichia coli (E. coli) comprise part of the normal vaginal microflora. Transfer from mother to neonate can occur during delivery resulting, sometimes, in neonatal bacterial disease. Here, we aim to report the first outbreak of CTX-M ESBL-producing E. coli with evidence of mother-to-neonate transmission in an Irish neonatal intensive care unit (NICU) followed by patient-to-patient transmission. METHODS: Investigation including molecular typing was conducted. Infection was defined by clinical and laboratory criteria and requirement for antimicrobial therapy with or without positive blood cultures. Colonisation was determined by isolation without relevant symptoms or indicators of infection. RESULTS: Index case was an 8-day-old baby born at 34 weeks gestation who developed ESBL-producing E. coli infections at multiple body sites. Screening confirmed their mother as colonised with ESBL-producing E. coli. Five other neonates, in the NICU simultaneously with the index case, also tested positive. Of these, four were colonised while one neonate developed sepsis, requiring antimicrobial therapy. The second infected neonate's mother was also colonised by ESBL-producing E. coli. Isolates from all eight positive patients (6 neonates, 2 mothers) were compared using pulsed-field gel electrophoresis (PFGE). Two distinct ESBL-producing strains were implicated, with evidence of transmission between mothers and neonates for both strains. All isolates were confirmed as CTX-M ESBL-producers. There were no deaths associated with the outbreak. CONCLUSIONS: Resources were directed towards control interventions focused on hand hygiene and antimicrobial stewardship, which ultimately proved successful. Since this incident, all neonates admitted to the NICU have been screened for ESBL-producers and expectant mothers are screened at their first antenatal appointment. To date, there have been no further outbreaks.