Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection.

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. METHODS: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. RESULTS: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%). CONCLUSION: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival. CLINICALTRIALS: gov, Number: NCT03712722.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy.

BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 µg/mL (range 0.005-0.12 µg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] µg/mL) and without (3.1 [range 0.7-11.0] µg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

Changes in the urinary metabolome accompanied alterations in body mass and composition in women with overweight - impact of high versus low protein breakfast.

INTRODUCTION: Understanding why subjects with overweight and with obesity vary in their response to dietary interventions is of major interest for developing personalized strategies for body mass regulation. OBJECTIVES: The aim of this study was to investigate the relationship between changes in the urine metabolome and body mass during a breakfast meal intervention. Furthermore, we aimed to elucidate if the baseline urine metabolome could predict the response to the two types of breakfast meals (high versus low protein) during the intervention. METHODS: A total of 75 young, women with overweight were randomly allocated to one of two intervention groups: (1) High-protein (HP) or (2) low-protein (LP) breakfast as part of their habitual diet during a 12-week intervention. Beside the breakfast meal, participants were instructed to eat their habitual diet and maintain their habitual physical activity level. Nuclear magnetic resonance-based metabolomics was conducted on urine samples collected at baseline (wk 0), mid-intervention (wk 6), and at endpoint (wk 12). At baseline and endpoint, body mass was measured and DXA was used to measure lean body mass and fat mass. RESULTS: The baseline urine metabolite profile showed a slightly higher correlation (R2 = 0.56) to body mass in comparison with lean body mass (R2 = 0.51) and fat mass (R2 = 0.53). Baseline 24-h urinary excretion of trigonelline (p = 0.04), N, N-dimethylglycine (p = 0.02), and trimethylamine (p = 0.03) were significantly higher in individuals who responded with a reduction in body mass to the HP breakfast. CONCLUSIONS: Differences in the urine metabolome were seen for women that obtained a body weight loss in the response to the HP breakfast intervention and women who did not obtain a body weight loss, indicating that the urine metabolome contains information about the metabolic phenotype that influences the responsiveness to dietary interventions.

Collecting pieces for the 'puzzle': Nurses' intraprofessional collaboration in the hospital-to-home transition of older patients.

BACKGROUND AND AIM: Communication is a key factor in intraprofessional collaboration between hospital nurses and homecare nurses in hospital-to-home transitions of older patients with complex care needs. Gaining knowledge of the nature of cross-sectoral communication is crucial for understanding how nurses collaborate to ensure a seamless patient trajectory. This study explores how cross-sectoral electronic health records communication influences collaboration between hospital nurses and homecare nurses when discharging older patients with complex care needs. METHOD: The study is based on qualitative group interviews with six hospital nurses and 14 homecare nurses working at different hospitals and municipalities across Denmark. Data were analysed using reflexive thematic analysis, as described by Braun and Clark. FINDINGS: The themes Collecting pieces for the 'puzzle': Losing the holistic picture of the patient; Working blindfolded: limited provision of and access to critical information; and Bypassing the 'invisible wall': dialogue supports cohesion illustrate the impact of organisational structures within electronic health records have on hospital nurses' and homecare nurses' intraprofessional collaboration across sectors. Challenges with predefined and word-limited elements in digital communication, and inadequate and limited access to significant medical information were identified. To compensate for the inadequacy of the electronic health records, direct contact and dialogue were emphasised as ways of fostering successful collaboration and overcoming the barriers created by electronic health records. CONCLUSION: Despite hospital nurses' and homecare nurses' desire to conduct holistic patient assessments, their ability to collaborate was hindered by failures in electronic health record communication resulting from restrictive organisational structures across sectors. Thus, it became necessary for hospital nurses and homecare nurses to bypass the electronic health record system and engage in dialogue to provide holistic care when discharging older patients with complex care needs. However, by hospital nurses and homecare nurses compensating for counter-productive organisational structures, problems brought about by the electronic health record system paradoxically remain invisible.

Discharging older patients from hospital to homecare: conflicts in collaborative practices among nurses across sectors.

BACKGROUND: Collaboration is a key factor influencing the quality and safety in patients transition between sectors. However, specific collaborative practices may give rise to conflict between hospital nurses and community nurses. AIMS: To gain a deeper understanding of collaborative practices which have the potential to fuel tension in collaboration between hospital nurses and community nurses during discharge of older patients from hospital to homecare. METHODS: A meta-ethnography approach was used in this study and a systematic literature search was conducted in 2022. RESULTS: Five themes were identified in the analysis. These themes revealed how uncertainty, limited confidence in information and personal attitude in communication may fuel tension between hospital nurses and community nurses. Tensions arising from a negative loop emerged because of uncertainty, causing a growing rift between hospital nurses and community nurses, leaving them as opponents rather than collaborators. The authors suggest that policy makers and managers can break this loop by underpinning shared policies and awareness of common objectives.

Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females.

Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1  · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1  · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1  · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.

B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine.

BACKGROUND: High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS: Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS: Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION: FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.

Acute changes in the metabolome following resistance exercise combined with intake of different protein sources (cricket, pea, whey).

INTRODUCTION: Separately, both exercise and protein ingestion have been shown to alter the blood and urine metabolome. This study goes a step further and examines changes in the metabolome derived from blood, urine and muscle tissue extracts in response to resistance exercise combined with ingestion of three different protein sources. METHODS: In an acute parallel study, 52 young males performed one-legged resistance exercise (leg extension, 4 × 10 repetitions at 10 repetition maximum) followed by ingestion of either cricket (insect), pea or whey protein (0.25 g protein/kg fat free mass). Blood and muscle tissue were collected at baseline and three hours after protein ingestion. Urine was collected at baseline and four hours after protein ingestion. Mixed-effects analyses were applied to examine the effect of the time (baseline vs. post), protein (cricket, pea, whey), and time x protein interaction. RESULTS: Nuclear magnetic resonance (NMR)-based metabolomics resulted in the annotation and quantification of 25 metabolites in blood, 35 in urine and 21 in muscle tissue. Changes in the muscle metabolome after combined exercise and protein intake indicated effects related to the protein source ingested. Muscle concentrations of leucine, methionine, glutamate and myo-inositol were higher after intake of whey protein compared to both cricket and pea protein. The blood metabolome revealed changes in a more ketogenic direction three hours after exercise reflecting that the trial was conducted after overnight fasting. Urinary concentration of trimethylamine N-oxide was significantly higher after ingestion of cricket than pea and whey protein. CONCLUSION: The blood, urine and muscle metabolome showed different and supplementary responses to exercise and ingestion of the different protein sources, and in synergy the summarized results provided a more complete picture of the metabolic state of the body.

Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial.

BACKGROUND: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. OBJECTIVE: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. DESIGN: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring-13C6] phenylalanine tracer infusion with the collection of bilateral muscle biopsies. RESULTS: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). CONCLUSION: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. TRIAL REGISTRY: clinicaltrials.gov (ID: NCT03326284).

Influence of protein source (cricket, pea, whey) on amino acid bioavailability and activation of the mTORC1 signaling pathway after resistance exercise in healthy young males.

PURPOSE: New dietary proteins are currently introduced to replace traditional animal protein sources. However, not much is known about their bioaccessibility and ability to stimulate muscle protein synthesis compared to the traditional protein sources. We aimed to compare effects of ingesting a protein bolus (0.25 g/kg fat free mass) of either cricket (insect), pea, or whey protein on circulating amino acid levels and activation of the mTORC1 signaling pathway in the skeletal muscle at rest and after exercise. METHODS: In a randomized parallel controlled trial, young males (n = 50) performed a one-legged resistance exercise followed by ingestion of one of the three protein sources. Blood samples were collected before and in the following 4 h after exercise. Muscle biopsies were obtained at baseline and after 3 h from the non-exercised and exercised leg. RESULTS: Analysis of blood serum showed a significantly higher concentration of amino acids after ingestion of whey protein compared to cricket and pea protein. No difference between protein sources in activation of the mTORC1 signaling pathway was observed either at rest or after exercise. CONCLUSION: Amino acid blood concentration after protein ingestion was higher for whey than pea and cricket protein, whereas activation of mTORC1 signaling pathway at rest and after exercise did not differ between protein sources. TRIAL REGISTRATION NUMBER: Clinicaltrials.org ID NCT04633694.

Chronic loose stools following right-sided hemicolectomy for colon cancer and the association with bile acid malabsorption and small intestinal bacterial overgrowth.

AIM: Patients treated with right-sided hemicolectomy for colon cancer may suffer from long-term bowel dysfunction, including loose stools, urgency and faecal incontinence. The underlying causes are poorly understood. The aim of this case-control study was to investigate the aetiology of chronic loose stools among patients with right-sided hemicolectomy curatively operated for cancer. METHOD: Cases with chronic loose stools (Bristol stool type 6-7) after right-sided hemicolectomy were compared with a control group of patients with right-sided hemicolectomy without loose stools. All patients underwent a selenium-75 homocholic acid taurine (SeHCAT) scan to diagnose bile acid malabsorption (BAM) and a glucose breath test to diagnose small intestinal bacterial overgrowth (SIBO). Gastrointestinal transit time (GITT) was assessed with radiopaque markers. In a subgroup of patients, fibroblast growth factor 19 (FGF19) was measured in fasting blood. SIBO was treated with antibiotics and BAM was treated with bile acid sequestrants. RESULTS: We included 45 cases and 19 controls. In the case group, 82% (n = 36) had BAM compared with 37% (n = 7) in the control group, p < 0.001. SIBO was diagnosed in 73% (n = 33) of cases with chronic loose stools and in 74% (n = 14) of controls, p = 0.977. No association between BAM and SIBO was observed. GITT was similar in cases and controls. No difference in median FGF19 was observed between cases and controls (p = 0.894), and no correlation was seen between FGF19 and SeHCAT retention (rs 0.20, p = 0.294). Bowel symptoms among cases were reduced after treatment. CONCLUSION: BAM and SIBO are common in patients having undergone right-sided hemicolectomy for cancer. Chronic loose stools were associated with BAM but not with SIBO.

Neoehrlichia mikurensis in Danish immunocompromised patients: a retrospective cohort study.

BACKGROUND: The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. METHODS: Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher's exact test. RESULTS: Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 - 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8-11.5%) and 11/192 (5.7%, 95%: CI 3.2-10.0%). CONCLUSION: In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.

Oral 3-hydroxybuturate ingestion acutely lowers circulating testosterone concentrations in healthy young males.

Ketone bodies, such as 3-hydroxybutyrate (3-OHB), have been frequently used by endurance athletes, such as cyclists, to enhance performance and recovery and are recognized for their health benefits and therapeutic effects for decades. Testosterone is a potent regulator of red blood cell production. Evidence suggests that ketone bodies can increase the production of erythropoietin, which stimulates red blood cell production. Therefore, we investigated whether an acute increase in 3-OHB levels affects testosterone levels in healthy young men. We studied six healthy, young male participants who fasted overnight and were tested twice: (i) after drinking 37.5 g of Na-D/L-3-OHB dissolved in 500 mL of distilled water (KET), and (ii) after drinking 500 mL of placebo saline water (0.9% NaCl) (CTR). During the KET trial, 3-OHB levels increased to approximately 2.5 mM. Testosterone levels decreased significantly by 20% during KET compared to 3% during CTR. A simultaneous increase in luteinizing hormone was observed in KET. We observed no changes in other adrenal androgens, such as androstenedione and 11-keto androgens. In conclusion, an acute increase in 3-OHB levels decreases testosterone levels. Concomitantly, an increase in luteinizing hormone was observed. This suggests that 3-OHB may counteract some of the beneficial effects of endurance training. Further studies, involving larger sample sizes and performance outcomes, are required to fully understand this phenomenon.

Can protection motivation theory predict protective behavior against ticks?

BACKGROUND: Cases of reported tick-borne diseases in humans have increased over the past decades. Strategies informing the public about ticks, their associated diseases, and preventive measures are often highlighted as important in limiting pathogen transfer and disease. However, knowledge about the motivation for people to apply preventative measures is sparse. METHODS: The aim was to examine if Protection Motivation Theory, a model of disease prevention and health promotion, can predict the use of protective measures against ticks. Ordinal logistic regression and Chi-square tests were used on data from a cross-sectional survey with respondents from Denmark, Norway, and Sweden (n = 2658). We examined the effect of (1) the perceived seriousness of tick bites, Lyme borreliosis (LB), and tick-borne encephalitis (TBE), and (2) the perceived probability of getting a tick bite, Lyme borreliosis, and tick-borne encephalitis on protection against ticks. Finally, we examined if there was an association between the use of a protective measure and the perceived efficacy of that measure. RESULTS: The perceived seriousness of a tick bite and LB significantly predict who is more likely to apply protective measures for all three countries combined. The perceived seriousness of TBE did not significantly predict the level of adoption of protective measures applied by respondents. The perceived likelihood of getting a tick bite within the next 12 months and the perceived likelihood of getting LB if bitten by a tick significantly predicted the application of protective measures. However, the increases in the likelihood of protection were very small. The application of a certain type of protection was always correlated with the perceived efficacy of the same protective measure. CONCLUSION: Some variables of PMT may be used to predict the level of adoption of protection applied against ticks and tick-borne diseases. We found that the perceived seriousness of a tick bite and LB significantly predict the level of adoption protection. The perceived likelihood of getting a tick bite or LB also significantly predicted the level of adoption of protection, although the change was very small. The results regarding TBE were less clear. Lastly, there was an association between applying a protective measure and the perceived efficacy of the same measure.

Effects of transdermal estrogen therapy on satellite cell number and molecular markers for muscle hypertrophy in response to resistance training in early postmenopausal women.

PURPOSE: To investigate the effects of resistance training with or without transdermal estrogen therapy (ET) on satellite cell (SC) number and molecular markers for muscle hypertrophy in early postmenopausal women. METHODS: Using a double-blinded randomized controlled design, we allocated healthy, untrained postmenopausal women to perform 12 weeks of resistance training with placebo (PLC, n = 16) or ET (n = 15). Muscle biopsies obtained before and after the intervention, and two hours after the last training session were analyzed for fiber type, SC number and molecular markers for muscle hypertrophy and degradation (real-time PCR, western blotting). RESULTS: The analysis of SCs per Type I fiber showed a time x treatment interaction caused by a 47% decrease in PLC, and a 26% increase after ET after the training period. Also, SCs per Type II fiber area was lower after the intervention driven by a 57% decrease in PLC. Most molecular markers changed similarly in the two groups. CONCLUSION: A decline in SC per muscle fiber was observed after the 12-week training period in postmenopausal women, which was counteracted when combined with use of transdermal ET. CLINICAL TRIAL REGISTRATION NUMBER: nct03020953.

Vitamin D supplementation and increased dairy protein intake do not affect muscle strength or physical function in healthy 6-8-year-old children: the D-pro randomized trial.

PURPOSE: To investigate separate and combined effects of vitamin D supplementation during the extended winter and increased dairy protein intake on muscle strength and physical function in children, and furthermore to explore potential sex differences. METHODS: In a 2 × 2-factorial, randomized winter trial, 183 healthy, 6-8-year-old children received blinded tablets with 20 µg/day vitamin D3 or placebo, and substituted 260 g/day dairy with yogurts with high (HP, 10 g protein/100 g) or normal protein content (NP, 3.5 g protein/100 g) for 24 weeks during winter at 55° N. We measured maximal isometric handgrip and leg press strength, and physical function by jump tests and a 30 s sit-to-stand test. Physical activity was measured by 7-day accelerometry. RESULTS: Baseline (mean ± SD) serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased to 88.7 ± 17.6 nmol/L with vitamin D supplementation and decreased to 48.4 ± 19.2 nmol/L with placebo. Baseline protein intake was 15.5 ± 2.4 E%, which increased to 18.4 ± 3.4 E% with HP and was unchanged with NP. We found no separate or combined effects of vitamin D supplementation and/or increased dairy protein intake on muscle strength or physical function (all P > 0.20). There was an interaction on the sit-to-stand test (Pvitamin×yogurt = 0.02), which however disappeared after adjusting for physical activity (P = 0.16). Further, vitamin D supplementation increased leg press strength relatively more in girls compared to boys (mean [95% CI] 158 [17, 299] N; Pvitamin×sex = 0.047). CONCLUSION: Overall, vitamin D and dairy protein supplementation during the extended winter did not affect muscle strength or physical function in healthy children. Potential sex differences of vitamin D supplementation should be investigated further. REGISTERED AT CLINICALTRIALS.GOV: NCT0395673.

The Baby-friendly Hospital Initiative for neonatal wards. A mini review.

The Baby-friendly Hospital Initiative for Neonatal Wards (Neo-BFHI) is an expansion of the WHO/UNICEF Ten Steps to Successful Breastfeeding to address the needs of infants and families in all levels of neonatal care. The Neo-BFHI includes Three Guiding Principles as basic tenets, Ten Steps to protect, promote and support breastfeeding closely following the original Baby-friendly Hospital Initiative, and adherence to the International Code of Marketing of Breast-milk Substitutes. In 2020, the WHO/UNICEF published recommendations for breastfeeding small, sick and preterm newborns that aligns with the Neo-BFHI. Conclusion: This mini review provides a brief description of the content in the Neo-BFHI.

Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.

Influence of Second Generation Oral Contraceptive Use on Adaptations to Resistance Training in Young Untrained Women.

ABSTRACT: Dalgaard, LB, Jørgensen, EB, Oxfeldt, M, Dalgaard, EB, Johansen, FT, Karlsson, M, Ringgaard, S, and Hansen, M. Influence of second generation oral contraceptive use on adaptations to resistance training in young untrained women. J Strength Cond Res 36(7): 1801-1809, 2022-The study purpose was to determine effects of using second generation oral contraceptives (OC) on muscle adaptations to resistance training in young untrained women. Twenty users and 18 nonusers of OC completed a 10-week supervised progressive resistance training program. Before and after the intervention, muscle cross-sectional area (mCSA) of the quadriceps was measured using magnetic resonance imaging and muscle fiber CSA (fCSA) was determined by immunohistochemistry. In addition, body composition (DXA, fat mass/fat-free mass), maximal isometric muscle strength (dynamometry), 5 repetition maximum (5RM) leg press strength, counter movement jump (CMJ) height, and average power using a modified Wingate test were determined. Serum hormone analysis ensured OC compliance and 4-day food records documented dietary intake. After the training period, quadriceps mCSA (OC: 11.0 ± 6.0% vs. non-OC: 9.2 ± 5.0%, p = 0.001), type II fCSA (OC: 19.9 ± 7.9% vs. non-OC: 16.6 ± 7.2%, p = 0.05), muscle strength (knee extension, knee flexion and 5RM, p < 0.001), and functional power (CMJ, AP, p < 0.001) were significantly increased with no significant difference between the groups. However, a tendency toward a greater increase in fat-free mass (FFM) in the OC group was observed (OC: 3.7 ± 3.8% vs. non-OC: 2.7 ± 3.5%, p = 0.08). Collectively, use of second generation OCs in young untrained women did not significantly improve adaptations to 10 weeks of resistance training compared with nonusers. The trend toward greater gains in FFM in the OC group warrant future studies.

Glycogen supercompensation is due to increased number, not size, of glycogen particles in human skeletal muscle.

NEW FINDINGS: What is the central question of this study? Glycogen supercompensation after glycogen-depleting exercise can be achieved by consuming a carbohydrate-enriched diet, but the associated effects on the size, number and localization of intramuscular glycogen particles are unknown. What is the main finding and its importance? Using transmission electron microscopy to inspect individual glycogen particles visually, we show that glycogen supercompensation is achieved by increasing the number of particles while keeping them at submaximal sizes. This might be a strategy to ensure that glycogen particles can be used fast, because particles that are too large might impair utilization rate. ABSTRACT: Glycogen supercompensation after glycogen-depleting exercise can be achieved by consuming a carbohydrate-enriched diet, but the associated effects on the size, number and localization of intramuscular glycogen particles are unknown. We investigated how a glycogen-loading protocol affects fibre type-specific glycogen volume density, particle diameter and numerical density in three subcellular pools: between (intermyofibrillar) or within (intramyofibrillar) the myofibrils or beneath the sarcolemma (subsarcolemmal). Resting muscle biopsies from 11 physically active men were analysed using transmission electron microscopy after mixed (MIX), LOW or HIGH carbohydrate consumption separated by glycogen-lowering cycling at 75% of maximal oxygen consumption until exhaustion. After HIGH, the total volumetric glycogen content was 40% [95% confidence interval 16, 68] higher than after MIX in type I fibres (P < 0.001), with little to no difference in type II fibres (9% [95% confidence interval -9, 27]). Median particle diameter was 22.5 (interquartile range 20.8-24.7) nm across glycogen pools and fibre types, and the numerical density was 61% [25, 107] and 40% [9, 80] higher in the subsarcolemmal (P < 0.001) and intermyofibrillar (P < 0.01) pools of type I fibres, respectively, with little to no difference in the intramyofibrillar pool (3% [-20, 32]). In LOW, total glycogen was in the range of 21-23% lower, relative to MIX, in both fibre types, reflected in a 21-46% lower numerical density across pools. In comparison to MIX, particle diameter was unaffected by other diets ([-1.4, 1.3] nm). In conclusion, glycogen supercompensation after prolonged cycling is exclusive to type I fibres, predominantly in the subsarcolemmal pool, and involves an increase in the numerical density rather than the size of existing glycogen particles.