Early Life Surgency, but not Effortful Control or Negative Affectivity, Is a Mediating Variable Between Maternal Pre-Pregnancy Body Mass Index and Childhood Obesity Risk.

Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted ß = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted ß = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.

Kinematical alignment better restores native patellar tracking pattern than mechanical alignment.

PURPOSE: The purpose of this study was to assess whether kinematic alignment (KA) outperforms mechanical alignment (MA) in restoring patellar tracking to native patterns by using a clustering algorithm. METHODS: Twenty cadavers (40 knees) were evaluated. For each cadaver, one knee was randomly assigned to KA and the other to MA. KA total knee arthroplasty (TKA) procedures were performed using a caliper-verified technique, while MA TKA procedures utilized a measured resection technique. Subsequently, all specimens were mounted on a customized knee-testing system, and patellar tracking was measured using a motion analysis system. All patellar tracking data were clustered using the density-based spatial clustering of applications with noise algorithm. Differences in patellar tracking patterns and the restoration of native patellar tracking were compared between the two alignment strategies. RESULTS: Patellar tracking patterns following KA were considerably different from MA. Pre- and post-TKA patellar tracking patterns following MA were grouped into separate clusters, whereas a substantial proportion of patellar tracking patterns following KA were grouped into the pre-TKA dominant cluster. Compared to MA, a greater proportion of patellar tracking patterns following KA showed similar patterns to native knees (p < 0.05) and more patellar tracking patterns following KA paired with preoperative patterns (p < 0.01). CONCLUSION: KA restored native patellar tracking patterns more closely compared to MA. LEVEL OF EVIDENCE: Level I, therapeutic study.

Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.

Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with ß-glucan (HFS/OB), resistant starch (HFS/OR), or ß-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL-6, IL-10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber-treated rats into germ-free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.

No Blood Loss Increase in Cementless vs. Cemented Fixation Following Bilateral Total Knee Arthroplasty: A Propensity Score Matching Study.

Background and Objectives: Recent advancements in three-dimensional printing technology have enhanced the biologic fixation of cementless total knee arthroplasty (TKA), therefore increasing the utilization of newer-generation cementless implants. However, the lack of sealing and tamponade effect of cement on the resected bone surface after cementless TKA raises concerns regarding the potential for greater blood loss compared to cemented TKA. The aim of this study was to (1) compare blood loss and transfusion rates between cementless and cemented TKAs and (2) identify the risk factor for higher blood loss in patients who underwent 1-week-interval staggered bilateral (SB) TKA. Materials and Methods: This retrospective, propensity-matched study included 54 cementless and 53 cemented SB TKAs performed by a single surgeon from 2019 to 2023 with a single implant that has similar design features in both cementless and cemented implants. All patients underwent 1-week-interval SB TKA and received the same patient blood management (PBM) and rehabilitation protocol. The estimated total blood loss (TBL), transfusion rate, and total hemoglobin drop were assessed. Patients were categorized according to TBL into average TBL and higher TBL groups. Univariate and multiple logistic regression analyses were performed to identify risk factors for higher blood loss. Results: There was no difference in TBL between cementless and cemented TKA groups (1233 ± 299 and 1282 ± 309 mL, respectively; p > 0.05). In addition, no between-group differences in the transfusion rate and mean total hemoglobin drop were observed. The logistic regression analyses revealed that whether TKA was cementless or cemented was not associated with higher blood loss; rather, the only identified risk factor was the pre-TKA patient blood volume (odd ratio 1.001, 95% confidence interval 1.000-1002, p = 0.026). Conclusions: Contemporary cementless fixation does not increase blood loss or transfusion rates compared to cemented fixation in patients undergoing 1-week-interval staggered bilateral TKA.

Effect of supplementation with select human milk oligosaccharides on artificially reared newborn rats.

Early life nutrition fundamentally influences neonatal development and health. Human milk oligosaccharides (HMO) are key components of breast milk but not standard infant formula that support the establishment of the newborn gut microbiota. Using an artificial rearing system, our objective was to test the effect of two HMO on the whole body and organ growth, adiposity, glucose tolerance and faecal microbiota in young rat pups. From postnatal days 4 to 21, Sprague-Dawley rats were randomised to receive one of: (1) CTR (rat milk substitute); (2) 2'FL (CTR + 1·2 g/l 2'-fucosyllactose); (3) 3'SL (CTR + 1·2 g/l 3'-sialyllactose) and (4) 2'FL + 3'SL (CTR + 0·6 g/l 2'-FL + 0·6 g/l 3'-SL). Body weight (BW), bowel movements and food intake were monitored daily, faecal samples collected each week and oral glucose tolerance, body composition and organ weight measured at weaning. No significant differences were observed between groups in growth performance, body composition, organ weight and abundance of dominant faecal microbes. A decreased relative abundance of genus Proteus in week 1 faecal samples and Terrisporobacter in week 3 faecal samples (P < 0·05) was suggestive of a potential pathogen inhibitory effect of 3'SL. Longitudinal changes in the faecal microbiota of artificially reared suckling rats were primarily governed by age (P = 0·001) and not affected by the presence of 2'-FL and/or 3'-SL in rat milk substitutes (P = 0·479). Considering the known protective effects of HMO, further investigation of supplementation with these and other HMO in models of premature birth, extremely low BW or malnutrition may show more pronounced outcomes.

Guided-Motion Bicruciate-Stabilized Total Knee Arthroplasty Reproduces Native Medial Collateral Ligament Strain.

Background and Objectives: Guided-motion bicruciate-stabilized (BCS) total knee arthroplasty (TKA) includes a dual cam-post mechanism with an asymmetric bearing geometry that promotes normal knee kinematics and enhances anterior-posterior stability. However, it is unclear whether the improved biomechanics after guided-motion BCS TKA reproduce soft tissue strain similar to the strain generated by native knees. The purpose of this cadaveric study was to compare medial collateral ligament (MCL) strain between native and guided-motion BCS TKA knees using a video extensometer. Materials and Methods: Eight cadaver knees were mounted onto a customized knee squatting simulator to measure MCL strain during flexion in both native and guided-motion BCS TKA knees (Journey II-BCS; Smith & Nephew, Memphis, TN, USA). MCL strain was measured using a video extensometer (Mercury® RT RealTime tracking system, Sobriety s.r.o, Kurim, Czech Republic). MCL strain level and strain distribution during knee flexion were compared between the native and guided-motion BCS TKA conditions. Results: The mean and peak MCL strain were similar between native and guided-motion BCS TKA knees at all flexion angles (p > 0.1). MCL strain distribution was similar between native and BCS TKA knees at 8 of 9 regions of interest (ROIs), while higher MCL strain was observed after BCS TKA than in the native knee at 1 ROI in the mid portion of the MCL at early flexion angles (p < 0.05 at ≤30° of flexion). Conclusions: Guided-motion BCS TKA restored the amount and distribution of MCL strain to the values observed on native knees.

Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring.

OBJECTIVE: We examined the impact of maternal low-dose aspartame and stevia consumption on adiposity, glucose tolerance, gut microbiota and mesolimbic pathway in obese dams and their offspring. DESIGN: Following obesity induction, female Sprague-Dawley rats were allocated during pregnancy and lactation to: (1) high fat/sucrose diet (HFS) +water (obese-WTR); (2) HFS +aspartame (obese-APM; 5-7 mg/kg/day); (3) HFS +stevia (obese-STV; 2-3 mg/kg/day). Offspring were weaned onto control diet and water and followed until 18 weeks. Gut microbiota and metabolic outcomes were measured in dams and offspring. Cecal matter from offspring at weaning was used for faecal microbiota transplant (FMT) into germ-free (GF) mice. RESULTS: Maternal APM and STV intake with a HFS diet increased body fat in offspring at weaning and body weight long-term with APM. Maternal APM/HFS consumption impaired glucose tolerance in male offspring at age 8 weeks and both APM and STV altered faecal microbiota in dams and offspring. Maternal obesity/HFS diet affected offspring adiposity and glucose tolerance more so than maternal LCS consumption at age 12 and 18 weeks. APM and STV altered expression of genes in the mesolimbic reward system that may promote consumption of a palatable diet. GF mice receiving an FMT from obese-APM and obese-STV offspring had greater weight gain and body fat and impaired glucose tolerance compared with obese-WTR. CONCLUSION: Maternal low-calorie sweetener consumption alongside HFS may disrupt weight regulation, glucose control and gut microbiota in dams and their offspring most notably in early life despite no direct low-calorie sweetener consumption by offspring.

Pathogenesis and therapeutic opportunities of gut microbiome dysbiosis in critical illness.

For many years, it has been hypothesized that pathological changes to the gut microbiome in critical illness is a driver of infections, organ dysfunction, and other adverse outcomes in the intensive care unit (ICU). The advent of contemporary microbiome methodologies and multi-omics tools have allowed researchers to test this hypothesis by dissecting host-microbe interactions in the gut to better define its contribution to critical illness pathogenesis. Observational studies of patients in ICUs have revealed that gut microbial communities are profoundly altered in critical illness, characterized by markedly reduced alpha diversity, loss of commensal taxa, and expansion of potential pathogens. These key features of ICU gut dysbiosis have been associated with adverse outcomes including life-threatening hospital-acquired (nosocomial) infections. Current research strives to define cellular and molecular mechanisms connecting gut dysbiosis with infections and other outcomes, and to identify opportunities for therapeutic modulation of host-microbe interactions. This review synthesizes evidence from studies of critically ill patients that have informed our understanding of intestinal dysbiosis in the ICU, mechanisms linking dysbiosis to infections and other adverse outcomes, as well as clinical trials of microbiota-modifying therapies. Additionally, we discuss novel avenues for precision microbial therapeutics to combat nosocomial infections and other life-threatening complications of critical illness.

Intrapartum antibiotic use is associated with higher child body mass index (BMI) z-score at 4 years of age.

Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum.

Select human milk oligosaccharide supplementation in post-weanling rats affects metabolism and gut microbiota into adulthood.

OBJECTIVE: Feeding infants with human milk versus formula can produce long-lasting benefits, including reduced risk of inflammatory diseases. Most infant formulas do not contain human milk oligosaccharides (HMOs), which are important carbohydrates in human breast milk displaying prebiotic properties. The study's aim was to examine the effect of select HMOs in the post-weaning period. METHODS: Metabolic and microbial outcomes were measured in female and male rats whose post-weaning diet was supplemented with 3'sialyllactose and 2'-O-fucosyllactose (low dose, 0.75% of each, or high dose, 2% of each). It was determined whether exposure to the HMOs would attenuate metabolic dysfunction associated with a high fat/sucrose (HFS) diet. RESULTS: HMO supplementation resulted in dose-dependent and sex-dependent effects, with the high HMO female group displaying reduced food intake and percentage body fat and an increase in Blautia abundance. Early life HMO supplementation did not prevent the effects of an HFS diet on metabolic outcomes; however, rats that received high dose HMOs followed by the HFS diet were the only HFS group that maintained a measurable abundance of Blautia. CONCLUSIONS: This study highlights the potential for HMOs in follow-up infant formulas. Further investigation should include variable HMO mixtures and doses to optimize infant nutrition at this critical stage.

Postoperative Hemodynamics of Total Knee Arthroplasty Unaffected by Cementless Approach under Contemporary Patient Blood Management Protocol: A Propensity Score-Matched Study.

(1) Background: A cementless total knee arthroplasty (TKA) is a recent and an increasingly popular innovation that enhances porous fixation surfaces. However, the lack of cemented sealing of an exposed resected bone has raised concerns about the potential for greater blood loss. The goals of this study were to determine if a cementless approach impacts post-TKA hemodynamics and to identify risk factors for blood loss in instances of cementless (vs. cemented) TKAs under a contemporary patient blood management (PBM) protocol. (2) Methods: We recruited 153 consecutive patients undergoing unilateral TKAs between 2019 and 2023. All enrollees received cementless or cemented prostheses of the same design (cementless, 87; cemented, 66). After propensity score matching for demographics, there were 46 patients in each group. We then compared blood loss metrics (total [TBL] and estimated [EBL]), drainage volumes, hemoglobin (Hb) levels, and transfusion rates by group. (3) Results: Post-TKA hemodynamics (i.e., TBL, EBL, drainage, Hb level, and transfusion rate) of cementless (n = 46) and cemented (n = 46) TKA groups did not differ significantly. In addition, the proportions of patients with Hb drops > 3.0 g/dL were similar for the two groups. A logistic regression analysis revealed that only preoperative Hb and EBL during the early postoperative period were predictive of a substantial fall in Hb levels. The fixation method was not associated with Hb decline > 3.0 g/dL by postoperative Day 3. (4) Conclusion: The cementless TKA has no impact on customary post-TKA hemodynamics and is not associated with greater TKA-related blood loss when implementing a contemporary PBM protocol.

Restoration of the Joint Line Configuration Reproduces Native Mid-Flexion Biomechanics after Total Knee Arthroplasty: A Matched-Pair Cadaveric Study.

Background: Recent evidence supports that restoration of the pre-arthritic condition via total knee arthroplasty (TKA) is associated with improved post-TKA performance and patient satisfaction. However, whether the restored pre-arthritic joint line simulates the native mid-flexion biomechanics remains unclear. Objective: We performed a matched-pair cadaveric study to explore whether restoration of the joint line via kinematically aligned (KA) TKA reproduced native knee biomechanics more accurately than the altered joint line associated with mechanically aligned (MA) TKA. Methods: Sixteen fresh-frozen cadaveric knees (eight pairs) were affixed onto a customized knee-squatting simulator for measurement of femoral rollback and medial collateral ligament (MCL) strain during mid-flexion. One knee from each cadaver was randomly designated to the KA TKA group (with the joint line restored to the pre-arthritic condition) and the other to the MA TKA group (with the joint line perpendicular to the mechanical axis). Optical markers were attached to all knees and rollback was analyzed using motion capture cameras. A video extensometer measured real-time variations in MCL strain. The kinematics and MCL strain prior to and following TKA were measured for all specimens. Results: KA TKA was better for restoring the knee kinematics to the native condition than MA TKA. The mid-flexion femoral rollback and axial rotation after KA TKA were consistently comparable to those of the native knee. Meanwhile, those of MA TKA were similar only at ≤40° of flexion. Furthermore, KA TKA better restored the mid-flexion MCL strain to that of the native knee than MA TKA. Over the entire mid-flexion range, the MCL strain of KA TKA and native knees were similar, while the strains of MA TKA knees were more than twice those of native knees at >20° of flexion. Conclusions: The restored joint line after KA TKA effectively reproduced the native mid-flexion rollback and MCL strain, whereas the altered joint line after MA TKA did not. Our findings may explain why patients who undergo KA TKA experience superior outcomes and more natural knee sensations during daily activities than those treated via MA TKA.

C-section birth increases offspring obesity risk dependent on maternal diet and obesity status in rats.

OBJECTIVE: The gut microbiota is a complex ecosystem that shapes host metabolism, especially in early life. Maternal vaginal and gut microbiota is vertically transmitted to offspring during natural birth. Offspring born by cesarean section (CS) do not receive these bacteria and exhibit higher obesity risk later in life. The objective of this study was to examine differences in obesity risk between offspring born naturally (NB) or by CS to lean/obese dams. METHODS: Lean and obese rat dams gave birth to offspring naturally or by CS. Offspring obesity risk was analyzed via body weight/composition, food intake, sucrose preference, gut microbiota, and gene expression in gut and brain tissues. RESULTS: Obese (O)+CS offspring showed greater weight gain and caloric intake but a reduction in hypothalamic agouti related neuropeptide, neuropeptide Y, and interleukin 1ß expression compared with O+NB offspring. Lean (L)+CS offspring had higher serum corticosterone concentration and reduced liver peroxisome proliferator-activated receptor γ expression compared with L+NB. O+CS offspring had long-term alterations to gut microbiota, including increased relative abundance of Faecalibaculum and reduced Muribaculaceae. CONCLUSIONS: Overall, CS alters obesity risk differentially based on maternal obesity status. Further studies looking at the risks of obesity associated with CS are needed, with special attention paid to maternal obesity status and gut microbiota.

Impaired Hypothalamic Microglial Activation in Offspring of Antibiotic-Treated Pregnant/Lactating Rats Is Attenuated by Prebiotic Oligofructose Co-Administration.

Microbial colonization of the gut early in life is crucial for the development of the immune and nervous systems, as well as influencing metabolism and weight gain. While early life exposure to antibiotics can cause microbial dysbiosis, prebiotics are non-digestible substrates that selectively promote the growth of beneficial gut microbiota. Our objective was to examine the effects of dietary prebiotic administration on the consequences of maternal antibiotic intake on offspring body weight, behavior, and neuroimmune responses later in life. Sprague-Dawley rat dams were given low-dose penicillin (LDP), prebiotic fiber (10% oligofructose), or both, during the third week of pregnancy and throughout lactation. Anxiety-like behavior, weight gain, body composition, cecal microbiota composition, and microglial responses to lipopolysaccharide (LPS) were assessed in offspring. Male and female prebiotic offspring had lower body weight compared to antibiotic offspring. Maternal antibiotic exposure resulted in lasting effects on select offspring microbiota including a lower relative abundance of Streptococcus, Lactococcus, and Eubacterium at 10 weeks of age. Maternal antibiotic use impaired microglial response to LPS in the hypothalamus compared to control, and this phenotype was reversed with prebiotic. Prebiotic fiber warrants further investigation as an adjunct to antibiotic use during pregnancy.

Prebiotic Oligofructose Prevents Antibiotic-Induced Obesity Risk and Improves Metabolic and Gut Microbiota Profiles in Rat Dams and Offspring.

SCOPE: Antibiotics in early life disrupt microbiota and increase obesity risk. Dietary agents such as prebiotics may reduce obesity risk. The authors examine how antibiotics administered with/without prebiotic oligofructose, alter metabolic and microbial outcomes in pregnant rats and their offspring. METHODS AND RESULTS: Pregnant rats are randomized to: 1) Control, 2) Antibiotic (ABT), 3) Prebiotic (PRE), 4) Antibiotic+Prebiotic (ABT+PRE) during the 3rd week of pregnancy and lactation. Offspring were fed a high fat/high sucrose (HFS) diet from 9-17 weeks of age to unmask obesity risk. ABT dams had higher body weight, body fat and leptin during lactation than all other groups. Prebiotics attenuate these outcomes and increase cecal Bifidobacterium. ABT offspring have higher body weight, fat mass, and liver triglycerides after HFS diet, with a stronger phenotype in males; prebiotics attenuate these. At weaning, male ABT offspring have lower Lactobacillus while PRE and ABT+PRE offspring had higher Bifidobacterium and Collinsella. Fecal microbiota transfer of adult offspring cecal matter could not reliably transfer the obese ABT phenotype. CONCLUSIONS: Antibiotic use during pregnancy/lactation increases adiposity and impairs post-partum weight loss in dams. Co-administering prebiotics with antibiotics in rat dams prevented obesity risk in offspring and is associated with altered gut microbiota.

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats.

OBJECTIVE: This study aimed to investigate the interaction between obesity, low-calorie sweeteners, and prebiotic oligofructose on reproductive parameters in rats. METHODS: Data were derived from two separate studies of female Sprague-Dawley rats with (1) Lean (n = 24), (2) Obese (n = 27), (3) Obese+Aspartame (n = 14), (4) Obese+Stevia (n = 15), and (5) Obese+Prebiotic (n = 15) groups. Obesity was induced with a high-fat/high-sucrose diet prior to pregnancy. In one study, human-approved doses of aspartame (5-7 mg/kg/d) and stevia (2-3 mg/kg/d) in drinking water were examined, and in the second, 10% prebiotics (oligofructose) in the diet was examined. Reproductive parameters, including fertility, pregnancy, and delivery indexes, were analyzed. RESULTS: Obesity significantly reduced pregnancy index in Obese dams (60.7% successful pregnancies) compared with lean (100%). Obesity also reduced the number of pups born alive and pup survival percentage compared with those of Lean dams (P < 0.001). Only 53.3% of rats were able to conceive in the Obese+Stevia group, but if rats did become pregnant, they had 100% pregnancy and delivery index. While prebiotic administration rescued the pregnancy index, it could not remediate pup survival percentage (P = 0.025) in Obese dams. CONCLUSIONS: Both obesity status and dietary ingredients affect the ability to conceive. Future rigorously controlled studies designed to examine reproductive outcomes in depth are needed to confirm these findings.