Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

A Cost-Effectiveness Analysis of Wittmann Patch-Assisted Abdominal Closure Compared to Planned Ventral Hernia in Management of the Open Abdomen.

BACKGROUND: Inability to achieve primary fascial closure after damage control laparotomy is a frequently encountered problem by acute care and trauma surgeons. This study aims to compare the cost-effectiveness of Wittmann patch-assisted closure to the planned ventral hernia closure. METHODS: A literature review was performed to determine the probabilities and outcomes for Wittmann patch-assisted primary closure and planned ventral hernia closure techniques. Average utility scores were obtained by a patient-administered survey for the following: rate of successful surgeries (uncomplicated abdominal wall closure), surgical site infection, wound dehiscence, abdominal hernia and enterocutaneous fistula. A visual analogue scale (VAS) was utilized to assess the survey responses and then converted to quality-adjusted life years (QALYs). Total cost for each strategy was calculated using Medicare billing codes. A decision tree was generated with rollback and incremental cost-utility ratio (ICUR) analyses. Sensitivity analyses were performed to account for uncertainty. RESULTS: Wittmann patch-assisted closure was associated with higher clinical effectiveness of 19.43 QALYs compared to planned ventral hernia repair (19.38), with a relative cost reduction of US$7777. Rollback analysis supported Wittmann patch-assisted closure as the more cost-effective strategy. The resulting negative ICUR of -156,679.77 favored Wittmann patch-assisted closure. Monte Carlo analysis demonstrated a confidence of 96.8% that Wittmann patch-assisted closure was cost-effective. CONCLUSIONS: This study demonstrates using the Wittmann patch-assisted closure strategy as a more cost-efficient management of the open abdomen compared to the planned ventral hernia approach.

Impact of concomitant necrotizing enterocolitis on mortality in very low birth weight infants with intraventricular hemorrhage.

OBJECTIVE: To evaluate the impact of necrotizing enterocolitis (NEC) on mortality in very low birth weight (VLBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: Data were collected on VLBW infants born 2014-2018 at Vermont Oxford Network (VON) centers. NEC and IVH were categorized by severity. Adjusted risk ratios (ARR) for in-hospital mortality were calculated. RESULTS: This study included 187 187 VLBW infants. Both medical and surgical NEC increased mortality risk compared to those without NEC. Stratification by IVH severity modified this effect (no IVH: ARR 3.04 (95%CI 2.74-3.38) for medical NEC and 4.17 (3.84-4.52) for surgical NEC; mild IVH: ARR 2.14 (1.88-2.44) for medical NEC and 2.49 (2.24-2.78) for surgical NEC; severe IVH: ARR 1.14 (1.03-1.26) for medical NEC and 1.10 (1.02-1.18) for surgical NEC). CONCLUSION: The relative impact of NEC on mortality decreased as IVH severity increased. Given the frequent coexistence of NEC and IVH, these data inform multidisciplinary management of these complex patients.

The relationship between sex and functional outcome in first-episode schizophrenia: the role of premorbid adjustment and insight.

BACKGROUND: Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences. METHODS: Our sample consisted of 137 individuals with first episode schizophrenia (males, n = 105; 77%) with a mean age of 22.1(s.d. = 4.1) years and mean education of 12.5(s.d. = 1.7) years. At entry, patients were within 2 years of their first psychotic episode onset. Baseline assessments were conducted for premorbid adjustment, symptoms, cognitive functioning, insight, and at 6-months for role and social functioning. RESULTS: Males as compared to females had poorer premorbid adjustment across several key developmental periods (p < 0.01), an earlier age of onset [M = 20.3(3.3) v. 22.8(5.6), p = 0.002], more negative symptoms (p = 0.044), poorer insight (p = 0.031), and poorer baseline and 6-month role (p = 0.002) and social functioning (p = 0.034). Several of these variables in which males showed impairment were significant predictors of 6-month role and social functioning. Premorbid adjustment and insight mediated the relationship between sex and role and social functioning at 6-months, but not negative symptoms. DISCUSSION: Males compared to females were at lower levels across several key premorbid and clinical domains which are strongly associated with functional outcome supporting the hypothesis that males might have a more disabling form of schizophrenia. The relationship between sex with role and social functioning was mediated through premorbid adjustment and insight suggesting pathways for understanding why females might have a less disabling form of schizophrenia.

Evaluating General Surgical Residency Education Structure and Incorporation of the Resident as Educator Model.

BACKGROUND: General surgery education has continued to evolve regarding test preparation, simulation, and skill acquisition. The "Resident as Educator" (RAE) model has been proposed and enacted by programs as a viable education model for general surgery education. This study examines the current education structures in general surgery residency programs in the United States and how many programs have adopted the RAE model or aspects of the model. METHODS: A 20-question survey regarding education structure was distributed to all program directors in October 2021. Questions focused on the involvement of residents in leading education sessions, creating the weekly education schedule, program feedback to residents on teaching, and recognition for distinguished resident educators. RESULTS: A total of 156 programs responded to the survey. The response rate was 60%. 76.4% of the respondents have a combination of resident and faculty-led didactic sessions, 8.5% have an RAE model, and 15% have faculty-led education sessions. In terms of concerns regarding resident-led didactics-24.4% of respondents stated that their main concern would be the quality of education provided, and 20.4% referenced low resident satisfaction levels with resident-led education. There were no differences among the groups regarding the American Board of Surgery board passage rates. CONCLUSIONS: Most residency programs have adopted a model in which residents have significant involvement in creating and maintaining the education calendar and leading formal education sessions. However, only 8.5% have a purely resident-led educational curriculum among the responding programs. More studies are needed to assess how to implement a resident as educator model successfully.

Antibiotic Therapy for Culture-Proven Bacterial Overgrowth in Children With Intestinal Failure Results in Improved Symptoms and Growth.

OBJECTIVES: To evaluate symptoms, enteral tolerance, growth, and antibiotic regimens in pediatric intestinal failure (IF) patients after treated with antibiotic therapy for small bowel bacterial overgrowth (SBBO). METHODS: Single-center retrospective review of children 0-18 years with IF with endoscopic cultures demonstrating >10 5 CFU/mL from 2010 to 2017. Symptoms, enteral tolerance, growth, and antibiotic regimens were evaluated at the time of endoscopy and 6 months later. RESULTS: Of 505 patients followed in our intestinal rehabilitation program, 104 underwent upper gastrointestinal endoscopy and 78 had positive duodenal cultures. Clinical data pre- and post-endoscopy were available for 56 patients. Compared to baseline, in the 6 months following targeted antibiotic treatment, children showed significant improvement in emesis or feeding intolerance (58.9% vs 23.2%, P < 0.001), abdominal pain (16.1% vs 7.1%, P = 0.02), high stool output (42.9% vs 19.6%, P = 0.002), and gross GI bleeding (19.6% vs 3.6%, P = 0.003). Mean BMI-for-age z scores increased significantly (-0.03 ± 0.94 vs 0.27 ± 0.82, P = 0.03); however, height-for-age z scores, weight-for-age z scores, and percent of calories from enteral intake were not significantly different after therapy. Antibiotic regimens remained highly variable. CONCLUSIONS: Children with IF and culture-positive SBBO showed significant improvement in symptoms and BMI-for-age z scores after duodenal culture with subsequent targeted antibiotic therapy. Longer follow-up may be needed to detect improvements in linear growth and percent of calories from enteral feeds. Antibiotic regimens remain highly variable. Long-term consequences of chronic antimicrobial therapy, including antimicrobial resistance, remain unknown. Prospective studies focused on standardizing duodenal sampling technique, correlating culture and pathology data, and evaluating antibiotic resistance patterns are needed.

Should Radiological Assessment be Part of Core General Surgery Competency? A Survey of the General Surgery Residents.

BACKGROUND: Radiological assessment is an important skill to develop in general surgery training. Therefore, we aimed to determine general surgery residents' points of view on receiving formal radiology didactics. METHODS: We performed an anonymous survey of general surgery residents throughout the USA. The survey queried the residents' postgraduate year, training program type, diagnostic radiology education in their training program, as well as the residents' comfort level in interpreting various imaging modalities, followed by a series of images to assess the residents' ability to interpret images showing various surgical disease processes. RESULTS: A total of 365 residents responded to the survey. In total, 76.6% of the respondent states that there is no structured didactic session in their program on radiological studies. However, 66.3% felt that interpretation of radiological images should be used to determine surgical competency and promotion to the next academic year. In terms of accurately reading images-68.7% of the residents were able to read an X-ray showing cecal volvulus correctly, 51.9% were able to read a cholangiogram correctly, and 95.3% were correctly read an X-ray showing free under the diaphragm. CONCLUSION: Most residents favored having radiological assessments as part of the competency evaluation. Furthermore, a curriculum and inbuilt training structure that aims to ensure residents develop competent clinical image interpretation abilities may enhance the development and retention of such skills, ultimately influencing patient outcomes.

Generic and Disease-specific Health-related Quality of Life in Pediatric Intestinal Failure.

OBJECTIVE: The aim of the study was to assess overall and disease-specific health-related quality of life (hrQOL) in patients with pediatric intestinal failure (PIF) and caregivers and elucidate differences from healthy and chronic gastrointestinal (GI) illness cohorts. METHODS: Cross-sectional study of patients with PIF and their caregivers managed at a multidisciplinary intestinal rehabilitation program using the PedsQL Generic Core and the Gastrointestinal Symptoms Module to assess generic and disease-specific hrQOL, respectively. These data were compared to established healthy and chronic GI disease controls. RESULTS: A total of 53 patients (mean age 6.2 ±â€Š3.9 years) and their caregivers were studied. Patients reported lower generic hrQOL than healthy children (73.0 vs 83.84, P < 0.001), but no difference from patients with chronic GI disease (73.0 vs 77.79). In contrast, PIF caregivers perceived similar generic hrQOL compared to a healthy cohort (78.9 vs 82.70), but higher when compared to the GI disease cohort (78.9 vs 72.74, P < 0.01). Patients with PIF and caregivers reported lower psychosocial health scores than healthy controls. Patients and caregivers reported similar disease-specific hrQOL to a cohort with chronic GI disease but significantly lower disease-specific hrQOL than a healthy cohort (P < 0.001 both groups). CONCLUSIONS: Patients with PIF and their caregivers have disparate perceptions of generic hrQOL when compared to healthy and chronic GI disease controls. Both patients and caregivers, however, had significantly lower scores in psychosocial health than healthy controls. In addition, disease-specific hrQOL was substantially lower than healthy controls for PIF patients and caregivers. Further investigation to expand on these findings and identify modifiable variables to improve the psychosocial health score and disease-specific factors would be of high value.

Trends in incidence and outcomes of necrotizing enterocolitis over the last 12 years: A multicenter cohort analysis.

OBJECTIVE: We sought to describe changes in the incidence and mortality of necrotizing enterocolitis (NEC) and associated surgical management strategies for very low birth weight (VLBW) infants. METHODS: Data were prospectively collected on VLBW infants (≤1500 g or < 29 weeks) born 2006 to 2017 and admitted to 820 U.S. centers. NEC was defined by the presence of at least one clinical and one radiographic finding. Trends analyses were performed to assess changes in incidence and mortality over time. RESULTS: Of 473,895 VLBW infants, 36,130 (7.6%) were diagnosed with NEC, of which 21,051 (58.3%) had medical NEC and 15,079 (41.7%) had surgical NEC. Medical NEC decreased from 5.3% to 3.0% (p < 0.0001). Surgical NEC decreased from 3.4% to 3.1% (p = 0.06). Medical NEC mortality decreased from 20.7% to 16.8% (p = 0.003), while surgical NEC mortality decreased from 36.6% to 31.6% (p < 0.0001). In the surgical cohort, the use of primary peritoneal drainage (PPD) versus initial laparotomy rose from 23.2% to 46.8%. CONCLUSION: The incidence and mortality of both medical and surgical NEC have decreased over time. Changes in surgical management during this time period included the increased utilization of primary peritoneal drainage. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Long-term outcomes of severe surgical necrotizing enterocolitis.

PURPOSE: We sought to describe long-term outcomes of infants with severe surgical necrotizing enterocolitis (NEC). METHODS: Data were collected on infants with surgical NEC (2009-2018). Severe surgical NEC was defined by extensive bowel loss with residual bowel length <30 cm, and "NEC totalis" was identified per operative report. Post-operative management and long-term outcomes were assessed, including enteral autonomy, severe neurodevelopmental disability, and educational attainment. RESULTS: Of 268 infants with surgical NEC, 41 (15%) had severe surgical NEC, and 14/41 were identified as "NEC totalis". Zero severe NEC vs. 8 (57%) "NEC totalis" patients were placed on comfort measures following initial surgery (p < 0.001). Twenty-five patients (93%) with severe NEC survived vs 3/6 with "NEC totalis" (p < 0.001). The 28 survivors (68%) were followed for a median (IQR) duration of 8(4,10) years. Nine (32%) with severe NEC were weaned from parenteral nutrition. Eight (29%) had ≥1 marker for severe neurodevelopmental disability, and 11/16(69%) (7-16 years) were attending school at last follow-up. CONCLUSION: Long-term survival is excellent following initial discharge, and achievement of enteral autonomy is feasible in patients with severe surgical NEC. The majority of patients who survive do not have severe neurodevelopmental disability and participate in school. Given current survivals and outcomes, focus on measured residual bowel length may be more appropriate than the subjective term "NEC-totalis." TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level II.

Tracheostomy in Very Low Birth Weight Infants: A Prospective Multicenter Study.

OBJECTIVES: In this study, we benchmark outcomes and identify factors associated with tracheostomy placement in infants of very low birth weight (VLBW). METHODS: Data were prospectively collected on infants of VLBW (401-1500 g or gestational age of 22-29 weeks) born between 2006 and 2016 and admitted to 796 North American centers. Length of stay (LOS), mortality, associated surgical procedures, and comorbidities were assessed, and infants who received tracheostomy were compared with those who did not. Multivariable logistic regressions were performed to identify risk factors for tracheostomy placement and for mortality in those receiving tracheostomy. RESULTS: Of 458 624 infants of VLBW studied, 3442 (0.75%) received tracheostomy. Infants with tracheostomy had a median (interquartile range) LOS of 226 (168-304) days and a mortality rate of 18.8%, compared with 58 (39-86) days and 8.3% for infants without tracheostomy. Independent risk factors associated with tracheostomy placement included male sex, birth weight <1001 g, African American non-Hispanic maternal race, chronic lung disease (CLD), intraventricular hemorrhage, patent ductus arteriosus ligation, and congenital neurologic, cardiac, and chromosomal anomalies. Among infants who received tracheostomy, male sex, birth weight <751 g, CLD, and congenital anomalies were independent predictors of mortality. CONCLUSIONS: Infants of VLBW receiving tracheostomy had twice the risk of mortality and nearly 4 times the initial LOS of those without tracheostomy. CLD and congenital anomalies were the strongest predictors of tracheostomy placement and mortality. These benchmark data on tracheostomy in infants of VLBW should guide discussions with patient families and inform future studies and interventions.

Long-Term Outcomes and Disease Burden of Neonatal Onset Short Bowel Syndrome.

PURPOSE: The study aims to describe long-term outcomes and disease burden of neonatal onset short bowel syndrome (SBS). METHODS: Utilizing the WHO criteria for adolescence, patients 10-19 years of age with neonatal onset SBS requiring parenteral nutrition (PN) for >90 days and followed by our multidisciplinary intestinal rehabilitation center between 2009 and 2018 were included for analysis. RESULTS: Seventy adolescents with SBS were studied. Median (IQR) age at last follow up in our center was 15 (11, 17) years. There was 0% mortality in the cohort, and 94% remained transplant free. Fifty-three patients (76%) achieved enteral autonomy. Three patients were weaned from PN without transplantation after six years of follow-up and another four after ten years of care at our multidisciplinary center. Disease burden remained higher in adolescents receiving PN, including inpatient hospitalizations (p < 0.01), procedures (p = 0.01), clinic visits (p < 0.01), and number of prescribed medications (p < 0.01). CONCLUSION: Survival for adolescents with neonatal onset SBS is excellent. Of the cohort studied, there was no mortality, and more than 75% achieved enteral autonomy. Disease burden remains high for adolescents who remain dependent on PN. However, achievement of enteral autonomy is feasible with long-term multidisciplinary rehabilitation. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Noninvasive assessment of liver fibrosis in pediatric intestinal failure patients using liver stiffness measurement by Vibration-Controlled Transient Elastography.

PURPOSE: The purpose of this study was to evaluate the diagnostic utility of noninvasive Vibration-Controlled Transient Elastography (VCTE) for assessing liver fibrosis in pediatric intestinal failure (PIF) patients. METHODS: Data from children with severe intestinal failure (≥90 days parenteral nutrition dependence) who underwent liver stiffness measurement (LSM), as measured by VCTE, at our institution between December 2015 and March 2018 were reviewed. LSM was compared to METAVIR fibrosis score (F0-F4) on liver biopsy performed within 1 year of VCTE. RESULTS: Seventy children underwent 75 LSM. Sixty-three patients (38% female) had at least one valid LSM, and 63% had a history of cholestasis (direct bilirubin ≥2 mg/dL). Median (IQR) age at first valid LSM was 4.5 years (2.6, 8.7). Sixteen patients had a liver biopsy. LSM differentiated between METAVIR F0-F1 (n = 6) and F2-F4 (n = 10) with an area under the receiver operating characteristic (AUROC) curve of 0.883 (95% CI: 0.686-0.999). The optimal cut-point derived to predict F2-F4 was an LSM ≥6 kPa (sensitivity 80%, specificity 100%). CONCLUSION: LSM as determined by VCTE can distinguish mild (F0-F1) from moderate/severe (F2-F4) liver fibrosis in PIF. VCTE could allow for serial noninvasive monitoring of liver injury, potentially facilitating timely modifications to hepatoprotective management. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: II.

Long-term outcomes of ultrashort bowel syndrome due to malrotation with midgut volvulus managed at an interdisciplinary pediatric intestinal rehabilitation center.

PURPOSE: The purpose of this study was to describe long-term outcomes of pediatric-onset ultrashort bowel syndrome owing to midgut volvulus managed at an interdisciplinary intestinal rehabilitation center. METHODS: Patients with a history of malrotation and pediatric-onset midgut volvulus causing extensive bowel loss (<20% residual small bowel length expected for postconception age) and treated between 2010 and 2017 were reviewed. Data are expressed as median (IQR). RESULTS: Twenty-three patients had midgut volvulus at age 1 (0-21) day leading to 9 (8-12) percent predicted residual bowel length. Eight (35%) had gastroschisis. Follow-up was 8.5 (6.6-12.2) years from volvulus. Five (22%) patients underwent intestinal/multivisceral transplantation, and all achieved enteral autonomy. Eighteen (78%) patients remained transplant-free, 7 of whom achieved enteral autonomy after 718 (682-1030) days of parenteral nutrition. Transplant-free enteral autonomy was achieved by 0/6 patients with gastroschisis, compared to 7/12 without gastroschisis (p = 0.04). For the overall group, 18 (78%) patients had small bowel bacterial overgrowth, and 7 manifested symptomatic D-lactic acidosis. We observed 2 mortalities, one awaiting transplant and one 4 years following transplantation. CONCLUSION: Midgut volvulus owing to malrotation with extensive bowel loss is associated with favorable long-term survival. Transplant-free enteral autonomy may be feasible, particularly in the absence of gastroschisis. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: IIb, retrospective cohort study.

Impact of disease-specific volume and hospital transfer on outcomes in gastroschisis.

BACKGROUND: Gastroschisis, a surgical condition requiring complex interdisciplinary care, may benefit from treatment at higher volume centers. Recent studies on surgical volume and outcomes have conflicting findings. METHODS: Data were collected prospectively on newborns ≥1500 g with gastroschisis born 2009-2015, admitted to 159 US centers, and separated into terciles based on number of annual gastroschisis repairs. Infants transferred after gastroschisis repair were excluded. RESULTS: There were 4663 infants included: 307 from 53 low, 1201 from 55 medium, and 3155 from 51 high volume centers. Infants at high volume centers had higher rates of intestinal atresia (P = 0.04) and outborn status (P < 0.0001). Outborn infants (N = 1134) had higher rates of gastrostomy/jejunostomy placement (P < 0.001). Mortality was universally low (2.0% low, 2.4% medium, and 1.7% high; 2.0% outborn and 1.9% inborn). On multivariate analysis, mortality, sepsis rates, and length of stay did not differ by center volume. Outborn status was associated with longer length of stay (P = 0.001), not mortality or sepsis. CONCLUSION: Infant characteristics and management vary based on gastroschisis surgical volume and transfer status. Center volume and early transfers were not associated with mortality. Further investigation to identify subsets of gastroschisis infants who would benefit from care at higher volume centers is warranted. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level II.

Surgical considerations for neonates with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a potentially devastating condition that preferentially affects premature and low birth weight infants, with approximately half requiring acute surgical intervention. Surgical consult should be considered early on, and deterioration despite maximal medical therapy or the finding of pneumoperitoneum are the strongest indications for emergent surgical intervention. There is no clear consensus on the optimal surgical approach between peritoneal drainage and laparotomy; the best course of action likely depends on the infant's comorbidities, hemodynamic status, size, disease involvement, and available resources. Patients who develop surgical NEC are at a significant risk for morbidity and mortality, with long-term complications including short bowel syndrome, growth failure, and neurodevelopmental impairment. Further research into strategies that optimize outcomes following surgery for NEC in the neonatal intensive care unit and long-term are paramount.

Effects of aging on mitochondrial hydrogen peroxide emission and calcium retention capacity in rat heart.

Aging is a risk factor for heart disease and heart failure, which result from a progressive impairment of cardiac functions, including stroke volume, cardiac output, blood flow, and oxygen consumption. Age-related cardiac dysfunction is associated with impaired cardiac structures, such as the loss of myocytes, structural remodeling, altered calcium (Ca2+) handling, and contractile dysfunction. However, the mechanism by which aging affects mitochondrial function in the heart is poorly understood. The purpose of this study was to determine the effects of aging on mitochondrial function in the rat heart. Male Fischer 344 rats were randomly assigned to very young sedentary (VYS, 1 month), young sedentary (YS, 4 months), middle-aged sedentary (MS, 10 months), and old sedentary (OS, 20 months) groups. mitochondrial complex protein levels and mitochondrial function (e.g., mitochondrial hydrogen peroxide (H2O2) emission and Ca2+ retention capacity) were analyzed in the left ventricle. Aging was associated with decreased levels of OXPHOS (oxidative phosphorylation) protein expression of complex I to IV in the function of the electron transport chain. Aging increased the mitochondrial H2O2 emitting potential in the heart. In contrast, mitochondrial Ca2+ retention capacity gradually decreased with age. These data demonstrate that aging impairs mitochondrial function in cardiac muscle, suggesting that mitochondrial dysfunction with aging may be a primary factor for aging-induced cardiac dysfunction in the heart.

Physical exercise promotes memory capability by enhancing hippocampal mitochondrial functions and inhibiting apoptosis in obesity-induced insulin resistance by high fat diet.

A high-fat diet induces obesity in mice, leading to insulin resistance, decreased mitochondrial function, and increased apoptosis in the hippocampus, which eventually result in memory loss. The present study investigated the effect of physical exercise on memory, hippocampal mitochondrial function, and apoptosis in mice with in insulin resistance caused by obesity due to high-fat diet. Mice were randomly divided into four groups: control (CON), control and exercise (CON + EX), high fat diet (HFD), and high fat diet and exercise (HFD + EX). After receiving a high-fat (60%) diet for 20 weeks to induce obesity, the animals were subjected to an exercise routine 6 times per week, for 12 weeks. The exercise duration and intensity gradually increased over 4-week intervals. Hippocampal memory was examined using the step-down avoidance task. Mitochondrial function and apoptosis were also examined in the hippocampus and dentate gyrus. We found that obesity owing to a high-fat diet induced insulin resistance and caused a decrease in memory function. Insulin resistance also caused a decrease in mitochondrial function in the hippocampus by reducing Ca2+ retention and O2, respiration, increasing the levels of H2O2, and Cyp-D, and mPTP opening. In addition, apoptosis in the hippocampus increased owing to decreased expression of Bcl-2 and increased expression of Bax, cytochrome c, and caspase-3 and TUNEL-positive cells. In contrast, physical exercise led to reduced insulin resistance, improved mitochondrial function, and reduced apoptosis in the hippocampus. The results suggest that physiological stimulations such as exercise improve hippocampal function and suppress apoptosis, potentially preventing the memory loss associated with obesity-induced insulin resistance.