Locally Acquired Melioidosis Linked to Environment - Mississippi, 2020-2023.

Melioidosis, caused by Burkholderia pseudomallei, is a rare but potentially fatal bacterial disease endemic to tropical and subtropical regions worldwide. It is typically acquired through contact with contaminated soil or fresh water. Before this investigation, B. pseudomallei was not known to have been isolated from the environment in the continental United States. Here, we report on three patients living in the same Mississippi Gulf Coast county who presented with melioidosis within a 3-year period. They were infected by the same Western Hemisphere B. pseudomallei strain that was discovered in three environmental samples collected from the property of one of the patients. These findings indicate local acquisition of melioidosis from the environment in the Mississippi Gulf Coast region.

TAB2 variants cause cardiovascular heart disease, connective tissue disorder, and developmental delay.

Congenital heart defects (CHD) are the most commonly occurring birth defect and can occur in isolation or with additional clinical features comprising a genetic syndrome. Autosomal dominant variants in TAB2 are recognized by the American Heart Association as causing nonsyndromic CHD, however, emerging data point to additional, extra-cardiac features associated with TAB2 variants. We identified 15 newly reported individuals with pathogenic TAB2 variants and reviewed an additional 24 subjects with TAB2 variants in the literature. Analysis showed 64% (25/39) of individuals with disease resulting from TAB2 single nucleotide variants (SNV) had syndromic CHD or adult-onset cardiomyopathy with one or more extra-cardiac features. The most commonly co-occurring features with CHD or cardiomyopathy were facial dysmorphism, skeletal and connective tissue defects and most subjects with TAB2 variants present as a connective tissue disorder. Notably, 53% (8/15) of our cohort displayed developmental delay and we suspect this may be a previously unappreciated feature of TAB2 disease. We describe the largest cohort of subjects with TAB2 SNV and show that in addition to heart disease, features across multiple systems are present in most TAB2 cases. In light of our findings, we recommend that TAB2 be included on the list of genes that cause syndromic CHD, adult-onset cardiomyopathy, and connective tissue disorder.

Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection.

Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.

Cognitive disinhibition and infrequent moderate-to-intense physical activity linked with obesity in U.S. soldiers.

PURPOSE: To explore the relationship between body weight status and neurocognitive functioning in soldiers. METHODS: U.S. soldiers (N = 109) answered survey questions and completed neurocognitive tests including simple reaction time, code substitution, procedural reaction time, go-no-go, matching to sample, code substitution recall, and four versions of the Stroop test including congruent (color and meaning of word agreed); incongruent (color and meaning of word differed); neutral (nonsense words appeared), and emotional (combat-related words such as "I.E.D" and "convoy" appeared). Self-reported heights and weights were used to calculate BMI. A BMI ≥ 30.00 kg/m2 was categorized as obese. Multivariate analysis of variance was used to analyze weight status differences (p ≤ 0.05) across neurocognitive variables. Binomial logistic regression analysis with obesity as the dependent variable was used to ascertain the contributions (p ≤ 0.05) of exercise and the neurocognitive measures that differed based on weight status. RESULTS: Twenty-nine participants (26.6%) were obese. The obese group had significantly lower scores on code substitution, and both neutral and emotional Stroop tasks. Only Stroop emotional scores, p = 0.022, OR = 0.97, and frequency of moderate/intense physical activity, p = 0.009, OR = 0.10, were significant predictors of weight status. CONCLUSIONS: Obesity was associated with less frequent moderate/intense physical activity and compromised executive functioning, namely decrements in response inhibition. Given the design and sample size, additional research is needed to better understand the direction of the relationship between these variables and to inform research related to the treatment and prevention of obesity within military populations. LEVEL OF EVIDENCE: Level III, case-control analytic study.

The impact of replacing breakfast grains with meat/meat alternatives: an evaluation of child nutrition policy.

OBJECTIVE: To evaluate the Child and Adult Care Food Program (CACFP) rule that allows a meat/meat alternative to replace the breakfast grain requirement three times per week. DESIGN: A 5-week menu including breakfast, lunch and snack was developed with meat/meat alternative replacing the breakfast grain requirement three times per week. Menu nutrients based on the minimum requirements were compared with reference values representing the Acceptable Macronutrient Distribution Range for fat and a range of reference values representing two-thirds the Dietary Reference Intake for 3-year-olds and 4-5-year-olds. The meal pattern minimum requirements were compared with two-thirds of those recommended by the Dietary Guidelines for Americans (DGA). SETTING: Evaluation took place between April and June 2019. PARTICIPANTS: Human subjects were not utilized. RESULTS: The CACFP minimum grain requirement is well below the DGA reference value (0·5-1·5 v. 3·33 ounce-equivalents). Energy (2208·52 kJ) was below the reference values (3126·83-4362·53 kJ). Protein (34·43 g) was above the reference values (9·87-10·81 g). Carbohydrate (76·65 g), fibre (7·46 g) and vitamin E (1·69 mg) were below their reference values of 86·67 g, 10·46-14·60 g and 4-4·76 mg, respectively. Fat (22·57 %) was below the reference range (25-40 %). CONCLUSIONS: The CACFP rule which allows a meat/meat alternative to replace the breakfast grain requirement three times per week may result in meal patterns low in energy, carbohydrate, fat, fibre and vitamin E, while providing an excessive amount of protein.

Nutritional Assessment in Inpatients With Cirrhosis Can Be Improved After Training and Is Associated With Lower Readmissions.

Malnutrition is widely prevalent in cirrhosis patients, which can worsen sarcopenia, hepatic encephalopathy (HE), and overall prognosis. We aimed to define the frequency of nutritional assessments of patients with cirrhosis in retrospective and prospective (after educational training) cohorts and to evaluate prospective changes along with their effects on 90-day readmissions. This study was conducted in 2 phases. Retrospectively, records of hospitalized patients with cirrhosis from the university and Veterans Affairs Medical Center (VAMC) settings were reviewed to assess nutritional status, if a nutrition consultation occurred, the number of days patients were nil per os (npo) and received inadequate nutrition, and if nutritional management was guideline directed. In the prospective phase, after dedicated educational efforts directed at the stakeholders regarding nutritional guidelines for patients with cirrhosis, subsequently hospitalized cirrhosis patients had nutritional and 90-day readmission data collected for comparison between groups. In total, 279 patients were included in the retrospective phase (150 university/129 VAMC), and 102 VAMC patients were in the prospective phase. Cirrhosis severity, reason for admission, and hospital course were similar between groups regardless of cohort, ie, prospective versus retrospective or VAMC versus university. The prospective group had significantly more nutritional consultations and assessments (74.5% versus 40.1%; P < 0.001) compared with the retrospective group regardless of comparisons between the VAMC and university cohorts. Both groups had a similar number of days npo, but the prospective group had fewer days of inadequate nutrition. The 90-day readmission rate was significantly lower in the prospective group versus the retrospective group (39.4% versus 28.4%; P = 0.04), which was associated with greater nutrition outpatient follow-up. In conclusion, nutritional consultation rates in inpatients with cirrhosis can be significantly improved after educational intervention and is associated with lower 90-day readmission rates.

Examining two different schedules of financial incentives for smoking cessation among pregnant women.

OBJECTIVE: To examine whether an efficacious voucher-based incentives intervention for decreasing smoking during pregnancy and increasing fetal growth could be improved without increasing costs. The strategy was to redistribute the usual incentives so that higher values were available early in the quit attempt. METHOD: 118 pregnant smokers in greater Burlington, Vermont (studied December, 2006-June, 2012) were randomly assigned to the revised contingent voucher (RCV) or usual contingent voucher (CV) schedule of abstinence-contingent vouchers, or to a non-contingent voucher (NCV) control condition wherein vouchers were provided independent of smoking status. Smoking status was biochemically verified; serial sonographic estimates of fetal growth were obtained at gestational weeks 30-34. RESULTS: RCV and CV conditions increased point-prevalence abstinence above NCV levels at early (RCV: 40%, CV: 46%, NCV: 13%, p=.007) and late-pregnancy (RCV: 45%; CV: 36%; NCV, 18%; p=.04) assessments, but abstinence levels did not differ between the RCV and CV conditions. The RCV intervention did not increase fetal growth above control levels while the CV condition did so (p<.05). CONCLUSION: This trial further supports the efficacy of CV for increasing antepartum abstinence and fetal growth, but other strategies (e.g., increasing overall incentive values) will be necessary to improve outcomes further.

Systematic review of mortality and survival rates for APDS.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in PIK3CD and PIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the PIK3CD gene, while loss of function variants in PIK3R1 have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. Despite available treatments, survival for individuals with APDS appears to be shortened from the average lifespan. A Kaplan-Meier survival analysis for APDS showed the conditional survival rate at the age of 20 years was 87%, age of 30 years was 74%, and ages of 40 and 50 years were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The overall mortality rate for HSCT in APDS1 and APDS2 cases was 15.6%, while the mortality rate for lymphoma was 47.6%. This survival and mortality data illustrate that new treatments are needed to mitigate the risk of death from lymphoma and other cancers as well as infection. These analyses based on real-world evidence gathered from the medical literature comprise the largest study of survival and mortality for APDS to date.

Perceived Factors That Facilitate or Prevent the Use of Speech-Generating Devices in Bilingual Individuals With Aphasia.

PURPOSE: The aim of this study was to explore practicing speech-language pathologists' (SLPs') perceptions of factors that could facilitate or prevent the use of speech-generating devices (SGDs) in bilingual individuals with aphasia. Specifically, this exploratory study sought to identify the facilitators and barriers to SGD use in individuals with culturally and linguistically diverse backgrounds. METHOD: An online survey was distributed to SLPs through an e-mail listserv and social media of an augmentative and alternative communication company. This article focused on the results of the survey items related to (a) the presence of bilingual individuals with aphasia on an SLP's caseload, (b) training related to SGD or bilingual aphasia, and (c) barriers and facilitators to SGD use. A thematic analysis was conducted to analyze the barriers and facilitators to SGD use reported by the respondents. RESULTS: A total of 274 SLPs who met the inclusion criteria had experience in implementing SGD for people with aphasia. Regarding relevant training, our results indicated that very few SLPs received bilingual aphasia intervention training (17.22%) or bilingual SGD training (0.56%) in graduate school. The results from our thematic analysis revealed four major themes of barriers and facilitators to SGD use, including (a) hardware and software, (b) cultural and language content, (c) SLP's cultural and linguistic competency, and (d) resources. CONCLUSIONS: Practicing SLPs reported several barriers to SGD use in bilinguals with aphasia. Most notably, language barriers for monolingual SLPs were seen as the greatest barrier to language recovery in individuals with aphasia whose primary language is not English. Several other barriers were consistent with previous research, such as financial factors and insurance disparities. The top three most important factors that facilitate SGD use in bilinguals with aphasia, as identified by the respondents, include user-friendly symbol organization, personalized words, and ease of programming.

Mindfulness Using a Wearable Brain Sensing Device for Health Care Professionals During a Pandemic: A Pilot Program.

OBJECTIVE: The purpose of this feasibility pilot study was to evaluate safety and adherence of a wearable brain sensing wellness device designed to reduce stress among healthcare professionals (HCP). METHODS: A total of 40 HCP were invited to participate in an open-label pilot study. Participants were asked to use a brain sensing wearable device (MUSE-S™) on a daily basis to reduce their stress, for a total of 90 days. Total study participation duration was 180 days. Study enrollment began in August 2021 and ended December 2021. The exploratory outcomes included stress, depression, sleep, burn-out, resilience, quality of life, and cognition. RESULTS: Among the 40 HCP in study, the majority were female (85%), white (87.5%) and with an average age of 41.3 ± 11.0 years (SD). Participants used the wearable device an average of 23.8 times over a 30-day period with a mean duration of 5.8 min with each use. Study results demonstrate the positive impact of guided mindfulness using the wearable device MUSE-S™ and its accompanying application (APP). A statistically significant improvement was found for a reduction in stress (P < .001) and improvement in resilience (P = .02), quality of life (P = .003), and cognition (P < .001). The majority (91.9%) of the participants indicated they felt more relaxed after using the device, and 73% indicated they would continue to use this device at end-of-study. No adverse effects were reported. CONCLUSION: Study results show that 3 to 10 min of guided meditation during work hours through the use of a brain sensing wearable device is safe and acceptable, with associated health benefits for HCP.

Attention deficit hyperactivity disorder subtypes and their relation to cognitive functioning, mood states, and combat stress symptomatology in deploying U.S. soldiers.

OBJECTIVES: To explore the relationship between adult attention deficit hyperactivity disorder (ADHD) subtypes and neuropsychological functioning among U.S. soldiers. METHODS: Deploying soldiers (N = 260) completed the World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener. Cognitive tests, a deployment health-history questionnaire, and the post-traumatic stress disorder (PTSD) Checklist-Military Version were completed by subsamples of available participants. RESULTS: The prevalence of positive ASRS screens was 10.4%. ASRS scores were correlated with PTSD avoidance (n = 63, p = 0.37, p = 0.003), hyperarousal (n = 63, p = 0.25, p = 0.047), and total PTSD scores (n = 62, p = 0.33, p = 0.009); and all six moods (e.g., anger, anxiety) scale scores (n = 110; p = -0.37 to 0.43). ASRS was also correlated with scores on the match-to-sample (n = 110, p = -0.23, p = 0.014) and emotional Stroop (n = 108, p = -0.23, p = 0.016) tasks. In addition, a differential pattern between subtypes of ADHD was noted with regard to cognitive functioning, mood, and combat stress symptomatology. CONCLUSIONS: Although the results are preliminary given the sample size, the prevalence and comorbidities of ADHD appear to be similar among military and nonmilitary populations.

The Nutritional Adequacy and Diet Quality of Vegetarian Menu Substitutions in Urban Kansas Childcare Centers.

While plant-based eating has become increasingly popular, little is known of how this trend has impacted childcare center meals. The purpose of this study was to measure the nutrient content and diet quality of vegetarian alternative lunches and compare these measures to those of standard childcare lunches and nutrient benchmarks representing one-third of the Dietary Reference Intake for 3-year-olds and 4-5-year-olds. Menu data were obtained from seven urban Kansas childcare centers participating in the Child and Adult Care Food Program and regularly providing a vegetarian alternative lunch. The centers provided detailed menu information for 27 days' worth of meals. The most common vegetarian substitution was cheese, which was used to fulfill all or part of the meat/meat alternative requirement in over three-quarters of the vegetarian alternative meals (n = 22). Compared to the standard meals, the vegetarian alternative meals were higher in calories, fat, saturated fat, calcium, and sodium and lower in protein, choline, and diet quality (p = 0.05). Both lunch options met the benchmarks for vitamin A, vitamin D, vitamin B12, calcium, and protein. Iron content for both (95% CI: standard 1.61-2.17 mg; vegetarian 1.37-2.7 mg) was below the benchmark. Although additional research is needed to better understand how vegetarianism has impacted childcare meals in the U.S., important differences in the nutrient contents were observed between the standard and vegetarian alternative meals. In addition, the results suggest vegetarian alternative meals that rely heavily on cheese may be of lower diet quality.

Energy-Adjusted Dietary Intakes Are Associated with Perceived Barriers to Healthy Eating but Not Food Insecurity or Sports Nutrition Knowledge in a Pilot Study of ROTC Cadets.

Military service is inherently demanding and, due to the nature of these demands, the term "tactical athlete" has been coined to capture the physical requirements of the profession. Reserve Officers' Training Corps (ROTC) cadets are a unique subset of the military service community, and the complexity of their training and educational pursuits increases their susceptibility to unhealthy eating patterns. The purpose of this pilot study was to explore the relationship between the perceived barriers to healthy eating, food insecurity, sports nutrition knowledge, and dietary patterns among Army ROTC cadets. The usual dietary intake was gathered from (N = 37) cadets using the General Nutrition Assessment Food Frequency Questionnaire. The perceived barriers to healthy eating were measured using a set of scales consisting of social barriers (6 items, α = 0.86), access barriers (2 items, α = 0.95), and personal barriers (2 items, α = 0.67), with higher-scale scores indicating greater perceived barriers. Spearman correlation coefficients were used to measure the association between the energy-adjusted dietary intakes and the scores on the barriers scales. Energy-adjusted intakes of calcium (ρ = -0.47, p ≤ 0.01), fiber (ρ = -0.35, p = 0.03), vitamin A (ρ = -0.46, p ≤ 0.01), vitamin C (ρ = -0.43, p ≤ 0.01), fruit (ρ = -0.34, p = 0.04), and vegetables (ρ = -0.50, p ≤ 0.01) were negatively correlated with the perceived personal barrier scores. The energy-adjusted intakes of fiber (ρ = -0.36, p = 0.03), vitamin C (ρ = -0.37, p = 0.03), and vitamin E (ρ = -0.45, p ≤.01) were negatively correlated with perceived social barriers, while energy-adjusted vitamin C intake was negatively correlated with perceived access barriers (ρ = -0.40, p = 0.01). Although additional research is needed to better understand the dietary patterns of ROTC cadets, among the participants in this study, greater perceived personal, social, and access barriers were associated with less nutrient-dense eating patterns. Interventions aimed at addressing such barriers may prove beneficial for the improvement of diet quality among ROTC cadets.

The importance of palpation in the skin cancer screening examination.

With the recent unprecedented shift toward contactless healthcare solutions, providers should recall the value that proper palpation adds to dermatologic practice. We present a case that demonstrates the limitations of touchless care and how proper palpation during skin cancer examinations may impact cosmetic outcomes. Our patient is an 86-year-old male patient with Sezary syndrome and monoclonal B-cell lymphocytosis whose squamous cell carcinoma invasion was missed by visual inspection alone. He delayed treatment of his biopsy-proven squamous cell carcinoma for 15 months. On follow-up, visual examination only showed a well-healed biopsy scar, and treatment was delayed another 2 months. Finally, thorough physical examination found perineural invasion. This helped guide the Mohs approach, but due to the delays resulted in a larger final defect and poorer cosmetic outcomes. Proper, deep palpation of skin lesions, especially prior biopsy sites, is imperative to the treatment of skin cancer in cosmetically sensitive areas. Biopsy scars on the face often heal well, and visual only inspection may miss crucial details. This case also reminds dermatologists of the importance of patient education in the prompt treatment of skin cancer for the best cosmetic outcomes.

Food Trying and Liking Related to Grade Level and Meal Participation.

School-based child nutrition programs provide students with meals and snacks that align with guidelines for a healthy eating pattern. However, participation is not universal, and research on the determinants of food selection is needed to improve school nutrition practices and policies. The purpose of this study was to examine the relationships between grade level (i.e., grade school, middle school, or high school) as well as meal participation category (i.e., only breakfast, only lunch, or both) and food trying and liking in a large urban school district. Outcomes were measured using an online survey completed by students from 2nd through 12th grade (n = 21,540). Breakfast and lunch item liking scores were higher among the grade school and middle school students than among the high school students. Breakfast and lunch liking scores were also higher among those who participated in both breakfast and lunch as opposed to those who only participated in one meal. Food item liking scores were positively correlated with the percentage of students who had tried the particular foods (r = 0.52, p < 0.001), and the number of foods tried was dependent on both grade level and meal participation category (F(4, 21,531) = 10.994, p < 0.001). In this survey of students, both grade level and meal participation category were found to be related to the liking of foods, while foods that were tried more often tended to be liked more. Future studies should consider grade level and meal participation when exploring student preferences. School nutrition programs should also consider these factors when assessing satisfaction.

A Model for Improving Diet Quality within Child Nutrition Programs: The U.S. Army's Child and Youth Services Healthy Menu Initiative.

The U.S. Army's Child, Youth, and School Services (CYS), which has the capacity to serve more than 70,000 meals/snacks per day, is a geographically dispersed system with facilities worldwide. This case report is a description and evaluation of the implementation of a major food program initiative within the CYS system. In collaboration with Kansas State University, the Healthy Menu Initiative was established to standardize the system's menus, reflect the guidance contained within the 2015-2020 Dietary Guidelines for Americans, and take into account the Child and Adult Care Food Program regulations that went into effect on 1 October 2017. Food storage space, food service equipment, product availability, food safety considerations, and staff shortages have all proven to be challenges in the development and implementation of the menus. Participant acceptance has been an issue in some instances, and special diet requirements add to the workload of the staff. To overcome these challenges, input was solicited from CYS management, care providers, food service staff, and participant families, as well as participants themselves. Taste testing and classroom cooking activities have been developed to increase acceptance, and over 500 CYS food program staff have attended in-depth training sessions to support the initiative. Overall, the initiative has been well received, and there has been an improvement in the diet quality of the foods served within the program. This improvement is noteworthy, as optimal growth and development during childhood and adolescence are reliant on sound nutrition.

What diet should I recommend my patient with Hepatic Encephalopathy?

PURPOSE OF REVIEW: The burden of malnutrition is high in patients with cirrhosis, especially in those with hepatic encephalopathy (HE). This has a bearing on increased morbidity and mortality. Heightened attention needs to be paid to screen the patients at high nutritional risk both in the outpatient and hospitalized settings. This review summarizes the current evidence for nutritional support in HE patients and compares the recommendations about nutritional requirement as laid out by various organizations. RECENT FINDINGS: On survey of the literature, there is a consensus on avoiding protein restriction of the diets in HE patients along with uniform recommendations on caloric requirements. An exciting field of manipulating the gut microbiome in nutritional sciences may hold promise as well as there may be a future role for branched chain amino acids in nutritional management of HE patients. SUMMARY: Even though the data suggest that nutritional improvement lead to better outcomes including lower readmission rates in cirrhosis, operationalizing these into practice remains a challenge. To achieve this, a multi-disciplinary approach with nutritional education of the frontline care providers, earlier nutritional risk screening of patients, involvement of the nutrition professionals as part of the team and repeated dietary counseling for the patient and caregiver/s is required. Ultimately, this may need more focus, resource allocation and uniform guidelines across all countries to make this a success.

LONP1 de novo dominant mutation causes mitochondrial encephalopathy with loss of LONP1 chaperone activity and excessive LONP1 proteolytic activity.

LONP1 is an ATP-dependent protease and chaperone that plays multiple vital roles in mitochondria. LONP1 is essential for mitochondrial homeostasis due to its role in maintenance of the mitochondrial genome and its central role in regulating mitochondrial processes such as oxidative phosphorylation, mitophagy, and heme biosynthesis. Bi-allelic LONP1 mutations have been reported to cause a constellation of clinical presentations. We report a patient heterozygous for a de novo mutation in LONP1: c.901C>T,p.R301W presenting as a neonate with seizures, encephalopathy, pachygyria and microcephaly. Assays of respiratory chain activity in muscle showed complex II-III function at 8% of control. Functional studies in patient fibroblasts showed a signature of dysfunction that included significant decreases in known proteolytic targets of LONP1 (TFAM, PINK1, phospho-PDH E1α) as well as loss of mitochondrial ribosome subunits MRPL44 and MRPL11 with concomitant decreased activity and level of protein subunits of oxidative phosphorylation complexes I and IV. These results indicate excessive LONP1 proteolytic activity and a loss of LONP1 chaperone activity. Further, we demonstrate that the LONP1 N-terminal domain is involved in hexamer stability of LONP1 and that the ability to make conformational changes is necessary for LONP1 to regulate proper functioning of both its proteolytic and chaperone activities.