Sepsis is a common, heterogeneous, and frequently lethal condition of organ dysfunction and immune dysregulation due to infection. The causes of its heterogeneity, including the contribution of the pathogen, remain unknown. Using cecal slurry, a widely used murine model of intraperitoneal polymicrobial sepsis, as well as 16S ribosomal RNA sequencing and measurement of immune markers, we performed a series of translational analyses to determine whether microbial variation in cecal slurry composition (representing intra-abdominal pathogens) mediated variation in septic response.
View Article and Find Full Text PDFSemin Respir Crit Care Med
June 2024
Connective tissue disease-related interstitial lung disease (CTD-ILD) is a frequent and serious complication of CTD, leading to high morbidity and mortality. Unfortunately, its pathogenesis remains poorly understood; however, one intriguing contributing factor may be the microbiome of the mouth and lungs. The oral microbiome, which is a major source of the lung microbiome through recurrent microaspiration, is altered in ILD patients.
View Article and Find Full Text PDFBackground And Purpose: Self-compassion is considered as a protective psychological construct that would shield against the development of emotional problems. The aim of the present study was to compare the 'protective nature' of two measures of self-compassion: the Self-Compassion Scale for Youth (SCS-Y) and the Sussex-Oxford Compassion for the Self Scale (SOCS-S).
Methods: Eighty-seven adolescents aged 12 to 18 years completed both self-compassion measures as well as scales of anxiety and depression symptoms.
Am J Respir Crit Care Med
April 2023
Among patients with sepsis, variation in temperature trajectories predicts clinical outcomes. In healthy individuals, normal body temperature is variable and has decreased consistently since the 1860s. The biologic underpinnings of this temperature variation in disease and health are unknown.
View Article and Find Full Text PDFBackground: The microbiome is an important and increasingly-studied mediator of organismal metabolism, although how the microbiome affects metabolism remains incompletely understood. Many investigators use antibiotics to experimentally perturb the microbiome. However, antibiotics have poorly understood yet profound off-target effects on behavior and diet, including food and water aversion, that can confound experiments and limit their applicability.
View Article and Find Full Text PDFThe dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host's antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat.
View Article and Find Full Text PDFComplex facial muscle movements are essential for many motoric and emotional functions. Facial muscles are unique in the musculoskeletal system as they are interwoven, so that the contraction of one muscle influences the contractility characteristic of other mimic muscles. The facial muscles act more as a whole than as single facial muscle movements.
View Article and Find Full Text PDFThe distance one can walk at a time could be considered an important functional outcome in people with a lower limb amputation. In clinical practice, walking distance in daily life is based on self-report (SIGAM mobility grade (Special Interest Group in Amputee Medicine)), which is known to overestimate physical activity. The aim of this study was to assess the number of consecutive steps and walking bouts in persons with a lower limb amputation, using an accelerometer sensor.
View Article and Find Full Text PDFIntroduction: Cross-cover, the process by which a nonprimary team physician cares for patients, usually during afternoons, evenings, and weekends, is common in academic medical centers. With the advent of residency duty-hour restrictions, cross-cover care has increased, making education in effective cross-coverage an urgent need.
Methods: We implemented a cross-cover didactic activity composed of 18 interactive cases with 29 senior medical students enrolled in an internal medicine residency preparation course.
Superior vena cava (SVC) syndrome results from the blockage of venous blood flow through the SVC, which is caused by either internal obstruction (eg, thrombus) or external compression (eg, thoracic malignancy and infection).1 While thrombus-related SVC syndrome is rising in prevalence, malignancy still accounts for the majority of cases.1 Regardless of cause, SVC syndrome is characterised by facial swelling and plethora, headache and dyspnoea.
View Article and Find Full Text PDFPersistent air leak (PAL) is a common problem after secondary pneumothorax due to cystic fibrosis (CF). These leaks, caused by either bronchopleural or alveolopleural fistula, are associated with higher morbidity and mortality [1]. Air leaks are traditionally treated with chronic chest tube drainage, chemical pleurodesis, or autologous blood patching in non-surgical candidates [1].
View Article and Find Full Text PDFWhat Is Known And Objective: Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs can affect thermoregulation through mechanisms including altering the neurotransmitters that cause increased heat production or decreased heat loss and may, therefore, be associated with hyperthermia. This study aimed to examine hospitalizations and emergency department (ED) presentations due to hyperthermia and to investigate the potential association with drug therapy.
View Article and Find Full Text PDFPurpose: Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia.
View Article and Find Full Text PDFThis single-blind randomized pilot study explored feasibility and safety of a self-management fall prevention program, hypothesizing that older persons can comply with this program, while it does not result in more (injurious) falls, or a decrease in mental wellbeing as an adverse effect of being focused on falls prevention. Eighty-six persons, community-dwelling or home for the aged (mean age 80.3 years [SD: 6.
View Article and Find Full Text PDFPurpose Of Study: The first aim is to evaluate, in a sub-study, the recruitment process of the Senior Step Study, which was an intervention study on the self-management of mobility and fall risk; the second aim is to explore the reasons mentioned by older people, from three different settings, for (not) participating.
Methods: Subjects were community-dwelling older persons, residents of homes for the elderly, and older persons regularly visiting community centres. The effectiveness of different recruitment procedures was analysed for each setting separately.
Mantle cell lymphoma is a mature B-cell non-Hodgkin lymphoma characterized by the hallmark (11;14) chromosomal translocation, which often presents with lymphadenopathy and extra-nodal involvement. Young, fit patients are generally treated with chemotherapy approaches that incorporate high-dose cytarabine (e.g.
View Article and Find Full Text PDFObjectives: Self-management of mobility and fall risk can be important in fall prevention; however, it remains unstudied. Therefore, the current study assessed whether community-dwelling older persons were able to repeatedly self-assess maximum step length (MSL) and gait speed (GS) in their own home for a 6-month period, how these tests changed during this period and if these changes were related to falling.
Design: This is a prospective study.
Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes).
View Article and Find Full Text PDFSkeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase.
View Article and Find Full Text PDFSelf-management of mobility and fall risk might be possible if older adults could use a simple and safe self-test to measure their own mobility, balance, and fall risk at home. The aim of this study was to determine the safety, feasibility, and intraindividual reliability of the maximal step length (MSL), gait speed (GS), and chair test (CT) as potential self-tests for assessing mobility and fall risk. Fifty-six community-dwelling older adults performed MSL, GS, and CT at home once a week during a four-week period, wherein the feasibility, test-retest reliability, coefficients of variation, and linear mixed models with random effects of these three self-tests were determined.
View Article and Find Full Text PDFBackground: Falling is a major health problem.
Objective: To investigate the predictive value for falls of the maximum step length and gait speed.
Design: A prospective cohort study.
Background: Frailty reflects a state of increased risk of negative health outcomes, such as falls and mortality. Self-management in recognition and monitoring of frailty is a prerequisite for effective and efficient care for the elderly. Mobility may be self-monitored with simple reliable tests, such as maximum step length (MSL) test, gait speed (GS) test, or chair rise test (CR).
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
August 2014
Immobilization causes skeletal muscle atrophy via complex signaling pathways that are not well understood. To better understand these pathways, we investigated the roles of p53 and ATF4, two transcription factors that mediate adaptations to a variety of cellular stresses. Using mouse models, we demonstrate that 3 days of muscle immobilization induces muscle atrophy and increases expression of p53 and ATF4.
View Article and Find Full Text PDFSkeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine.
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