The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well-elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age-related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross-sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy     

Ghrelin levels are associated with hunger as measured by the Three-Factor Eating Questionnaire in healthy young adults

Weight gain and appetite regulation are complex interplays between internal and external cues. Our aim was to investigate the association of eating behaviors with ghrelin taking into account lifestyle. We conducted a cross-sectional analysis in a sample of first-year university students at the Université de Sherbrooke. We collected medical history, anthropometric measurements, vital signs, fitness index, and fasting blood samples. Questionnaires included a lifestyle questionnaire and the Three-Factor Eating Questionnaire (TFEQ) estimating dietary restraint, disinhibition and hunger. We recruited 308 participants aged 20.7 ± 3.2 years and a mean BMI of 23.3 ± 3.4 kg/m². Hunger score was significantly associated with ghrelin levels (r = 0.11, P < 0.05). In women, this association was independent of age, BMI, dietary and lifestyle factors (P = 0.02). The association between ghrelin level and hunger score was observable in leaner individuals (r = 0.28, p < 0.0001) but not in heavier individuals (r = − 0.08, p = 0.34; stratified by BMI < vs > 22.6 kg/m²). Restraint (R) and disinhibition (D) were not associated with ghrelin levels. The three eating behaviors demonstrated expected correlations with lifestyle supporting the validity of the TFEQ in this cohort. In conclusion, we demonstrated that ghrelin, a biological marker, is associated with self-reported perception of hunger, independently of anthropometric measures and lifestyle.     

Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization

The increasing prevalence of antibiotic-resistant bacteria is a global threat to public health. Agricultural use of antibiotics is believed to contribute to the spread of antibiotic resistance, but the mechanisms by which many agricultural practices influence resistance remain obscure. Although manure from dairy farms is a common soil amendment in crop production, its impact on the soil microbiome and resistome is not known. To gain insight into this impact, we cultured bacteria from soil before and at 10 time points after application of manure from cows that had not received antibiotic treatment. Soil treated with manure contained a higher abundance of β-lactam–resistant bacteria than soil treated with inorganic fertilizer. Functional metagenomics identified β-lactam–resistance genes in treated and untreated soil, and indicated that the higher frequency of resistant bacteria in manure-amended soil was attributable to enrichment of resident soil bacteria that harbor β-lactamases. Quantitative PCR indicated that manure treatment enriched the bla_CEP-04 gene, which is highly similar (96%) to a gene found previously in a Pseudomonas sp. Analysis of 16S rRNA genes indicated that the abundance of Pseudomonas spp. increased in manure-amended soil. Populations of other soil bacteria that commonly harbor β-lactamases, including Janthinobacterium sp. and Psychrobacter pulmonis, also increased in response to manure treatment. These results indicate that manure amendment induced a bloom of certain antibiotic-resistant bacteria in soil that was independent of antibiotic exposure of the cows from which the manure was derived. Our data illustrate the unintended consequences that can result from agricultural practices, and demonstrate the need for empirical analysis of the agroecosystem.Agriculture affects human health through both the consumption and production of food for the human diet. Manure from pig and cattle farms is commonly used as a substitute for inorganic nitrogen and phosphorus fertilizers for agricultural crops worldwide, especially in organic farming practices (1–6). With the increasing consumer demand for organically produced food, the use of animal manure, which conforms to organic conventions, will likely increase in the future. According to the National Organic Program, raw manure may be used up to 90–120 d before harvest, depending on the crop, and composted manure may be applied at any time. There are no restrictions on the source of manure (1).Animal manure is an important reservoir of antibiotic-resistant bacteria, antibiotic-resistance genes (collectively known as the “resistome”), and pathogens (2, 7–12). Although antibiotic use increases antibiotic-resistance genes and resistant bacteria in manure (13–16), antibiotic-resistant bacteria are also abundant in manure from animals with no history of antibiotic treatment, indicating the natural presence of bacteria intrinsically resistant to antibiotics in animal gastrointestinal tracts (2, 17, 18).There is increasing concern about the use of manure as an agricultural amendment because of its possible contribution to the pool of resistance genes to resident soil bacteria and pathogens (2, 19). Antibiotic-resistance genes from the soil resistome can enter the food chain via contaminated crops or groundwater (5, 20), and have potential consequences for human health if transferred to human pathogens. Studies assessing the impact of fertilization with pig manure on the soil resistome have shown that excessive application of manure from farms with intensive sulfonamide use can lead to an increase of antibiotic-resistance genes in soil (2, 3); however, most studies have found that such increases are transient when the manure is applied at recommended rates (2, 21, 22). Cow manure from dairy farms, which use β-lactam antibiotics predominantly to prevent and treat diseases (23), is commonly used in crop production, but its impact on the soil resistome has yet to be investigated.Along with its impact on the soil resistome, the application of manure can affect the composition and functional properties of soil microbial communities, as has been demonstrated by community fingerprinting (21, 24). Recent advances in DNA-based analysis, such as metagenomics and quantitative PCR (qPCR), offer greater precision in such studies, enabling identification of affected community members (25) and their resistance genes (4).In the present study, we assessed the impact of cow manure on the composition and resistance profiles of bacterial communities in soil. Our results show that manure from cows that had not been treated with antibiotics increased the populations of resident soil bacteria harboring genes for resistance to β-lactam antibiotics, whereas inorganic fertilizers did not. These results demonstrate the complexity, and at times nonintuitive consequences, of agricultural practices.     

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research.     

Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome

BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sj?gren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.     

Molecular characterization of isolates of waterborne Cryptosporidium spp. collected during an outbreak of gastroenteritis in South Burgundy,France

In September 2001, a waterborne outbreak of gastroenteritis occurred in eastern France. Of 31 fecal samples from symptomatic individuals, 19 tested positive for Cryptosporidium with two PCRs targeting the Hsp70 and the 18S rRNA genes of CRYPTOSPORIDIUM: Sequencing of the PCR fragments produced sequences identical to that of Cryptosporidium parvum genotype 1.     

Prenatal diagnosis and molecular characterization of an interstitial 1q24.2q25.2 deletion

We report on the observation of an interstitial deletion of the long arm of chromosome 1 diagnosed prenatally in a 28 weeks gestation fetus by standard karyotype. Amniocentesis was performed because of an increased Down syndrome maternal serum screening and ultrasonographic abnormalities. Fetus autopsy showed an intrauterine growth retardation, dysmorphic features and limbs abnormalities. Using fluorescent in situ hybridization technique (FISH), we characterized the deletion boundaries corresponding to the bacterial artificial chromosomes (BAC) RP11-193J5 and RP11-162L13. Molecular studies identified the deletion of paternal origin. Therefore the karyotype was interpreted as 46,XY,del(1)(q24.2q25.2). This is the smallest deletion of the long arm of chromosome 1 reported prenatally and characterized at the molecular level. Its phenotype is compared to other similar cases described in the literature.