The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary ...site of nutrient absorption and microbiome interaction, however our understanding of intestinal adaptations to starvation and refeeding remains limited. Here we used RNA sequencing and 16S rRNA gene sequencing to uncover changes in the intestinal transcriptome and microbiome of zebrafish subjected to long-term starvation and refeeding compared to continuously fed controls.
Starvation over 21 days led to increased diversity and altered composition in the intestinal microbiome compared to fed controls, including relative increases in Vibrio and reductions in Plesiomonas bacteria. Starvation also led to significant alterations in host gene expression in the intestine, with distinct pathways affected at early and late stages of starvation. This included increases in the expression of ribosome biogenesis genes early in starvation, followed by decreased expression of genes involved in antiviral immunity and lipid transport at later stages. These effects of starvation on the host transcriptome and microbiome were almost completely restored within 3 days after refeeding. Comparison with published datasets identified host genes responsive to starvation as well as high-fat feeding or microbiome colonization, and predicted host transcription factors that may be involved in starvation response.
Long-term starvation induces progressive changes in microbiome composition and host gene expression in the zebrafish intestine, and these changes are rapidly reversed after refeeding. Our identification of bacterial taxa, host genes and host pathways involved in this response provides a framework for future investigation of the physiological and ecological mechanisms underlying intestinal adaptations to food restriction.
There is increasing evidence that early life microbial exposure aids in immune system maturation, more recently known as the “old friends” hypothesis. To test this hypothesis, 4-week-old mice were ...exposed to soils of increasing microbial diversity for four weeks followed by an intranasal challenge with either live or heat inactivated influenza A virus and monitored for 7 additional days. Perturbations of the gut and lung microbiomes were explored through 16S rRNA amplicon sequencing. RNA-sequencing was used to examine the host response in the lung tissue through differential gene expression. We determined that compared to the gut microbiome, the lung microbiome is more susceptible to changes in beta diversity following soil exposure with Lachnospiraceae ASVs accounting for most of the differences between groups. While several immune system genes were found to be significantly differentially expressed in lung tissue due to soil exposures, there were no differences in viral load or weight loss. This study shows that exposure to diverse microbial communities through soil exposure alters the gut and lung microbiomes resulting in differential expression of specific immune system related genes within the lung following an influenza challenge.
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•Soil exposure affected gut and lung microbiome composition and changes were driven by the family Lachnospiraceae•Cytokine and chemokine genes were generally upregulated in the soil exposed mice•The lung shapes microbiome diversity; soil exposure alters lung gene expression with no effect on viral load or weight loss.
Abstract
Background
Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not ...well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity.
Methods
We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms.
Results
Nasopharyngeal microbiome composition varied with age (PERMANOVA, P < .001; R2 = 0.06) and between SARS-CoV-2–infected individuals with and without respiratory symptoms (PERMANOVA, P = .002; R2 = 0.009). SARS-CoV-2–infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (OR: .38; 95% CI: .18–.81). Using generalized joint attributed modeling, we identified 9 bacterial taxa associated with SARS-CoV-2 infection and 6 taxa differentially abundant among SARS-CoV-2–infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age.
Conclusions
We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.
We demonstrate that the nasopharyngeal microbiome undergoes marked shifts in composition with age during childhood and adolescence, and age-associated changes in nasopharyngeal microbiome composition are associated with SARS-CoV-2 infection and SARS-CoV-2–associated respiratory symptoms among children, adolescents, and young adults.
Previous studies of the lung microbiome have focused on characterizing the community and attempts to understand the role of community membership concerning disease or exposures such as cigarette ...smoke. However, we still lack an understanding of two critical aspects of the lung microbiome: the origin of the community members and their fate. As we continue to better understand how the lung microbiome influences human health, it is essential to determine how the environment shapes the lung microbiome membership. Using a pig model, we explored the relationship that the surrounding environment has on the resident lung bacteria by collecting environmental samples (soil, air, water, feed) to compare with lung samples (swab, lavage, and tissue). Results suggest that airborne bacteria make up the highest portion of the lung microbiome. Furthermore, bacteria from samples taken from the bronchioles can be correctly identified by which farm they originated, whereas those from alveolar samples are indistinguishable. The findings suggest that while the environment may shape the microbiome of the bronchioles, a distinct community exists within the alveoli. Our findings expand upon the current understanding of the lung microbiome and provide a model of how microbial communities within the lung relate to their surrounding environment.
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•Most bacteria found in the bronchioles can be sourced from local ambient air.•There are differences between lung alveolar and bronchiolar microbiomes.•The environment influences bacteria found at the bronchiolar level but not alveolar.
Extracellular vesicles (EVs) are nano-sized, biocolloidal proteoliposomes that have been shown to be produced by all cell types studied to date and are ubiquitous in the environment. Extensive ...literature on colloidal particles has demonstrated the implications of surface chemistry on transport behavior. Hence, one may anticipate that physicochemical properties of EVs, particularly surface charge-associated properties, may influence EV transport and specificity of interactions with surfaces. Here we compare the surface chemistry of EVs as expressed by zeta potential (calculated from electrophoretic mobility measurements). The zeta potentials of EVs produced by Pseudomonas fluorescens, Staphylococcus aureus, and Saccharomyces cerevisiae were largely unaffected by changes in ionic strength and electrolyte type, but were affected by changes in pH. The addition of humic acid altered the calculated zeta potential of the EVs, especially for those from S. cerevisiae. Differences in zeta potential were compared between EVs and their respective parent cell with no consistent trend emerging; however, significant differences were discovered between the different cell types and their EVs. These findings imply that, while EV surface charge (as estimated from zeta potential) is relatively insensitive to the evaluated environmental conditions, EVs from different organisms can differ regarding which conditions will cause colloidal instability.
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•EVs produced by Pseudomonas fluorescens, Staphylococcus aureus, and Saccharomyces cerevisiae.•EV zeta potential largely unaffected by changes in ionic strength/electrolyte type.•EV zeta potential affected by changes in pH.•S. cerevisiae EVs affected by presence of humic acid.•No consistent trend for relationship between EV and corresponding parent cell.
To improve women’s access to pre-exposure prophylaxis (PrEP) in family planning (FP) clinics, we examined readiness to provide PrEP, and barriers and facilitators at the clinic level to integrate ...PrEP services into Title X-funded FP clinics across the Southern US. Title X-funded FP clinics across DHHS regions III (Mid-Atlantic), IV (Southeast), and VI (Southwest), comprising the Southern US. From February to June, 2018, we conducted a web-based, geographically targeted survey of medical staff, providers and administrators of Title X-funded FP clinics in DHHS regions III (Mid-Atlantic), IV (Southeast), and VI (Southwest). Survey items were developed using the Consolidated Framework for Implementation Research to assess constructs relevant to PrEP implementation. One-fifth of 283 unique Title X clinics across the South provided PrEP. Readiness for PrEP implementation was positively associated with a climate supportive of HIV prevention, leadership engagement, and availability of resources, and negatively associated with providers holding negative attitudes about PrEP’s suitability for FP. The Title X FP network is a vital source of sexual health care for millions of individuals across the US. Clinic-level barriers to providing PrEP must be addressed to expand onsite PrEP delivery in Title X FP clinics in the Southern US.
The pollex (i.e., thumb) is critical to hand function. Abduction, generated by the abductor pollicis longus (APL) and brevis (APB) muscles, and extension, primarily generated by the extensor pollicis ...longus (EPL) and brevis (EPB), are two major pollex movements. Uncharacteristic cleavage of APB during development can form an accessory APB (a-APB). In addition, APL, EPB, and EPL can develop accessory tendons (a-tendons) to the pollex. However, reports of these anomalies occurring simultaneously and interconnected are scarce. The objective of this study is to analyze a unique case of bilateral APL a-tendons which distally form the origins of a-APB muscles and discuss its clinical implications.
Left and right forearms and hands of one human cadaver with bilateral APL a-tendons forming the origins of a-APB muscles were dissected, and the attachment sites of the anomalies were noted. The left side anomalies were photographed in situ since they exhibited a cleaner dissection field. The left side interconnected APL, a-APB, and APB were collectively detached from the cadaver, splayed, and photographed. The tissues were returned to their in-situ positions, cross-sectioned with EPB in the first extensor compartment, and photographed. Fascicle bundle length, pennation angle, and mass were measured for each left and right APL, a-APB, and APB muscle belly to calculate the physiological cross-sectional area and maximal isometric force (Fmax) generating capacity of each muscle. Averages of left and right data were used to discuss the functional impacts of the non-typical morphologies and their respective clinical implications.
The typical APL tendon displayed normal distal attachment to the base of the first metacarpal. The APL a-tendon originated from the deep surface of the APL muscle belly and exhibited two distal attachments: its main portion (137.48 mm long, 2.44 mm wide) to the origin of a-APB and a short, distal bifurcation to the trapezium. The APL tendon had three distinct slips, and stenosis of the APL a-tendon in the first extensor compartment was visible. Mean Fmax for APL, a-APB, and APB were 63.24 N, 8.31 N, and 12.05 N, respectively.
This study presents a rare case of interconnected APL and a-APB via APL a-tendon with bifurcation to trapezium. The cumulative Fmax of APL and a-APB may be limited by the short a-tendon attachment angle to trapezium, and forceful pull on the trapezium with concurrent pressure from the APL a-tendon's distal attachment may lead to subluxation and/or osteoarthritis of the thumb's carpometacarpal joint. As suggested by visible stenosis of the APL a-tendon, its presence in the first extensor compartment would likely crowd APL and EPB and cause de Quervain's tenosynovitis. Furthermore, the long, robust APL a-tendon may instigate intersection syndrome from wrapping over the extensor carpi radialis longus tendon, but the APL a-tendon may at least serve as a sufficient candidate for tendon transfer or graft surgeries. In these regards, this report may serve as a valuable resource for orthopedic surgeons, occupational and physical therapy providers, and medical educators when presented with a similar clinical or educational case.
•Gross presentation of interconnected APL and APB muscles.•Clinical implications of APL accessory tendons.•Force generating capacities of non-typical forearm musculature.
The literature regarding the route of the dorsal nerve of the clitoris is sparse and lacks surgical focus. With an increasing number of procedures being performed on the labia, it is important to ...elucidate the route and note any variation from normal of the nerve.
Fifty-one cadavers were dissected to yield 97 dorsal nerve of the clitoris samples. Measurements were taken from (1) the dorsal nerve of the clitoris penetration point of the perineal membrane to the urethra, (2) the nerve's penetration point of the perineal membrane to the pubic bone, (3) the angle of the clitoris to the branch point of the dorsal nerve of the clitoris, and (4) the branch point of the nerve to the distalmost point of the glans clitoris. Any anomalous branching patterns of the dorsal nerve of the clitoris were recorded and classified.
The means and standard deviations of each measurement were used to create a surgical danger zone. The mean of each measurement was (1) 34.63 mm, (2) 5.74 mm, (3) -3.07 mm, and (4) 30.40 mm, respectively. In addition, six distinct branching patterns were observed, organized, and classified based on the location and number of branches observed.
The dorsal nerve of the clitoris has multiple branching patterns and typically travels along the same course in most women. Further investigation of the course and three-dimensional position of the dorsal nerve of the clitoris is warranted to preserve sexual sensation as the frequency of procedures involving the female pudendum increases.
Independent movement of the pollex (thumb) and index finger is critical for proper hand function. Accordingly, extension of the pollex and index finger is predominantly performed by the separate ...extensor pollicis longus (EPL) and extensor indicis proprius (EIP) muscles, respectfully. Non-typical muscles such as the extensor pollicis et indicis accessorius (EPIA) can inhibit pollex and index finger independence by connecting the otherwise autonomous digits. The objective of this study was to present a case of bilateral EPIA muscles with gross imaging, MRI, histological inspection, biomechanical analysis, and clinical implications.
Left and right EPIA muscles and tendons were discovered during routine cadaver dissection. Three-tesla (3T) T1-weighted magnetic resonance imaging (MRI) visualized the left EPIA in relation to contiguous anatomy. The dissection field of the left EPIA was cleaned and photographed, and the innervation and sites of proximal and distal attachment for EIP, EPIA, and EPL muscles were noted bilaterally. The bilateral EIP, EPIA, and EPL were detached, splayed, photographed, and weighed. Pennation angle, muscle length, and fascicle length for each muscle were measured, and left and right fascicle lengths were normalized via histological inspection of EPIA mean sarcomere lengths. Physiological cross-sectional area (PCSA), maximum isometric force (Fmax), and difference index (δ) were calculated to compare EIP, EPIA, and EPL biomechanics and structural similarity. Mean results of left and right structures were discussed when no significant difference existed between sides.
Gross analysis and MRI showed an independent muscle belly of EPIA originating on the distal third of the ulna and interosseus membrane (posterior aspects), positioned between EIP and EPL. Its common tendon coursed through the fourth extensor compartment of the wrist, bifurcated over the trapezoid, and inserted on the first distal phalanx (via EPL and extensor expansion of the index finger. The posterior interosseous nerve (PIN) coursed through the EPIA to innervate EIP. Mean sarcomere lengths of left and right EPIA muscles were 2.38 ± 0.12 μm and 2.92 ± 0.07 μm, respectively. The PCSA of the EIP, EPIA, and EPL was 0.68 cm2, 0.41 cm2, and 0.76 cm2 and constituted a Fmax of 15.22 N, 9.19 N, and 17.00 N, respectively. Left and right EPIA muscles were structurally similar (δ < 0.30), and EPIA was structurally similar to EIP bilaterally.
While EPIA generates synergistic movement of the pollex and index finger during simultaneous extension, it may limit extension and/or flexion during complex, antagonistic movements of the pollex and index finger. According to the present study, EPIA may increase the force of extension from EIP or EPL by 60.38% or 54.06% respectively, or 30.19% and 27.03% if distributed equally. EPIA may entrap PIN and the resulting compression could cause potential paralysis of EIP, exacerbating clinical implications and complicating diagnosis and symptom treatment. The gross analysis, MRI, histological inspection, biomechanical analysis, and clinical implications in this report may serve as valuable resources for orthopedic surgeons, occupational and physical therapy providers, and medical educators when presented with a similar clinical or educational case.
•Gross dissection and presentation of non-typical forearm musculature.•Magnetic resonance imaging (MRI) of the extensor pollicis et indicis accessorius.•Histological inspection of skeletal muscle fascicles and sarcomere states.•Analysis of extensor pollicis et indicis force generating capacities.
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