Epidemiology and reporting characteristics of preclinical systematic reviews

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common—along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE’s] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015–2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

A cross sectional study of a sample of recent preclinical systematic reviews reveals deficiencies in reporting and provides the justification and evidence to inform the development of specific guidelines for conducting and reporting preclinical systematic reviews.     

Comparison of Effects of Trichuris muris and Spontaneous Colitis on the Proximal Colon Microbiota in C3H/HeJ and C3Bir IL10–/– Mice

The nematode Trichuris muris has been shown to interact with specific enteric bacteria, but its effects on the composition of its host''s microbial community are not fully understood. We hypothesized that Trichuris muris-infected mice would have altered colon microbiota as compared with uninfected mice. Colon histopathology and microbial community structure and composition were examined in mouse models of colitis (C3BirTLR4^−/− IL10^−/− and C3H/HeJ TLR4^−/− IL10^+/+ mice) with and without T. muris infection, in uninfected C3BirIL10^−/− mice with and without spontaneous colitis, and in normal C3H/HeJ mice. T. muris-infected mice developed colon lesions that were more severe than those seen in IL10-deficient mice. Approximately 80% of infected IL10^−/− mice had colon neutrophilic exudates, and some had extraintestinal worms and bacteria. The composition and structure of proximal colon microbiota were assessed by using terminal restriction fragment length polymorphism analysis targeting the bacterial 16S rRNA gene. Colon microbiota in C3BirIL10^−/− and C3H/HeJ mice differed both qualitatively and quantitatively. Trichuris infection significantly altered the relative abundance of individual operational taxonomic units [OTU] but not the composition (presence or absence of OTU) of colon microbiota in the 2 mouse genotypes. When C3BirIL10^−/− and C3H/HeJ mouse OTU were considered separately, Trichuris was found to affect the microbiota of C3BirIL10^−/− mice but not of C3H/HeJ mice. Even though 34 of the 75 (45%) C3BirIL10^−/− mice had spontaneous colitis, neither qualitative nor quantitative differences were detected in microbiota between colitic or noncolitic C3BirIL10^−/− mice or noncolitic C3H/HeJ mice. Therefore, Trichuris-infected mice developed distinct microbial communities that were influenced by host background genes; these alterations cannot be attributed solely to colonic inflammation.roup method with arithmetic averaging; OTU, operational taxonomic unit; qPCR, quantitative real-time PCR; SIMPER, similarity percentage; T-RFLP, terminal restriction fragment length polymorphism

Trichuris spp. are gastrointestinal nematodes that dwell in close association with a complex bacterial community in the host''s colon. After ingestion, embryonated eggs hatch in the cecum or colon releasing first-stage larvae that penetrate the epithelium and undergo 4 molts before becoming sexually mature. Both larval and adult Trichuris form syncytial tunnels in the colonic epithelium^21,30 that anchor the organisms in the proximal colon, where females produce eggs that pass in feces and embryonate in the environment.T. suis excretory secretory products (ESP) condition the colonic environment for enhanced worm survival, including effects on intestinal bacteria. Previous work demonstrated that T. suis ESP had dose-dependent effects on the tight junctions of epithelial cells.¹ The ESP fraction below a molecular weight of 10,000 kDa was mainly composed of an antimicrobial moiety² with bactericidal activity against gram-negative (Campylobacter jejuni, C. coli, and Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria. In addition, due to several enzymatic activities, T. suis ESP have been demonstrated to aid the worms in burrowing into the host''s colonic epithelium and in feeding.^1,10,12 In addition to a 20-kDa diagnostic antigen,^10,11 higher molecular-weight fractions of ESP harbored a 42-kDa zinc metalloprotease that likely functions to provide nutrition for the worms through collagenase and elastase activities.¹⁰ Furthermore, a serine protease inhibitor (TsCEI) was purified from adult-stage T. suis by using acid precipitation, affinity chromatography, and reverse-phase HPLC.³³ This 6.43-kDa TsCEI inhibited chymotrypsin, pancreatic elastase, neutrophil elastase, and cathepsin G and was suggested to function as a parasite defense mechanism by modulating host immune responses. Indeed, exposure of cultured epithelial cells to T. suis ESP elicited IL6 and IL10 cytokine responses.³¹Trichuris has also been reported to interact with bacteria in vivo. Early studies demonstrated development of diarrhea in weaning age pigs concurrently harboring T. suis and various bacteria.³⁵ A mixed inoculum of T. suis and cecal scrapings containing Brachyspira, Campylobacter spp., or Salmonella spp. were implicated in this diarrhea by means of passive transfer to SPF pigs.³⁵ Interactions between this helminth and enteric bacteria were also explored by antibiotic treatment of T. suis-infected pigs.^20,27 Results of both passive transfer and antibiotic treatment experiments in pigs showed that Trichuris and various bacterial strains were necessary to produce the type of diarrhea and colonic lesions seen in weaning aged pigs in production, but did not implicate a single bacterial agent. In 2003, synergism between T. suis and C. jejuni was proven to cause mucohemorrhagic colitis in that germ-free piglets inoculated with both agents developed disease, whereas those infected with a single agent did not.²⁵ Recent studies in T. suis-infected pigs show changes in the microbial community of the colon with some accompanying metabolic changes.^22,45 Similar interactions have been found in extensive studies of captive rhesus monkeys with chronic enterocolitis. In these monkeys, severe disease was associated with presence of Trichuris trichiura and several enteric pathogens including C. coli, C. jejuni, Shigella flexneri, Yersinia enterocolitica, adenovirus, and Strongyloides fulleborni.³⁸ Therefore, Trichuris interacts with and may demonstrate synergy in disease production with the host''s colonic microflora.Interactions between Trichuris and bacteria have also been studied in mice.^9,20,36 One study found 100% morbidity in C57BL/6 IL10^−/− and congenic IL10^−/− IL4^−/− mice after challenge with T. muris.³⁶ The authors hypothesized that this high morbidity was due to an overgrowth of opportunistic invasive bacteria that use the mechanical damage caused by T. muris larvae to breach the intestinal tract. Adding the broad-spectrum antibiotic neomycin sulfate to the drinking water of IL10^−/− IL4^−/− mice and then infecting them with T. muris resulted in a statistically significant increase in the percentage of mice that survived infection.³⁶ The authors concluded that growth of opportunistic bacteria may have contributed to the previously observed morbidity and mortality. Most recently, another group⁹ found that increased levels of colonic microflora favor increased numbers of T. muris and chronic infections. The group also demonstrated that T. muris eggs hatched more efficiently in vitro when incubated with explants of mouse cecum containing 5 isolates of bacteria (E. coli, Staphylococcus aureus, Salmonella typhimurium, or Pseudomonas aeruginosa) and the yeast Saccharomyces cerevisiae, with the greatest effects seen at 37 °C. Similarly, work from our laboratory²⁰ demonstrated that treatment of T. muris-infected C57BL/6 IL10^−/− mice with metronidazole but not prednisolone increased survival.²⁰ Most recently, chronic infections with T. muris in C57BL/6 mice have been shown to decrease the diversity of intestinal microbiota,¹³ increase the abundance of Lactobacillus spp., and alter the metabolome.¹⁴Taken together, these data suggest an important microbial component to the pathogenesis of Trichuris infections in a variety of species. Given that Trichuris suis has been administered to patients with inflammatory bowel disease (IBD), and in some studies appeared to diminish IBD symptoms^42,43 we sought to understand the community-wide interactions of this worm with enteric bacteria in a mouse model of colitis. We hypothesized that the microbiota of the proximal colon would differ significantly in mice infected with T. muris as compared with uninfected mice. We theorized that these effects would occur due to the worm''s immunomodulatory properties in the host and may contribute to the successful outcomes of Trichuris treatment in patients with IBD.     

Wound botulism: a life-threatening complication of hand injuries

Botulism is usually associated with the ingestion of food contaminated with Clostridium botulinum, and these organisms occasionally contaminate traumatic injuries. It is unusual for them to result in clinical infection, but when this occurs, it is a catastrophe completely out of proportion to the degree of wound injury. A case is presented in which typical manifestations of descending cranial nerve and generalized motor paralysis were noted. Prolonged respiratory and general supportive assistance was required, as is usually the case. Although mortality rates in this disease are high, recovery is usually complete in survivors and was true in this instance.     

Fungal communities decline with urbanization—more in air than in soil

Increasing evidence suggests that degradation of biodiversity in human populated areas is a threat for the ecosystem processes that are relevant for human well-being. Fungi are a megadiverse kingdom that plays a key role in ecosystem processes and affects human well-being. How urbanization influences fungi has remained poorly understood, partially due to the methodological difficulties in comprehensively surveying fungi. Here we show that both aerial and soil fungal communities are greatly poorer in urban than in natural areas. Strikingly, a fivefold reduction in fungal DNA abundance took place in both air and soil samples already at 1 km scale when crossing the edge from natural to urban habitats. Furthermore, in the air, fungal diversity decreased with urbanization even more than in the soil. This result is counterintuitive as fungal spores are known to disperse over large distances. A large proportion of the fungi detectable in the air are specialized to natural habitats, whereas soil fungal communities comprise a large proportion of habitat generalists. The sensitivity of the aerial fungal community to anthropogenic disturbance makes this method a reliable and efficient bioindicator of ecosystem health in urban areas.Subject terms: Community ecology, Fungal ecology     

Prey location,biomechanical constraints,and motor program choice during prey capture in the tomato frog, <Emphasis Type="Italic">Dyscophus guineti</Emphasis>

This study investigated how visual information about prey location and biomechanical constraints of the feeding apparatus influence the feeding behavior of the tomato frog, Dyscophus guineti. When feeding on prey at small azimuths (less than ± 40°), frogs aimed their heads toward the prey but did not aim their tongues relative to their heads. Frogs projected their tongues rapidly by transferring momentum from the lower jaw to the tongue. Storage and recovery of elastic energy by the mouth opening muscles amplified the velocities of mouth opening and tongue projection. This behavior can only occur when the lower jaw and tongue are aligned (i.e., within the range of motion of the neck). When feeding on prey at large azimuths (greater than ± 40°), frogs aimed both the head and tongue toward the prey and used a muscular hydrostatic mechanism to project the tongue. Hydrostatic elongation allows for frogs to capture prey at greater azimuthal locations. Because the tongue moves independently of the lower jaw, frogs can no longer take advantage of momentum transfer to amplify the speed of tongue projection. To feed on prey at different azimuthal locations, tomato frogs switch between alternative strategies to circumvent these biomechanical constraints.     

Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women

ObjectiveTo investigate the pharmacokinetics of 17β-estradiol (E2) administered orally versus those of 17β-E2 administered sublingually in transgender women.MethodsSingle doses of 17β-E2 were administered orally (1 mg) to 10 transgender women and then sublingually (1 mg) after a 1-week washout period. Blood samples were collected at baseline (0 hour) and at 1, 2, 3, 4, 6, and 8 hours after dosing. The samples were frozen and analyzed using liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay.ResultsThe results demonstrated that sublingual E2 had a significantly higher peak serum E2 concentration of 144 pg/mL, measured using LC-MS/MS, compared with an oral E2 concentration of 35 pg/mL, measured using LC-MS/MS (P = .003). Sublingual E2 peaked at 1 hour and oral E2 peaked at 8 hours, as measured using LC-MS/MS. The area under the curve (AUC) (0-8 hours) for sublingual E2, measured using LC-MS/MS, was 1.8-fold higher than the AUC (0-8 hours) for oral E2, measured using LC-MS/MS. Additionally, sublingual E2 was found to have an increased E2-to-estrone ratio at all time points (1.1 ± 1.0 vs 0.7 ± 0.4, P ≤ .0001), the clinical significance of which is unclear.ConclusionOral E2 administered sublingually has a different pharmacokinetic profile, with higher serum E2 levels and AUC (0-8 hours) than traditionally administered oral E2. Multidaily dosing may be necessary to suppress testosterone levels with sublingual E2. The appropriate dosing, efficacy, and safety of sublingual E2, compared with those of other E2 preparations, are unknown.     

A checklist for choosing between R packages in ecology and evolution

1. The open source and free programming language R is a phenomenal mechanism to address a multiplicity of challenges in ecology and evolution. It is also a complex ecosystem because of the diversity of solutions available to the analyst.
2. Packages for R enhance and specialize the capacity to explore both niche data/experiments and more common needs. However, the paradox of choice or how we select between many seemingly similar options can be overwhelming and lead to different potential outcomes.
3. There is extensive choice in ecology and evolution between packages for both fundamental statistics and for more specialized domain‐level analyses.
4. Here, we provide a checklist to inform these decisions based on the principles of resilience, need, and integration with scientific workflows for evidence.
5. It is important to explore choices in any analytical coding environment—not just R—for solutions to challenges in ecology and evolution, and document this process because it advances reproducible science, promotes a deeper understand of the scientific evidence, and ensures that the outcomes are correct, representative, and robust.