Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes

A Comparison of Defense and Plaintiff Expert Witnesses in Orthopaedic Surgery Malpractice Litigation.

BackgroundAccording to the American Academy of Orthopaedic Surgeons (AAOS) Standards of Professionalism, the responsible testimony of expert witnesses in orthopaedic surgery malpractice lawsuits is important to the public interest. However, these expert witnesses are recruited and compensated without established standards, and their testimony can potentially sway court opinion, with substantial consequences. The objective of this study was to characterize defense and plaintiff expert orthopaedic surgeon witnesses in orthopaedic surgery malpractice litigation.MethodsUtilizing the WestlawNext legal database, defense and plaintiff expert witnesses involved in orthopaedic surgery malpractice lawsuits from 2013 to 2017 were identified. Each witness's subspecialty, mean years of experience, involvement in academic or private practice, fellowship training, and scholarly impact, as measured by the Hirsch index (h-index), were determined through a query of professional profiles, the Scopus database, and a PubMed search. Statistical comparisons were made for each parameter among defense and plaintiff expert witnesses.ResultsBetween 2013 and 2017, 306 expert medical witnesses for orthopaedic cases were identified; 174 (56.9%) testified on behalf of the plaintiff, and 132 (43.1%) testified on behalf of the defense. Orthopaedic surgeons who identified themselves as general orthopaedists comprised the largest share of expert witnesses on both the plaintiff (n = 61) and defense (n = 25) sides. The plaintiff witnesses averaged 36 years of experience versus 31 years for the defense witnesses (p < 0.001); 26% of the plaintiff witnesses held an academic position versus 43% of the defense witnesses (p = 0.013). Defense witnesses exhibited a higher proportion of fellowship training in comparison to plaintiff expert witnesses (80.5% versus 64.5%, respectively, p = 0.003). The h-index for the plaintiff group was 6.6 versus 9.1 for the defense group (p = 0.04). Two witnesses testified for both the plaintiff and defense sides.ConclusionsDefense expert witnesses held higher rates of academic appointments and exhibited greater scholarly impact than their plaintiff counterparts, with both sides averaging >30 years of experience. These data collectively show that there are differences in characteristics between plaintiff and defense witnesses. Additional study is needed to illuminate the etiology of these differences

Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome.

Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts

Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection.

BackgroundIntrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.PurposeThis study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.Study design/settingRandomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.MethodsUtilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.ResultsThe (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56).ConclusionsVancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate.Clinical significanceVancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma

Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection.

BackgroundIntrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce.PurposeThis study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment.Study design/settingRandomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation.MethodsUtilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups.ResultsThe (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56).ConclusionsVancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate.Clinical significanceVancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma

Tears, trauma and suicide: everyday violence among street youth in Puebla, Mexico

Despite considerable ethnographic research with young people in street situations and a growing interest in violence, little attention has been paid to suicide. The occurrence of suicide is a dramatic event that reveals weaknesses in support systems established by governments and civil society organisations, as well as perceived failings of friends. While an interest in suicide usually considers cause, in this paper we explore effect. How does the death of a member of a tightly knit group of street youth affect others and what does the suicide tell us about their identification with death more generally? Research for the paper was part of an in-depth study of identities among street youth in Mexico