Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host

Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species

Uncovering the spatially distant feedback loops of global trade: A network and input-output approach

Land-use change is increasingly driven by global trade. The term “telecoupling” has been gaining ground as a means to describe how human actions in one part of the world can have spatially distant impacts on land and land-use in another. These interactions can, over time, create both direct and spatially distant feedback loops, in which human activity and land use mutually impact one another over great expanses. In this paper, we develop an analytical framework to clarify spatially distant feedbacks in the case of land use and global trade. We use an innovative mix of multi-regional input-output (MRIO) analysis and stochastic actor-oriented models (SAOMs) for analyzing the co-evolution of changes in trade network patterns with those of land use, as embodied in trade. Our results indicate that the formation of trade ties and changes in embodied land use mutually impact one another, and further, that these changes are linked to disparities in countries' wealth. Through identifying this feedback loop, our results support ongoing discussions about the unequal trade patterns between rich and poor countries that result in uneven distributions of negative environmental impacts. Finally, evidence for this feedback loop is present even when controlling for a number of underlying mechanisms, such as countries' land endowments, their geographical distance from one another, and a number of endogenous network tendencies

Challenges in pancreatic adenocarcinoma surgery - National survey and current practice guidelines.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers in Europe and the USA. There is consensus that radical tumor surgery is the only viable option for any long-term survival in patients with PDAC. So far, limited data are available regarding the routine surgical management of patients with advanced PDAC in the light of surgical guidelines. METHODS:A national survey on perioperative management of patients with PDAC and currently applied criteria on their tumor resectability in German university and community hospitals was carried out. RESULTS:With a response rate of 81.6% (231/283) a total of 95 (41.1%) participating departments practicing pancreatic surgery in Germany are certified as competence and reference centers for surgical diseases of the pancreas in 2016. More than 95% of them indicate to carry out structured and interdisciplinary therapies along with an interdisciplinary pre- and postoperative tumor board. The majority of survey respondents prefer the pylorus-preserving partial pancreatoduodenectomy (93.1%) with standard lymphadenectomy for cancer of the pancreatic head. Intraoperative histological evaluation of the resection margins is used regularly by 99% of the survey respondents. 98.7% of survey respondents carry out partial or complete vein resection, 126 respondents (54.5%) would resect tumor adjacent arteries, and 102 respondents (44.2%) would perform metastasectomy if complete PDAC resection (R0) is possible. CONCLUSION:Evidence-based and standardized pancreatic surgery is practiced by a large number of hospitals in Germany. However, a significant number of survey respondents support an extended radical tumor resection in patients with advanced PDAC even when not indicated by current clinical guidelines

Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery

Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT

Suppurative thyroiditis caused by ingested fish bone in the thyroid gland: a case report on its diagnostics and surgical therapy

Background Accidental ingestion of fish bone is a common cause of otolaryngological emergency. Migration of the ingested bone into the thyroid gland, however, occurs very rarely. The associated clinical presentation, symptoms and duration of discomfort are also highly variable between patients and can be diagnostically challenging. Case presentation Here, we report the case of a 71-year-old female patient presenting with an ingested fish bone that migrated into the right thyroid lobe as a rare cause of suppurative thyroiditis with the clinical features of sepsis. We outline the diagnostic approach, peri- and intraoperative management as well as complications. It is proposed that besides endoscopy, imaging methods such as ultrasound or computed tomography may be necessary to verify the diagnosis and location of an ingested fish bone. Prompt surgical removal of the foreign body and resection of the infectious focus is recommended to minimize the risk of local inflammation, recurrent nerve lesions and septic complications arising from the spread of infection. Conclusion Fish bone migration into the thyroid gland is an extremely rare event, the successful detection and surgical management of which can be achieved through a careful interdisciplinary approach

The impact of ISGylation during Mycobacterium tuberculosis infection in mice

Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell. Recent studies indicated that ISG15 can function via conjugation-independent mechanisms to suppress the type I IFN response. These data raised the question of whether ISG15 may have diverse and sometimes opposing functions during M. tuberculosis infection. To address this, we analyzed ISGylation during M. tuberculosis infection and show that ISGylated proteins accumulate following infection in an IFNAR-dependent manner. Type I IFN and ISG15 both play transient roles in promoting bacterial replication. However, as the disease progresses, ISGylation deviates from the overall effect of type I IFN and, ultimately, mice deficient in ISGylation are significantly more susceptible than IFNAR mice. Our data demonstrate that ISGs can both protect against and promote disease and are the first to report a role for ISGylation during M. tuberculosis infection

Challenges in pancreatic adenocarcinoma surgery - National survey and current practice guidelines

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers in Europe and the USA. There is consensus that radical tumor surgery is the only viable option for any long-term survival in patients with PDAC. So far, limited data are available regarding the routine surgical management of patients with advanced PDAC in the light of surgical guidelines.METHODS: A national survey on perioperative management of patients with PDAC and currently applied criteria on their tumor resectability in German university and community hospitals was carried out.RESULTS: With a response rate of 81.6% (231/283) a total of 95 (41.1%) participating departments practicing pancreatic surgery in Germany are certified as competence and reference centers for surgical diseases of the pancreas in 2016. More than 95% of them indicate to carry out structured and interdisciplinary therapies along with an interdisciplinary pre- and postoperative tumor board. The majority of survey respondents prefer the pylorus-preserving partial pancreatoduodenectomy (93.1%) with standard lymphadenectomy for cancer of the pancreatic head. Intraoperative histological evaluation of the resection margins is used regularly by 99% of the survey respondents. 98.7% of survey respondents carry out partial or complete vein resection, 126 respondents (54.5%) would resect tumor adjacent arteries, and 102 respondents (44.2%) would perform metastasectomy if complete PDAC resection (R0) is possible. CONCLUSION: Evidence-based and standardized pancreatic surgery is practiced by a large number of hospitals in Germany. However, a significant number of survey respondents support an extended radical tumor resection in patients with advanced PDAC even when not indicated by current clinical guidelines.</p

Questionable value of [99m^{99m}Tc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound

Purpose A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [$^{99m}$Tc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. Methods A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. Results From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [$^{99m}$Tc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [$^{11}$C]-methionine or [$^{11}$C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56). Conclusion [$^{11}$C]-Methionine or [$^{11}$C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA

Criteria for tumor resectability.

<p>Intraoperative decision and percentages of surgical (non-) resectability in PDAC.</p

Questionnaire consisting of twelve question blocks with a total of 34 parameters.

<p>Questionnaire consisting of twelve question blocks with a total of 34 parameters.</p