Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted ...by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H(2) receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Probiotics-host communication Thomas, Carissa M.; Versalovic, James
Gut microbes,
05/2010, Letnik:
1, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The intestinal microbiota includes a diverse group of functional microorganisms, including candidate probiotics or viable microorganisms that benefit the host. Beneficial effects of probiotics ...include enhancing intestinal epithelial cell function, protecting against physiologic stress, modulating cytokine secretion profiles, influencing T lymphocyte populations, and enhancing antibody secretion. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects remain to be fully elucidated. Accumulating evidence demonstrates that probiotics communicate with the host by modulating key signaling pathways, such as NF-κB and MAPK, to either enhance or suppress activation and influence downstream pathways. Beneficial microbes can profoundly alter the physiology of the gastrointestinal tract, and understanding these mechanisms may result in new diagnostic and therapeutic strategies.
Objective
To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages ...of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications.
Methods
Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined.
Results
Seventy‐three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001).
Conclusions
Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre‐operatively in this patient population with consideration for regional flaps in the appropriate patient.
Level of Evidence
3 Laryngoscope, 134:688–694, 2024
Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is relatively low, however, many OPSCC patients receive bilateral neck treatment. This study evaluates the ...oncological outcomes with management of the contralateral cN0 neck based on lymphatic mapping with single photon emission computed tomography (SPECT-CT).
Retrospective evaluation of patients with lateralized cT1-2 and contralateral cN0 OPSCC treated with primary surgery between December 2017 and October 2019. All patients underwent pre-operative lymphatic mapping using SPECT-CT. Clinical parameters including demographics, tumor characteristics and oncological outcomes were recorded.
Thirteen patients underwent primary site resection with transoral robotic surgery (TORS) and ipsilateral neck dissection with or without adjuvant therapy. Twelve patients (92.3%) had ipsilateral drainage on SPECT-CT, whereas 1 (7.7%) patient had bilateral neck lymphatic drainage. Four patients (30.8%) underwent post-operative radiation therapy (PORT). Three patients with unilateral drainage on SPECT-CT underwent PORT with unilateral neck irradiation, and 1 patient with bilateral drainage underwent PORT with bilateral neck irradiation. Seven (53.8%) patients were staged as pT1, 6 (46.2%) patients as pT2, 6 (46.2%) patients were pN0, 3 (23.1%) patients were pN1, 1 (7.7%) patient was pN2a for and 3 (23.1%) patients were N2b. The median distance of the tumor from midline was 1.05 cm (0.0-1.58). Primary sites included tonsil (n = 10, 76.9%) and tongue base (n = 3, 23.1%). The median follow-up time was 15.4 months. All patients were disease free at the latest follow-up with no contralateral neck failures.
Pre-operative mapping of lymphatic drainage in early stage OPSCC with SPECT-CT is a promising tool which can reduce treatment to the contralateral neck potentially without compromising oncological outcomes.
Proteorhodopsins (PRs) are retinal-binding photoproteins that mediate light-driven proton translocation across prokaryotic cell membranes. Despite their abundance, wide distribution and contribution ...to the bioenergy budget of the marine photic zone, an understanding of PR function and physiological significance in situ has been hampered as the vast majority of PRs studied to date are from unculturable bacteria or culturable species that lack the tools for genetic manipulation. In this study, we describe the presence and function of a horizontally acquired PR and retinal biosynthesis gene cluster in the culturable and genetically tractable bioluminescent marine bacterium Vibrio campbellii. Pigmentation analysis, absorption spectroscopy and photoinduction assays using a heterologous over-expression system established the V. campbellii PR as a functional green light absorbing proton pump. In situ analyses comparing PR expression and function in wild type (WT) V. campbellii with an isogenic ΔpR deletion mutant revealed a marked absence of PR membrane localization, pigmentation and light-induced proton pumping in the ΔpR mutant. Comparative photoinduction assays demonstrated the distinct upregulation of pR expression in the presence of light and PR-mediated photophosphorylation in WT cells that resulted in the enhancement of cellular survival during respiratory stress. In addition, we demonstrate that the master regulator of adaptive stress response and stationary phase, RpoS1, positively regulates pR expression and PR holoprotein pigmentation. Taken together, the results demonstrate facultative phototrophy in a classical marine organoheterotrophic Vibrio species and provide a salient example of how this organism has exploited lateral gene transfer to further its adaptation to the photic zone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and ...outcomes.
Methods
Multi‐institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260).
Results
Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30‐day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04).
Conclusion
Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.
Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can ...be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor‐targeted fluorescence‐guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence‐guided surgical resection of a T2N0M0 transglottic tumor using panitumumab‐IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near‐infrared (NIR) dye. Laryngoscope, 134:1837–1841, 2024
We present a novel use of fluorescence‐guided surgery to improve intraoperative tumor geography evaluation in a patient undergoing TLM ablation of a T2 recurrent glottic carcinoma. We observed a decrease in fluorescent uptake, both qualitatively and quantitatively, in areas of clinically apparent tumor compared to the pre‐ablation state.
Objectives/Hypothesis
The objectives of this study were to summarize externship experiences among recent graduates and current residents in otolaryngology residency programs and determine whether ...externships affect the match process.
Study Design
Cross‐sectional survey.
Methods
A survey was distributed to otolaryngology residents in allopathic US residency programs and otolaryngology graduates from the past 5 years (2011–2015). There were 2,141 surveys distributed.
Results
There were 654 subjects who responded, for a 30.5% response rate. Most respondents were residents (n = 438, 67%). Of the residents, 85.6% had completed at least one externship compared to 75.9% of graduates (P = .002). The most common reasons for selecting a particular externship were geographic location (74.2%) and program reputation (71.1%), whereas the most common reason for not completing an externship was being advised not to (59.1%). Furthermore, 82.6% of respondents received at least one interview from their externships, 90% went to those interviews, and 89.1% reported that externship experiences affected their rank list. Respondents had a 32.7% match rate to the externship residency program if it was ranked versus a 48.8% match rate if the program was ranked first. Respondents who matched at the externship residency program matched higher on their rank list (P < .001). Of the respondents, 90.7% found externships to be valuable, and 74.5% recommended completing one.
Conclusions
Externships are beneficial because they influence the rank list of applicants and are viewed as valuable experiences. Completing an externship is advisable for the experience, but applicants should weigh the benefits versus the possible risk of being judged more harshly during a month‐long rotation.
Level of Evidence
NA Laryngoscope, 127:2242–2246, 2017
The nine-banded armadillo (Dasypus novemcinctus) is currently considered an invasive species in parts of its range in the US, and this range continues to expand to the north and east. Nine-banded ...armadillos are one of a handful of mammals known to contract leprosy (also known as Hansen's disease); range expansion thus leads to public health concerns about whether this might increase human exposure to infected animals. We collected blood samples from 61 road-killed armadillos over two summers (2021 and 2022) in Tennessee, a US state near the northern extreme of the species' current range, and screened them for exposure to Mycobacterium leprae, the causative agent of leprosy. All animals were seronegative, providing no evidence that range expansion is increasing the distribution of leprosy in the US.
•Infectious complications following oral cancer surgery affect up to 60 % of patients.•Modification of known risk factors has had minimal impact on rates of infection.•The contribution of the oral ...microbiome in this area remains under-explored.
Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant—the oral microbiome—is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.
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