IL-17 receptor A functions to help maintain barrier integrity and limit activation of immunopathogenic response to H. pylori infection.

Activation of Th17 cell responses, including the production of IL-17A and IL-21, contributes to host defense and inflammatory responses by coordinating adaptive and innate immune responses. IL-17A and IL-17F signal through a multimeric receptor, which includes the IL-17 receptor A (IL-17RA) subunit and the IL-17RC subunit. IL-17RA is expressed by many cell types, and data from previous studies suggest that loss of IL-17 receptor is required to limit immunopathology in the Helicobacter pylori model of infection. Here, an Il17ra-/- mouse was generated on the FVB/n background, and the role of IL-17 signaling in the maintenance of barrier responses to H. pylori was investigated. Generating the Il17ra-/- on the FVB/n background allowed for the examination of responses in the paragastric lymph node and will allow for future investigation into carcinogenesis. While uninfected Il17ra-/- mice do not develop spontaneous gastritis following H. pylori infection, Il17ra-/- mice develop severe gastric inflammation accompanied by lymphoid follicle production and exacerbated production of Th17 cytokines. Increased inflammation in the tissue, increased IgA levels in the lumen, and reduced production of Muc5ac in the corpus correlate with increased H. pylori-induced paragastric lymph node activation. These data suggest that the cross talk between immune cells and epithelial cells regulates mucin production, IgA production, and translocation, impacting the integrity of the gastric mucosa and therefore activating of the adaptive immune response.

Cancer Demographics and Time-to-Care in Belize.

BACKGROUND: Belize is a middle-income Caribbean country with poorly described cancer epidemiology and no comprehensive cancer care capacity. In 2018, GO, Inc., a US-based NGO, partnered with the Ministry of Health and the national hospital in Belize City to create the first public oncology clinic in the country. Here, we report demographics from the clinic and describe time intervals to care milestones to allow for public health targeting of gaps. PATIENTS AND METHODS: Using paper charts and a mobile health platform, we performed a retrospective chart review at the Karl Heusner Memorial Hospital (KHMH) clinic from 2018 to 2022. RESULTS: During this time period, 465 patients with cancer presented to the clinic. Breast cancer (28%) and cervical cancer (12%) were most common. Most patients (68%) presented with stage 3 or 4 disease and were uninsured (78%) and unemployed (79%). Only 21% of patients ever started curative intent treatment. Median time from patient-reported symptoms to a biopsy or treatment was 130 and 189 days. For the most common cancer, breast, similar times were seen at 140 and 178 days. Time intervals at the clinic: <30 days from initial visit to biopsy (if not previously performed) and <30 days to starting chemotherapy. CONCLUSION: This study reports the first clinic-based cancer statistics for Belize. Many patients have months between symptom onset and treatment. In this setting, the clinic has built infrastructure allowing for minimal delays in care despite an underserved population. This further affirms the need for infrastructure investment and early detection programs to improve outcomes in Belize.

Introduction of surgical site surveillance post transrectal ultrasound (TRUS) guided prostate biopsy and the impact on infection rates.

Background: Transrectal ultrasound (TRUS)-guided prostate biopsy is associated with infection rates between 0.3 % and 3.2%. Infectious complications include urinary tract infection, prostatitis, bacteraemia and sepsis. Surgical site surveillance in this patient cohort is becoming increasingly important given global increases in antimicrobial resistance. Methods: Surgical site surveillance for patients undergoing TRUS biopsies was introduced in our hospital in 2017. All patients had a risk assessment form completed to assess for carriage or risk of carriage of multi-drug resistant organisms. An intense analysis was completed on any patient who developed an infection post-TRUS biopsy. Data was fed back on a quarterly basis to a multi-disciplinary working group. Members of this group include a Consultant Microbiologist, Infection Prevention and Control Nurse, Consultant Urologist, Antimicrobial Pharmacists and Clinical Nurse Ward Managers. Results: 784 TRUS-guided biopsy of the prostate procedures were performed between January 1 st 2017 and the end of the third quarter, 2021. The rate of infection post-TRUS was 2.7% in 2017, 3.4% in 2018 and 3.2% in 2019. This improved to 0% in 2020 and 0.8% in the first three quarters of 2021. Conclusions: Several interventions were introduced resulting in a sustained reduction in infection rates in this cohort. These include changing the choice of surgical antibiotic prophylaxis, improvement in the timing of antibiotic prophylaxis and scheduling of other urology procedures. The introduction of surgical site surveillance and multi-disciplinary input has demonstrated a reduction in infection rates post TRUS biopsy.

Efficacy of observational hand hygiene audit with targeted feedback on doctors' hand hygiene compliance: A retrospective time series analysis.

BACKGROUND: Healthcare-associated infection compromises patient safety. Compliance with hand hygiene (HH) guidelines has been shown to be an effective method of reducing infection; however, it remains suboptimal and poorer among doctors compared to other healthcare workers. The aim of this study is to determine the relationship between an individualised observational hand hygiene audit (OHHA) and feedback intervention with observed HH compliance. METHODS: We used a retrospective interrupted time series design using OHHA data from a five-year period, 2011-2015. OHHA indicated poorer HH compliance among doctors than other healthcare workers in a 345-bed acute private hospital. An increase in orthopaedic surgical site infection prompted additional auditing of the orthopaedic unit further identifying substandard HH compliance among orthopaedic surgeons. In addition to ongoing HH interventions, an individualised hand hygiene audit and feedback intervention focusing on consultant orthopaedic surgeons was implemented. Observed HH compliance improved. The intervention was then extended to include all consultant doctors at the study site. Audit was implemented by trained clinical nurse managers during clinical rounds. Written audit feedback was provided by the infection prevention and control team. RESULTS: HH compliance increased significantly among both orthopaedic surgeons and other consultant doctors, P < 0.05. CONCLUSION: An individualised audit and feedback intervention was effective in improving compliance. Incorporation of OHHA with individualised feedback into routine daily practice needs to be considered as a quality improvement opportunity. This study has the potential to inform other audit and feedback interventions to maximise effectiveness and ensure implementation.

Host-delivered RNAi: an effective strategy to silence genes in plant parasitic nematodes.

Root-knot nematodes (Meloidogyne spp.) are obligate, sedentary endoparasites that infect many plant species causing large economic losses worldwide. Available nematicides are being banned due to their toxicity or ozone-depleting properties and alternative control strategies are urgently required. We have produced transgenic tobacco (Nicotiana tabacum) plants expressing different dsRNA hairpin structures targeting a root-knot nematode (Meloidogyne javanica) putative transcription factor, MjTis11. We provide evidence that MjTis11 was consistently silenced in nematodes feeding on the roots of transgenic plants. The observed silencing was specific for MjTis11, with other sequence-unrelated genes being unaffected in the nematodes. Those transgenic plants able to induce silencing of MjTis11, also showed the presence of small interfering RNAs. Even though down-regulation of MjTis11 did not result in a lethal phenotype, this study demonstrates the feasibility of silencing root-knot nematode genes by expressing dsRNA in the host plant. Host-delivered RNA interference-triggered (HD-RNAi) silencing of parasite genes provides a novel disease resistance strategy with wide biotechnological applications. The potential of HD-RNAi is not restricted to parasitic nematodes but could be adapted to control other plant-feeding pests.