The association of breast surgery ASPIRE: breast pain pathway rapid evaluation project - study protocol.

Background: Breast pain accounts for 20-40% of new referrals to breast units in the UK and these patients have a very low risk of breast cancer. Patients have previously been assessed in resource-intensive, cancer-exclusion, one stop clinics, which are now failing to meet government targets due to excessive demand. UK Breast units are increasingly piloting Breast Pain-only Pathways (BPP) to assess these patients, and there is no consensus for the optimal pathway. The aim of this prospective multicentre study is to assess the safety and patient satisfaction of different BPPs to inform future BPP design and implementation. Methods: All UK breast units will be invited to join the ASPIRE study between January 2023 and December 2023. Units with a BPP are invited to submit their pathway for evaluation; and those without a BPP who see patients with breast pain-only in a one stop clinics setting are also invited to join the study to evaluate the traditional pathway model concurrently. Patient satisfaction assessments will be collected after their initial consultation and patient outcomes, including subsequent cancer diagnosis, will be followed up at 12 months to determine if they have cancer diagnosis after discharge to assess pathway safety.

Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay.

Background: We used an ultrasensitive, quantitative single molecule array (Simoa) immunoassay to test whether concentrations of Clostridioides (formerly Clostridium) difficile toxins A and/or B in the stool of adult inpatients with C. difficile infection (CDI) were higher than in asymptomatic carriers of toxinogenic C. difficile. Methods: Patients enrolled as CDI-NAAT had clinically significant diarrhea and a positive nucleic acid amplification test (NAAT), per US guidelines, and received CDI treatment. Potential carriers had recently received antibiotics and did not have diarrhea; positive NAAT confirmed carriage. Baseline stool samples were tested by Simoa for toxin A and B. Results: Stool toxin concentrations in both CDI-NAAT (n = 122) and carrier-NAAT (n = 44) cohorts spanned 5 logs (0 pg/mL to >100000 pg/mL). Seventy-nine of 122 (65%) CDI-NAAT and 34 of 44 (77%) carrier-NAAT had toxin A + B concentration ≥20 pg/mL (clinical cutoff). Median toxin A, toxin B, toxin A + B, and NAAT cycle threshold (Ct) values in CDI-NAAT and carrier-NAAT cohorts were similar (toxin A, 50.6 vs 60.0 pg/mL, P = .958; toxin B, 89.5 vs 42.3 pg/mL, P = .788; toxin A + B, 197.2 vs 137.3 pg/mL, P = .766; Ct, 28.1 vs 28.6, P = .354). However, when CDI/carrier cohorts were limited to those with detectable toxin, respective medians were significantly different (A: 874.0 vs 129.7, P = .021; B: 1317.0 vs 81.7, P = .003, A + B, 4180.7 vs 349.6, P = .004; Ct, 25.8 vs 27.7, P = .015). Conclusions: Toxin concentration did not differentiate an individual with CDI from one with asymptomatic carriage. Median stool toxin concentrations in groups with CDI vs carriage differed, but only when groups were defined by detectable stool toxin (vs positive NAAT).

The neural response of female zebra finches (Taeniopygia guttata) to conspecific, heterospecific, and isolate song depends on early-life song exposure.

The auditory forebrain regions caudo-medial nidopallium (NCM) and caudo-medial mesopallium (CMM) of songbirds exhibit differential expression of the immediate-early gene ZENK in response to playback of different song stimuli, and dependent on early-life auditory experience. Similarly, song preferences depend both on auditory experience and unlearned biases for particular song features. We explored the contributions of early-life auditory experience and the type of song stimuli on the Zenk response in the auditory forebrain of female zebra finches. Females were raised in three different early tutoring conditions: conspecific tutors that sang isolate song, heterospecific tutors, or conspecific tutors that sang wild-type song. At maturity, these females were exposed to one of five different playback conditions: wild-type song, isolate song, tutor song, heterospecific song, or white noise. Subsequently, the number of cells immunoreactive for ZENK in CMM and NCM was measured. We predicted that birds exposed to conspecific song early in life, and during the song playback in adulthood, would have the highest neural response. Instead, we found that the Zenk response varied across playback conditions with the highest response to conspecific wild-type and conspecific isolate song. In addition, we found a main effect of tutoring, with the lowest overall Zenk response in females tutored by males singing isolate song. Most importantly, there was a significant interaction in that females tutored by wild-type conspecific or heterospecific songs showed a similar increased response to zebra finch songs (wild-type or isolate), but females tutored by isolate song showed no differential response to conspecific song and only showed elevated Zenk response to the particular songs they were tutored with. Combined, our results indicate that unlearned response biases to conspecific song elements depend on previous auditory experience. That is, early experience appears to modulate the expression of innate biases.