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Purpose: Bowel complaints are very common among patients with colorectal cancer. However, the most used questionnaires for colorectal cancer survivors do not comprehensively comprise bowel symptoms. This study aimed to examine construct and criterion validity, as well as internal consistency, of the Chilean Version of the International Consultation on Incontinence Questionnaire Bowel Module (ICIQ-B) among people with colorectal cancer., Methods: Cross-sectional, validation study performed with 106 colorectal cancer patients from Hospital del Salvador, Chile. Bowel function was assessed with the ICIQ-B. Construct validity was assessed with confirmatory factor analysis and hypothesis testing. Specific items of a quality-of-life questionnaire (EORTC QLQ-CR29) were used to correlate with similar ICIQ-B items for criterion validity. For internal consistency, Cronbach's alpha was computed., Results: For construct validity, the confirmatory factor analysis showed that the three factors model did not fit our data. Meanwhile, hypothesis testing favored the construct validity of the instrument, considering that rectal cancer patients showed worse bowel pattern (p = 0.001), bowel control (p = 0.001) and quality of life (p < 0.001) scores compared to colon cancer patients. In addition, those patients assessed before surgery also presented worse scores bowel control (p = 0.023) and quality of life (p = 0.009) compared to post-surgical patients. Regarding criterion validity, the ICIQ-B items showed a significant correlation with similar QLQ-CR29 items. The internal reliability of the instrument was good (Cronbach's α = 0.909)., Conclusion: Considering that this questionnaire appraises bowel function in more depth, it is recommended for use in clinical practice and research with colorectal cancer patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A potent, noncytotoxic indazole sulfonamide was identified by high-throughput screening of >100,000 synthetic compounds for activity against Mycobacterium tuberculosis (Mtb). This noncytotoxic compound did not directly inhibit cell wall biogenesis but triggered a slow lysis of Mtb cells as measured by release of intracellular green fluorescent protein (GFP). Isolation of resistant mutants followed by whole-genome sequencing showed an unusual gene amplification of a 40 gene region spanning from Rv3371 to Rv3411c and in one case a potential promoter mutation upstream of guaB2 (Rv3411c) encoding inosine monophosphate dehydrogenase (IMPDH). Subsequent biochemical validation confirmed direct inhibition of IMPDH by an uncompetitive mode of inhibition, and growth inhibition could be rescued by supplementation with guanine, a bypass mechanism for the IMPDH pathway. Beads containing immobilized indazole sulfonamides specifically interacted with IMPDH in cell lysates. X-ray crystallography of the IMPDH-IMP-inhibitor complex revealed that the primary interactions of these compounds with IMPDH were direct pi-pi interactions with the IMP substrate. Advanced lead compounds in this series with acceptable pharmacokinetic properties failed to show efficacy in acute or chronic murine models of tuberculosis (TB). Time-kill experiments in vitro suggest that sustained exposure to drug concentrations above the minimum inhibitory concentration (MIC) for 24 h were required for a cidal effect, levels that have been difficult to achieve in vivo. Direct measurement of guanine levels in resected lung tissue from tuberculosis-infected animals and patients revealed 0.5-2 mM concentrations in caseum and normal lung tissue. The high lesional levels of guanine and the slow lytic, growth-rate-dependent effect of IMPDH inhibition pose challenges to developing drugs against this target for use in treating TB.

A study was undertaken to evaluate the effect of alternating bulls between a single and a multiple sire mating (MSM) program on the reproductive performance of suckled Zebu cows raised under range conditions in the humid tropics of Costa Rica. Multiparous Zebu cows (n=94) suckling calves were distributed between two experimental trials (A and B) consisting of 47 animals each. A single sire mating (SSM) system was alternated weekly with a MSM system with three bulls. This period lasted for 8 weeks. To facilitate estrous expression, four cows were strategically synchronized (estrus-stimulated) in alternate weeks. Courtship predominated over mounting under non-stimulated estrus, for each mounting performed an average of 6.0 and 6.3 courtship activities were recorded in the SSM and MSM, respectively. Under the influence of strategic synchronization corresponding values were 3.9 and 4.2 in the SSM and MSM, respectively (P>0.05). Blood samples for progesterone evaluation were taken twice weekly. All cows in trial A were in anestrus at the start of the study. By second week, 5 out of the 47 cows had initiated estrous cycles and by the third week six were pregnant. In contrast in trial B, 9 out of 47 had initiated estrous cycles before interacting with the bulls and on week 3, only two females had become pregnant and three had initiated estrous cycles. Significant differences were found in the cumulative percentage of cows pregnant between trials A and B (P<0.05). Even though these results occurred, the rotation of the bulls (one or three), or the type of cows (estrus-stimulated or not) did not influence the results in this study.

The prolactin-releasing effects of buspirone, an azaspirodecanedione anxiolytic drug unrelated to the benzodiazepines in structure and pharmacologic properties, was examined in developing and adult male and female rats. The possibility that effects of this drug on hormone release could be modulated by neonatal brain sexual differentiation was also evaluated. A single injection of buspirone, 2 or 10 mg/kg body wt, increased serum prolactin (PRL) levels in both sexes; the increase was significant from Day 12 onward. The PRL-releasing effect increased with age. No significant sexual differences were observed in younger rats, but in peripubertal and adult animals, the hyperprolactinemic response was higher in the female. Neonatal androgenization of females or orchidectomy of males failed to modify the PRL-releasing action of buspirone. Serum titers of luteinizing hormone and follicle-stimulating hormone were not modified by buspirone at any age. The present results show for the first time the ontogeny of the PRL-releasing effect of buspirone in male and female rats, and provide evidence that the response is higher in the female and that the effect does not depend on brain sexual differentiation.