Subjects are often willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No Info) vs. a leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%) and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the anterior cingulate cortex, orbitofrontal cortex, basolateral amygdala, or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of the anterior cingulate cortex destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that previous choice predicted current choice in all conditions, however previously rewarded Info trials strongly predicted preference in all conditions except in female rats following anterior cingulate cortex inhibition. The results reveal a causal, sex-dependent role for the anterior cingulate cortex in decisions involving information.
Basolateral Nuclear Complex , Humans , Female , Male , Animals , Rats , Gyrus Cinguli , Amygdala , Cues , Prefrontal Cortex
Subjects often are willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No-info) vs a leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%), and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory DREADDs in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), basolateral amygdala (BLA), or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of ACC destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that the previous choice strongly predicted preference in control animals, but not in female rats following ACC inhibition. The results reveal a causal, sex-dependent role for ACC in decisions involving information.
BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. METHODS: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. RESULTS: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. CONCLUSIONS: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.
BACKGROUND: Bladder cancer is the second most incident malignancy among Lebanese men. The purpose of this study was to investigate potential risk factors associated with this observed high incidence. METHODS: A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently selected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposure data were collected using a structured face-to-face interview questionnaire. Blood samples were collected to determine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariate and multivariate logistic regression, along with checks for effect modification. RESULTS: The odds of having bladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure to occupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The odds of prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showed different clustering patterns of NAT1 alleles. No significant differences between cases and controls were found for consumption of alcohol, coffee, tea, or artificial sweeteners. CONCLUSIONS: This is the first case-control study investigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factors in the literature, particularly smoking and occupational exposure to diesel. The herein observed associations should be used to develop appropriate prevention policies and intervention strategies, in order to control this alarming disease in Lebanon.
Coffee , Occupational Exposure/adverse effects , Smoking/adverse effects , Tea , Urinary Bladder Neoplasms/etiology , Aged , Arylamine N-Acetyltransferase/genetics , Case-Control Studies , Female , Follow-Up Studies , Genotype , Humans , Isoenzymes/genetics , Male , Polymerase Chain Reaction , Polymorphism, Genetic/genetics , Polymorphism, Restriction Fragment Length , Prognosis , Risk Factors
In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1) genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently identified and selected from the same settings. Data was collected using interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR-RFLP. Statistical analysis revolved around univariate, bivariate, and multivariate logistic regression models, along with checks for effect modification. Results showed NAT1(∗)14A allele, smoking, occupational exposure to combustion fumes, and prostate-related symptoms, to be risk factors for bladder cancer. The odds of carrying at least one NAT1(∗)14A allele are 7 times higher in cases compared to controls (OR = 7.86, 95% CI: 1.53-40.39). A gene-environment interaction was identified for NAT1(∗)14A allele with occupational exposure to combustion fumes. Among carriers of NAT1(∗)14A allele, the odds of bladder cancer dropped to 2.03 from 3.72. Our study suggests NAT1(∗)14A allele as a possible biomarker for bladder cancer. Further research is recommended to confirm this association.
