Inhibition of Nitric Oxide and Soluble Guanylyl Cyclase Signaling Affects Olfactory Neuron Activity in the Moth, \u3cem\u3eManduca sexta\u3c/em\u3e

Nitric oxide is emerging as an important modulator of many physiological processes including olfaction, yet the function of this gas in the processing of olfactory information remains poorly understood. In the antennal lobe of the moth, Manduca sexta, nitric oxide is produced in response to odor stimulation, and many interneurons express soluble guanylyl cyclase, a well-characterized nitric oxide target. We used intracellular recording and staining coupled with pharmacological manipulation of nitric oxide and soluble guanylyl cyclase to test the hypothesis that nitric oxide modulates odor responsiveness in olfactory interneurons through soluble guanylyl cyclase-dependent pathways. Nitric oxide synthase inhibition resulted in pronounced effects on the resting level of firing and the responses to odor stimulation in most interneurons. Effects ranged from bursting to strong attenuation of activity and were often accompanied by membrane depolarization coupled with a change in input resistance. Blocking nitric oxide activation of soluble guanylyl cyclase signaling mimicked the effects of nitric oxide synthase inhibitors in a subset of olfactory neurons, while other cells were differentially affected by this treatment. Together, these results suggest that nitric oxide is required for proper olfactory function, and likely acts through soluble guanylyl cyclase-dependent and -independent mechanisms in different subsets of neurons

Matrix Metalloproteinase 13 Is Induced in Fibroblasts in Polyomavirus Middle T Antigen-Driven Mammary Carcinoma without Influencing Tumor Progression

Matrix metalloproteinase (MMP) 13 (collagenase 3) is an extracellular matrix remodeling enzyme that is induced in myofibroblasts during the earliest invasive stages of human breast carcinoma, suggesting that it is involved in tumor progression. During progression of mammary carcinomas in the polyoma virus middle T oncogene mouse model (MMTV-PyMT), Mmp13 mRNA was strongly upregulated concurrently with the transition to invasive and metastatic carcinomas. As in human tumors, Mmp13 mRNA was found in myofibroblasts of invasive grade II and III carcinomas, but not in benign grade I and II mammary intraepithelial neoplasias. To determine if MMP13 plays a role in tumor progression, we crossed MMTV-PyMT mice with Mmp13 deficient mice. The absence of MMP13 did not influence tumor growth, vascularization, progression to more advanced tumor stages, or metastasis to the lungs, and the absence of MMP13 was not compensated for by expression of other MMPs or tissue inhibitor of metalloproteinases. However, an increased fraction of thin collagen fibrils was identified in MMTV-PyMT;Mmp13−/− compared to MMTV-PyMT;Mmp13+/+ tumors, showing that collagen metabolism was altered in the absence of MMP13. We conclude that the expression pattern of Mmp13 mRNA in myofibroblasts of invasive carcinomas in the MMTV-PyMT breast cancer model recapitulates the expression pattern observed in human breast cancer. Our results suggest that MMP13 is a marker of carcinoma-associated myofibroblasts of invasive carcinoma, even though it does not make a major contribution to tumor progression in the MMTV-PyMT breast cancer model

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity

BACKGROUND: Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). RESULTS: A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = −0.359; P = 0.011) and Δglucose (r = −0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = −0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. CONCLUSIONS: Plasma NT-proBNP and MR-proANP concentrations increase and MR-proADM concentration decreases during weight loss, underlining the dynamic impact of BMI, body composition and glucose metabolism on these cardiovascular biomarkers

Understanding the role of peace of mind in childhood vaccination: A qualitative study with members of the general public.

BACKGROUND: Recent debates on the introduction of new childhood vaccines in the UK have suggested that 'peace of mind' (PoM) might influence decision making. The aim of this study is to ascertain the importance of 'PoM' in individuals' decision making. METHODS: Four focus groups were conducted in the UK. Participants were 22 females and 2 males, aged 18-74 years, with a selection of non-parents, parents, guardians and foster carers. Data were analysed using an inductive thematic framework approach and conceptualised using the Health Belief Model, which provided an overview of participants' perceptions and behaviours about childhood vaccinations. RESULTS: Vaccine associated PoM was associated with individuals' perceptions of disease severity, with individuals feeling more reassurance after obtaining vaccinations against diseases that they considered to be severe compared to relatively mild diseases. Conversely, concerns about vaccination side-effects reduced participants PoM, but the duration of this effect varied between individuals. Other factors, such as social pressure and the emotional anxiety related to children's feelings, or physical reactions, to vaccinations also negatively impacted on participants' vaccine associated PoM. CONCLUSION: Vaccine associated PoM was a consideration for some participants seeking vaccinations but was only a minor motivating factor for these individuals. These differences stemmed from whether participants received PoM from the uptake of a vaccination because they perceived some intrinsic benefit from it or, conversely, they considered vaccinations as a routine health intervention. Overall, vaccine related PoM varied between participants in magnitude and fluctuated over time, even in the same individuals

Non-medical factors in prehospital resuscitation decision-making:a mixed-methods systematic review

AIM: This systematic review explored how non-medical factors influence the prehospital resuscitation providers’ decisions whether or not to resuscitate adult patients with cardiac arrest. METHODS: We conducted a mixed-methods systematic review with a narrative synthesis and searched for original quantitative, qualitative, and mixed-methods studies on non-medical factors influencing resuscitation of out-of-hospital cardiac arrest. Mixed-method reviews combine qualitative, quantitative, and mixed-method studies to answer complex multidisciplinary questions. Our inclusion criteria were peer-reviewed empirical-based studies concerning decision-making in prehospital resuscitation of adults > 18 years combined with non-medical factors. We excluded commentaries, case reports, editorials, and systematic reviews. After screening and full-text review, we undertook a sequential exploratory synthesis of the included studies, where qualitative data were synthesised first followed by a synthesis of the quantitative findings. RESULTS: We screened 15,693 studies, reviewed 163 full-text studies, and included 27 papers (12 qualitative, two mixed-method, and 13 quantitative papers). We identified five main themes and 13 subthemes related to decision-making in prehospital resuscitation. Especially the patient’s characteristics and the ethical aspects were included in decisions concerning resuscitation. The wishes and emotions of bystanders further influenced the decision-making. The prehospital resuscitation providers’ characteristics, experiences, emotions, values, and team interactions affected decision-making, as did external factors such as the emergency medical service system and the work environment, the legislation, and the cardiac arrest setting. Lastly, prehospital resuscitation providers’ had to navigate conflicts between jurisdiction and guidelines, and conflicting values and interests. CONCLUSIONS: Our findings underline the complexity in prehospital resuscitation decision-making and highlight the need for further research on non-medical factors in out-of-hospital cardiac arrest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13049-022-01004-6