Hypothalamic leptinoceptive neurones can be visualized by histochemical demonstration of leptin-induced nuclear translocation of the signalling molecule STAT3. We investigated the relationship of the leptinoceptive neurones to the somatostatin signalling system. With double-labelling immunohistochemistry, we studied the colocalization of leptin-activated transcription factor, STAT3, with somatostatin receptor subtypes, sst1, sst2A, sst2B, sst3 and sst4, or the neuropeptide itself, in the rat hypothalamus. Immunoreactivity for all the entities was widely distributed throughout the entire hypothalamus. Despite the wide distribution, only few cases of colocalization of somatostatin with leptin-activated STAT3 were detected in the paraventricular, arcuate and dorsomedial nuclei. A moderate to high degree of colocalization of nuclear STAT3 and all investigated subtypes of somatostatin receptors was found in the lateral and dorsal hypothalamic areas and in the dorsomedial hypothalamic nucleus. Immunoreactivity for sst1, sst2B and sst4 was present in STAT3-containing nuclei of the paraventricular, periventricular, arcuate and ventromedial hypothalamic neurones, as well as in the retrochiasmatic and posterior hypothalamic areas. Despite the wide distribution of sst2A in the rat hypothalamus, few events of colocalization with leptin-activated STAT3 were observed in the dorsomedial nucleus and in the lateral and dorsal hypothalamic areas only. Many leptin-responsive neurones of the dorsal, lateral, periarcuate, perifornical and posterior hypothalamic areas, as well as in the ventromedial and dorsomedial hypothalamic nuclei, displayed sst3 immunoreactivity at their neuronal cilia. These results provide strong anatomical evidence for the direct interaction of leptin and the somatostatin systems in neuroendocrine control loops such as the energy homeostasis, growth or stress response.
BACKGROUND: Vertigo and dizziness are extremely common conditions in the adult population and therefore place a significant social and economic burden on both patients and the healthcare system. However, limited information is available for the economic burden of vertigo and dizziness across various health care settings. OBJECTIVE: Estimate the economic burden of vertigo and dizziness, controlling for demographic, socioeconomic, and clinical comorbidities. METHODS: A retrospective analysis of data from the Medical Expenditures Panel Survey (2007–2015) was performed to analyze individuals with vertigo or dizziness from a nationally representative sample of the United States. Participants were included via self-reported data and International Classification of Diseases, 9th Revision Clinical Modification codes. A cross-validated 2-component generalized linear model was utilized to assess vertigo and dizziness expenditures across demographic, socioeconomic and clinical characteristics while controlling for covariates. Costs and utilization across various health care service sectors, including inpatient, outpatient, emergency department, home health, and prescription medications were evaluated. RESULTS: Of 221,273 patients over 18 years, 5,275 (66% female, 34% male) reported either vertigo or dizziness during 2007–2015. More patients with vertigo or dizziness were female, older, non-Hispanic Caucasian, publicly insured, and had significant clinical comorbidities compared to patients without either condition. Furthermore, each of these demographic, socioeconomic, and clinical characteristics lead to significantly elevated costs due to having these conditions for patients. Significantly higher medical expenditures and utilization across various healthcare sectors were associated with vertigo or dizziness (p < 0.001). The mean incremental annual healthcare expenditure directly associated with vertigo or dizziness was $2,658.73 (95% CI: 1868.79, 3385.66) after controlling for socioeconomic and demographic characteristics. Total annual medical expenditures for patients with dizziness or vertigo was $48.1 billion. CONCLUSION: Vertigo and dizziness lead to substantial expenses for patients across various healthcare settings. Determining how to limit costs and improve the delivery of care for these patients is of the utmost importance given the severe morbidity, disruption to daily living, and major socioeconomic burden associated with these conditions.
Although the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP.
Retraction of the MRM toward the choanae provided the least length of exposure, and external retraction exposed the least height and total area. Transseptal MRM retraction was most favorable and provided the largest endoscopic corridor to the medial intraconal space. A four-handed approach for endoscopic intraconal surgery of the orbit may offer advantages in dynamic adjustments in retraction.
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