NPY2 receptor activation in the dorsal vagal complex increases food intake and attenuates CCK-induced satiation in male rats.

Neuropeptide Y (NPY), peptide YY (PYY), and their cognate receptors (YR) are expressed by subpopulations of central and peripheral nervous system neurons. Intracerebroventricular injections of NPY or PYY increase food intake, and intrahypothalamic NPY1 or NPY5 receptor agonist injections also increase food intake. In contrast, injection of PYY in the periphery reduces food intake, apparently by activating peripheral Y2R. The dorsal vagal complex (DVC) of the hindbrain is the site where vagal afferents relay gut satiation signals to the brain. While contributions of the DVC are increasingly investigated, a role for DVC YR in control of food intake has not been examined systematically. We used in situ hybridization to confirm expression of Y1R and Y2R, but not Y5R, in the DVC and vagal afferent neurons. We found that nanoinjections of a Y2R agonist, PYY-(3-36), into the DVC significantly increased food intake over a 4-h period in satiated male rats. PYY-(3-36)-evoked food intake was prevented by injection of a selective Y2R antagonist. Injection of a Y1R/Y5R-preferring agonist into the DVC failed to increase food intake at doses reported to increase food intake following hypothalamic injection. Finally, injection of PYY-(3-36) into the DVC prevented reduction of 30-min food intake following intraperitoneal injection of cholecystokinin (CCK). Our results indicate that activation of DVC Y2R, unlike hypothalamic or peripheral Y2R, increases food intake. Furthermore, in the context of available electrophysiological observations, our results are consistent with the hypothesis that DVC Y2R control food intake by dampening vagally mediated satiation signals in the DVC.

COVID-19 Vaccine Related Cervical Radiculitis and Parsonage-Turner Syndrome: Case Report and Review of the Literature.

Parsonage-Turner Syndrome, or neuralgic amyotrophy, is an acute-onset upper limb and shoulder girdle palsy that can occur in a post-viral, post-surgical or idiopathic setting. There have also been some reported cases of the syndrome occurring following vaccinations. The pathophysiology of neuralgic amyotrophy is not completely understood and many of the commonly used diagnostic imaging modalities we use to try and diagnose this syndrome are inaccurate and misleading. We present the case of a 40-year-old gentleman who presented with acute onset burning pain and fasciculations in his right upper extremity following vaccination with the second dose of the Pfizer-BioNTech COVID-19 vaccine. His symptoms progressed to weakness in isolated muscle groups with electromyographic evidence of decreased nerve conduction. MRI of the cervical spine demonstrated multilevel central and foraminal stenosis, suggesting a diagnosis of cervical radiculopathy. The patient underwent a C4-5/C5-6 and C6-7 laminoforaminotomy and tolerated the procedure well. Post-operatively, the patient has experienced gradual symptom improvement with residual right triceps and pectoralis muscle weakness as well as paresthesias of the right elbow and forearm. Parsonage-Turner Syndrome is a brachial plexus palsy that can affect one or multiple branches of the brachial plexus. It causes acute-onset pain and weakness, and the diagnosis can be difficult to make with the commonly used diagnostic imaging methods. We reviewed other case reports about neuralgic amyotrophy following vaccinations as well as the current literature on more accurate diagnostic imaging modalities that may help our diagnosis and understanding of the pathophysiology of this condition.

Proximal Tubule Dysfunction Secondary to Salicylate Intoxication.

Aspirin overdose is still a common cause of presentation to the emergency department and is commonly seen in the setting of one-time, accidental or intentional ingestion of large amounts of salicylate-containing compounds, though can occur with long-term ingestion of super-therapeutic doses of medications. Salicylate toxicity has a predictable progression from early respiratory alkalosis to late metabolic acidosis. We present the case of a 14-year-old girl who intentionally ingested a handful of Aspirin and despite appropriate therapy, developed transient proximal tubule dysfunction. This case highlights the need for a change in the short-term medical management of children presenting with salicylate toxicity.

Overall and cause-specific survival for mucoepidermoid carcinoma of the major salivary glands: Analysis of 2210 patients.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is a rare malignancy of the head and neck; however, it accounts for a majority of the tumors of the salivary glands. This study used a national population-based registry to describe the pre-treatment and treatment-related prognostic factors that influence survival in patients with MEC of the major salivary glands. To our knowledge, this is the largest population-based study examining predictors of both overall and cause-specific survival of MEC of the major salivary glands. AIM: To identify prognostic factors influencing overall survival (OS) and cause-specific survival (CSS) of patients with MEC of the major salivary glands. METHODS: We used the Surveillance, Epidemiology and End-Results Database of the National Cancer Institute to investigate a variety of factors that could influence survival of patients diagnosed with mucoepidermoid carcinoma of the major salivary glands. A total of 2210 patients diagnosed with MEC of the major salivary glands during the years of 1975-2016 were studied. The primary endpoints were OS and CSS. Cox regression analysis was used to perform univariate and multivariate analyses of clinical variables such as age at diagnosis, diagnosis year, sex, race, tumor size, stage, grade, treatment with or without surgical excision, and adjuvant radiotherapy treatment. RESULTS: A total of 2210 patients diagnosed with MEC of the major salivary glands met inclusion criteria. In this study, 95% of patients underwent surgical excision and 41% received adjuvant radiation therapy. Median OS time for Grade I, II, and III/IV was 401 mo (± 48.25, 95%CI), 340 mo (± 33.68, 95%CI) and 55 mo (± 11.05, 95%CI), respectively. Univariate analysis revealed that lack of surgical excision was associated with decreased OS [hazard ratio (HR) 4.26, P < 0.0001] and that patients with localized disease had improved OS compared to both regional and distant disease (HR 3.07 and 6.96, respectively, P < 0.0001). Additionally, univariate analysis demonstrated that male sex, age over 50 at diagnosis, Grade III tumors, and increasing tumor size were associated with worsened OS (P < 0.0006). Univariate analysis of CSS similarly revealed that lack of surgical excision and Grade III carcinoma conferred decreased CSS (HR 4.37 and 5.44, respectively, P < 0.0001). Multivariate analysis confirmed that increasing age, in 10-year age bands, advanced tumor stage, increasing tumor size, Grade III carcinoma, male sex, and lack of surgical excision were associated with a statistically significant decrease in OS and CSS (P < 0.04). Of note, multivariate analysis revealed that the use of adjuvant radiation therapy was not associated with improved OS or CSS. CONCLUSION: Multivariate analysis demonstrated increasing age, advanced tumor stage, increasing tumor size, Grade III carcinoma, male sex, and lack of surgical excision were associated with decreased OS and CSS (P < 0.04).

Clinicopathologic Features and Survival Trends for Acinic Cell Carcinoma of the Major Salivary Glands: A Surveillance, Epidemiology, and End Results Population Analysis.

BACKGROUND: We analyzed a population-based national registry to identify the most influential patient pretreatment and treatment factors affecting overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with acinic cell carcinoma (ACC) of the major salivary glands. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) related to survival, a total of 1,254 patients with diagnosed ACC of the major salivary glands from 1975 to 2016 met inclusion criteria. Factors significant for OS and CSS were determined using univariate and multivariate analysis with the Cox proportional hazards model. RESULTS: Univariate OS analysis demonstrated that surgery favorably influenced longer survival compared to no surgery (hazard ratio (HR) 2.35, P < 0.05). Patient age was found to be highly predictive of superior OS (divided into 10-year age bands, P < 0.0001, younger age better). In multivariate OS analysis, there were statistically significant worse outcomes for men (HR 1.54, P < 0.05), grades III/IV (HR 2.5, P < 0.05), and distant disease (HR 3.55, P < 0.05) or regional disease (HR 1.22, P < 0.05). Patients diagnosed during years 1996 - 2016 had better OS when compared to earlier decades 1975 - 1995 (HR 1.38, P < 0.05). In univariate analysis, the mean CSS for grades I, II, and III/IV were 429 months (95% confidence interval (CI), ± 38.39), 426 months (95% CI, ± 25.73) and 198 months (95% CI, ± 66.38). Multivariate analysis of CSS further demonstrated that there were statistically significant worse outcomes for men (HR 1.68, P < 0.05), grade III/IV (HR 3.2, P < 0.05), tumor size greater than 40 mm (P < 0.001), and distant disease (HR 4.48, P < 0.05) or regional disease (HR 1.84, P < 0.05). CONCLUSIONS: To our knowledge, this is the largest population-based study of OS and CSS of major salivary gland ACC. We found that the patient pretreatment and treatment factors including younger age at diagnosis, female sex, early stage, lower grade, surgical excision, and recent year of diagnosis are associated with improved survival in patients diagnosed with ACC of the major salivary glands. We hope that this information will aid in construction of further research projects that better refine optimal treatment protocol of individualized patient care.

Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat.

The fatty acid conjugated linoleic acid (CLA) and the antioxidant R-(+)-alpha-lipoic acid (R-ALA) individually enhance glucose tolerance and insulin action on skeletal muscle glucose transport in the insulin-resistant obese Zucker rat. To date, no study has assessed the potential interactions between these 2 interventions in treating insulin resistance. The present study was designed to determine whether chronic treatment with CLA and R-ALA in combination would enhance skeletal muscle glucose transport to a greater extent than either intervention individually. CLA, R-ALA, or a combination treatment of R-ALA and CLA were administered to female obese Zucker rats for 20 days at low or high doses. Whereas low-dose R-ALA (10 mg/kg body weight) alone did not alter muscle glucose transport, low-dose CLA (0.3 g/kg) induced a significant increase (38%, P <.05) in insulin-mediated glucose transport in epitrochlearis, but not in soleus. Low-dose combination therapy brought about the greatest enhancement of insulin-mediated glucose transport in epitrochlearis (77%) and soleus (54%), with the latter effect being associated with a 50% reduction in protein carbonyls (an index of tissue oxidative stress) and a 33% diminution in muscle triglycerides. High-dose treatments with CLA (1.5 g/kg), R-ALA (50 mg/kg), and the combination of CLA and R-ALA elicited increases in insulin-mediated glucose transport in epitrochlearis (57%, 58%, and 77%) and soleus (32%, 35%, and 54%). However, whereas the individual high-dose treatments with CLA and R-ALA reduced protein carbonyls (63% and 49%) and triglycerides (29% and 28%) in soleus, no further reductions were observed with the high-dose combination treatment groups. These findings support a significant interaction between low doses of CLA and R-ALA for enhancement of insulin action on skeletal muscle glucose transport, possibly via reductions in muscle oxidative stress and in lipid storage.

Contemporary outcomes after superficial femoral artery angioplasty and stenting: the influence of TASC classification and runoff score.

OBJECTIVE: A recent randomized trial suggested nitinol self-expanding stents (SES) were associated with reduced restenosis rates compared with simple percutaneous transluminal angioplasty (PTA). We evaluated our results with superficial femoral artery (SFA) SES to determine whether TransAtlantic InterSociety Consensus (TASC) classification, indication for intervention, patient risk factors, or Society of Vascular Surgery (SVS) runoff score correlated with patency and clinical outcome, and to evaluate if bare nitinol stents or expanded polytetrafluoroethylene (ePTFE) covered stent placement adversely impacts the tibial artery runoff. METHODS: A total of 109 consecutive SFA stenting procedures (95 patients) at two university-affiliated hospitals from 2003 to 2006 were identified. Medical records, angiographic, and noninvasive studies were reviewed in detail. Patient demographics and risk factors were recorded. Procedural angiograms were classified according to TASC Criteria (I-2000 and II-2007 versions) and SVS runoff scores were determined in every patient; primary, primary-assisted, secondary patency, and limb salvage rates were calculated. Cox proportional hazard model was used to determine if indication, TASC classification, runoff score, and comorbidities affected outcome. RESULTS: Seventy-one patients (65%) underwent SES for claudication and 38 patients (35%) for critical limb ischemia (CLI). Average treatment length was 15.7 cm, average runoff score was 4.6. Overall 36-month primary, primary-assisted, and secondary rates were 52%, 64%, and 59%, respectively. Limb salvage was 75% in CLI patients. No limbs were lost following interventions in claudicants (mean follow-up 16 months). In 24 patients with stent occlusion, 15 underwent endovascular revision, only five (33%) ultimately remained patent (15.8 months after reintervention). In contrast, all nine reinterventions for in-stent stenosis remained patent (17.8 months). Of 24 patients who underwent 37 endovascular revisions for either occlusion or stenosis, eight (35%) had worsening of their runoff score (4.1 to 6.4). By Cox proportional hazards analysis, hypertension (hazard ratio [HR] 0.35), TASC D lesions (HR 5.5), and runoff score > 5 (HR 2.6) significantly affected primary patency. CONCLUSIONS: Self-expanding stents produce acceptable outcomes for treatment of SFA disease. Poorer patency rates are associated with TASC D lesions and poor initial runoff score; HTN was associated with improved patency rates. Stent occlusion and in-stent stenosis were not entirely benign; one-third of patients had deterioration of their tibial artery runoff. Future studies of SFA interventions need to stratify TASC classification and runoff score. Further evaluation of the long-term effects of SFA stenting on tibial runoff is needed.

Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat.

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker (fa/fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced (P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides (r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.