In Vivo Identification of H3K9me2/H3K79me3 as an Epigenetic Barrier to Carcinogenesis.

The highly dynamic nature of chromatin's structure, due to the epigenetic alterations of histones and DNA, controls cellular plasticity and allows the rewiring of the epigenetic landscape required for either cell differentiation or cell (re)programming. To dissect the epigenetic switch enabling the programming of a cancer cell, we carried out wide genome analysis of Histone 3 (H3) modifications during osteogenic differentiation of SH-SY5Y neuroblastoma cells. The most significant modifications concerned H3K27me2/3, H3K9me2, H3K79me1/2, and H3K4me1 that specify the process of healthy adult stem cell differentiation. Next, we translated these findings in vivo, assessing H3K27, H3K9, and H3K79 methylation states in biopsies derived from patients affected by basalioma, head and neck carcinoma, and bladder tumors. Interestingly, we found a drastic decrease in H3K9me2 and H3K79me3 in cancer specimens with respect to their healthy counterparts and also a positive correlation between these two epigenetic flags in all three tumors. Therefore, we suggest that elevated global levels of H3K9me2 and H3K79me3, present in normal differentiated cells but lost in malignancy, may reflect an important epigenetic barrier to tumorigenesis. This suggestion is further corroborated, at least in part, by the deranged expression of the most relevant H3 modifier enzymes, as revealed by bioinformatic analysis. Overall, our study indicates that the simultaneous occurrence of H3K9me2 and H3K79me3 is fundamental to ensure the integrity of differentiated tissues and, thus, their combined evaluation may represent a novel diagnostic marker and potential therapeutic target.

The prognostic value of subjective nasal symptoms and SNOT-22 score in middle ear surgery.

BACKGROUND: The relationship between nasal functions and middle ear surgery is still under debate. Nasal obstruction is considered as a negative prognostic factor in middle ear surgery. This is based on the theory that it may cause Eustachian tube dysfunction (ETD) by leading to reduced ventilation of the middle ear, as found in several patients with nasal septal deviation, chronic rhinitis and nasal polyps. OBJECTIVES: To assess how the subjective feeling of nasal function, evaluated by a preoperative questionnaire, may be predictive of surgical outcome and/or risk of failure in middle ear surgery. METHODS: We prospectively evaluated data of patients undergoing middle ear surgery for chronic otitis media with and without cholesteatoma. All patients completed the SNOT-22 and ETDQ-7 questionnaires. They underwent surgery for their pathology, as appropriate. RESULTS: The SNOT-22 score was higher in patients with retraction pocket and in patients whose retraction pockets recurred after surgery (p < 0.05). Patients with higher score at SNOT-22 questionnaire, were more likely to show recurrence of atelectasis aftersurgery. CONCLUSIONS: The SNOT-22 questionnaire, administrered before surgical procedure, can help in the identification of patients who are at risk of failure in the post-operative period, as well as ETDQ-7.

Predictive factors of severity and persistence of oropharyngeal dysphagia in sub-acute stroke.

PURPOSE: This study aims to understand the factors contributing to the severity of oropharyngeal dysphagia and its persistence in the sub-acute phase of stroke. METHODS: We retrospectively collected the data of all the patients suffering from a stroke in the last year. The severity of stroke was reported according to the NIHSS score. All the patients were evaluated with the Dysphagia Risk Score and with a FEES. We classified the Dysphagia Risk Score and FEES results using the PAS score and ASHA-NOMS levels. The data were analysed statistically with ANOVA test, Student's t test and Pearson's correlation coefficient. RESULTS: A series of 54 patients were evaluated. The ANOVA test did not find any difference in the mean score of Dysphagia Risk Score, PAS and ASHA-NOMS when compared with the brain area of stroke. An NIHSS at hospital admission (stroke unit) of more than 12 was predictive of ASHA-NOMS score 1-4 after 60 days (p < 0.05). A PAS score between 6 and 8 at first FEES evaluation was predictive of poor (1-4) ASHA-NOMS score after 60 days (p < 0.01). A moderate positive linear correlation was found between NIHSS score and both PAS (r 0.65) and Dysphagia Risk Score (r 0.50); a moderate negative linear correlation was recorded between NIHSS and ASHA-NOMS (r - 0.66) scores. CONCLUSION: In the sub-acute phase of stroke, the predictive factors of persistent dysphagia are not linked to the damaged neuroanatomical region and others factors such as NIHSS value and high PAS score seem more useful.

Anti-Inflammatory and Proliferative Properties of Luteolin-7-O-Glucoside.

Flavonoids display a broad range of structures and are responsible for the major organoleptic characteristics of plant-derived foods and beverages. Recent data showed their activity, and in particular of luteolin-7-O-glucoside (LUT-7G), in reduction of oxidative stress and inflammatory mechanisms in different physiological systems. In this paper, we tried to elucidate how LUT-7G could exert both antioxidant and anti-inflammatory effects in endothelial cells cultured in vitro. Here, we showed that LUT-7G is able to inhibit the STAT3 pathway, to have an antiproliferative action, and an important antioxidant property in HUVEC cells. These properties are exerted by the flavone in endothelial through the transcriptional repression of a number of inflammatory cytokines and their receptors, and by the inhibition of ROS generation. ROS and STAT3 activation has been correlated with the production of oxysterols and other hydroxylated fatty acids, and they have been recognized important as players of atherogenesis and cardiocirculatory system diseases. The analysis of the general production pathway of these hydroxylated species, showed a strong decrease of cholesterol hydroxylated species such as 7-alpha-hydroxicholesterol, 7-beta-hydroxicholesterol by the treatment with LUT-7G. This confirms the anti-inflammatory properties of LUT-7G also in the endothelial district, showing for the first time the molecular pathway that verify previous postulated cardiovascular benefits of this flavone.

Oropharyngeal dysphagia in elderly population suffering from mild cognitive impairment and mild dementia: Understanding the link.

PURPOSE: To evaluate the prevalence of oropharyngeal dysphagia in elderly patients suffering from minimal or mild cognitive decline. PATIENTS AND METHODS: We retrospectively collected the data of patients suffering from mild cognitive impairment or mild dementia and were undergoing management for suspected oropharyngeal dysphagia, in our department. All our patients were subjected to Mini Mental State Examination test, MD Anderson dysphagia inventory and caregiver mealtime and dysphagia questionnaire. We performed a mealtime observation study and endoscopic evaluation of swallowing in all our patients. Following evaluation, we then analysed the data statistically. RESULTS: Out of 708 patients who visited us for cognitive decline and suspected oropharyngeal dysphagia in the last two years, 52 patients were confirming to the inclusion criteria of this study. Classification of oropharyngeal dysphagia patients according to ASHA-NOMS scale showed that 32.7% of patients presented with grade 4 of dysphagia followed by another 32.7% with grade 5 and 30.8% presented with grade 6. Only 3.8% of our patients were considered normal (grade 7 of ASHA-NOMS scale). MD Anderson dysphagia inventory could collected swallowing alterations in only 23.1% of the cases. The caregiver mealtime and dysphagia questionnaire showed acceptable caregivers patient management in 53.8% of patients. CONCLUSION: Our study underscores the fact that oropharyngeal dysphagia is present in many cases of mild cognitive decline. While patients understate their swallowing problems, the caregivers are not competent enough to manage this situation in a great percentage of cases. Only a mealtime observation by a speech-language pathologist along with FEES is able to identify the true prevalence of the condition.

Plasma and erythrocyte membrane phospholipids and fatty acids in Italian general population and hemodialysis patients.

BACKGROUND: Dyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): ω-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between ω-3 and ω-6 fatty acids and the possible differences in PUFAs concentrations were also investigated. METHODS AND RESULTS: After obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from "Tor Vergata" University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector.The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p < 0.001). Most plasma and erythrocyte PUFA were also reduced significantly in HD patients (p < 0.001). CONCLUSIONS: Our results suggest that many classes of PUFAs are lacking in HD patients, due to the removal of nutrients during the dialysis and to persistent malnutrition. A dietary treatment addressed to increase plasma ω-3 PUFAs and to optimize ω-6/ω-3 ratio may exert a protective action and reduce the risk of CVD in HD patient.

Role of L-type Ca2+-channels in the vasorelaxing response to finerenone in arteries of human visceral adipose tissue.

Inadequate blood supply to the expanding adipose tissue (AT) is involved in the unhealthy AT remodeling and cardiometabolic consequences of obesity. Because of the pathophysiological role of upregulated mineralocorticoid receptor (MR) signaling in the complications of obesity, this study tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries of human AT. Arteries isolated from the visceral AT of obese subjects were studied in a wire myograph. Finerenone resulted in a concentration-dependent relaxation of arteries precontracted with either the thromboxane-A2 analog U46619, ET-1, or high-K+ solution; the steroidal MR antagonist potassium canrenoate, by contrast, did not relax arteries contracted with either U46619 or high-K+ solution. Finerenone-induced relaxation after precontraction with U46619 was greater in the arteries of obese versus nonobese subjects. Mechanistically, the vasorelaxing response to finerenone was not influenced by preincubation with the nitric oxide synthase inhibitor L-NAME or by endothelium removal. Interestingly, finerenone, like the dihydropyridine Ca2+-channel blocker nifedipine, relaxed arteries contracted with the L-type Ca2+-channel agonist Bay K8644. In conclusion, finerenone relaxes arteries of human visceral AT, likely through antagonism of L-type Ca2+ channels. This finding identifies a novel mechanism by which finerenone may improve AT perfusion, hence protecting against the cardiometabolic complications of obesity.

Sudden sensorineural hearing loss: results of intratympanic steroids as salvage treatment.

OBJECTIVE: The aim of the present study was to verify the efficacy and the safety of intratympanic dexamethasone to treat sudden sensorineural hearing loss as salvage therapy. MATERIALS AND METHODS: A prospective study was conducted on patients affected by idiopathic sudden hearing loss who were treated before with some systemic therapy, but without recovery of the hearing The patients able to undergo the study, but who refused salvage treatment were considered as control group. A solution of Dexamethasone 4 mg/ml was then injected through the posterior-inferior quadrant filling completely the middle ear. The follow-up in the following 6 months included an audiogram every month. RESULTS: The number of patients treated with salvage therapy was 36. The patients who refused treatment were further 10. The salvage treatment was done with a mean delay of 24.3 days from the onset of symptoms. Mean hearing threshold after the onset of sudden hearing loss at PTA was 66.5 dB. After the failed treatment the mean PTA was 59.6 dB. The mean PTA after the intratympanic steroid administration was 46.8 dB, with a mean improvement of 12.8 dB. No hearing change was noted in the 10 patients who refused salvage therapy. The patients that assumed systemic steroid as first therapy showed a better PTA threshold after the salvage intratympanic treatment (p<0.01). A significant difference (p<0.05) of hearing recovery was evidenced between non-smoker patients and those with smoking habit. CONCLUSIONS: Our data showed that a salvage treatment with intratympanic dexamethasone should be suggested to all patients who failed the first systemic treatment. The systemic steroid therapy done before the salvage treatment seems to exert a protective role for the inner ear, as shown by our series. On the contrary the smoke habit is a negative prognostic factor in the hearing recovery.

A novel tumour enhancer function of Insulin-like growth factor II mRNA-binding protein 3 in colorectal cancer.

CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.

Comparison of repositioning maneuvers for benign paroxysmal positional vertigo of posterior semicircular canal: advantages of hybrid maneuver.

OBJECTIVE: The prevalence of benign paroxysmal positional vertigo (BPPV) is becoming more frequent in elderly population. The presence of comorbid factors has to be considered before assessment as well as before commencing any repositioning treatment. Our aims were evaluation of the maneuvers efficacy and evaluation of the applicability of hybrid maneuver (HM) in patients with physical limitation. STUDY DESIGN AND SETTING: This is a randomized study in 2 tertiary referral centers. INTERVENTION: This is a therapeutic intervention. PATIENTS: All consecutive patients with diagnosis of BPPV of posterior canal matching the inclusion criteria were enrolled. Patients underwent treatment soon after the initial diagnosis in all cases with a repositioning maneuver. The maneuver was casually selected among Semont, Epley, and hybrid. Patients were divided into 3 groups according to the maneuver adopted. RESULTS: Eighty-eight patients with posterior canal BPPV were enrolled for treatment. Fisher exact test showed that no statistical differences exist between HM and other maneuvers in terms of efficacy. Latency of repositioning nystagmus appeared longer in HM in comparison with other maneuvers (P < .05). Efficacy of maneuvers used for BPPV decreases in case of cupulolithiasis (P < .0001). We found no relationship between age, sex, and length of disturbance on response to maneuvers. CONCLUSIONS: All maneuvers evaluated demonstrated similar efficacy. The HM, as our data showed, allows us to obtain a good percentage of success similar to most maneuvers used. It is also more comfortable for the patients with hip or neck functional limitation allowing an effective treatment of the posterior canal BPPV.

Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside.

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α1-adrenergic receptors.

AIM: As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of ß3-adrenoceptors which also seem to mediate endothelium-dependent vasodilation in disparate human vascular beds. We characterized, therefore, the vasomotor function of mirabegron in human adipose tissue arteries and the underlying mechanisms. METHODS: Small arteries (116-734 µm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions. RESULTS: Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-K+ (both P > 0.05). Notably, mirabegron markedly blunted the contractile effect of the α1-adrenergic receptor agonist phenylephrine (P < 0.001) either in presence or absence of the vascular endothelium. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective ß3-adrenoceptor blocker L-748,337 (P < 0.05); lack of involvement of ß3-adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry. CONCLUSIONS: Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α1-adrenoceptors.

Are postural restrictions necessary for management of posterior canal benign paroxysmal positional vertigo?

OBJECTIVES: An important component of management of benign paroxysmal positional vertigo (BPPV) has been the application of postural restrictions after use of a canalith repositioning maneuver (CRM) to prevent the return of otolithic debris into the posterior semicircular canal (PSC). This study was designed to explore the effectiveness of postural restrictions in patients with BPPV caused by otolithic debris in the PSC. METHODS: Seventy-four adult patients with unilateral PSC BPPV were enrolled into this study. All patients were managed with a CRM--either the modified Epley maneuver or the Semont maneuver. The patients were divided randomly into 2 groups: group A, with postural restrictions, and group B, without postural restrictions. The statistical analysis was performed with X2 tests and t-tests. RESULTS: No patients in either group showed positional nystagmus in the posttreatment evaluation under infrared videonystagmoscopy. No patients had symptoms of vertigo after the therapy. The results of follow-up vestibular tests were normal in both groups. CONCLUSIONS: In our experience, postural restrictions do not enhance the beneficial effect of the CRMs. They do not seem to have any protective role and therefore should not be recommended as an adjunct to the treatment of PSC BPPV.

Benign paroxysmal positional vertigo following whiplash injury: a myth or a reality?

OBJECTIVE: The aim of the study was to evaluate the true incidence, diagnosis, and treatment of benign paroxysmal positional vertigo (BPPV) arising after whiplash injury and to distinguish this type of posttraumatic vertigo from other types of dizziness complained after trauma. METHODS: This was a retrospective study comprising patients referred to our center after whiplash injury. The patients were evaluated with neurotologic examination including bedside and instrumental tests. A Dizziness Handicap Inventory evaluating the symptoms of patients was submitted before and after treatment and was evaluated. The BPPV patients were separately evaluated from those with cervicogenic vertigo, and a comparison between our data about idiopathic BPPV was done. RESULTS: Eighteen patients of whiplash who had BPPV were evaluated. The mean age was 38.2 years. BPPV was the cause of vertigo in 33.9% of total whiplash patients. In 16 cases, the posterior semicircular canal was involved; the lateral semicircular canal was involved in 2 cases. The instrumental neurotologic assessment did not show any alteration of either vestibulospinal reflexes or dynamic ocular movements. Duration of symptoms before treatment ranged from 3 to 26 days. A total of 55.5% of patients had relief from their symptoms after first repositioning maneuver. The Dizziness Handicap Inventory score improved in all patients treated with repositioning maneuvers, but no difference emerged with idiopathic BPPV data. CONCLUSION: BPPV after whiplash injury could be unveiled with a simple bedside examination of peripheral vestibular system, and a treatment could be done in the same session. The diagnosis of posttraumatic BPPV is not different from the idiopathic form, but the treatment may require more maneuvers to achieve satisfactory results.

Spontaneous nystagmus in benign paroxysmal positional vertigo.

OBJECTIVE: The purpose of this study was to evaluate the presence and eventually to study the features of spontaneous nystagmus (Ny) in our patients with diagnosis of benign paroxysmal positional vertigo (BPPV). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients who presented with vertigo spells and were managed at our tertiary care referral center. Patients with only idiopathic BPPV presenting with typical vertigo spells and positioning Ny characteristic of the disease were included in this study. To investigate the positioning Ny, we studied the patients in the sitting position, during the head shaking test, and during the Dix-Hallpike test and the McClure-Pagnini test (Ny provoked by rotation of the head in a supine patient). Ny responses in all patients were observed using infrared videoscopy. RESULTS: We managed 412 patients affected by BPPV. Of the 412 patients, 292 (70.87%) were diagnosed to be having posterior canal-BPPV and 110 (26.99%) patients had horizontal canal-BPPV (HC-BPPV). The remaining 10 patients (2.44%) were identified to have anterior canal-BPPV. Spontaneous Ny in sitting position was observed, by infrared videoscopy, only in the patients affected by HC-BPPV. CONCLUSION: Spontaneous Ny in BPPV can be observed with infrared videoscopy in patients affected by HC-BPPV. The origin of this Ny is most likely due to a natural inclination of horizontal semicircular canal with respect to the horizontal plane. This Ny stops after flexion of the head in neutral position, and for this reason, it should be considered as a seemingly spontaneous Ny. This Ny, in our experience, is observed in most HC-BPPV patients but does not indicate the need for a different management protocol or any different prognostic value of HC-BPPV.

Treatment of sudden sensorineural hearing loss with transtympanic injection of steroids as single therapy: a randomized clinical study.

The aim of this study was to verify the efficacy and the safety of transtympanic dexamethasone to treat sudden sensorineural hearing loss as first and single drug method. Considering ethical implication of performing a mininvasive procedure on middle ear, we matched such proposed treatment with systemic prednisone administration that represents the widest adopted protocol. Randomized prospective study was conducted. The inclusion criterion was a sudden sensorineural hearing loss of at least 30 dB across three contiguous frequencies over a period of 24 h. Group A received transtympanic steroid injections; Group B received oral administration of steroids. 25 patients were treated with transtympanic therapy whereas 21 underwent systemic treatment. The mean of initial PTA was 59 dB for the whole series: 65 dB for group A and 51 dB for group B. The recovery better than 10 dB was obtained in 80% of patients of group A and in 17 81% of patients of group B, with a total of 80.5%. The mean relative gain in PTA was 41.16% in the group A and 44.7% in the group B. In the frequencies tested (0.5, 1, 2, and 4 kHz) PTA improvements after transtympanic treatment were higher than after systemic treatment, but these differences were not statistically significant (P = 0.61). Both transtympanic and systemic treatment had similar clinical recovery times. This prospective randomized clinical study showed good result in terms of hearing recovery, better than the expected results of the simple observation without treatment. We can consider transtympanic administration as a first line treatment, because of the statistical analysis confirmed similar results with systemic therapy, reducing possible side effects of systemic drug administration. The delay of treatment does not influence the outcome, allowing treating patients within 10 days of onset.

Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue.

As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116-734 µm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals (P=0.02). The vasorelaxing response to canagliflozin was not modified (P=0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H2O2 scavenging (catalase); also, canagliflozin-induced relaxation was similar (P=0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na+/H+ exchanger 1 inhibitor BIX (P=0.67), but greater than that to the Na+/Ca++ exchanger inhibitor SEA 0400 (P=0.001), hinting a role of Na+/H+ exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide (P=0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.

Changes in Speech Range Profile Are Associated with Cognitive Impairment.

BACKGROUND AND PURPOSE: The aim of this study was to describe the variations in the speech range profile (SRP) of patients affected by cognitive decline. METHODS: We collected the data of patients managed for suspected voice and speech disorders, and suspected cognitive impairment. Patients underwent an Ear Nose and Throat evaluation and Mini-Mental State Examination (MMSE). To obtain SRP, we asked the patients to read 18 sentences twice, at their most comfortable pitch and loudness as they would do in daily conversation, and recorded their voice on to computer software. RESULTS: The study included 61 patients. The relationship between the MMSE score and SRP parameters was established. Increased severity of the MMSE score resulted in a statistically significant reduction in the average values of the semitones to the phonetogram, and the medium and maximum sound pressure levels (p<0.001). The maximum predictivity of MMSE was based on the highly significant values of semitones (p<0.001) and the maximum sound pressure levels (p=0.010). CONCLUSIONS: The differences in SRP between the various groups were analyzed. Specifically, the SRP value decreased with increasing severity of cognitive decline. SRP was useful in highlighting the relationship between all cognitive declines tested and speech.

Otoneurological management of petrous apex cholesterol granuloma.

OBJECTIVE: The aim of the study is to review the management of petrous apex cholesterol granuloma. The surgical approaches for drainage or total removal and the wait and see policy were analyzed, and outcomes were evaluated. METHODS: Retrospective charts of 27 patients managed for petrous apex cholesterol granuloma with a minimum follow-up of 12 months were analyzed in a quartenary skull base center. Presenting symptoms and signs were recorded, and radiologic imaging was evaluated. Management options included wait and see policy and surgery by several approaches. RESULTS: The mean age of patients affected by the lesion was 38.8 years. The mean follow-up was 56.7 months. Patients complained of hearing loss, vertigo, tinnitus, diplopia, hemifacial spasm, trigeminal neuralgia, and facial paresthesia. Twelve patients were managed by wait and see policy, and in this category, only one lesion showed growth during the follow-up. Depending upon size and location, 15 patients were surgically treated by infralabyrinthine approach (9 patients), infratemporal type B approach (3 patients), combined infratemporal type B transotic approach (2 patients), and transotic approach (1 patient). One recurrence was recorded during the follow-up. CONCLUSIONS: Radiologic evaluation is required for diagnosis and management. Patients with good hearing can be treated by infralabyrinthine approach. Infratemporal fossa type B approach is advocated in patients with extensive disease and internal carotid artery involvement. Wait and see policy is recommended for asymptomatic cases. Drainage and permanent ventilation are the goals of treatment. Complete removal is indicated in selected cases where placement of drainage tube is not feasible.