When orofacial pain needs a heart repair

Objectives: The association of chronic orofacial pain (COFP) and congenital heart disease has never previously been reported. We report the first case of COFP secondary to a right-to-left shunt (RLS) due to asymptomatic patent foramen ovale (PFO) in a patient with prothrombotic states. Materials and methods: A 48-year-old female patient presented with a 10-month history of left-sided facial pain who was initially diagnosed with persistent idiopathic facial pain (PIFP) on account of its similar characteristics. Magnetic resonance imaging (MRI) of the brain revealed gliosis and carotid siphon tortuosity; in addition, hyperhomocysteinaemia due to the homozygosis mutation for 5,10 MethyleneTetraHydroFolate Reductase was identified. Transcranial doppler ultrasonography was requested from a neurology consultant which revealed a high degree of RLS. Subsequently, a cardiological evaluation was performed; the specialist requested a transesophageal echocardiography that detected an interatrial septum aneurysm with PFO. Results: Based on the analysis of the patient's high degree of RLS, prothrombotic state and gliosis in relation to age, the cardiological consultant chose to perform a percutaneous closure of the PFO to avoid the risk of a cryptogenic stroke. After PFO closure, a complete remission of the pain was obtained. Conclusions: The disappearance of the pain supports the possible association between RLS and COFP. PFO with RLS has been suggested as a risk factor for cryptogenic stroke, especially in association with other thromboembolic risk factors. Therefore, the early detection, in this case, could be considered a possible lifesaver. Communication between different care providers is essential when the patient presents symptoms of facial pain which are of an atypical nature

Human Papilloma Virus Vaccination and Oropharyngeal Cancer: Knowledge, Perception and Attitude among Italian Pediatric Dentists

Background: Pediatric dentists could play a key role in the prevention of human papilloma virus (HPV)-related oropharyngeal cancer (OP-cancer). The aim of this study was to assess knowledge, perception, and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccination among Italian pediatric dentists. Methods: A cross-sectional study was conducted. Pediatric dentists received, by email, a link to participate in the questionnaire online. The questionnaire comprised four parts: (i) demographic information, (ii) knowledge on HPV-related OP-cancer, HPV infection, and HPV vaccine, (iii–iiii) perceptions and attitude on HPV-related OP-cancer, HPV infection, and HPV vaccine. Data were statistically analyzed with Kruskal–Wallis and Mann–Whitney test and Pearson’s chi-square test. Results: A total of 271 pediatric dentists completed the questionnaire. Results showed a good overall knowledge; a positive perception of their role in HPV disease prevention; a good attitude in discussing sensitive topics; a need for acquiring more information about HPV’s connection to cancer, HPV infection, and HPV vaccine. Conclusions: Improving educational training programs, as well as informing about prevention of HPV-related OP-cancer, will place pediatric dentists in the front line of HPV diseases primary prevention

The control on growth hormone release by free fatty acids is maintained in acromegaly

Free fatty acids (FFA) physiologically regulate GH release via a negative feedback. The aim of this study was to examine whether such feedback is preserved in acromegaly, a condition in which alterations in other regulatory mechanisms of GH release occur. Eight acromegalic patients (group 1: five women and three men, 43.0 +/- 4.2 yr old, mean +/- SE) received per os on two different days, at a 3 day-interval, in a random order, placebo or 250 mg of acipimox, an inhibitor of lipolysis analogous to nicotinic acid, at 0700 and 1100 h. In both tests GHRH (1-29 NH2), 50 microg, was administered i.v. at 1300 h. Blood samples for GH, FFA, immunoreactive insulin (IRI), and glucose were taken from 0900 to 1500 h, and the time period considered for statistical analysis was 1200-1500 h, representative of steady-state condition for FFA, IRI, and glucose. Mean plasma FFA levels (1200-1500 h) were significantly lower after acipimox than after placebo (0.05 +/- 0.01 vs. 0.17 +/- 0.01 g/L, P < 0.01). In contrast, both mean basal GH levels (1200-1300 h) and the mean GH response to GHRH (GH delta area, 1300-1500 h) were significantly higher after acipimox than after placebo (12.0 +/- 1.9 vs. 7.8 +/- 1.2 microg/L, P < 0.01; 2937 +/- 959 vs. 1154 +/- 432 microg/L x 120 min, P < 0.01). The increase in both basal GH levels and GH delta area occurred in all eight patients. Acipimox also reduced mean serum IRI (83 +/- 12 vs. 112 +/- 14 pmol/L) and blood glucose (5.1 +/- 0.1 vs. 5.7 +/- 0.1 mmol/L) levels, as compared with placebo (P < 0.03 or less). Eight acromegalic patients (group 2: six women and two men, 46.6 +/- 5.7 yr old) underwent a constant i.v. 10% lipid infusion (150 mL/h), started at 0900 h and continued until 1500 h. Mean plasma FFA levels (1200-1500 h) were significantly higher during lipid infusion than after placebo (0.27 +/- 0.01 vs. 0.16 +/- 0.01 g/L, P < 0.02); in contrast, mean basal GH levels (1200-1300 h) were reduced by lipid infusion, as compared with placebo (9.9 +/- 3.1 vs. 16.6 +/- 4.4 microg/L, P < 0.01), and the same occurred for the GH delta area after GHRH (2498 +/- 1643 vs. 4512 +/- 1988 microg/L x 120 min, P < 0.01). Serum IRI and blood glucose levels were similar after placebo and during lipid infusion. These data indicate that, in acromegaly, the acute reduction of circulating FFA levels results in increased GH release, whereas the increase in circulating FFA levels is accompanied by a reduced GH release. Taken together, these findings suggest that, in acromegaly, the control of FFA on GH release is preserved

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). Materials and Methods: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). Results: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group −0.1% [−0.5%−0.3%] vs. control group −0.1% [−0.4%−0.2%]; p =.482). Also, no difference was found in ΔBMI (p =.316) or ΔGlucose (p =.538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p =.041 for the trend among PGWBS tertiles) and BMI (p =.022). Conclusions: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report

BACKGROUND: The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. CASE PRESENTATION: The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. CONCLUSION: This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms

HSP 27 aspossible prognostic factor in patients with oral squamous cell carcinoma.

Summary. HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stressinduced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. Materials and methods: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. Results: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor (“mosaic” pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. Conclusion: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers

Pharmacokinetics and pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in mice and non-human primates

Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer

Clinical features of patients with type 2 diabetes with and without Covid-19: a case control study (CoViDiab I)

Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. Results: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59–3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42–9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18–8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13–0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12–0.54, p &lt; 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16–0.93, p = 0.033) were found among cases. Conclusions: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes