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La demenza e una patologia strettamente correlata all’invecchiamento che interessa circa 50 milioni di persone nel mondo, con un notevole impatto socio-economico; la malattia di Alzheimer rappresenta piu del 50% dei casi. Sebbene non esistano attualmente terapie in grado di modificare significativamente la progressione di malattia, la necessita di una diagnosi precoce ha portato a un crescente interesse per i fattori di rischio modificabili, ponendo l’accento sulla complessa interazione tra sistema endocrino e funzioni cognitive.

BackgroundPrevious studies have shown increased risk of fracture in older patients with poor or strict glycemic control (glycated hemoglobin, HbA1c, ≥ 8% or < 6-7% respectively); however, these reports did not investigate the oldest-old population. Comprehensive geriatric assessment (CGA) and a patient-centered approach have been proven to improve the quality of care in the management of Type 2 Diabetes Mellitus (T2DM) in the older patients, but data regarding T2DM in patients with fragility fractures are still lacking.AimTo investigate the prognostic role of HbA1c and frailty level in older diabetic patients admitted for hip fracture.MethodsProspective observational cohort study conducted on diabetic geriatric patients consecutively hospitalized for hip fracture in the orthogeriatric unit of a tertiary care hospital. Preoperative comprehensive geriatric assessment (CGA) was performed. Using the Clinical Frailty Scale (CFS), diabetic patients were categorized in robust (CFS < 5) and frail (CFS ≥ 5), and further stratified according to HbA1c values [Tertile 1 (T1) HbA1c < 48 mmol/mol, Tertile 2 (T2) 48-58 mmol/mol and Tertile 3 (T3) > 58 mmol/mol). Comparisons between continuous variables were performed with analysis of non-parametric test for independent samples, while relationships between categorical variables were assessed by chi-square test. Using logistic multivariate regression, we evaluated the determinants of 1-year all-cause mortality in diabetic older patients with hip fracture.ResultsAmong the 1319 older patients (mean age 82.8 ± 7.5 years, 75.9% females) hospitalized for hip fracture, 204 (15.5%) had a previous diagnosis of T2DM. T2DM patients showed an increased proportion of multiple concurrent fractures occurred during the accidental fall or syncope (12.7% vs 11.2%, p=0.02). One-year mortality after hip fracture surgery was significantly higher in T2DM as compared to not diabetic patients (21.2% vs 12.5%, pvs 5%, p=0.001 for T2 and 43.5% vs 13.3%, p=ConclusionsFrail patients with HbA1c ≥ 48 mmol/L showed an increased mortality risk as compared to robust counterparts. CFS represents an important tool to select diabetic subjects with higher likelihood of adverse outcome.

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed.

Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development. 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy–Weinberg equilibrium was performed. None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development. Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

The aim of this single-center, open-label, randomized controlled study was to evaluate which formulation of vitamin D—between cholecalciferol and calcifediol—is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history, and comprehensive geriatric assessment were recorded at admission. Eligible patients were randomly assigned an equivalent vitamin D supplement, either with cholecalciferol or calcifediol, from the time of hospital admission to three months after discharge. Among the 140 older patients included (mean age 83 ± 6.6 years, 57.8% females), 69 received cholecalciferol and 71 received calcifediol. The mean plasma values of 25-hydroxyvitamin D3 (25OH-vitamin D3) found at the time of enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p = 0.31). At the three month follow-up, the mean concentration of 25OH-vitamin D3 was significantly higher in patients treated with calcifediol than in those receiving cholecalciferol (30.7 ± 8.4 vs. 45.4 ± 9.8 ng/mL, respectively; p < 0.001). Supplementation with either cholecalciferol or calcifediol effectively results in reaching the optimal circulating values of 25OH-vitamin D3 in older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH-vitamin D3 that were significantly higher (over 50%) than those obtained with cholecalciferol.

In this paper we will consider the results of the investigation of ceramic shards from four Neolithic sites located in the south-east of Albania using different analytical methods. The sites of Vashtemi, Podgori, Dunavec and Maliq, situated at the plateau of Korca, represent the Neolithic culture at the different stages from Early Neolithic to Eneolithic. The application of EDXRF, micro-XRF, XRD and Optical Microscopy (OM) allowed us to collect data on the mineralogical and elemental composition of the ceramics and the materials used for the external decorations. The results indicate that coarse to medium coarse, non-calcareous clays were used for the ceramic manufacture in all the sites. Mineral inclusions rich in Si, Ca, K, and Fe were identified, some of which could have been intentionally added to the clays during the production process. The similarities of the elemental composition of the shards indicate that the ceramics in each site were prepared from different clay deposits that should have been close to each site. Minerals rich in Ca, Fe and Mn have been used respectively for the white, red and dark brown surface decorations, while bitumen has been applied after the firing in a black decoration.

Hypothyroidism is characterized by increased thyrotropin (TSH) levels and reduced free thyroid hormone fractions while, subclinical hypothyroidism (sHT) by elevated serum TSH in the face of normal thyroid hormones. The high frequency of hypothyroidism among the general population in Western Countries made levothyroxine (LT4) one of the 10 most prescribed drugs. However, circulating TSH has been demonstrated to increase with aging, regardless the existence of an actual thyroid disease. Thus, when confronting an increase in circulating TSH levels in the elderly, especially in the oldest old, it is important to carry an appropriate diagnostic path, comprehensive of clinical picture as well as laboratory and imaging techniques. In the current review, we summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly-therapy. The treatment of choice for hypothyroid patients is hormone replacement with LT4 but, it is important to consider multiple factors before commencing the therapy, from the age dependent TSH increase to the presence of an actual thyroid disease and comorbidities. When treatment is necessary, a tailored therapy should be chosen, considering poly-pharmacy and frailty. A careful follow-up and treatment re-assessment should be always considered to avoid the risk of over-treatment. It is important to stress the need of educating the patient for a correct administration of LT4, particularly when poly-therapy is in place, and the importance of a tailored therapeutic approach and follow-up, to avoid overtreatment.

L’ipotiroidismo e frequente negli anziani ed e noto l’incremento del TSH con l’invecchiamento. Un valore di TSH >10 mU/L e generalmente rilevante. La necessita di terapia sostitutiva con LT4 va valutata caso per caso, bilanciando attentamente i rischi e i benefici del trattamento e ponendo al centro dell’iter diagnostico-terapeutico non solo i livelli di TSH circolante, ma anche la presenza o meno di una effettiva patologia tiroidea cosi come le comorbidita e l’eventuale presenza di “fragilita”.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Thyroid nodules are common in the general population and vary widely in their propensity to harbor thyroid malignancies. The category of follicular lesion of undetermined significance, for instance, carries only a 15% risk of malignancy. The overarching aim of this work was the proteomic study of thyroid cancer because more effort needs to be placed on differentiating malignant thyroid nodules to avoid unnecessary thyroidectomy. We used 2-dimensional electrophoresis coupled to nano-liquid chromatography electrospray ionization tandem mass spectrometry, to examine fine-needle aspiration (FNA), which was easily attainable from the wash of the syringe used for classical FNA biopsy. Overall, we found 25 different proteins able to discriminate benign from malignant samples. The different expression of moesin; annexin A1 (ANXA1); cornulin (CRNN); lactate dehydrogenase; enolase; protein DJ-1; and superoxide dismutase was confirmed in FNA by enzyme-linked immunosorbent assay or Western blot. Receiver operating characteristic curves were calculated to investigate the discriminative power of our marker. The best performance in diagnosis was obtained by combining ANXA1, enolase, protein DJ-1, superoxide dismutase, and CRNN. In addition, the most highly ranked proteins, from the perspective of follicular lesion of undetermined significance, were ANXA1 and CRNN. The research of these candidate biomarkers has then been widened to other biological fluids, such as serum and whole saliva. In conclusion, we believe that when a decision by a thyroid nodule biopsy cannot be distinctly made, the combination of our biomarkers may be one of the criteria to be taken into account for the final decision, together with the identification of ANXA1 in serum and saliva.

L’ipertiroidismo e una sindrome caratterizzata da un eccesso di sintesi e secrezione di ormoni tiroidei (OT). La forma conclamata e caratterizzata da aumento degli OT liberi circolanti con TSH soppresso; l’ipertiroidismo subclinico e invece definito dalla presenza di livelli di TSH inferiori ai limiti della norma e OT liberi entro il “range” di riferimento. Le cause piu frequenti di ipertiroidismo nell’anziano sono il gozzo multinodulare (60%), specialmente nelle aree a carenza iodica, e l’adenoma (30%), piu raro l’ipertiroidismo autoimmune. Nel paziente anziano e molto importante eseguire una corretta anamnesi e un attento esame obiettivo, poiche i segni e i sintomi di ipertiroidismo possono essere sfumati (ipertiroidismo apatetico). La tireotossicosi iodio-indotta e piu frequente nell’anziano rispetto al giovane, spesso determinata dall’utilizzo di farmaci (amiodarone) o dall’esecuzione di esami radiologici con mezzo di contrasto iodato. I soggetti anziani sono piu vulnerabili agli effetti dell’ipertiroidismo (subclinico e conclamato), soprattutto per cio che attiene l’apparato cardiovascolare, il metabolismo osseo, il metabolismo intermedio e il sistema nervoso centrale. E generalmente opportuno trattare anche l’ipertiroidismo subclinico al fine di prevenire le complicanze cardiovascolari e metaboliche, soprattutto nel “grande anziano” (>80 anni) e nei pazienti con preesistente patologia cardiovascolare e/o metabolica. La strategia terapeutica da intraprendere deve essere sempre modulata sul singolo paziente considerando i potenziali rischi del trattamento oltre allo stato generale in termini di prognosi globale, complessita clinica e fragilita.

ObjectiveMicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules.DesignIn this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA.MethodsThe prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed.ResultsUsing data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules.ConclusionsThe expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method.

The monitoring of organic matter, suspended or dissolved in the water column, is relevant for the study of the aquatic environment. Actually, the Dissolved Organic Matter (DOM) represents a major reservoir of reactive carbon in the global carbon cycle, thus influencing significantly the marine ecosystem. Due to the strong absorption in the near ultraviolet, DOM reduces considerably the extinction path of solar light in the water column, affecting phytoplankton population and its vertical distribution. The measurement of the DOM absorption coefficient has to be regarded as a good parameter for the monitoring of water quality. This paper deals with the measurements carried out during the oceanographic campaign 'Marine Fronts,' which took place in the Western Mediterranean Sea and Atlantic Ocean from July 14 to August 5, 1998. In this measurement campaign, a high spectral resolution fluorescence lidar (FLIDAR) was installed on the rear-deck of the O/V 'Urania,' acquiring remote fluorescence spectra both in ship motion and in stations. A particular attention was devoted to the monitoring of DOM distribution in the different water masses in marine frontal areas. The lidar data were compared and integrated with SST satellite data and biological samplings. The results show that FLIDAR data agree with satellite imagery, particularly for marine front detection. The comparison with water sample data gave indications for retrieving the DOM absorption coefficient directly from fluorescence remote spectra. In addition, a protein like fluorescence band was detected in the measurements carried out on total suspended matter filtered from the water samplings.

Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n = 114), papillary classical variant (cPTC) (n = 34) and papillary tall cell variant (TcPTC) (n = 14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.