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We analysed the embryonic epidermis of the pool frog, Pelophylax lessonae, by light and electron microscopy techniques, and characterized preliminarily its mucous secretions with conventional histochemistry (Toluidine Blue, Periodic Acid-Schiff, Alcian blue pH 2.5 and Alcian blue pH 1.0). At Gosner's developmental stage 21, the epidermis consisted of a bilayered epithelium with five cell types. Basal cells (BCs) constituted the basal layer, presented a large nucleus and were sometimes observed in mitosis. Ciliated cells (CCs) had a ciliated apical membrane, with carboxylated glycans in the sub-apical portion. TEM analysis revealed small vesicles just below the surface, a central nucleus, and evident yolk plates. Goblet cells (GCs) and small secretory cells (SSCs) showed secreting vesicles and vacuoles, respectively. In the mucus secretion of GCs sialosulphomucins appeared, while in that of SSCs sulphation was not observed. Under TEM, GCs had irregular shaped nuclei and a less electron-dense cytoplasm with respect to SSCs. Ionocytes (INs) presented apical microvilli and a high electron-dense cytoplasm with vacuoles. SEM analysis revealed that GCs outnumbered the other cell types and that SSCs and INs were usually located together near to GCs. The relatively simple structure of the epidermis and its direct interfacing with the environment renders it a good model for the study of structure and development of mucociliary epithelia, as well as of its alterations in the presence of toxicants. Highlights: The embryonic epidermis of Pelophylax lessonae reveals a good model for the study of mucociliary epithelia. The embryonic epidermis of Pelophylax lessonae is made of two layers and five cell types. In the basal layer, there are basal cells, and in the apical layer, ciliated, goblet, and small secretory cells are found, as well as ionocytes. Goblet cells present secreting vesicles with sialosulphomucins. Small secretory cells show apical vacuoles with sialomucins only. [ABSTRACT FROM AUTHOR]

Context Current evidence of cardiovascular (CV) risk in primary hyperparathyroidism (PHPT) is still inconsistent. Objective To prospectively investigate changes of early atherosclerosis in patients with PHPT undergoing parathyroidectomy (PTx) or conservative management, according to consensus criteria. Methods Biochemical parameters of PHPT, CV risk factors (systolic and diastolic blood pressure, cholesterol [total, high-density, and low-density], triglyceride, HbA1c, HOMA-IR), and carotid intima-media thickness (IMT) and plaque were assessed in 52 consecutive postmenopausal PHPT patients both at baseline and ≥ 24 months after surgery (PTx, n = 22) or conservative management (non-PTx, n = 30). Results At baseline, PTx and non-PTx showed comparable age, BMI, renal function, and 25(OH)D levels, and did not differ for CV risk factors, IMT and plaques, or for prevalence of smoking, diabetes mellitus, or antihypertensive or statin therapy, while all parameters characterizing PHPT differed. Follow-up duration in PTx was longer than in non-PTx (P =.004). Parameters characterizing PHPT significantly improved ≥ 24 months after surgery, whereas in non-PTx serum phosphate slightly decreased and parathyroid hormone increased. Systolic and diastolic blood pressure increased at follow-up in both groups, while other CV risk factors did not significantly vary. In PTx, IMT did not significantly vary after surgery (0.85 ± 0.14 to 0.89 ± 0.22 mm, P =.366), whereas it significantly increased in non-PTx (0.80 ± 0.18 to 0.93 ± 0.23 mm, P =.008), even adjusting for blood pressure. Plaque prevalence and incidence did not significantly differ in the 2 groups. Conclusion Our results suggest that in postmenopausal patients with PHPT, subclinical atherosclerosis could be halted by PTx, whereas it worsens over time in nonoperated patients with milder disease. [ABSTRACT FROM AUTHOR]

Background: There are few and controversial results on 24,25(OH)2D and FGF23 acute changes following supplementation with cholecalciferol. Methods: Twenty-seven subjects with 25(OH)D < 30 ng/mL were randomized into three groups to receive a single oral dose of 25,000 I.U. or 600,000 I.U. of cholecalciferol or placebo, respectively. We measured 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and FGF23 levels at baseline and after 72 h. The 1,25(OH)2D/25(OH)D, 1,25(OH)2D/24,25(OH)2D, and 24,25(OH)2D/25(OH)D ratios were also calculated. Results: There was an increase in 25(OH)D and 1,25 (OH)2D following both doses of cholecalciferol. In the group administered 600,000 I.U., there was a significant increase in the delta changes in 25(OH)D and 1,25(OH)2D compared to the placebo and in the delta 24,25(OH)D2 compared to the placebo and 25,000 I.U. groups (all p < 0.05). A decrease in both the 1,25(OH)2D/25(OH)D and 1,25(OH)2D/24,25(OH)2D ratio (all p < 0.05) was observed in the 600,000 I.U. group. FGF23 values significantly increased only in the group administered 600,000 I.U. Conclusions: 25(OH)D and 1,25(OH)D levels significantly increased following 600,000 IU cholecalciferol administration compared to 25,000 I.U. and placebo. Following the massive administration of cholecalciferol, the CYP24A1 enzyme is actively involved in catabolism, thus, avoiding toxic effects. [ABSTRACT FROM AUTHOR]

Context The risk of vertebral fractures (VFx) in patients with nonfunctioning adrenal incidentalomas (NFAI) is unknown. Objective This work aimed to assess in NFAI patients the prevalence and incidence of VFx and a hormonal marker to identify patients at risk. Methods A retrospective, cross-sectional, and longitudinal study of outpatients was conducted. A total of 306 NFAI patients (cross-sectional arm) and 213 controls were evaluated for VFx prevalence; 85 NFAI patients (longitudinal arm, follow-up 30.3 ± 17.5 months) were evaluated for VFx incidence. Main outcome measures included serum cortisol after 1 mg-dexamethasone test (F-1mgDST), lumbar spinal (LS), and femoral neck (FN) bone mineral density (BMD) and VFx presence, by radiograph of the spine. Results Cross-sectional arm: prevalent VFx associated with F-1mgDST with a cutoff of 1.2 µg/dL (33 nmol/L, area under the curve 0.620 ± 0.39; P =.002). Compared with controls and NFAI patients with F-1mgDST less than 1.2 µg/dL (group A), NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (group B) showed a higher VFx prevalence (10.8%, 12.6%, and 29.5%, respectively; P <.001 all comparisons), which was associated with F-1mgDST greater than or equal to 1.2 µg/dL (odds ratio 3.02; 95% CI, 1.63-5.58; P <.001) accounting to confounders. Longitudinal arm: the VFx incidence was higher in group B than in group A (19.3% vs 3.6%; P =.05). In group B, all incident VFx occurred in patients without low BMD. The F-1mgDST cutoff for predicting an incident VFx was 1.2 µg/dL, although statistical significance was not reached after adjustment for confounders (P =.061). Conclusion In NFAI patients, F-1mgDST levels greater than or equal to 1.2 µg/L (33 nmol/L) are associated with prevalent VFx and may identify patients at risk of incident VFx. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs) are important for water transport in the gastrointestinal tract. Changes in their expression and/or localization could cause in disorders and be used as therapeutic targets. Aquaporin‐4 (AQP4) is expressed predominantly on the basolateral membrane of the parietal cells in the corpus of the murine gastric glands. Although the secretion of gastric juice is not affected in AQP4‐deficient knockout, we evaluated by light microscopy whether the lack of AQP4 affects the glycopatterns of secreting gastric cells. Wild type (WT) and AQP4‐deficient knockout mice (KO) were fed a standard diet ad libitum before sacrifice. Segments of stomach corpus were collected, fixed in buffered formalin, and embedded in paraffin wax. Sections, 5‐μm thick, were analyzed by histochemical methods (Periodic acid‐Schiff, Alcian Blue pH 2.5), and binding of lectins specific to GalNAc (SBA, DBA), Gal (PNA) GlcNAc (WGA, GSAII) mannose and/or glucose (ConA), and fucose (UEA‐I, AAA, LTA). Immunohistochemical methods such as anti‐Muc6 for neck cells and anti‐ β‐ H+/K+‐ATPase for parietal cells were also performed. Compared to WT mice, in the mucous cells of KO lower amounts of glycans with galactosyl/galactosaminylated, glycosyl/glycosaminylated, and fucosylated residues were observed; lower fucosylation resulted also in the parietal cells. The observed differences of KO in respect to WT could lead to severer pathological conditions. Research Highlights: Glycopatterns in gastric glands were compared between wild type (WT) and AQP4‐deficient knockout (KO) mice by histochemical and lectin‐binding methods.In the mucous cells of KO lower amounts of glycans with galactosyl/galactosaminylated, glycosyl/glycosaminylated and fucosylated residues were observed.In the parietal cells lower fucosylation also resulted.AQP4‐deficiency affects glycosylation and could result in altered functionality and pathological conditions. [ABSTRACT FROM AUTHOR]

Aluminum (Al) is used in everyday life and present in food drugs, packaging, industry, and agriculture. Although it is the most common metal in the Earth crust, a correlation has been demonstrated between its presence and various pathologies, even serious ones, especially of a neurological type. However, there is a histological gap regarding the role Al can have in contact with the covering and secreting epithelia. The alterations of the ventral and dorsal foot mucocytes and their secretions of the snail Eobania vermiculata caused by Al were investigated in situ by histochemical and lectin‐histochemical techniques. Administration to different experimental groups took place for 3 and 9 days with 50 and 200 μM of AlCl3. Several types of mucocytes were detected with a prevalent secretion of acid glycans in the foot of E. vermiculata. Sulfated glycans prevail in the dorsal region, with one type showing only fucosylated residues and another also having galactosaminylated and glycosaminylated residues. Carboxylated glycans prevail in the ventral region, with presence of galactosaminylated, glycosaminylated, and fucosylated residuals in both cells. Snails treated presented a general decrease of mucin amount in the secreting cells and affected the mucus composition. These changes could alter the rheological and functional properties of the mucus with possible implications for the health of the treated animals. Research Highlights: Snails were fed with Al‐contaminated lettuce at different concentrations.In the foot mucocytes produced mucus with prevailing acidic glycans.In the treated resulted a reduction in the amount of mucus and an alteration of glycan composition. [ABSTRACT FROM AUTHOR]

Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGFβ) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGFβ signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGFβ transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is a rare endocrine neoplasm that typically presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, and neuropsychiatric symptoms. We describe the case of a 48-year-old woman, presenting with a large painful hematoma in the cervicomediastinal area. The neck ultrasound (US) demonstrated a solid lesion measuring 40 × 80 × 55 mm, markedly hypoechoic, which extended from the right thyroid lobe to the mediastinum. The blood tests showed elevated serum calcium and parathyroid hormone (PTH) concentrations, consistent with hypercalcemic primary hyperparathyroidism. The patient was rehydrated and treated with furosemide, cholecalciferol, and bisphosphonate, and underwent right lower parathyroidectomy, right hemithyroidectomy, and lymphadenectomy of the right VI cervical level. Histological examination was diagnostic for nonangioinvasive or neuroinvasive PC, and the thyroid lobe was the site of lymphocytic thyroiditis; all removed lymph nodes were benign. The postoperative course was regular. Postoperative neck US showed a hypoechoic left thyroid lobe without evidence of residual neoplasm in the right thyroid bed. Levothyroxine therapy of 50 mcg/day was started because of serum thyrotropin concentrations elevated at 18 mcIU/mL (normal reference range, 0.35-4.0 mIU/mL). Eight years after diagnosis, the patient is in good general condition, with no clinical, biochemical, or imaging evidence of disease persistence/recurrence. [ABSTRACT FROM AUTHOR]

Context The risk of vertebral fractures (VFx) in patients with adrenal incidentalomas (AI) and mild autonomous cortisol secretion (MACS) is debated. Objective To evaluate the VFx prevalence and incidence in patients with AI and MACS. Methods This cross-sectional and longitudinal study using retrospective data from 4 Italian endocrinology units included 444 patients (cross-sectional arm) and 126 patients (longitudinal arm, 24.9 ± 5.3 months follow-up) to evaluate prevalent and incident VFx, respectively, in patients with MACS (MACS-yes) and without MACS (MACS-no). The main outcome measures were serum cortisol after a 1-mg dexamethasone test (F-1mgDST), bone mineral density (BMD) by dual-energy x-ray absorptiometry at spine (LS) and femur (FN), and VFx presence by x-ray. Results Cross-sectional arm: 214 and 230 patients were MACS-yes and MACS-no, respectively, based on F-1mgDST >1.8 µg/dL (50 nmol/L). Patients with MACS had higher VFx prevalence (62.6%) than those without MACS (22.9%, P <.001); MACS was associated with prevalent VFx (odds ratio, 5.203; 95% CI, 3.361-8.055; P <.001; relative risk [RR] 2.07), regardless of age, body mass index, gender distribution, LS-BMD, and presence of type 2 diabetes mellitus (T2D). Longitudinal arm: 66 and 60 patients were MACS-no and MACS-yes, respectively. Patients without MACS showed higher number of incident VFx (36.4%) than patients without MACS (10.0%, P <.001); MACS was associated with the presence of an incident VFx (RR 4.561; 95% CI, 1.600-13.003; P =.005) regardless of age, LS-BMD, gender distribution, presence of prevalent VFx, and T2D. Results were confirmed in women and men when separately evaluated. Conclusion Women and men with AI and MACS are at higher risk of VFx. [ABSTRACT FROM AUTHOR]

The Eurasian beaver (Castor fiber) became extinct in Italy between the end of the 16th century and the beginning of the 17th century. A few animals were recorded at the border with Austria in 2018 and 2020. Between 2021 and 2023, beavers were reported in six Central and Southern Italy areas at more than 350-400 km from the nearest colonies. Following an official position by the Italian Mammal Society, this paper aims to explore the possible origin of these nuclei, suggests their removal and provide an analysis of the concerns and management recommendations. Given the distances between beaver locations in Central and Southern Italy and the rapid appearance of numerous small nuclei with few individuals in just a couple of years, the most plausible explanation is multiple unlawful releases. Unplanned and unauthorised reintroductions are unacceptable in terms of a sound wildlife management approach and represent a dangerous precedent stimulating further unlawful release of mammals. Therefore, we urge competent authorities to remove these animals from the field. [ABSTRACT FROM AUTHOR]

An in situ analysis of mucin secretions along the annual cycle was performed on the striped Venus clam, Chamelea gallina. Individuals of both sexes from an exploited stock of Margherita di Savoia (Southern Adriatic Sea, Central Mediterranean Sea) were made in June 2020 and 2021, and in January 2021 and 2022, representative of summer and winter seasons, respectively. Tissues from the foot and the gills were analyzed for histochemical and lectin-histochemical analyses. Staining with Periodic Acid-Schiff, Alcian Blue pH 2.5 and High-Iron-Diamine indicated that mucins from both the foot and the gills were acidic, mostly sulfated. Lectin-binding analyses with PNA, SBA, WGA, LTA, UEA-I, AAA, SNA, MAA-II and ConA indicated the presence of N-acetyl-glycosaminylated, mannosylated and fucosylated residuals in the saccharidic chains. In the gills, the amount of acidic and glycosaminylated residuals was higher in summer in both sexes, whereas fucosylation was similar along the sampling period and mannosylation was never observed. In the foot, both surface epithelial and subepidermal secreting cells increased sulfation in winter in males, but not in females. Glycosaminylation and fucosylation were observed only in the surface cells of males. Mannosylated residuals were observed in all the foot cell types in both sexes. It is hypothesized that the observed qualitative and quantitative variations in mucin secretion is linked to the reproductive cycle. The mucocytes present in the gill filaments of the clam produce an acid mucus, with sulfate residues and N-acetylglucosamine and fucose chains. In the foot, the subepithelial mucocytes produce an acidic, sulfate secretion with mannosylated residuals. The foot epithelium shows an acidic, sulfated mucus composition with N-acetylglucosamine, fucose and mannose chains. The results show that males have greater variability in mucus composition. The observed variation could be related to different energy allocation between sexes in the development of gametes. [ABSTRACT FROM AUTHOR]

Background: Similarly to cortisol-secreting adrenal tumors, also non-functioning adrenal tumors (NFAT) may be associated with an increased cardiovascular risk. We assessed in NFAT patients: (i) the association between hypertension (HT), diabetes mellitus (DM), obesity (OB), dyslipidemia (DL) and cardiovascular events (CVE) and cortisol secretion; (ii) the cut-off of the cortisol secretion parameters for identifying NFAT patients with a worse cardiometabolic profile. Patients and methods: In 615 NFAT patients (with cortisol levels after 1 mg overnight dexamethasone suppression test, F-1mgDST < 1.8 µg/dL [50 nmol/L]) F-1mgDST and adrenocorticotroph hormone (ACTH) levels and data on HT, DM, OB, DL and CVEs prevalence were retrospectively collected. Results: HT, DM and HT plus DM were associated with F-1mgDST levels (area under the ROC curve: 0.588 ± 0.023, 0.610 ± 0.028, 0.611 ± 0.033, respectively, p < 0.001 for all comparisons) but not with ACTH. The cut-off for identifying patients with either HT or DM or HT plus DM was set at ≥ 1.2 µg/dL (33 nmol/L). As compared with patients with F-1mgDST < 1.2 µg/dL (n = 289), patients with F-1mgDST 1.2–1.79 µg/dL (33–49.4 nmol/L) (n = 326) had lower ACTH levels (17.7 ± 11.9 vs 15.3 ± 10.1 pg/mL, respectively, p = 0.008), older age (57.5 ± 12.3 vs 62.5 ± 10.9 years, respectively, p < 0.001), and higher prevalence of HT (38.1% vs 52.5% respectively p < 0.001), DM (13.1% vs 23.3%, respectively, p = 0.001), HT plus DM (8.3% vs 16.9%, respectively, p < 0.002) and CVE (3.2% vs 7.3%, respectively, p = 0.028). F-1mgDST 1.2–1.79 µg/dL was associated with either HT (odd ratio, OR, 1.55, 95% confidence interval, 95% CI 1.08–2.23, p = 0.018) or DM (OR 1.60, 95% CI 1.01–2.57, p = 0.045) after adjusting for age, gender, OB, DL, and DM (for HT) or HT (for DM), and with the presence of HT plus DM (OR 1.96, 95% CI 1.12–3.41, p = 0.018) after adjusting for age, gender, OB and DL. Conclusions: In NFAT patients, F-1mgDST 1.2–1.79 µg/dL seems to be associated with a higher prevalence of HT and DM and a worse cardiometabolic profile, even if the poor accuracy of these associations suggests caution in interpreting these results. [ABSTRACT FROM AUTHOR]

Background: Similarly to cortisol-secreting adrenal tumors, also non-functioning adrenal tumors (NFAT) may be associated with an increased cardiovascular risk. We assessed in NFAT patients: (i) the association between hypertension (HT), diabetes mellitus (DM), obesity (OB), dyslipidemia (DL) and cardiovascular events (CVE) and cortisol secretion; (ii) the cut-off of the cortisol secretion parameters for identifying NFAT patients with a worse cardiometabolic profile. Patients and methods: In 615 NFAT patients (with cortisol levels after 1 mg overnight dexamethasone suppression test, F-1mgDST < 1.8 µg/dL [50 nmol/L]) F-1mgDST and adrenocorticotroph hormone (ACTH) levels and data on HT, DM, OB, DL and CVEs prevalence were retrospectively collected. Results: HT, DM and HT plus DM were associated with F-1mgDST levels (area under the ROC curve: 0.588 ± 0.023, 0.610 ± 0.028, 0.611 ± 0.033, respectively, p < 0.001 for all comparisons) but not with ACTH. The cut-off for identifying patients with either HT or DM or HT plus DM was set at ≥ 1.2 µg/dL (33 nmol/L). As compared with patients with F-1mgDST < 1.2 µg/dL (n = 289), patients with F-1mgDST 1.2–1.79 µg/dL (33–49.4 nmol/L) (n = 326) had lower ACTH levels (17.7 ± 11.9 vs 15.3 ± 10.1 pg/mL, respectively, p = 0.008), older age (57.5 ± 12.3 vs 62.5 ± 10.9 years, respectively, p < 0.001), and higher prevalence of HT (38.1% vs 52.5% respectively p < 0.001), DM (13.1% vs 23.3%, respectively, p = 0.001), HT plus DM (8.3% vs 16.9%, respectively, p < 0.002) and CVE (3.2% vs 7.3%, respectively, p = 0.028). F-1mgDST 1.2–1.79 µg/dL was associated with either HT (odd ratio, OR, 1.55, 95% confidence interval, 95% CI 1.08–2.23, p = 0.018) or DM (OR 1.60, 95% CI 1.01–2.57, p = 0.045) after adjusting for age, gender, OB, DL, and DM (for HT) or HT (for DM), and with the presence of HT plus DM (OR 1.96, 95% CI 1.12–3.41, p = 0.018) after adjusting for age, gender, OB and DL. Conclusions: In NFAT patients, F-1mgDST 1.2–1.79 µg/dL seems to be associated with a higher prevalence of HT and DM and a worse cardiometabolic profile, even if the poor accuracy of these associations suggests caution in interpreting these results. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to overproduction of fibroblast growth factor 23 (FGF23), with profound effects on patient morbidity. TIO is an underdiagnosed disease, whose awareness should be increased among physicians for timely and proper management of patients. Symptoms reported by patients with TIO are usually nonspecific, thus rendering the diagnosis elusive, with an initial misdiagnosis rate of more than 95%. Biochemical features of TIO are represented by hypophosphatemia, increased or inappropriately normal levels of FGF23, and low to low normal circulating 1,25-dihydroxyvitamin D (1,25(OH)2D). Phosphaturic mesenchymal tumors are the pathological entities underlying TIO in most affected patients. There is now evidence that FN1-FGFR1 and FN1-FGF1 fusion genes are present in about half of tumors causing this paraneoplastic syndrome. Tumors causing TIO are small and grow slowly. They can occur in all parts of the body from head to toe with similar prevalence in soft tissue and bone. There are a number of functional and anatomical imaging techniques used for tumor localization; 68Ga DOTA-based technologies have better sensitivity. Surgery is the treatment of choice; several medical treatments are now available in case of inability to locate the tumor or in case of incomplete excision. [ABSTRACT FROM AUTHOR]

Irisin is a myokine synthesized by skeletal muscle, which performs key actions on whole-body metabolism. Previous studies have hypothesized a relationship between irisin and vitamin D, but the pathway has not been thoroughly investigated. The purpose of the study was to evaluate whether vitamin D supplementation affected irisin serum levels in a cohort of 19 postmenopausal women with primary hyperparathyroidism (PHPT) treated with cholecalciferol for six months. In parallel, to understand the possible link between vitamin D and irisin, we analyzed the expression of the irisin precursor, Fndc5, in the C2C12 myoblast cell line treated with a biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Our results demonstrate that vitamin D supplementation resulted in a significant increase in irisin serum levels (p = 0.031) in PHPT patients. In vitro, we show that vitamin D treatment on myoblasts enhanced Fndc5 mRNA after 48 h (p = 0.013), while it increased mRNAs of sirtuin 1 (Sirt1) (p = 0.041) and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) (p = 0.017) over a shorter time course. Overall, our data suggest that vitamin-D-induced modulation of Fndc5/irisin occurs through up-regulation of Sirt1, which together with Pgc1α, is an important regulator of numerous metabolic processes in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: The reproductive cycle of the recently described sponge Tethya meloni was investigated for a period of 15 months (September 2018 – November 2019) in the Mar Piccolo of Taranto (Southern Italy) and was compared with data previously collected for the other two sympatric species of the same genus known for Mediterranean Sea, T. citrina and T. aurantium. Results: T. meloni is a gonochoric species with a sex ratio strongly shifted towards females. Asexual budding was a seasonal process, limited to few specimens. In a specimen collected in September 2018 both oocytes and buds occurred, suggesting that in T. meloni the sexual and asexual phases may coexist both at the population and individual levels. Conclusions: The data obtained from this research compared with the available literature confirm the high temporal variability of the reproductive cycles in the Mediterranean species of Tethya, but with common general characteristics. In sexual reproduction, the oocyte production period lasts several months, with a peak between summer and autumn while spermatogenesis, shorter but with greater reproductive effort, follows the onset of oogenesis. The asexual reproduction phase of T. meloni, on the other hand, occurs in a short period and seems to have less importance in the overall reproductive process. [ABSTRACT FROM AUTHOR]

Objective: The best approach to patients with adrenal incidentaloma (AI) and possible autonomous cortisol secretion (PACS) is debated. The aim of this study was to assess the metabolic effect of adrenalectomy in AI patients with PACS in relation to cortisol secretion parameters, peripheral activation, and glucocorticoid sensitivity. Design: This is a multicenter randomized study (NCT number: NCT04860180). Methods: Sixty-two AI outpatients (40–75 years) with AI >1 cm and cortisol after overnight dexamethasone suppression test (F-1mgDST) between 50 and 138 nmol/L were randomized to adrenalectomy (Arm A) or a conservative approach (Arm B). Fifty-five patients completed the 6-month follow-up, 25 patients in Arm A (17 female patients, aged 62.5 ± 10.4 years) and 30 patients in Arm B (24 female patients, 66.1 ± 9.1 years). Plasma adrenocorticotroph hormone (ACTH), 24-h urinary free cortisol, 24-h urinary free cortisone, F-1mgDST, glucose, lipids, glycated hemoglobin (HbA1c) levels, blood pressure (BP), body weight, and treatment variations were assessed. The 24-h urinary free cortisol/cortisone ratio (an 11-beta hydroxysteroid dehydrogenase type 2 activity marker), BclI, and the N363S variants of glucocorticoid receptor (GR) polymorphisms were also evaluated. Results: BP control improved in 68% and 13% of the subjects in Arm A and Arm B, respectively (p = 0.001), and the glycometabolic control improved in 28% and 3.3% of the subjects in Arm A and Arm B patients, respectively (p = 0.02). Arm A subjects more rarely showed the BP and/or glycometabolic control worsening than Arm B patients (12% and 40%, respectively, p = 0.03). The surgical approach was independently associated with BP amelioration (OR 3.0, 95% CI 3.8–108.3, p < 0.001) but not with age, F-1mgDST levels, BMI, and hypertension and diabetes mellitus presence at baseline. The 24-h urinary free cortisol/cortisone ratio and the presence of sensitizing GR polymorphisms were not associated with the surgical outcome. The receiver operating characteristic (ROC) curve analysis showed that the BP control amelioration was associated with F-1mgDST [area under the curve (AUC), 0.82 ± 0.09 p = 0.012]. The F-1mgDST cutoff with the best compromise in predicting the BP amelioration was set at 75 nmol/L (sensitivity 77%, specificity 75%). Conclusions: AI patients with PACS benefit from surgery in terms of BP and glycometabolic control. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze variants of the gene glia l cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma. Design: We characterized 2 families with hypoparathyroidism and 19 wit h FIHP in which we examined the mechanism of action of GCM2 variants. Methods: Leukocyte DNA of hypoparathyroid individuals was Sanger sequen ced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses. Results: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid f amilies. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previo usly reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory doma in were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitro transcriptional activity, including increased stimulation of the PTH promoter. Conclusions: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide e vidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease. [ABSTRACT FROM AUTHOR]

The glycopatterns of the glycans secreted by the mucosa of stomach and duodenal ampulla of the striped dolphin, Stenella coeruleoalba were studied by histochemical (Periodic acid‐Schiff, Alcian Blue pH 2.5, High Iron Diamine) and lectin‐binding (SBA, DBA, PNA, WGA, MAA‐II, SNA, ConA, UEA‐I, AAA, LTA) techniques. The stomach can be divided into four compartments: main stomach, two connecting chambers and pylorus. The pylorus is followed by the duodenal ampulla. Mucins are secreted by surface cells and intramucosal glands specific for each compartment. In the main stomach glands, neck cells were weakly sulphated, with prevailing glycosaminylated, glycosylated/mannosylated, and fucosylated residuals. Parietal and chief cells in general were scarcely reactive. In the connecting chambers glands, there were high levels of sulphation, glycosaminylation, glycosylation/mannosylation, and fucosylation, the latter with more complex patterns than those observed in the main stomach glands. In the pyloric glands sulphated, glycosaminylated and fucosylated residuals decreased, whereas the opposite was observed for galactosyl/galactosaminylated residuals. Glycosylation patterns in the glands of the duodenal ampulla differed from those of the pyloric ones, with similar levels of sulphation, lower levels of galactosyl/galactosaminylation and glycosaminylation, and higher level of fucosylation. The results are compared with those available in literature. [ABSTRACT FROM AUTHOR]

Purpose: It has been hypothesized that specific early-life stress (ES) procedures on CD-1 male mice produce diabetes-like alterations due to the failure of negative feedback of glucocorticoid hormone in the pituitary. The aim of this study is to investigate the possible mechanism that leads to this pathological model, framing it in a more specific clinical condition. Methods: Metabolic and hypothalamic–pituitary–adrenal-related hormones of stressed mice (SM) have been analyzed immediately after stress procedures (21 postnatal days, PND) and after 70 days of a peaceful (unstressed) period (90 PND). These data have been compared to parameters from age-matched controls (CTR), and mice treated during ES procedures with oligonucleotide antisense for pro-opiomelanocortin (AS-POMC). Results: At 21 PND, SM presented an increased secretion of hypothalamic CRH and pituitary POMC-derived peptides, as well as higher plasmatic levels of ACTH and corticosterone vs. CTR. At 90 PND, SM showed hyperglycemia, with suppression of hypothalamic CRH, while pituitary and plasmatic ACTH levels, as well as plasma corticosterone, were constantly higher than in CTR. These values are accompanied by a progressive acceleration in gaining total body weight, which became significant vs. CTR at 90 PND together with a higher pituitary weight. Treatment with AS-POMC prevented all hormonal and metabolic alterations observed in SM, both at 21 and 90 PND. Conclusions: These findings show that these specific ES procedures affect the negative glucocorticoid feedback in the pituitary, but not in the hypothalamus, suggesting a novel model of ACTH-dependent hypercortisolism that can be prevented by silencing the POMC gene. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prevalence of less severe hypercortisolism (LSH) in fractured patients, and its association with hypertension, hyperglicemia, dyslipidemia, and obesity. Method: From July 2015 to October 2018 we enrolled all fractured patients admitted in our outpatient center for metabolic bone diseases, after exclusion of patients with secondary osteoporosis apart from diabetes and taking drugs known to affect bone metabolism. In all enrolled patients we collected data regarding gonadal status, history of diabetes, high blood pressure, dyslipidemia, and measured blood pressure, lipid profile, fasting glycaemia. Bone mass was measured with DXA at lumbar spine and femoral neck and the presence of fractures was evaluated with X-ray of thoracic and lumbar spine. All patients performed twice, 1 mg overnight dexametasone suppression test (DST) and, as confirmatory, 2day low-dose DST for diagnosing hypercortisolism. Results: We enrolled 101 fractured patients (75 females, 26 males), aged 65 ± 10.3 years. Five out of 101 (5.0%) patients were diagnosed as LSH. Fifty-five (54.5%) out of 101 were hypertensive, 57 (56.4%) dyslipidemic, 17 (16.8%) hyperglicaemic, 28(27.7%) obese patients. LSH tended to be associated to blood hypertension [5/5 vs 50/96 (Fisher exact test, p = 0.06) hypertensive patients]. Four out five LSH patients were hypogonadic. Conclusions: Our study confirms that a nonnegligible percentage of fractured subjects actually presents an unrecognized hypercortisolism. Accordingly, regardless of age, we suggest to screen for hypercortisolism all patients with established osteoporosis and in particular hypertensive subjects. [ABSTRACT FROM AUTHOR]

For an efficient allocation of the limited resources to alien species management, the most damaging species should be prioritised. Comparing alien species based on their impacts is not straightforward, as the same species can cause different types and magnitudes of impacts when introduced to different contexts, making it difficult to summarise its overall impact. The Environmental Impact Classification for Alien Taxa (EICAT) systematically summarises and compares detrimental impacts caused by alien populations to native biota and has been adopted by the International Union for Conservation of Nature. For each alien species, all reported impacts to native populations within the introduced range are classified into five levels of severity, from negligible impact to irreversible local extinction. Currently, EICAT only compares alien species based on their highest impact, thereby ignoring variation in impact magnitudes. Here, we used information on the variation in impact magnitudes of alien species to estimate their risks to cause high impacts if introduced to a novel environment. We demonstrate the usefulness of this approach by classifying the global impacts of alien ungulates. We found impact reports for 27 of the 66 alien ungulate species established worldwide, highlighting substantial knowledge gaps in invasion science. We classified a total of 441 impacts to native fauna and flora caused by these 27 species. Twenty‐six of the species were found to cause harmful impacts (native population declines or local extinctions). Mouflon (Ovis orientalis, Gmelin, 1774) and dromedary (Camelus dromedarius, Linnaeus, 1758) had a higher risk of causing local extinctions if introduced to a novel environment than sika deer (Cervus nippon, Temminck, 1838) and goats (Capra hircus, Linnaeus, 1758). Including risk of high impacts allows to discriminate among species with the same EICAT classification and improves alien species prioritisation for management. [ABSTRACT FROM AUTHOR]

Bone remodelling is a complex mechanism regulated by osteoclasts and osteoblasts and perturbation of this process leads to the onset of diseases, which may be characterised by altered bone erosion or formation. In this review, we will describe some bone formation-related disorders as sclerosteosis, van Buchem disease, hypophosphatasia and Camurati-Engelmann disease. In the past decades, the research focused on these rare disorders offered the opportunity to understand impor tant pathways regulating bone formation. Thus, the identification of the molec ular defects behind the etiopathology of these diseases will open the way for new therapeutic approaches applicable also to the management of more common bone diseases including osteoporosis. [ABSTRACT FROM AUTHOR]

Context: Cushing's syndrome frequently causes mental health impairment. Data in patients with adrenal incidentaloma (AI) are lacking.Objective: We aimed to evaluate psychiatric and neurocognitive functions in AI patients, in relation to the presence of subclinical hypercortisolism (SH), and the effect of adrenalectomy on mental health.Design: We enrolled 62 AI patients (64.8 ± 8.9 years) referred to our centers. Subclinical hypercortisolism was diagnosed when cortisol after 1mg-dexamethasone suppression test was >50 nmol/L, in the absence of signs of overt hypercortisolism, in 43 patients (SH+).Interventions: The structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders-5, and 5 psychiatric scales were performed. The Brief Assessment of Cognition in Schizophrenia (Verbal and Working Memory, Token and Symbol Task, Verbal Fluency, Tower of London) was explored in 26 patients (≤65 years).Results: The prevalence of psychiatric disorders was 27.4% (SH+ 30.2% vs SH- 21.1%, P = 0.45). SH+ showed a higher prevalence of middle insomnia (by the Hamilton Depression Rating Scale) compared with SH- (51% vs 22%, P = 0.039). Considering the Sheehan Disability Scale, SH+ showed a higher disability score (7 vs 3, P = 0.019), higher perceived stress (4.2 ± 1.9 vs 2.9 ± 1.9, P = 0.015), and lower perceived social support (75 vs 80, P = 0.036) than SH-. High perceived stress was independently associated with SH (odds ratio [OR] = 5.46, confidence interval 95% 1.4-21.8, P = 0.016). Interestingly, SH+ performed better in verbal fluency (49.5 ± 38.9 vs 38.9 ± 9.0, P = 0.012), symbol coding (54.1 ± 6.7 vs 42.3 ± 15.5, P = 0.013), and Tower of London (15.1 vs 10.9, P = 0.009) than SH-. In 8 operated SH+, no significant changes were found.Conclusions: Subclinical hypercortisolism may influence patients' mental health and cognitive performances, requiring an integrated treatment. [ABSTRACT FROM AUTHOR]

A role for long non‐coding RNAs (lncRNAs) in endocrine cancer pathogenesis is emerging. However, knowledge regarding their expression pattern, correlation with known genetic defects, and clinical implications in parathyroid tumors is still unclear. Here, we profiled 90 known lncRNAs in a first series of normal (PaN = 2), adenomatous (PAd = 12), and carcinomatous (PCa = 4) parathyroid glands and we confirmed deregulation of 11 lncRNAs using an independent cohort of patients (PaN = 4; PAd = 26; PCa = 9). Expression of lncRNAs was correlated with cytogenetic aberrations, status of genes multiple endocrine neoplasia 1 (MEN1) and cell division cycle 73 (CDC73), or clinical features. Globally, lncRNAs discriminate according to tissue histology. BC200 consistently identifies parathyroid cancers from adenomas and atypical adenomas. Loss‐of‐heterozygosity (LOH) at chromosomes 1, 11, 15, 21, and 22 significantly impacts expression of lncRNAs in PAds. Silencing of the key parathyroid gene MEN1 modulates the expression of six lncRNAs in primary PAds‐derived cultures. Analogous levels of lncRNAs are measured in PAds with the mutation in the MEN1 gene compared with PAds with wild‐type MEN1. Similarly, carcinomas with mutated CDC73 differ from PCas with wild‐type protein in terms of expression of lncRNAs. PCas harboring CDC73 mutations overexpress BC200 compared to wild‐type carcinomas. Overall, these findings shed light on deregulation of lncRNAs in human parathyroid tumors and propose that circuits between lncRNAs and the oncosuppressors MEN1 or CDC73 may have a role in parathyroid tumorigenesis as epigenetic modulators. © 2020 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Cognitive impairments have profound implications for the management of severe mental disorders; however, they are rarely assessed in everyday clinical practice due to constraints in time, resource and expertise. Novel and short instruments, such as the Screen for Cognitive Impairment in Psychiatry (SCIP), which overcome such limitations are greatly needed. The study aims to assess the validity and reliability, among healthy subjects, of the Italian translation of the SCIP, a brief, accessible tool to detect cognitive impairments among individuals suffering from mental disorders, as the first step to validate the instrument in clinical settings. One-hundred and twenty healthy subjects completed two of the three alternative forms of the SCIP. Cronbach Alpha (0.70) supported the reliability of the SCIP scores. Correlation coefficients supported the test–retest reliability of the tool. Learning effects were observed despite the use of alternative forms. Factor analysis indicated a two-factor solution explaining 55.4% of the total variance: the first factor ("memory") loading for VLT-I and VLT-D and less for WMT; the second factor ("executive function") loading for VFT and PST and less for WMT. The study proved the validity and reliability of the Italian version of the SCIP as a reliable and simple instrument to screen for cognitive impairment in the general population. [ABSTRACT FROM AUTHOR]

The European Union (EU) has recently adopted a regulation on invasive alien species that foresees the possibility of developing lists of species of National Concern. We developed a prioritisation process for alien mammals already established in Italy, but not yet included in the EU list (n = 6 species) and a systematic horizon-scanning procedure to obtain ranked lists for those species that are already introduced worldwide or traded in Italy (n = 213). Experts were asked to score these species, by evaluating their likeli-hood of establishment and spread and the magnitude of their potential impacts on biodiversity, economy, human-health and society. The manageability of each species was also evaluated, both for the proritisation and the horizon-scanning processes. We produced five lists that ranked species according to their potential spread and impacts and their manageability. These will allow policy-makers to select outputs according to a balance between risk assessment and risk management, establishing priorities for alien species management at the national level. [ABSTRACT FROM AUTHOR]

Background In patients with adrenal incidentalomas (AIs), there is uncertainty on how to rule out hypercortisolism. The occurrence of postsurgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of presurgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after the 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC), and adrenocorticotropin (ACTH) to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by a low-dose corticotropin stimulation test or insulin tolerance test when needed. We searched for the lowest presurgical value of F-1mgDST, UFC, and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results The lowest values of F-1mgDST, UFC, and MSC and the highest value for ACTH in PSH patients were 1.2 µg/dL (33 nmol/L), 10.4 µg/24 hours (29 nmol/24 hours), 1.2 µg/dL (33 nmol/L), and 26.9 pg/mL (6 pmol/L), respectively, but only F-1mgDST <1.2 µg/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST <1.2 µg/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome, and these subjects tended to have a better metabolic profile than those with F-1mgDST ≥1.2 µg/dL (33 nmol/L) Conclusion In AI patients a F-1mgDST <1.2 µg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients. [ABSTRACT FROM AUTHOR]

Summary: This paper reports our personal experience filling the gap regarding changes of bone mineral density after surgical treatment in patient suffering from tumor-induced osteomalacia. Introduction: No systematic data are available regarding long-term bone mineral density (BMD) changes after surgical cure of patients with tumor-induced osteomalacia. Methods: From October 2001 through April 2018, we studied 10 consecutive patients (mean age ± SD, 45.5 ± 13.8 years; 5 males and 5 females) with tumor-induced osteomalacia. We evaluated BMD when initially presented at our Center and after surgical removal of the tumor. Results: Basal BMD and corresponding Z-score values (mean values ± SD) measured by DXA were as follows: L1–L4 = 0.692 ± 0.15 g/cm2, Z-score = − 2.80 ± 1.60; femur neck 0.447 ± 0.10 g/cm2, Z-score = − 2.66 ± 0.93; total femur = 0.450 ± 0.08 g/cm2, Z-score = −3.04 ± 0.85). Furthermore, Trabecular Bone Score (TBS) was evaluated in three patients (basal values, 0.990 ± 0.32). Seven patients were intermittently followed after surgical excision of the tumor while supplemented with cholecalciferol and calcium salts; the remaining three were lost to follow-up. There was a striking increase of BMD values that peaked at 26.7 ± 6.50 months: L1–L4 = 1.289 ± 0.247 g/cm2, p < 0.001, Z-score + 1.75 ± 1.42; femur neck = 0.890 ± 0.235 g/cm2, p = 0.028, Z-score = + 0.50 ± 1.40; total femur = 0.834 ± 0.150 g/cm2, p = 0.005, Z-score = − 0.74 ± 1.14. In patients with the greatest bone involvement at lumbar site, there was a striking increase of an average 1.5% (p < 0.01) in respect to baseline Z-score value for each additional month of observation during the first 2–3 years post-surgery. An improvement of trabecular microarchitecture was also documented (TBS, 1.255 ± 0.16). Conclusion: This is the first case series documenting an impressive increase of BMD at both lumbar and femoral sites, together with an improvement of trabecular microarchitecture as documented by TBS. This is the consequence of huge mineralization of the large amount of osteoid tissue after resolution of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Cortisol secretion, peripheral activation, and sensitivity seem to be associated with hypertension (HY), type 2 diabetes (T2D), and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cutoff(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence of HY, T2D, and FX (comorbidities). Methods: In 206 postmenopausal females (157 with ≥1 comorbidities and 49 without any), we assessed the ratio between 24-h urinary free cortisol and cortisone (R-UFF/UFE, cortisol activation index), cortisol after 1 mg-overnight-dexamethasone (F-1mgDST, cortisol secretion index), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP, cortisol sensitivity index). Results: The cutoffs for F-1mgDST and R-UFF/UFE were set at 0.9 μg/dL (area under the curve, AUC 0.634 ± 0.43, p = 0.005) and 0.17 (AUC 0.624 ± 0.5, p = 0.017), respectively, predicted the presence of ≥1 comorbidities. The presence of F-1mgDST > 0.9 μg/dL plus R-UFF/UFE > 0.17 showed 82.1% specificity for predicting the presence of ≥1 comorbidities, while the simultaneous presence of F-1mgDST ≤ 0.9 μg/dL and R-UFF/UFE ≤ 0.17 showed 88% sensitivity for predicting the absence of comorbidities. The F-1mgDST > 0.9 μg/dL or R-UFF/UFE > 0.17 was associated with 2.8 and 2.1-fold increased risk of having ≥1 comorbidities, respectively. The F-1mgDST ≤ 0.9 μg/dL plus R-UFF/UFE ≤ 0.17 or F-1mgDST > 0.9 μg/dL plus R-UFF/UFE > 0.17 was associated with 2.8-fold reduced or 4.9-fold increased risk of having ≥1 comorbidities regardless of age, BMI, and N363S-SNP. Conclusions: F-1mgDST > 0.9 μg/dL and R-UFF/UFE > 0.17 may be used for predicting the presence of ≥1 among HY, T2D, and fragility FX. [ABSTRACT FROM AUTHOR]

Objective. Atypical parathyroid adenoma is a rare neoplasm, showing atypical histological features intermediate between classic benign adenoma and the rarest parathyroid carcinoma, whose the clinical behaviour and outcome is not yet understood or predictable. Up to date only two cases of atypical adenoma were found associated to a MEN1 syndrome, and only one was proved to carry a pathogenic variant of the MEN1 gene. Design. We report the clinical, histologic, and molecular findings of a 44-year-old woman, presenting with a histologically proved atypical parathyroid adenoma with an apparent aggressive behaviour. Methods and Results. CDC73 gene was screened at germline and somatic levels with no results. Whole exome sequencing performed on DNA extracted from blood leukocytes and tumour tissue revealed a somatic MEN1 gene heterozygous variant, c.912+1G > A, of the splicing donor site of exon 6. On immunohistochemistry, downregulation of the menin protein expression in the neoplastic cells was also observed. Conclusions. We report the second case of a rare association of a somatic MEN1 gene mutation in a patient with atypical parathyroid adenoma. We suggest that MEN1 gene could be an underestimate genetic determinant of these rare histological entities, and we highlight the utility of a complete genetic screening protocol, by the use of next-generation sequencing technology in such undetermined clinical cases with no frank clinical presentation. [ABSTRACT FROM AUTHOR]

High-fat diet (HFD) alters the glycosylation patterns of intestinal mucins leading to several health problems. We studied by histochemical and lectin-binding methods mucin alterations in the duodenum of mice fed a HFD for 25 weeks. Histochemical methods included periodic acid–Schiff, alcian blue pH 2.5, and high-iron diamine. Lectin-binding experiments were performed with SBA, PNA, WGA, MAA-II, SNA, ConA, UEA-I, LTA, and AAA. SBA, PNA, WGA, MAA-II, and SNA were tested also after desulfation and ConA after periodate-sodium borohydrate treatments (paradoxical ConA). Duodenal mucins are secreted by Brunner's glands and goblet cells in the villi. Brunner's glands of HFD mice showed increased secreting activity and a general reduction of glycosylated residuals, such as fucose and terminal α1,4-linked GlcNAc. Moreover, a general reduction of glycosylated residuals in the goblet cells of villi such as the fucosylated and sulfated ones was observed. Since the cited residuals are involved in cytoprotective and cytostatic functions, as well as in interactions with the intestinal microbiota and protection against parasites and inflammatory disorders, we conclude that HFD can predispose duodenum to several possible health disorders. [ABSTRACT FROM AUTHOR]

The localization of intestinal glycoconjugates of the blunthead pufferfish Sphoeroides pachygaster and the grey triggerfish Balistes capriscus from the north‐western Ionian Sea was analysed by histochemical methods (PAS, AB pH 2.5, HID) and lectin binding experiments (WGA, LFA, SBA, sialidase‐SBA, PNA, sialidase‐PNA, ConA, AAA, UEA‐I, LTA) to assess how evolutionary loss of a functional stomach in S. pachygaster affects intestinal secretions relative to the B. capriscus, which retains the plesiomorphic gastric condition. Sphoeroides pachygaster had a lower content of acid mucins but more complex sialylation patterns than B. capriscus. GalNAc and GlcNAc residuals were present in both, but GalNAc residuals in S. pachygaster were subterminal to sialic acid. Balistes capriscus lacked galactosylated residuals and its enterocytes had a glycocalyx that differed in composition between the small intestine and the rectum and was missing from S. pachygaster. Functional and ecological implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas (n = 15). Through in situ hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets CDKN1A/p21 and LATS2 at both mRNA and protein levels. Although the viability of parathyroid cells was not affected by miR-372 overexpression, the miRNA blunted camptothecin-induced apoptosis in primary PAd-derived cultures. miR-372 overexpression in parathyroid tumor cells increased parathormone (PTH) mRNA levels, and it positively correlated in vivo with circulating PTH levels. Conversely, the parathyroid-specific genes TBX1 and GCM2 were not affected by miR-372 mimic transfection. Finally, miR-372 dampened the Wnt pathway in parathyroid tumor cells through DKK1 upregulation. In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effect of denosumab, which is used in primary osteoporosis (PO), in primary hyperparathyroidism (PHPT)‐related osteoporosis. Design: Retrospective, longitudinal study. Setting: Outpatient osteoporosis clinic. Participants: Older women with PHPT (78.6 ± 5.5) (n = 25) and PO (78.8 ± 5.2) (n = 25) matched on age, body mass index, familial history of hip fracture, femoral bone mineral density (BMD), and personal history of fragility fractures. Intervention: Twenty‐four months of denosumab therapy. Measurements: We assessed the calcium‐phosphorus metabolism parameters; BMD at the lumbar spine (LS), femoral neck (FN), and total hip (TH) using dual X‐ray absorptiometry; and morphometric vertebral fractures using radiographs in all subjects at baseline and after 24 months. Changes in BMD and total alkaline phosphatase (ALP) activity were considered significant if they were greater than the least significant change (LS 2.8%, FN 5.9%, TH 4.8%, ALP –22%) and were expressed as percentage difference between end of follow‐up and baseline (Δ). Results: After 24 months, women with PHPT had greater ΔALP (−30.6 ± 11.3), ΔFN (5.6 ± 4.8), and ΔTH (4.8 ± 4.4) than those with PO (ΔALP −21.4 ± 13.1, ΔFN 2.9 ± 4.8, ΔTH 1.2 ± 4.1, P < .05 for all comparisons). A significant increase in BMD was more frequent in women with PHPT (92%) than in those with PO (52%, P < .05) and it was 13.4 times as likely in women with PHPT as in those with PO (P = .02), regardless of possible confounders. Two subjects in each group had an incident fracture. Conclusions: Denosumab therapy is effective in older women with PHPT‐related osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: This population-based study investigated the incidence, in-hospital and long-term all-cause mortality, for hip fracture (HipFx), stroke (STR), and myocardial infarction (MI) in residents hospitalized between 2000 and 2014. Methods: Data about hospitalization were drawn from the administrative discharge database, whereas information about residents and all-cause mortality from the municipality of our town. Patients were followed-up from the first hospital admission until death or study end. For each cause, crude and age-adjusted all-cause mortality of men and women were compared by Mann-Whitney's test and Poisson models. Separate age-sex adjusted Cox models were estimated and the corresponding adjusted survival curves were drawn. Results: Among 1292 hospitalizations (of 1109 patients), 434 were for HipFx, 526 for STR, 332 for MI (183 with and 149 without coronary revascularization -MIwCR and MIwoCR, respectively). The incidence of HipFx and STR did not vary over time, MI slightly increasing in men. Age-adjusted in-hospital mortality for HipFx was lower than for STR and MIwoCR in the whole sample and in women ( p < 0.001), but not in men. After discharge, men with HipFx had shorter survival and higher crude and age-adjusted mortality rate than women. The estimated HRs(95%CI) in respect to patients with MIwCR (having the lowest mortality) were: 6.11(3.12-11.97), p < 0.001 for HipFx; 5.78(2.93-11.32), p < 0.001 for STR; 2.68(1.27-5.66), p = 0.010 for MIwoCR in the whole sample [ HR: 16.58(6.70-40.98) p < 0.001 for HipFx; 7.35(3.01-17.93) p < 0.001 for STR, in men]. Conclusions: HipFx markedly impacts hospital care, and causes high in-hospital and long-term all-cause mortality, comparable to the two commonest non-tumor causes of death. [ABSTRACT FROM AUTHOR]

Background: Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS). Methods: The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength). Discussion: The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions. [ABSTRACT FROM AUTHOR]

Background: Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation analysis in an HPT-JT family and confirm carrier status of the proband's daughter. Methods: The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata. Her father and daughter had hyperparathyroidism (parathyroid adenoma) but no other manifestations of HPT-JT. CDC73 mutation analysis (sequencing of all 17 exons) and whole-genome copy number variation (CNV) analysis was done on leukocyte DNA of the three affecteds as well as the proband's unaffected sister. Results: A novel deletion of exons 4 to 10 of CDC73 was detected by CNV analysis in the three affecteds. A novel insertion in the 5'UTR (c.-4_-11insG) that co-segregated with the deletion was identified. By in vitro assay the 5'UTR insertion was shown to significantly impair the expression of the parafibromin protein. Screening for the mutated CDC73 confirmed carrier status in the proband's daughter and the biochemistry and ultrasonography led to pre-emptive surgery and resolution of the hyperparathyroidism. Conclusions: A novel gross deletion mutation in CDC73 was identified in a three-generation HPT-JT family emphasizing the importance of including screening for large deletions in the molecular diagnostic protocol. [ABSTRACT FROM AUTHOR]

Inactivating mutations of the multiple endocrine neoplasia 1 (MEN1) gene cause MEN1 syndrome, characterized by primary hyperparathyroidism (pHPT), and parathyroid and gastro‑entero‑pancreatic pituitary tumors. At present, only 14 cases of malignant parathyroid tumor have been associated with the syndrome, with 6 cases carrying an inactivating mutation of the MEN1 gene. The present study presents the case of a 48‑year‑old female who presented with multigland pHPT and multiple pancreatic lesions. The patient underwent surgery several times for the excision of parathyroid hyperplasia, carcinoma and adenoma. The MEN1 gene was screened, revealing three variants (in cis) at the intron/exon 3 boundary (IVS2‑3G>C, c.497A>T and c.499G>T) detected on the DNA of the proband, not shared by her relatives. RNA sequencing revealed that the IVS2‑3C>G variant caused the skipping of the exon 3. Therefore, the present study reports on a novel rare association of MEN1 syndrome and parathyroid carcinoma. The reported splicing mutation was previously identified in subjects who always developed malignant lesions; thus, a possible genotype‑phenotype association may be considered. [ABSTRACT FROM AUTHOR]

Intracellular glycans in the urothelium of urinary bladder of 10 adult male Landrace pigs were characterized in situ by immunohistochemical detection of Muc1 mucin by anti MUC1 from rabbit, conventional histochemical techniques (Periodic-Acid Schiff, Alcian Blue pH 2.5, High-Iron Diamine), and binding with 13 lectins (PNA, DBA, RCA-I, WGA, SBA, BSI-B4, ConA, AAA, UEA-I, LTA, LFA, MAA-II, SNA) combined with chemical and enzymatic pre-treatments (β-elimination, desulfation and neuraminidase) to gather reference data for this model animal. Muc1 mucin was detected in the secreting granules of superficial cells and the underlying layer of intermediate cells. The secreting granules in both intermediate cells and superficial cells were rich in carbohydrates, with the oligosaccharidic chains mostly O-linked to proteins. Glycoproteins were prevailing over glycosaminoglycans (GAGs). In both superficial and intermediate cells sulfated and/or sialylated glycans were present, sulfation decreasing in the deeper layers. Lectin-binding detected presence of terminal sialic acid linked mostly in α2,6 to GalNAc, Gal terminal or subterminal to sulfates, GalNAc, GlcNAc, and Fuc, mostly linked in α1,6, α1,3 α1,4 and α1,2 to GlcNAc or Gal, but not to lactosamine chains. Except for fucosylation, the oligosaccharidic chains in the glycoproteins of the urothelium of pig urinary bladder were similar to those linked to human MUC1, which is fundamental in cell adhesion and immunological processes in the urothelium. The co-distribution of Muc1 and saccharidic residues suggests that many of them are linked to the glycoprotein. [ABSTRACT FROM AUTHOR]

Seasonal variation of liver glycogen, lipids and melanomacrophages were investigated in a non-hibernating population of Pelophylax kl. esculentus from Calabria by histochemical methods and computer-assisted image analysis. Twenty individuals of both sexes were sampled in a tank in Roseto Capo Spulico (Cosenza, Calabria) in four periods of the year 2016 (February, May, July, October). Portions of liver from each individual were included in paraffin for glycogen and melanomacrophages, and epoxydic resin-araldite for lipid analysis. Sections were stained with periodic acid-Schiff (PAS) for glycogen (with diastase-PAS as control) or osmium-tetroxide for lipids, or left unstained for melanomacrophages (appearing naturally black due to melanin). Image analyses were performed on 9–12 grayscale converted pictures per individual. Total areas per µm2 of glycogen, lipids and melanomacrophages, as well as counts of lipid droplets and melanomacrophages and mean area of single lipid droplets and melanomacrophages, were measured. Statistical analyses were performed by analysis of variance (ANOVA) with bootstrap resampling. Significant variation among sampling periods was found for each variable. Glycogen and lipids co-vary, with higher values observed in October–February and lower values in May–July, whereas melanomacrophages reach a peak in May and have much lower values in the other months. It is concluded that, in the absence of a hibernating period, reproduction is the main force regulating the annual cycles of reserve storing and melanin production. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1186/s12933-023-01836-1 Correction to: Cardiovascular Diabetology (2023) 22:102 https://doi.org/10.1186/s12933-023-01836-1 Following publication of the original article [[1]], the author noticed the error in funding section. References 1 Favero V, Aresta C, Parazzoli C. The degree of cortisol secretion is associated with diabetes mellitus and hypertension in patients with nonfunctioning adrenal tumors. [Extracted from the article]