Association between osteocalcin and residual ß-cell function in children and adolescents newly diagnosed with type 1 diabetes: a pivotal study.

PURPOSE: This pivotal study aimed to evaluate circulating levels of bone remodeling markers in children and adolescents at the onset of type 1 diabetes (T1D). Additionally, we assessed their correlation with glucose control, residual ß-cell function, and the severity of presentation. METHODS: In this single-center cross-sectional study, we recruited children and adolescents newly diagnosed with T1D at our tertiary-care Diabetes Centre. Anamnestic, anthropometric, clinical, and biochemical data at T1D diagnosis were collected. Basal and stimulated C-peptide levels were assessed, along with the following bone remodeling biomarkers: osteocalcin (OC), alkaline phosphatase (ALP), parathormone (PTH), 25-OH Vitamin D (25OH-D), and the C-terminal cross-linked telopeptide of type 1 collagen (CTX). RESULTS: We enrolled 29 individuals newly diagnosed with T1D, with a slight male prevalence (51.7%). The mean age was 8.4 ± 3.7 years. A positive correlation between OC and stimulated C-peptide (R = 0.538; p = 0.026) and between PTH and serum HCO3- (R = 0.544; p = 0.025) was found. No other correlations between bone remodeling biomarkers and clinical variables were detected. CONCLUSION: Our data showed a positive correlation between OC levels and residual ß-cell function in children and adolescents at T1D presentation. Further longitudinal studies evaluating OC levels in pediatric subjects with T1D are needed to better understand the complex interaction between bone and glucose metabolisms.

Anomalous Diffusion in the Long-Range Haken-Strobl-Reineker Model.

We analyze the propagation of excitons in a d-dimensional lattice with power-law hopping ∝1/r^{α} in the presence of dephasing, described by a generalized Haken-Strobl-Reineker model. We show that in the strong dephasing (quantum Zeno) regime the dynamics is described by a classical master equation for an exclusion process with long jumps. In this limit, we analytically compute the spatial distribution, whose shape changes at a critical value of the decay exponent α_{cr}=(d+2)/2. The exciton always diffuses anomalously: a superdiffusive motion is associated to a Lévy stable distribution with long-range algebraic tails for α≤α_{cr}, while for α>α_{cr} the distribution corresponds to a surprising mixed Gaussian profile with long-range algebraic tails, leading to the coexistence of short-range diffusion and long-range Lévy flights. In the many-exciton case, we demonstrate that, starting from a domain-wall exciton profile, algebraic tails appear in the distributions for any α, which affects thermalization: the longer the hopping range, the faster equilibrium is reached. Our results are directly relevant to experiments with cold trapped ions, Rydberg atoms, and supramolecular dye aggregates. They provide a way to realize an exclusion process with long jumps experimentally.

Effects of competitive physical activity on serum irisin levels and bone turnover markers.

BACKGROUND: Irisin, a myokine, is a polypeptide derived from the cleavage of the extracellular domain of fibronectin domain-containing protein 5, a receptor that is present on different tissues (skeletal muscle, pericardium, myocardium, and brain), whose functions are not yet fully defined. PURPOSE: The main aim of our study was to evaluate the effect of competitive physical activity on serum irisin levels and bone turnover markers. METHODS: Fifteen male footballers and an equal number of subjects of the same age and gender, but with a predominantly sedentary lifestyle, had their serum levels of irisin and bone turnover markers measured. Bone mineral status was evaluated in both groups by quantitative bone ultrasound of the calcaneus. In addition, only in footballers, biochemical analyses were repeated after 3 months. RESULTS: We did not observe significant differences in the serum levels of calcium, phosphorus, and parathyroid hormone between the two groups. The footballers had significantly higher quantitative bone ultrasound, 25-OH vitamin D, and creatinine values than the controls. There were also no significant differences in the bone alkaline phosphatase, carboxy-terminal telopeptide of type I collagen, osteoprotegerin, sclerostin or Dkk-1 values, while the irisin levels (+ 89%, p < 0.001) and RANKL were significantly higher in the footballers compared to those in the controls. CONCLUSION: Our study shows that footballers have significantly higher serum irisin values than the general population. Irisin could be the "trait d'union" between bone health and physical activity.

The association between hypoparathyroidism and cognitive impairment: a systematic review.

CONTEXT AND PURPOSE: Hypocalcemia and low parathyroid hormone levels have been commonly suggested as factors able to induce central nervous system disturbances. However, evidences on the occurrence of cognitive impairment are limited or underestimated. The aim of this review is, therefore, to systematically summarize the available evidence concerning the occurrence of cognitive impairment among subjects suffering from idiopathic or secondary hypoparathyroidism. METHODS: A systematic selection of the available literature was performed by searching the online databases PubMed, Scopus and Web of Knowledge. RESULTS: The present systematic review included sixteen case report articles and one cross-sectional controlled study. Case reports were the most representative literature sources and involved ten women and seven men. The presence of cognitive impairment was mostly discussed in association with idiopathic hypoparathyroidism (HPT); five articles described the occurrence of cognitive impairment following postsurgical HPT. The case-controlled study reported a significant presence of peculiar cognitive deficits (e.g. reduced inhibitory control, impairment in visuo-spatial functioning among, and psychomotor retardation) among HPT subjects compared to healthy controls, with serum total calcium and its product with phosphorus as independent predictors of neuropsychological dysfunctions. CONCLUSION: Even though mostly based on single case reports, the presence of neuropsychological dysfunctions in the context of HPT appears to be a consistent core finding.

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility.

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.

Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. METHODS: Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33 years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. RESULTS: After 18 months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (ß = 0.37, SE = 2.44, p < 0.001). CONCLUSIONS: TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

Preterm birth after loop electrosurgical excision procedure (LEEP): how cone features and microbiota could influence the pregnancy outcome.

OBJECTIVE: In the last years, the mean age of women who underwent cervical treatment for high-grade cervical intraepithelial neoplasia (CIN 2-3) is similar to the age of women having their first pregnancy. The aim of this study was to evaluate the risk of preterm birth in subsequent pregnancies after loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: From January 2013 to January 2016 the study identified a total of 1435 women, nulliparous, who underwent LEEP for CIN 2-3, and who wished to have their first pregnancy. Before surgery, the lengths of the cervix were calculated by transvaginal sonography. After the treatment, the dimension of the removed tissue was evaluated. During the pregnancy, all women carried out periodic transvaginal sonography and vaginal-cervical swabs. RESULTS: The average age of patients was 31.96±5.24 years; the interval between the surgical procedure and pregnancy was 12.04±4.67 months; the gestational age at births was 37.53±2.91 weeks. The first vaginal and cervical swab performed during pregnancy was negative in 81.8% of patients. The most prevalent infections were related to C. Albicans, G. Vaginalis, and Group B Streptococcus (GBS). The rate of preterm delivery was significantly higher in women with a minor cervical length. CONCLUSIONS: The length and the volume of cervical tissue excised have been shown to be directly related to the risk for preterm birth. Furthermore, vaginal infections and their persistence during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP.

Incidence of hypocalcemia and hypercalcemia in hospitalized patients: Is it changing?

Disorders of calcium metabolism are frequently encountered in routine clinical practice. However limited data are available on the epidemiology of hypocalcemia and hypercalcemia in hospitalized patients. Our aim was to evaluate the frequency of hypocalcemia and hypercalcemia in hospitalized patients. This is a retrospective study based on the laboratory results of all hospitalized subjects (n = 12,334) whose calcemia was determined between January 1st, 2011 and December 31st, 2014. Measurements of serum calcium were carried out by a single centralized laboratory. Hypocalcemia was defined as serum calcium levels <8.2 mg/dl and hypercalcemia as serum calcium levels >10.4 mg/dl. Albumin correction was applied to adjust serum calcium values. Overall, hypocalcemia accounted for 27.72% (n = 3420) and hypercalcemia for 4.74% (n = 585) of the 12,334 inpatients. The highest prevalence of hypocalcemia was found in patients over 65 yr. (n = 2097, 61.31%) vs. younger subjects, while the highest prevalence of hypercalcemia was observed in patients aged 0-18 yr. (n = 380, 64.95%). Hypocalcemia was more often encountered in males (n = 1952, 57.07%) while no gender differences were found regarding hypercalcemia. Incidence of hypocalcemia changed over time varying from 35.42% (n = 1061) in 2011 to 21.93% (n = 672) in 2014 (r = -0.98; p = 0.01). Differently, incidence of hypercalcemia did not significantly increase significantly from 3.47% (n = 104) in 2011 to 6.92% (n = 211) in 2014 (r = 0.94; p = 0.052). Despite increased awareness about electrolytes disturbance, physicians should consider calcium levels because of life-threatening consequences associated to hypo- and hypercalcemia. Patient's gender and age could be associated to a different risk of calcium disturbance in hospitalized patients.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

PURPOSE: Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. METHODS: 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). RESULTS: In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). CONCLUSIONS: Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

A small porous-plug burner for studies of combustion chemistry and soot formation.

We have developed and built a small porous-plug burner based on the original McKenna burner design. The new burner generates a laminar premixed flat flame for use in studies of combustion chemistry and soot formation. The size is particularly relevant for space-constrained, synchrotron-based X-ray diagnostics. In this paper, we present details of the design, construction, operation, and supporting infrastructure for this burner, including engineering attributes that enable its small size. We also present data for charactering the flames produced by this burner. These data include temperature profiles for three premixed sooting ethylene/air flames (equivalence ratios of 1.5, 1.8, and 2.1); temperatures were recorded using direct one-dimensional coherent Raman imaging. We include calculated temperature profiles, and, for one of these ethylene/air flames, we show the carbon and hydrogen content of heavy hydrocarbon species measured using an aerosol mass spectrometer coupled with vacuum ultraviolet photoionization (VUV-AMS) and soot-volume-fraction measurements obtained using laser-induced incandescence. In addition, we provide calculated mole-fraction profiles of selected gas-phase species and characteristic profiles for seven mass peaks from AMS measurements. Using these experimental and calculated results, we discuss the differences between standard McKenna burners and the new miniature porous-plug burner introduced here.

Expression of E6/E7 HPV-DNA, HPV-mRNA and colposcopic features in management of CIN2/3 during pregnancy.

OBJECTIVE: The incidence of abnormal cervical cytology in pregnancy is similar to that reported for non-pregnant women. Furthermore, 1% of pregnant women annually screened for cervical cancer will be diagnosed with cervical intraepithelial neoplasia (CIN) of various degrees. For this reason, Pap smear should be performed in the first trimester of pregnancy. The persistence of HR-HPV infection is related to the development of CIN. However, the relationship between CIN and HR-HPV infection during pregnancy and postpartum can hardly be found. The aim of this work was to assess the proper management of abnormal cytology during and after pregnancy evaluating regression rate, persistence rate and risk of progression and the predictive role of HPV molecular tests. PATIENTS AND METHODS: Patients with abnormal cervical cytology were followed-up using colposcopy and colposcopy-directed biopsies every 12 weeks. Molecular tests were performed at the moment of the cytological diagnosis. Patients not treated in pregnancy were re-evaluated with cytology, colposcopy, biopsies, HPV-DNA test and HPV-mRNA test for a final diagnosis 8 weeks postpartum. Women with a persistent CIN 2-3 lesion at this follow-up check, underwent an excisional procedure by LEEP and then re-evaluated every 6 months for a year. RESULTS: HPV-DNA test showed a sensitivity of 90.5% and a negative predictive value of 96.4%. Specificity and positive predictive values were 67.9% and 43.2%, respectively. For HPV-mRNA test, a sensitivity of 76.2% and a NPV of 93.9% were found; specificity and PPV were 98.7% and 94.1% respectively. CONCLUSIONS: An observational management based on the use of molecular test and particularly HPV-mRNA test for its higher specificity, is a reasonable possibility in the follow-up of CIN2/3 lesions during pregnancy.

Effects of teriparatide on bone mineral density and quality of life in Duchenne muscular dystrophy related osteoporosis: a case report.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by secondary osteoporosis and increased fractures. We describe the case of a 20-year-old boy with DMD suffering from back pain due to multiple vertebral fractures who was treated with teriparatide. Improvement of bone density, pain, and quality of life was achieved. DMD is an X-linked recessive muscle disease with secondary osteoporosis and related frequently occurring fractures. To date, only bisphosphonates have been used to treat osteoporosis in DMD. Black bear parathyroid hormone has been previously reported to enhance bone mass in the dystrophin-deficient mouse. This study reports the positive effect of osteoanabolic treatment with once-daily recombinant human parathyroid hormone 1-34 (rhPTH 1-34, teriparatide) in a 20-year-old DMD boy suffering from multiple vertebral fractures causing back pain. Bone formation and resorption markers (osteocalcin and C-telopeptide of type I collagen, respectively), as expected, increased within 6 months and intensity of back pain early decreased, with no pain reported after 6 months at visual analog scale. Over a 18-month period of treatment with teriparatide, bone mineral density and quality of life, assessed by the 36-item short-form questionnaire, considerably improved and no side effects were reported. Further studies on large cohorts are warranted to test the efficacy of this promising treatment for DMD related osteoporosis.

Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

OBJECTIVE: The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. PATIENTS AND METHODS: Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. RESULTS: Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. CONCLUSIONS: None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

A uterus soaked in blood with low haemoglobin in a case of unrecognized uterine sarcoma.

INTRODUCTION: Uterine sarcomas are rare and aggressive tumors. In some cases they can cause rupture of the uterus with or without clinical and radiological symptoms. Therefore, it is important to observe patients with clinical and/or radiological suspicion of sarcoma, even when there are no clinical manifestations. CASE REPORT: A 71-year old woman, who was under the authors' observation for pain in the right iliac fossa. The US and the CT scan showed an abdominal-pelvic mass.Laboratory tests showed a slight but progressive reduction of haemoglobin, which could not be explained by the clinical symptoms and by the results of the imaging tests. During the surgical intervention, a small amount of peritoneal fluid, an increased uterine volume, and a subverted anatomy were observed A haematoma was found in the uterus and this could explain the progressive reduction of haemoglobin and the very low presence of peritoneal effusion. CONCLUSION: The rupture of the uterus could not have been suspected as the patient did not have any type of symptoms, except for the slow and progressive reduction in the haemoglobin value. Therefore, it is important to observe patients with clinical and/or radiological suspicion of sarcoma, even when there are no clinical manifestations.

Feasibility of office CO2 laser surgery in patients affected by benign pathologies and congenital malformations of female lower genital tract.

OBJECTIVE: Traditional surgery presents some disadvantages, such as the necessity for general anesthesia, hemorrhage, recurrence of pathology, and the possible onset of dyspareunia due to an excessive scarring. CO2 laser surgery might resolve these problems and might be employed in a wider range of clinical indications than usual. We examined the results of CO2 laser surgery in patients affected by benign pathologies and congenital malformations of the female lower genital tract. PATIENTS AND METHODS: In this observational study, we enrolled 49 women who underwent CO2 laser surgery for the following indications: Bartholin's gland cyst, imperforate hymen, vaginal septum, Nabothian cyst, and vaginal polyps. Feasibility, cost-effectiveness, complication rate, recurrence rate, short- and long-term outcomes were assessed. RESULTS: All procedures were carried out in a short operative time, without any intraoperative complications. Only 1 (2.0%) out of 49 patients required a hemostatic suture for bleeding. Postoperative period was uneventful in all patients, except 6 (12.2%) out of 49 patients who reported pain one day after surgery, successfully treated with paracetamol. Healing was rapid and excellent in all cases; no wound infection, scarring or stenosis were noticed. Preoperative symptoms reduced or disappeared in all cases. No recurrence was observed and no re-intervention was needed. CONCLUSIONS: CO2 laser surgery provides several advantages over traditional surgery, as its systematic use in treating pre-invasive, benign, and congenital pathologies of the female lower genital tract reduces patient discomfort, improves short- and long-term outcomes, and optimizes cost-effectiveness.

Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate.

OBJECTIVE: Vitamin D deficiency is widespread and often reported in subjects treated for osteoporosis. Optimal vitamin D repletion was previously shown to maximize the efficacy of anti-resorptive agents. To date, no information exists about the role of vitamin D in the response to strontium ranelate (SrR) treatment. The aim of our study was to investigate the BMD response to SrR in accordance with change of vitamin D status. METHODS: A retrospective analysis of 108 women receiving SrR for postmenopausal osteoporosis was carried out. Women were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were measured at baseline after 18-months. All participants were divided into two groups according to the median variation of 25(OH)D over the observation period. RESULTS: SrR was associated with improvement of BMD at lumbar spine (p < 0.0001) and to a non significant variation at femoral neck (p = 0.2). Only subjects with Δ25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p = 0.03). Change of BMD at femoral neck was positively associated with modification of ALP (r = 0.28, p = 0.01). This association was not maintained when considering only women with Δ25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple regression analysis, ALP change was the only predictor of femoral neck BMD modification (ß 0.13; SE 0.05; p = 0.01). CONCLUSION: Improvement of vitamin D status was associated with enhancement of BMD response to SrR in women with postmenopausal osteoporosis, in particular, at femoral neck.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.