Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients.

UNLABELLED: We evaluated the effect of parathyroid hormone (PTH) on Wnt10b production by immune system cells in humans. We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. INTRODUCTION: The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hypersecretion in primary hyperparathyroidism (PHP). METHODS: Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) or plus 1-84 PTH (42), or intravenous ibandronate (18). Wnt10b production by unfractioned blood nucleated cells and by T, B cells and monocytes was assessed by real-time RT-PCR and ELISA at baseline, 3, 6, 12 and 18 months of treatment. The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma. WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex. RESULTS: iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects' level. Thus, chronic elevation of PTH does not significantly increase WNT10b production as respect to control. CONCLUSIONS: This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.

A promising eco-sustainable wound dressing based on cellulose extracted from Spartium junceum L. and impregnated with Glycyrrhiza glabra L extract: Design, production and biological properties.

Glycyrrhiza glabra extract is widely known for its antioxidant and anti-inflammatory properties and can improve the wound healing process. The aim of this work was to shorten the time of the healing process by using an eco-sustainable wound dressing based on Spanish broom flexible cellulosic fabric by impregnation with G. glabra extract-loaded ethosomes. Chemical analysis of G. glabra extract was performed by LC-DAD-MS/MS and its encapsulation into ethosomes was obtained using the ethanol injection method. Lipid vesicles were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In vitro release studies, biocompatibility, and scratch test on 3T3 fibroblasts were performed. Moreover, the structure of Spanish broom dressing and its ability to absorb wound exudate was characterized by Synchrotron X-ray phase contrast microtomography (SR-PCmicroCT). Ethosomes showed a good entrapment efficiency, nanometric size, good stability over time and a slow release of polyphenols compared to the free extract, and were not cytotoxic. Lastly, the results revealed that Spanish broom wound dressing loaded with G. glabra ethosomes is able to accelerate wound closure by reducing wound healing time. To sum up, Spanish broom wound dressing could be a potential new green tool for biomedical applications.

Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.

BACKGROUND: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. METHODS: Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. RESULTS: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. CONCLUSION: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.

Teriparatide increases the maturation of circulating osteoblast precursors.

UNLABELLED: This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis. INTRODUCTION: Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors. METHODS: We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover. RESULTS: Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation. CONCLUSIONS: We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.

Optimal correlations in many-body quantum systems.

Information and correlations in a quantum system are closely related through the process of measurement. We explore such relation in a many-body quantum setting, effectively bridging between quantum metrology and condensed matter physics. To this aim we adopt the information-theory view of correlations and study the amount of correlations after certain classes of positive-operator-valued measurements are locally performed. As many-body systems, we consider a one-dimensional array of interacting two-level systems (a spin chain) at zero temperature, where quantum effects are most pronounced. We demonstrate how the optimal strategy to extract the correlations depends on the quantum phase through a subtle interplay between local interactions and coherence.

Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures.

UNLABELLED: This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. INTRODUCTION: Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. METHODS: We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor ß (TGFß), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. RESULTS: We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGFß was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFß compared to bone, whereas the production of DKK-1 and SOST was higher in bone. CONCLUSIONS: We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Double-band sarcomeric SHG pattern induced by adult skeletal muscles alteration during myofibrils preparation.

To understand the reported difference between double band, sarcomeric second harmonic generation pattern of isolated myofibril and predominant single band pattern found in thick muscle tissues, we studied the effect of myofibril preparation on the second harmonic generation pattern. We found that double band sarcomeric second harmonic generation pattern usually observed in myofibrils (prepared from fresh tissue) is due to muscle alteration during the mixing and triton treatment processes. Single band sarcomeric second harmonic generation pattern could be observed in isolated myofibrils when this alteration is previously prevented using paraformaldehyd fixed tissue. We conclude that single band sarcomeric second harmonic generation pattern is a signature of adult muscle myofibrils in normal physiological condition, suggesting that sarcomeric second harmonic generation patterns could be used as a valuable diagnosis tool of muscle health.

Open versus robotic-assisted transabdominal preperitoneal (R-TAPP) inguinal hernia repair: a multicenter matched analysis of clinical outcomes.

PURPOSE: To compare the perioperative outcomes of initial, consecutive robotic-assisted transabdominal preperitoneal (R-TAPP) inguinal hernia repair (IHR) cases with consecutive open cases completed by the same surgeons. METHODS: Multicenter, retrospective, comparative study of perioperative results from open and robotic IHR using standard univariate and multivariate regression analyses for propensity score matched (1:1) cohorts. RESULTS: Seven general surgeons at six institutions contributed 602 consecutive open IHR and 652 consecutive R-TAPP IHR cases. Baseline patient characteristics in the unmatched groups were similar with the exception of previous abdominal surgery and all baseline characteristics were comparable in the matched cohorts. In matched analyses, postoperative complications prior to discharge were comparable. However, from post discharge through 30 days, fewer patients experienced complications in the R-TAPP group than in the open group [4.3% vs 7.7% (p = 0.047)]. The R-TAPP group had no reoperations post discharge through 30 days of follow-up compared with five patients (1.1%) in the open group (p = 0.062), respectively. Multivariate logistic regression analysis which demonstrated patient age > 65 years and the open approach were risk factors for complications within 30 days post discharge in the matched group [age > 65 years: odds ratio (OR) = 3.33 (95% CI 1.89, 5.87; p < 0.0001); open approach: OR = 1.89 (95% CI 1.05, 3.38; p = 0.031)]. CONCLUSIONS: In this matched analysis, R-TAPP provides similar postoperative complications prior to discharge and a lower rate of postoperative complications through 30 days compared to open repair. R-TAPP is a promising and reproducible approach, and may facilitate adoption of minimally invasive repairs of inguinal hernias.

Isolation and concentration of bacteria from blood using microfluidic membraneless dialysis and dielectrophoresis.

A microfluidic system that combines membraneless microfluidic dialysis and dielectrophoresis to achieve label-free isolation and concentration of bacteria from whole blood is presented. Target bacteria and undesired blood cells are discriminated on the basis of their differential susceptibility to permeabilizing agents that alter the dielectrophoretic behavior of blood cells but not bacteria. The combined membraneless microdialysis and dielectrophoresis system isolated 79 ± 3% of Escherichia coli and 78 ± 2% of Staphylococcus aureus spiked into whole blood at a processing rate of 0.6 mL h-1. Collection efficiency was independent of the number of target bacteria up to 105 cells. Quantitative PCR analysis revealed that bacterial 16S rDNA levels were enriched more than 307-fold over human DNA in the fraction recovered from the isolation system compared with the original specimen. These data demonstrate feasibility for an instrument to accelerate the detection and analysis of bacteria in blood by first isolating and concentrating them in a microchamber.

Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group.

Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.

The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss.

Depressed levels of atheroprotective large HDL particles are common in obesity and cardiovascular disease (CVD). Increases in large HDL particles are favourably associated with reduced CVD event risk and coronary plaque burden. The objective of the study is to compare the effectiveness of low-carbohydrate diets and weight loss for increasing blood levels of large HDL particles at 1 year. This study was performed by screening for body mass index (BMI) and metabolic syndrome in 160 consecutive subjects referred to our out-patient Metabolic Unit in South Italy. We administered dietary advice to four small groups rather than individually. A single team comprised of a dietitian and physician administered diet-specific advice to each group. Large HDL particles at baseline and 1 year were measured using two-dimensional gel electrophoresis. Dietary intake was assessed via 3-day diet records. Although 1-year weight loss did not differ between diet groups (mean 4.4 %), increases in large HDL particles paralleled the degree of carbohydrate restriction across the four diets (p<0.001 for trend). Regression analysis indicated that magnitude of carbohydrate restriction (percentage of calories as carbohydrate at 1 year) and weight loss were each independent predictors of 1-year increases in large HDL concentration. Changes in HDL cholesterol concentration were modestly correlated with changes in large HDL particle concentration (r=0.47, p=.001). In conclusion, reduction of excess dietary carbohydrate and body weight improved large HDL levels. Comparison trials with cardiovascular outcomes are needed to more fully evaluate these findings.

Retraction: The improvement of large High-Density Lipoprotein (HDL) particle levels, and presumably HDL metabolism, depend on effects of low-carbohydrate diet and weight loss.

[This retracts the article DOI: 10.17179/excli2015-642.].

First Report of Aberia caffra and Quercus cerris as Hosts of Inonotus rickii.

Inonotus rickii (Pat.) D. Reid (Hymenochaetaceae), widespread in tropical and subtropical countries, produces cankers and decay in several hardwoods. In Italy, it was recorded for the first time approximately 20 years ago on Parkinsonia sp. and Schinus molle L. in Sicily (2) and more recently on Acer negundo L. and Celtis australis L. in Rome (1). During May 2004, a survey was performed in Sicily in public and botanical gardens where the fungus had been detected in the past. Although the previously attacked plants had been removed, more trees were showing decline symptoms, with sparse foliage and some dieback. Typical brown, powdery masses of chlamydospores of I. rickii were observed near wounds or pruning cuts on Quercus cerris L. in Palermo and Sambucus nigra L. and Aberia caffra Hook. F. & Harv. in Catania. From each fungal specimen, fragments were isolated and cultured on malt agar. Cultures produced acute, thick-walled, brown setae (as much as 250 µm long) and abundant chlamydospores that were yellowish brown, thick walled, irregularly shaped, and 10 to 12 × 8 to 12 µm. Each isolate conformed to I. rickii (3). Cultures and voucher specimens have been deposited in the ISPaVe collection (PF40, PF41, and PF42) and the ROPV herbarium (772, 773, and 774). To our knowledge, this is the first report of I. rickii in living Q. cerris and A. caffra. S. nigra is a new host in Italy. This record shows that the pathogen has fully established itself in southern Europe where it may expand its host range. References: (1) T. Annesi et al. For. Pathol. 33:405, 2003. (2) M. Intini. Micol. Ital. 20:49, 1988. (3) J. A. Stalpers. Karstenia 40:167, 2000.

[Videophone assistance and home hospitalization: the ViSaDom program]. / Téléassistance en hospitalisation b domicile: le programme ViSaDom.

OBJECTIVE: The purpose of this project was to study the clinical feasibility of videophone-based communication between patients in their homes, and the care teams who work in the Home Hospitalization department (HH). METHODS: This pilot study of videophone users compared them with a group of control patients also in HH. They came from either the adult, maternity or pediatric departments. Patients who met the inclusion criteria and consented to participate in the study were randomly assigned to one of two groups: those who had a videophone installed in their homes (telemedicine group), and those who received the standard HH care (control group). Sixteen patients in the telemedicine group were matched with 16 from the control group, according to age, Karnofsky Index score, and the reason for HH admission. RESULTS: The mean videophone call lasted six minutes, and patients averaged 23 calls each over the study period (0.7 calls per patient per working day). The videophone enabled better follow-up of wounds: for example, the nurse could transmit photos from the patient's home for real-time coordination. It was also useful for following patients suffering from pain, for technical nursing care, and for educating patients and their caregivers. Anxiety (measured with the Hospital Anxiety and Depression Scale) diminished during the study period for the telemedicine patients, compared with the control group (p=0.048). Within the telemedicine group, all patients and their families were very satisfied or satisfied with their care and with the communication (15/15), although the staff's level of satisfaction was slightly lower (14/16); there were no significant differences between groups. CONCLUSION: The ViSaDom program indicates that videophone communication is feasible and acceptable and could be a useful tool for improving the quality, efficiency and effectiveness of care.

Cerebrovascular complications of mucinous cancers.

Six patients with mucinous cancer (2 colonic, 2 pancreatic, and 2 pulmonary origin) had necropsy evidence of thrombosis of large and small systemic, extracranial, and intracranial arteries and veins, and multiple cerebral infarcts and small hemorrhages. On microscopic examination, we found small infarcts and hemorrhages within the brain and mucin within vessels, macrophages, and in areas of infarction. The clinical picture included strokes and encephalopathy. Mucin-producing cancers can be associated with a coagulopathy that causes extensive occlusive vascular disease.

Transient global amnesia and thalamic infarction.

We describe the clinical and neuroradiologic features of a patient with two episodes of transient amnesia who later developed persistent amnesia and an acute infarction in the left thalamus. The neurobehavioral manifestations were strikingly similar in all three episodes. Cranial computed tomography was normal following the first two episodes. Thalamic ischemia could explain some cases of transient global amnesia.

Intraluminal clot of the carotid artery detected radiographically.

Nine patients had intraluminal filling defects identifiable as clot within the internal carotid artery at angiography. Thrombus was unilateral in eight, bilateral in one. Eight of the 10 clots were attached to atheromatous plaques. Three patients had serious concurrent illness: pancreatic cancer, rheumatoid arthritis with arteritis, and chronic pulmonary disease with polycythemia. In three patients, the clot was related to severe atherosclerosis. In three other patients, all young, the carotid thrombi remained unexplained though two of these patients had coagulation abnormalities. No patient had a new stroke after surgical or anticoagulant treatment.

The developmental and physiological basis of body size evolution in an insect.

The evolution of body size is a dominant feature of animal evolution. However, little is known about how the underlying developmental mechanisms that determine size change as body size evolves. Here we report on a case of body size evolution in the tobacco hornworm Manduca sexta that occurred over a period of nearly 30 years. We take advantage of an extensive series of physiological studies performed in the early 1970s that established the parameters that regulate body size in this species and compare their values with those of modern individuals that are descendants of the same colony. We show that three of the five processes that determine adult body size changed during this period, while two remained constant. Changes in these three developmental processes completely account for the observed evolutionary change in body size.

Giant aneurysm of the pericallosal artery.

A rare case of a giant aneurysm of the pericallosal artery, evaluated by computed tomography, magnetic resonance imaging, and angiography, is reported, and the other 7 cases in the literature are reviewed. Giant aneurysms are exceptional in the distal segments of the anterior cerebral arteries, and may simulate a callosal tumor or hematoma on computed tomographic scan. The clinical, radiological, surgical, and pathological findings of giant aneurysms of this location are discussed and the other reported cases are analyzed. The role of magnetic resonance imaging in diagnosing and characterizing giant aneurysms is stressed.

The role of low levels of juvenile hormone esterase in the metamorphosis of Manduca sexta.

The activity of juvenile hormone esterase (JHE) in feeding fifth instar larvae of Manduca sexta increases gradually with larval weight and rises to a peak after larvae pass the critical weight when juvenile hormone secretion ceases. Starvation of larvae of Manduca sexta (L.) that had exceeded the critical weight inhibited peak levels of JHE, but did not delay entry into the wandering stage when larvae leave the plant in search of a pupation site. This suggests that peak levels of JHE may not be essential for the normal timing of metamorphosis. Starved larvae pupated normally, indicating the peak of JHE was not necessary for a morphologically normal pupation. Treatments of larvae with the selective JHE inhibitor O-ethyl-S-phenyl phosphoramidothiolate (EPPAT) that began immediately after larvae achieved the critical weight (6.0 to 6.5 grams for our strain of Manduca) delayed entry into the wandering stage. By contrast, EPPAT treatment of larvae at weights above 8.0 g had no effect on the subsequent timing of the onset of wandering. Therefore, although the normal timing of the onset of wandering does not require peak levels of JHE, it requires low to moderate levels of JHE to be present until larvae reach a weight of about 8.0 g.