Fixed dental prosthesis on six zirconia implants for an anterior maxillary rehabilitation: case report with 10-year follow-up.

This article reports a case of maxillary rehabilitation with an implant-supported fixed partial denture on six zirconia implants. A female patient with impacted maxillary canines attended our dental clinic seeking a metal-free maxillary restoration. After the extraction of both impacted maxillary canines and the placement of autogenous bone graft, six one-piece zirconia implants with conical abutments were placed in the anterior maxillary region. Two zirconia fixed dental prosthesis with porcelain veneering, separated at the mid-line, were placed on these zirconia implants. The ten-year follow-up monitored the adequate evolution of both implants and restorations with no signs of peri-implant disease.

Body weight distortions in an auditory-driven body illusion in subclinical and clinical eating disorders.

Previous studies suggest a stronger influence of visual signals on body image in individuals with eating disorders (EDs) than healthy controls; however, the influence of other exteroceptive sensory signals remains unclear. Here we used an illusion relying on auditory (exteroceptive) signals to manipulate body size/weight perceptions and investigated whether the mechanisms integrating sensory signals into body image are altered in subclinical and clinical EDs. Participants' footstep sounds were altered to seem produced by lighter or heavier bodies. Across two experiments, we tested healthy women assigned to three groups based on self-reported Symptomatology of EDs (SED), and women with Anorexia Nervosa (AN), and used self-report, body-visualization, and behavioural (gait) measures. As with visual bodily illusions, we predicted stronger influence of auditory signals, leading to an enhanced body-weight illusion, in people with High-SED and AN. Unexpectedly, High-SED and AN participants displayed a gait typical of heavier bodies and a widest/heaviest visualized body in the 'light' footsteps condition. In contrast, Low-SED participants showed these patterns in the 'heavy' footsteps condition. Self-reports did not show group differences. The results of this pilot study suggest disturbances in the sensory integration mechanisms, rather than purely visually-driven body distortions, in subclinical/clinical EDs, opening opportunities for the development of novel diagnostic/therapeutic tools.

Rapid and Sequential Dual Oxime Ligation Enables De Novo Formation of Functional Synthetic Membranes from Water-Soluble Precursors.

Cell membranes define the boundaries of life and primarily consist of phospholipids. Living organisms assemble phospholipids by enzymatically coupling two hydrophobic tails to a soluble polar head group. Previous studies have taken advantage of micellar assembly to couple single-chain precursors, forming non-canonical phospholipids. However, biomimetic nonenzymatic coupling of two alkyl tails to a polar head-group remains challenging, likely due to the sluggish reaction kinetics of the initial coupling step. Here we demonstrate rapid de novo formation of biomimetic liposomes in water using dual oxime bond formation between two alkyl chains and a phosphocholine head group. Membranes can be generated from non-amphiphilic, water-soluble precursors at physiological conditions using micromolar concentrations of precursors. We demonstrate that functional membrane proteins can be reconstituted into synthetic oxime liposomes from bacterial extracts in the absence of detergent-like molecules.

Long term follow-up of a full- arch rehabilitation with an implant-supported overdenture on four zirconia implants and a zirconia bar. A case report.

This clinical report describes a mandibular full-arch rehabilitation by means of an implant-supported overdenture on four zirconia implants. A female patient with an edentulous mandibular arch attended our dental clinic seeking a metal-free mandibular restoration. After oral and radiographic evaluation, four one-piece zirconia implants with conical abutments were placed in the intermentonian region. After a 3-month osseointegration period, an acrylic overdenture with plastic matrices was manufactured, supported by a zirconia bar cemented to the conical abutments of the zirconia implants. Radiographic and clinical follow-up after 12 years observed adequate implant evolution, without any signs of peri-implant disease. Maintenance events were principally the periodic replacement of the plastic matrices and prophylaxis. Key words:Zirconia implants, overdenture, full-arch rehabilitation, dental implants, case report.

Effects of pitch and musical sounds on body-representations when moving with sound.

The effects of music on bodily movement and feelings, such as when people are dancing or engaged in physical activity, are well-documented-people may move in response to the sound cues, feel powerful, less tired. How sounds and bodily movements relate to create such effects? Here we deconstruct the problem and investigate how different auditory features affect people's body-representation and feelings even when paired with the same movement. In three experiments, participants executed a simple arm raise synchronised with changing pitch in simple tones (Experiment 1), rich musical sounds (Experiment 2) and within different frequency ranges (Experiment 3), while we recorded indirect and direct measures on their movement, body-representations and feelings. Changes in pitch influenced people's general emotional state as well as the various bodily dimensions investigated-movement, proprioceptive awareness and feelings about one's body and movement. Adding harmonic content amplified the differences between ascending and descending sounds, while shifting the absolute frequency range had a general effect on movement amplitude, bodily feelings and emotional state. These results provide new insights in the role of auditory and musical features in dance and exercise, and have implications for the design of sound-based applications supporting movement expression, physical activity, or rehabilitation.

Lipids: chemical tools for their synthesis, modification, and analysis.

Lipids remain one of the most enigmatic classes of biological molecules. Whereas lipids are well known to form basic units of membrane structure and energy storage, deciphering the exact roles and biological interactions of distinct lipid species has proven elusive. How these building blocks are synthesized, trafficked, and stored are also questions that require closer inspection. This tutorial review covers recent advances on the preparation, derivatization, and analysis of lipids. In particular, we describe several chemical approaches that form part of a powerful toolbox for controlling and characterizing lipid structure. We believe these tools will be helpful in numerous applications, including the study of lipid-protein interactions and the development of novel drug delivery systems.

ImmunoPET helps predicting the efficacy of antibody-drug conjugates targeting TENB2 and STEAP1.

The efficacy of antibody-drug conjugates (ADCs) targeted to solid tumors depends on biological processes that are hard to monitor in vivo. 89Zr-immunoPET of the ADC antibodies could help understand the performance of ADCs in the clinic by confirming the necessary penetration, binding, and internalization. This work studied monomethyl auristatin E (MMAE) ADCs against two targets in metastatic castration-resistant prostate cancer, TENB2 and STEAP1, in four patient-derived tumor models (LuCaP35V, LuCaP70, LuCaP77, LuCaP96.1). Three aspects of ADC biology were measured and compared: efficacy was measured in tumor growth inhibition studies; target expression was measured by immunohistochemistry and flow cytometry; and tumor antibody uptake was measured with 111In-mAbs and gamma counting or with 89Zr-immunoPET. Within each model, the mAb with the highest tumor uptake showed the greatest potency as an ADC. Sensitivity between models varied, with the LuCaP77 model showing weak efficacy despite high target expression and high antibody uptake. Ex vivo analysis confirmed the in vivo results, showing a correlation between expression, uptake and ADC efficacy. We conclude that 89Zr-immunoPET data can demonstrate which ADC candidates achieve the penetration, binding, and internalization necessary for efficacy in tumors sensitive to the toxic payload.

Comparative effectiveness of home blood pressure telemonitoring (HBPTM) plus nurse case management versus HBPTM alone among Black and Hispanic stroke survivors: study protocol for a randomized controlled trial.

BACKGROUND: Black and Hispanic stroke survivors experience higher rates of recurrent stroke than whites. This disparity is partly explained by disproportionately higher rates of uncontrolled hypertension in these populations. Home blood pressure telemonitoring (HBPTM) and nurse case management (NCM) have proven efficacy in addressing the multilevel barriers to blood pressure (BP) control and reducing BP. However, the effectiveness of these interventions has not been evaluated in stroke patients. This study is designed to evaluate the comparative effectiveness, cost-effectiveness and sustainability of these two telehealth interventions in reducing BP and recurrent stroke among high-risk Black and Hispanic stroke survivors with uncontrolled hypertension. METHODS/DESIGN: A total of 450 Black and Hispanic patients with recent nondisabling stroke and uncontrolled hypertension are randomly assigned to one of two 12-month interventions: 1) HBPTM with wireless feedback to primary care providers or 2) HBPTM plus individualized, culturally-tailored, telephone-based NCM. Patients are recruited from stroke centers and primary care practices within the Health and Hospital Corporations (HHC) Network in New York City. Study visits occur at baseline, 6, 12 and 24 months. The primary outcomes are within-patient change in systolic BP at 12 months, and the rate of stroke recurrence at 24 months. The secondary outcome is the comparative cost-effectiveness of the interventions at 12 and 24 months; and exploratory outcomes include changes in stroke risk factors, health behaviors and treatment intensification. Recruitment for the stroke telemonitoring hypertension trial is currently ongoing. DISCUSSION: The combination of two established and effective interventions along with the utilization of health information technology supports the sustainability of the HBPTM + NCM intervention and feasibility of its widespread implementation. Results of this trial will provide strong empirical evidence to inform clinical guidelines for management of stroke in minority stroke survivors with uncontrolled hypertension. If effective among Black and Hispanic stroke survivors, these interventions have the potential to substantially mitigate racial and ethnic disparities in stroke recurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT02011685 . Registered 10 December 2013.

ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models.

UNLABELLED: An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma half-life of a probe based on a full-length antibody coupled with a residualizing radionuclide would be able to catch the wave of drug-induced apoptosis and lead to a specific accumulation in apoptotic tumor tissue. METHODS: The imaging probe is based on a 89Zr-labeled monoclonal antibody PGN635 targeting phosphatidylserine. The probe was evaluated pre-clinically in four tumor xenograft models: one studied treatment with paclitaxel to trigger the intrinsic apoptotic pathway, and three others interrogated treatment with an agonistic death-receptor monoclonal antibody to engage the extrinsic apoptotic pathway. RESULTS: High accumulation of 89Zr-PGN635 was observed in treated tumors undergoing apoptosis reaching 30 %ID/g and tumor-to-blood ratios up to 13. The tumor uptake in control groups treated with vehicle or imaged with a non-binding antibody probe was significantly lower. CONCLUSIONS: The results demonstrate the ability of 89Zr-PGN635 to image drug-induced apoptosis in animal models and corroborate our hypothesis that radiolabeled antibodies binding to intracellular targets transiently exposed on the cell surface during apoptosis can be employed for detection of tumor response to therapy.

The development of peptide-based tools for the analysis of angiogenesis.

Limitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. (18)F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, (18)F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using (18)F-Z-3B as a PET probe with VEGF levels increasing with tumor size.

Site-specifically 89Zr-labeled monoclonal antibodies for ImmunoPET.

UNLABELLED: Three thiol reactive reagents were developed for the chemoselective conjugation of desferrioxamine (Df) to a monoclonal antibody via engineered cysteine residues (thio-trastuzumab). The in vitro stability and in vivo imaging properties of site-specifically radiolabeled (89)Zr-Df-thio-trastuzumab conjugates were investigated. METHODS: The amino group of desferrioxamine B was acylated by bromoacetyl bromide, N-hydroxysuccinimidyl iodoacetate, or N-hydroxysuccinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate to obtain thiol reactive reagents bromoacetyl-desferrioxamine (Df-Bac), iodoacetyl-desferrioxamine (Df-Iac) and maleimidocyclohexyl-desferrioxamine (Df-Chx-Mal), respectively. Df-Bac and Df-Iac alkylated the free thiol groups of thio-trastuzumab by nucleophilic substitution forming Df-Ac-thio-trastuzumab, while the maleimide reagent Df-Chx-Mal reacted via Michael addition to provide Df-Chx-Mal-thio-trastuzumab. The conjugates were radiolabeled with (89)Zr and evaluated for serum stability, and their positron emission tomography (PET) imaging properties were investigated in a BT474M1 (HER2-positive) breast tumor mouse model. RESULTS: The chemoselective reagents were obtained in 14% (Df-Bac), 53% (Df-Iac) and 45% (Df-Chx-Mal) yields. Site-specific conjugation of Df-Chx-Mal to thio-trastuzumab was complete within 1 h at pH 7.5, while Df-Iac and Df-Bac respectively required 2 and 5 h at pH 9. Each Df modified thio-trastuzumab was chelated with (89)Zr in yields exceeding 75%. (89)Zr-Df-Ac-thio-trastuzumab and (89)Zr-Df-Chx-Mal-thio-trastuzumab were stable in mouse serum and exhibited comparable PET imaging capabilities in a BT474M1 (HER2-positive) breast cancer model reaching 20-25 %ID/g of tumor uptake and a tumor to blood ratio of 6.1-7.1. CONCLUSIONS: The new reagents demonstrated good reactivity with engineered thiol groups of trastuzumab and very good chelation properties with (89)Zr. The site-specifically (89)Zr-labeled thio-antibodies were stable in serum and showed PET imaging properties comparable to lysine conjugates.

A modular platform for the rapid site-specific radiolabeling of proteins with 18F exemplified by quantitative positron emission tomography of human epidermal growth factor receptor 2.

Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional (18)F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing (18)F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [(18)F]FPEGMA, which was used to produce site-specifically (18)F-labeled protein ((18)F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 +/- 3% and a specific activity of 2.2 +/- 0.2 Ci/micromol. (18)F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.

PET of glial metabolism using 2-18F-fluoroacetate.

UNLABELLED: Imaging of the glial activation that occurs in response to central nervous system trauma and inflammation could become a powerful technique for the assessment of several neuropathologies. The selective uptake and metabolism of 2-(18)F-fluoroacetate ((18)F-FAC) in glia may represent an attractive strategy for imaging glial metabolism. METHODS: We have evaluated the use of (18)F-FAC as a specific PET tracer of glial cell metabolism in rodent models of glioblastoma, stroke, and ischemia-hypoxia. RESULTS: Enhanced uptake of (18)F-FAC was observed (6.98 +/- 0.43 percentage injected dose per gram [%ID/g]; tumor-to-normal ratio, 1.40) in orthotopic U87 xenografts, compared with healthy brain tissue. The lesion extent determined by (18)F-FAC PET correlated with that determined by MRI (R(2) = 0.934, P = 0.007). After transient middle cerebral artery occlusion in the rat brain, elevated uptake of (18)F-FAC (1.00 +/- 0.03 %ID/g; lesion-to-normal ratio, 1.90) depicted the ischemic territory and correlated with infarct volumes as determined by 2,3,5-triphenyltetrazolium chloride staining (R(2) = 0.692, P = 0.010) and with the presence of activated astrocytes detected by anti-glial fibrillary acidic protein. Ischemia-hypoxia, induced by permanent ligation of the common carotid artery with transient hypoxia, resulted in persistent elevation of (18)F-FAC uptake within 30 min of the induction of hypoxia. CONCLUSION: Our data support the further evaluation of (18)F-FAC PET for the assessment of glial cell metabolism associated with neuroinflammation.

The effects of anesthetic agent and carrier gas on blood glucose and tissue uptake in mice undergoing dynamic FDG-PET imaging: sevoflurane and isoflurane compared in air and in oxygen.

PURPOSE: We sought to identify an anesthetic regime that, unlike isoflurane in air, would maintain glucose homeostasis in mice undergoing Positron emission tomography (PET) imaging with 2-deoxy-2-[18F]fluoro-D: -glucose (FDG). MATERIALS AND METHODS: FDG uptake was also measured in normal and tumor tissues. Athymic and Balb/c nude mice were studied. Blood glucose levels were measured before and after 30 min of FDG PET imaging under isoflurane or sevoflurane carried in air or oxygen. FDG uptake was quantified as a percentage of the injected dose and using Patlak analysis yielding Ki values. RESULTS: Blood glucose levels were more stable under sevoflurane than under isoflurane, especially in the athymic nude mice. Under isoflurane, FDG uptake into myocardium was higher than under sevoflurane and was strongly correlated with the intrascan change in blood glucose. CONCLUSION: Sevoflurane should be preferred for physiologic imaging in mice, minimizing changes in glucose and, for FDG PET, reducing signal spillover from the myocardium.

Rapid evolution of congenital hepatic fibrosis after liver transplantation for acute liver failure: the potential role of extrahepatic factors.

A 9-year-old male underwent deceased donor liver transplantation for idiopathic fulminant hepatic failure. In the postoperative period, a review of perioperative biopsies of the donor liver revealed mild features of congenital hepatic fibrosis. Over the ensuing year, the recipient developed severe complications of congenital hepatic fibrosis including multiple episodes of cholangitis and progressive portal hypertension. After a second transplant, the patient had no further episodes of cholangitis and/or features of portal hypertension. Examination of the explanted liver revealed remarkable progression of the congenital hepatic fibrosis, suggesting that the phenotype of this disease may be dependent in part on extrahepatic factors.

Selective 5HT2A and 5HT6 receptor antagonists promote sleep in rats.

STUDY OBJECTIVES: Serotonin (5-HT) has long been implicated in the control of sleep and wakefulness. This study evaluated the hypnotic efficacy of the 5-HT6 antagonist RO4368554 (RO) and the 5-HT2A receptor antagonist MDL100907 (MDL) relative to zolpidem. DESIGN: A randomized, repeated-measures design was utilized in which Wistar rats received intraperitoneal injections of RO (1.0, 3.0, and 10 mg/kg), MDL (0.1, 1.0 and 3.0 mg/kg), zolpidem (10 mg/kg), or vehicle in the middle of the dark (active) period. Electroencephalogram, electromyogram, body temperature (Tb) and locomotor activity were analyzed for 6 hours after injection. MEASUREMENTS AND RESULTS: RO, MDL, and zolpidem all produced significant increases in sleep and decreases in waking, compared with vehicle control. All 3 doses of MDL produced more consolidated sleep, increased non-rapid eye movement sleep (NREM) sleep, and increased electroencephalographic delta power during NREM sleep. The highest dose of RO (10.0 mg/kg) produced significant increases in sleep and decreases in waking during hour 2 following dosing. These increases in sleep duration were associated with greater delta power during NREM sleep. ZO Zolpidem induced sleep with the shortest latency and significantly increased NREM sleep and delta power but also suppressed rapid eye movement sleep sleep; in contrast, neither RO nor MDL affected rapid eye movement sleep. Whereas RO did not affect Tb, both zolpidem and MDL reduced Tb relative to vehicle-injected controls. CONCLUSIONS: These results support a role for 5-HT2A receptor modulation in NREM sleep and suggest a previously unrecognized role for 5-HT6 receptors in sleep-wake regulation.

Pattern recognition of sleep in rodents using piezoelectric signals generated by gross body movements.

Current research on sleep using experimental animals is limited by the expense and time-consuming nature of traditional EEG/EMG recordings. We present here an alternative, noninvasive approach utilizing piezoelectric films configured as highly sensitive motion detectors. These film strips attached to the floor of the rodent cage produce an electrical output in direct proportion to the distortion of the material. During sleep, movement associated with breathing is the predominant gross body movement and, thus, output from the piezoelectric transducer provided an accurate respiratory trace during sleep. During wake, respiratory movements are masked by other motor activities. An automatic pattern recognition system was developed to identify periods of sleep and wake using the piezoelectric generated signal. Due to the complex and highly variable waveforms that result from subtle postural adjustments in the animals, traditional signal analysis techniques were not sufficient for accurate classification of sleep versus wake. Therefore, a novel pattern recognition algorithm was developed that successfully distinguished sleep from wake in approximately 95% of all epochs. This algorithm may have general utility for a variety of signals in biomedical and engineering applications. This automated system for monitoring sleep is noninvasive, inexpensive, and may be useful for large-scale sleep studies including genetic approaches towards understanding sleep and sleep disorders, and the rapid screening of the efficacy of sleep or wake promoting drugs.

Prevalencia de bajo y deficiente peso al nacer en niños menores de 2 años Estudio aproximativo realizado en la primera seccion de Quillacollo 2005) / s

De los 20 bulis (100 por ciento) que representan la muestra, el 10 por ciento corresponde a niños con bajo peso al nacer y el 90 por ciento corresponde a niños con deficit de peso al nacer. La relacion del bajo peso al nacer con la edad gestacional y la talla al nacer determina que el 100 por ciento de los prematuros sufre de retraso de crecimiento intrauterino, asimismo los niños con deficit de peso pueden ser prematuros. Los niños con bajo y deficiente peso al nacer, provienen de madres que se encuentra en union libre o concubinato (52 por ciento), casadas (25 por ciento), respecto a fla ocupacion se dedican a labores de casa (68 por ciento y a comerciantes minoristas 16 por ciento)

Prevalencia de bajo y deficiente peso al nacer en niños menores de 2 años Estudio aproximativo realizado en la primera seccion de Quillacollo 2005) / s

De los 20 bulis (100 por ciento) que representan la muestra, el 10 por ciento corresponde a niños con bajo peso al nacer y el 90 por ciento corresponde a niños con deficit de peso al nacer. La relacion del bajo peso al nacer con la edad gestacional y la talla al nacer determina que el 100 por ciento de los prematuros sufre de retraso de crecimiento intrauterino, asimismo los niños con deficit de peso pueden ser prematuros. Los niños con bajo y deficiente peso al nacer, provienen de madres que se encuentra en union libre o concubinato (52 por ciento), casadas (25 por ciento), respecto a fla ocupacion se dedican a labores de casa (68 por ciento y a comerciantes minoristas 16 por ciento)

Prevalencia de bajo y deficiente peso al nacer en recien nacidos y factores asociados: Municipio de Tapacari durante el segundo trimestre de 2006 / Prevalence of poor and low birth weight in infants and factors associated: Tapacari Municipality during the second quarter of 2006

De 40 niños (100 por ciento) que representa la muestra, el 10 por ciento corresponde a niños con bajo peso al nacer y el 15 por ciento corresponde a niños con deficit de peso al nacer. Los niños con bajo y deficiente peso al nacer, provienen de madres que se encuentran solteras (30 por ciento), casadas (40 por ciento), en union libre o concubinato (30 por ciento). Los niños con bajo y deficiente peso al nacer provienen de familias de nivel socioeconomico bajo, asimismo, los niños de madres menores de 20 años (30 por ciento) y madres añosas (20 por ciento), tambien el 60 por ciento de madres que cursaron el nivel primario y un 40 por ciento no tuvieron ningun grado de instruccion.