Locus heterogeneity in autosomal dominant congenital external ophthalmoplegia (CFEOM)

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain in his left side 1 month before his death. Ultrasonography and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left-upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophilic cytoplasm and blunt-ended nuclei showed interwoven fascicular growth, and mitotic figures were easily encountered. Immunohistochemically, the tumor cells were labeled by alpha-smooth muscle actin and vimentin. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.     

New-onset psychogenic seizures after surgery for epilepsy

BACKGROUND: The emergence of psychogenic seizures after surgery for epilepsy is not well recognized. OBJECTIVES: To identify the frequency of psychogenic seizures in an 11-year surgical experience and to characterize the patients with this complication. METHODS: Ninety-six patients underwent surgery for epilepsy between 1985 and 1996. The surgical database was reviewed and all patients who experienced postoperative psychogenic seizures were identified. Patients were characterized by sex, age, psychopathologic conditions, full-scale IQ, duration of epilepsy, surgical procedure, and operative complications. Patients were compared with the surgical group as a whole for these variables. SETTING: A comprehensive epilepsy center. RESULTS: Five patients were identified: 3 men and 2 women. Mean full-scale IQ was 73 (range, 66-82). Mean age was 29.8 years (range, 22-36 years). Three patients were diagnosed as having psychosis, 1 with borderline personality disorder and 1 with generalized anxiety. Operations included 4 anterior temporal lobectomies and 1 occipital lobectomy. Two patients experienced operative complications. Compared with the surgical cohort, patients had a higher frequency of preoperative psychopathologic conditions, lower mean full-scale IQ, and a greater occurrence of operative complications. CONCLUSIONS: (1) Patients can develop new-onset psychogenic seizures after surgery for epilepsy. (2) Low full-scale IQ, serious preoperative psychopathologic conditions, and major surgical complications may be risk factors. (3) Atypical postoperative seizures should be evaluated with video electroencephalographic monitoring before concluding that they are epileptic.     

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.     

Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation.     

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

Removal of fluoride from electronic industrial effluentby RO membrane separation

The electronics industry generates large amounts of fluoride-containing effluents. The objective of this studyis to study the feasibility of applying reverse osmosis (RO) membrane separation to reduce fluoride load to less than 1 kg/d. The effect of transmembrane pressure on the removal of fluoride ion has been investigated in detail, and the design parameters of a small RO separation unit were estimated. The present study indicated that the rejection of fluoride ion is typically higher than 98%, considering that the RO membrane was fully regenerated after each set of experiments. The effect of upstream concentration on the required mechanical pressure was determined by estimating the theoretical osmotic pressure of the feed solution. For industrial effluents, the process developed in this work allows us to reduce the treated volume from 6 m³/d to 0.36 m³/d without any pretreatment or adding additional compounds. The cost of the designed RO separation plant (€76,000) is much less than that of the conventional treatment (€533/m³) that deals mainly with volumes rather than specific     

Serotonin and serotonin receptors in the central auditory system

Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.     

FSE–Ag complex NS: preparation and evaluation of antibacterial activity

Silver (Ag) complexes of drugs and their nanosystems have great potential as antibacterials. Recently, an Ag complex of furosemide (Ag–FSE) has shown to be a promising antimicrobial. However, poor solubility of Ag–FSE could hamper its introduction into clinics. Therefore, the authors developed a nanosuspension of Ag–FSE (Ag–FSE_NS) for its solubility and antibacterial activity enhancement. The aim of this study was to introduce a novel nanoantibiotic with enhanced antibacterial efficacy. Ag–FSE_NS was prepared by precipitation–ultrasonication technique. Size, polydispersity index (PI) and zeta potential (ZP) of prepared Ag–FSE_NS were measured by dynamic light scattering, whereas surface morphology was determined using scanning electron microscopy (SEM). In vitro antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa using broth microdilution method. Size, PI and ZP of optimised Ag–FSE_NS1 were 191.2 ± 19.34 nm, 0.465 ± 0.059 and −55.7 ± 8.18 mV, respectively. SEM revealed that Ag–FSE_NS1 particles were rod or needle‐like with smooth surfaces. Saturation solubility of Ag–FSE in NS increased eight‐fold than pure Ag–FSE. Ag–FSE_NS1 exhibited two‐fold and eight‐fold enhancements in activity against E. coli and S. aureus, respectively. The results obtained showed that developed Ag–FSE_NS1 holds a promise as a topical antibacterial.Inspec keywords: nanomedicine, nanofabrication, light scattering, surface morphology, silver, particle size, solubility, suspensions, scanning electron microscopy, electrokinetic effects, drugs, biomedical materials, antibacterial activity, microorganisms, nanoparticles, drug delivery systems, transmission electron microscopyOther keywords: saturation solubility, topical antibacterial, size 171.86 nm to 210.54 nm, voltage ‐47.52 mV to ‐63.88 mV, Ag, broth microdilution method, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, SEM, scanning electron microscopy, surface morphology, dynamic light scattering, particle size, polydispersity index, precipitation–ultrasonication technique, nanoantibiotic, nanosuspension, furosemide, nanosystems, drugs, Ag–FSE_NS preparation, in vitro antibacterial activity, pure Ag–FSE, Ag–FSE_NS1 particles, optimised Ag–FSE_NS1, zeta potential, enhanced antibacterial efficacy, antibacterials     

Development of an automated platform for high-throughput P1-phage transduction of Escherichia coli

Synthetic biology depends on the ability to rapidly produce strains with improved phenotypes but is limited by the ability to rapidly produce strain collections with directed mutations. Here, we present a system capable of overcoming this limitation through automated P1-phage transductions of Escherichia coli. By combining the Keio collection of single-gene deletion E. coli mutants with P1-phage, it is possible to generate an engineered host-strain collection consisting of every possible gene deletion mutant. This strategy was tested by transducing 355 genetic markers from the Keio collection into five different host strains, and it achieved a 98% success rate. This method offers an improved mechanism for rapidly engineering collections of microbes and provides one method for rapidly deploying a broader synthetic biology effort.     

Indoor robot gardening: design and implementation

This paper describes the architecture and implementation of a distributed autonomous gardening system with applications in urban/indoor precision agriculture. The garden is a mesh network of robots and plants. The gardening robots are mobile manipulators with an eye-in-hand camera. They are capable of locating plants in the garden, watering them, and locating and grasping fruit. The plants are potted cherry tomatoes enhanced with sensors and computation to monitor their well-being (e.g. soil humidity, state of fruits) and with networking to communicate servicing requests to the robots. By embedding sensing, computation, and communication into the pots, task allocation in the system is de-centrally coordinated, which makes the system scalable and robust against the failure of a centralized agent. We describe the architecture of this system and present experimental results for navigation, object recognition, and manipulation as well as challenges that lie ahead toward autonomous precision agriculture with multi-robot teams.