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ObjectiveTo identify common genetic variants associated with the presence of brain microbleeds (BMBs).MethodsWe performed genome-wide association studies in 11 population-based cohort studies and 3 case–control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.ResultsBMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21–1.45]; p = 2.5 × 10−10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19–1.50]; p = 1.0 × 10−6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86–1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.ConclusionsGenetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.

PURPOSE: Quantitative assessment of white matter hyperintensities (WMH) on structural Magnetic Resonance Imaging (MRI) is challenging. It is important to harmonise results from different software tools considering not only the volume but also the signal intensity. Here we propose and evaluate a metric of white matter (WM) damage that addresses this need. METHODS: We obtained WMH and normal-appearing white matter (NAWM) volumes from brain structural MRI from community dwelling older individuals and stroke patients enrolled in three different studies, using two automatic methods followed by manual editing by two to four observers blind to each other. We calculated the average intensity values on brain structural fluid-attenuation inversion recovery (FLAIR) MRI for the NAWM and WMH. The white matter damage metric is calculated as the proportion of WMH in brain tissue weighted by the relative image contrast of the WMH-to-NAWM. The new metric was evaluated using tissue microstructure parameters and visual ratings of small vessel disease burden and WMH: Fazekas score for WMH burden and Prins scale for WMH change. RESULTS: The correlation between the WM damage metric and the visual rating scores (Spearman ρ > =0.74, p =0.72, p

The sensitivity of plant cell culture to fluid forces, or fluid-mechanical sensitivity, in a stirred bioreactor is evaluated by shearing the cells in viscometers for short duration under a range of laminar and turbulent conditions. This short-term evaluation is compared with the experiments in a stirred bioreactor under chemostat mode at various agitation speeds. Fluid-mechanical sensitivity was quantified by measuring various biological parameters including regrowth ability, membrane integrity, mitochondrial activity, aggregate size and lysis. A critical hydrodynamic variable was derived based on a model whereby the biological activity of cells after a given period in a defined shearing environment was a cumulative effect of the total work done by fluid forces on the cells. This hydrodynamic variable, calculated as total energy dissipation on cells per unit volume, was used as a common basis to quantify the agitation-based shear forces under laminar and turbulent flow conditions. Fluid-mechanical sensitivity data for plant cell suspensions under different flow conditions was successfully correlated with this hydrodynamic variable. This correlation established a hierarchy of response, ranging from a subtle biological inhibitory effect on regrowth ability or sublytic effect, to the gross physical effect of aggregate breakup and lysis. Inhibition of growth rather than lysis was found to dictate the performance of plant cell culture in the bioreactor.

This project focused on the relationship between cultivation conditions and glycosylation pattern of a recombinant fusion protein produced by a CHO derived cell line. During the investigation it was found that the glycosylation pattern changed during fed-batch cultivation: sialic acid content and antennary complexity increased with cultivation time although ammonium concentration and most likely glycosidase activities — two factors which reportedly can decrease sialic acid concentration-increased simultaneously. Continuous cultures were performed to identify which environmental and kinetic variables impact the glycosylation process. A change in glycosylation pattern was only found when the specific productivity during a continuous culture was increased transiently by an increase in ferric citrate concentration. This indicated that it is a kinetic variable which influences the glycosylation of the studied fusion protein. Further experiments focused on the glycosylation of intracellular fusion protein and support the hypothesis that specific productivity, or rather the residence time of the protein in the Golgi apparatus, is crucial to the extent of glycosylation. Notably, concentration, molecular weight, and sialic acid content of the fusion protein increased with cultivation time, suggesting that a prolonged residence time in the Golgi apparatus leads to more complete glycosylation.

Erroneous signals of vestibular origin can cause sudden falls without warning. Drop attacks of vestibular origin in our experience most commonly occurred in patients with late or end-stage endolymphatic hydrops (usually idiopathic, ie, Meniere's disease). Eponymically termed Tumarkin's otolithic crisis, drop attacks of vestibular origin must be distinguished from drop attacks due to cardiovascular abnormalities, seizure disorders, vertebral basilar arterial insufficiency (transitory brain stem ischemia), multiple sclerosis, and drug-induced motor control disturbances. The treatment of choice for drop attacks of vestibular origin is either surgical ablation (labyrinthectomy) in the absence of serviceable hearing or middle fossa vestibular nerve section in order to preserve serviceable hearing.

• A major goal of any surgical program for patients with tumors is to cure their cancer. Patients requiring total glossectomy usually are seen initially with faradvanced disease, often after failure of other treatment modalities. As a result, they may be suffering from constant pain as well as impairment of speech and deglutition. The prognosis is poor, and palliative surgery with good rehabilitation of the speaking and swallowing mechanisms becomes a reasonable, albeit limited, objective. Our series does not have sufficient follow-up to assess cure rates. However, our initial results have been encouraging. Our series does show that properly selected patients can be successfully rehabilitated after total glossectomy without laryngectomy. This successful rehabilitation begins with good patient selection and preoperative preparation. Postoperative rehabilitation requires the interplay of a highly motivated patient and a well-coordinated health care team. The physician, nurse, speech pathologist, dietitian, and social worker all have important roles in ensuring the patient's return to a good quality of life. The surgeon will direct the efforts of the team. To the nurse and the speech pathologist falls much of the bedside job of instructing and motivating the patient. Because such effective rehabilitation has been demonstrated by the success of our patients, we advocate preserving the larynx whenever possible in the patient who must undergo total glossectomy. ( Arch Otolaryngol 1981;107:694-697)

Various reactor configurations for suspension, immobilized and surface culture of plant cells are presented. Relative advantages and disadvantages of various reactor configurations and selection criteria for different applications are discussed.

Chronic otitis media with effusion (OME) has been assumed to be sterile, since several reports in the literature have described unsuccessful attempts to culture bacteria from it. However, several recent studies have confirmed an earlier report that there is a significant frequency of bacteria in the middle ears of children with chronic and/or recurrent OME. Similar studies in young infants with chronic and/or recurrent OME have not been previously reported. In this study, cultures were obtained at the time of myringotomy and tympanostomy tube insertion from 50 infants aged 1–12 months who had chronic and/or recurrent OME. From the 80 ears of 40 infants without cleft palate, 32% had bacteria isolated from their middle ears; 22% had Streptococcus pneumoniae or Haemophilus influenzae. In 21 of these ears, no effusion was apparent at myringotomy, but in 28% bacteria were isolated from middle ear washings. From the 20 ears of 10 infants with an unrepaired cleft palate, 55% had bacteria present in their middle ear aspirates; 50% had S. pneumoniae or H. influenzae. Even though the significance of bacteria in chronic OME in children, and now in young infants, is unclear at present, a therapeutic trial with an antimicrobial agent prior to surgical intervention would appear to be reasonable until such therapy is tested in a randomized, clinical trial.

Purpose of this article is to review the current status of bioreactor design for mammalian cell culture. Morphological and biochemical features of two major mammalian cell groups, anchorage-dependent and independent cells are proposed as a basis for different behavior at their cultivation. Different bioreactor configurations are systematically discussed through enumerating elementary physical phenomena and through stressing their physiological significance. Special considerations are given to those areas which are inherent to mammalian cell bioreactor.

The inflammatory nasal polyp is the most common benign or malignant nasal mass seen in children. Nasal polyps in the pediatric population appear to occur as inflammatory responses to bacterial infections. In 33% of the patients with polyps whom we studied, antral choanal polyps were noted, and in 20% of the patients the polyps were unilateral but not antral choanal. In 18% of the patients the polyps were bilateral and in an additional 29% they occurred bilaterally in association with cystic fibrosis. History of an allergy is infrequently associated with nasal polyps; allergies are potentially major contributing factors to nasal polyps only in patients without cystic fibrosis whose nasal polyps are bilateral. Patients with antral choanal polyps are most successfully managed by simultaneous Caldwell-Luc antrostomy and polypectomy. Sixty percent of patients with nasal polyps and cystic fibrosis are adequately managed with a single intranasal polypectomy. Simultaneous sinus surgery and polypectomy should be considered for all patients with recurrent polyps and for all patients with clinical or radiographic evidence of significant sinusitis. Complications, including epistaxis and intranasal synechia, occurred in 3% of the 170 surgical procedures performed.