Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

D-dimer as a predictor of early neurologic deterioration in cryptogenic stroke with active cancer.

BACKGROUND AND PURPOSE: The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer-specific mechanisms. However, cryptogenic stroke in patients with cancer was considered to be more related to cancer-specific hypercoagulability. In this study, we investigated the potential of the D-dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer. METHODS: We recruited 109 cryptogenic stroke patients with active cancer within 72 h of symptom onset. We defined END as an increase of ≥1 point in the motor National Institutes of Health Stroke Scale (NIHSS) score or ≥2 points in the total NIHSS score within 72 h of admission. After adjusting for potential confounding factors in the multivariate analysis, we calculated the odds ratios (ORs) and confidence intervals (CIs) of D-dimer in the prediction of END. RESULTS: Among 109 patients, END events were identified in 34 (31%) patients within 72 h. END was significantly associated with systemic metastasis, multiple vascular territory lesions on the initial magnetic resonance imaging (MRI), initial NIHSS score and D-dimer levels. In the multivariate analysis, the D-dimer level (adjusted OR, 1.11; 95% CI, 1.04-1.17; P < 0.01) and initial NIHSS score (adjusted OR, 1.08; 95% CI, 1.01-1.15; P = 0.03) predicted END after adjusting for potential confounding factors. In the subgroup analysis of 72 follow-up MRIs, D-dimer level was also correlated with new territory lesions on the follow-up MRI in a dose-dependent manner. CONCLUSION: Ischemic stroke patients with active cancer and elevated D-dimer levels appear to be at increased risk for END recurrent thromboembolic stroke.

Prolonged sleep increases the risk of intracerebral haemorrhage: a nationwide case-control study.

BACKGROUND AND PURPOSE: Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study. METHODS: A nationwide, multicentre matched case-control study was performed to investigate the risk factors for haemorrhagic stroke, using patients from 33 hospitals in Korea. In all, 490 patients with ICH and 980 age- and sex-matched controls were enrolled. Detailed information regarding sleep, sociodemographic factors, lifestyle and medical history before ICH onset was obtained using qualified structured questionnaires. Sleep duration was categorized and the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression with 7 h as the reference duration. RESULTS: The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). After controlling for relevant confounding factors, longer sleep duration was found to be independently associated with the risk of ICH in a dose-response manner (8 h, OR 1.57, 95% CI 1.00-2.47; ≥9 h, OR 5.00, 95% CI 2.18-11.47). CONCLUSIONS: Our study suggested that long sleep duration is positively associated with an increased ICH risk in a dose-dependent manner. Further studies on the relationship linking long sleep duration with increased risk of ICH are required.

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run.

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100-200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.

An assessment of oropharyngeal airway position using a fibreoptic bronchoscope.

Selecting the appropriate oropharyngeal airway for safe and effective airway management is important in clinical practice. In this prospective observational study, we examined the position of the distal end of oropharyngeal airways using a fibreoptic bronchoscope. We enrolled 149 adults (72 men and 77 women). The correct airway size was determined by inserting four adult sizes Guedel airway (Hudson RCI; Teleflex Medical, Research Triangle, Park, NC, USA) (sizes 8, 9, 10 and 11) sequentially in anaesthetised patients. The 'best fit' airway was size 10 in 45 (62%) men, and size 9 in 58 (75%) women. However, when these airways were inserted, the distal end of the airway either touched or passed beyond the epiglottis tip in 20 (27%) men and six (8%) women, respectively. When a size-9 airway was inserted in men and a size-8 airway inserted in women, the distal ends were obstructed by the tongue in three (2%) patients. In conclusion, a size-9 airway in men and a size-8 airway in women are the most acceptable sizes for adults of average height.

Overexpression of acdS in petunia reduces ethylene production and improves tolerance to heat stress.

Petunia hybrida, widely grown as a bedding plant, has reduced growth and flower quality at temperatures above 30 °C (heat stress), primarily due to heat stress-induced ethylene (ET) production. The gene acdS encodes the 1-aminocyclopropane-1-carboxylate (ACC) deaminase (ACCD) enzyme, which is known for its role in reducing ET production by breaking down the ET precursor, ACC, in plant tissues. This study investigated the impact of heat stress on both 'Mirage Rose' WT petunia and its acdS-overexpressing transgenic lines. Heat stress-induced growth inhibition was observed in WT plants but not in transgenic plants. The increased stress tolerance of transgenic plants over WT plants was associated with lower ET production, ROS accumulation, higher SPAD values, water content, and relative water content. Furthermore, higher sensitivity of the WT to heat stress than the transgenic plants was confirmed by analysing ET signalling genes, heat shock transcription factor genes, and antioxidant- and proline-related genes, more strongly induced in WT than in transgenic plants. Overall, this study suggests the potential application of acdS overexpression in other floriculture plants as a viable strategy for developing heat stress-tolerant varieties. This approach holds promise for advancing the floricultural industry by overcoming challenges related to heat-induced growth inhibition and loss of flower quality.

Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

Determinants of muscle carnosine content.

The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of ß-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD's resulting in muscle levels two or more times higher. ß-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of ß-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5-9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in ß-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.

Bronchial hyperresponsiveness to methacholine/AMP and the bronchodilator response in asthmatic children.

Bronchodilator response (BDR) is assessed to estimate the reversibility of airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is usually measured by means of bronchial challenges using direct or indirect stimuli. The aim of the present study was to compare BHR to methacholine (direct) and that to adenosine 5'-monophosphate (AMP) (indirect) with regard to their relationships to BDR in asthmatic children. Methacholine and AMP challenge tests were performed on 138 children with mild-to-moderate asthma, and the provocative concentration causing a 20% decline in forced expiratory volume in 1 s (FEV1) (PC20) was determined for each challenge. BDR was calculated as the change in FEV(1), expressed as a percentage of the initial value, after inhalation of 400 µg salbutamol. Methacholine PC20 correlated significantly but weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and strong correlation between AMP PC20 and BDR (r = -0.489; p = 0.000). For AMP PC20, the relationship was closer than for methacholine PC20 (p = 0.024 for comparison between correlation coefficients). The same figures were observed when BDR was expressed as a percentage of the predicted value. A stronger correlation of BDR with AMP PC20 than with methacholine PC20 suggests that BDR may be better reflected by BHR as assessed by AMP challenge than by methacholine challenge.

Bronchial hyperresponsiveness to methacholine and adenosine 5'-monophosphate, and the presence and degree of atopy in young children with asthma.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, and is usually measured by bronchial challenges using direct or indirect stimuli. The relationship between atopy and BHR remains to be clarified, particularly in a population selected for asthma. Furthermore, data for young children are limited, although asthma frequently occurs in early childhood. OBJECTIVE: The aim of this study was to investigate methacholine (direct stimulus) and adenosine 5'-monophosphate (AMP) (indirect stimulus) responsiveness according to the presence and degree of atopy in young children with asthma. METHODS: A retrospective analysis of data from 122 preschool children (median age [range]: 5.3 years [4.0-6.8]) presenting with the diagnosis of asthma was performed. These children were characterized by skin-prick tests (SPTs) and bronchial challenges with methacholine and AMP, using a modified auscultation method. The end-point concentration, resulting in audible wheezing and/or oxygen desaturation, was determined for each challenge. Atopy was defined by at least one positive reaction to SPTs, and its degree was assessed using serum total IgE levels, number of positive SPTs, and atopic scores (sum of graded weal size). RESULTS: Atopic patients (n=97) had a significantly lower AMP end-point concentration than non-atopic patients (n=25), whereas the methacholine end-point concentration was not different between the two groups. Among the atopic patients, there was no association between the methacholine end-point concentration and any of the atopy parameters. By contrast, a significant association was found between the AMP end-point concentration and the degree of atopy reflected in serum total IgE and atopic scores (χ² test for trend, P=0.001, 0.003, respectively). CONCLUSION AND CLINICAL RELEVANCE: Young children with atopic asthma had a significantly greater AMP responsiveness than those with non-atopic asthma, whereas methacholine responsiveness was not significantly different between the two groups. The degree of atopy appeared to be an important factor in AMP responsiveness, but not in methacholine responsiveness, and thus might be a marker of airway inflammation in asthma.

Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein-2 on periodontal regeneration.

BACKGROUND AND OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP-2 on the in vitro and in vivo biologic activity of well-characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP-2. MATERIAL AND METHODS: hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP-2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8-wk healing period. The effects of rhBMP-2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP-2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed. RESULTS: In the present study, rhBMP-2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs in vitro, and the in vivo potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down-regulated following treatment with rhBMP-2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles. CONCLUSION: In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP-2 on cementum and PDL tissue regeneration by hPDLSCs.

Viral agents associated with acute gastroenteritis in Seoul, Korea.

BACKGROUND: The present study was carried out to describe the epidemiologic characteristics of viral gastroenteritis and determine the phylogenetic composition of norovirus strains detected in hospitalized children with acute gastroenteritis in Seoul, Korea. METHODS AND RESULTS: In total, 10,603 stool samples were collected from 2004 to 2008 and tested by RT-PCR or ELISA. In 4,170 (39.3%) samples at least one viral pathogen was present. Rotavirus (RoV) (1,864, 17.5%) was found to be the causative agent followed by norovirus (NoV) (1,845, 17.4%), human adenovirus (HAdV) (266, 2.5%), human astrovirus (HAstV) (194, 1.8%), and sapovirus (SV) (1, 0.009%). Five GI genotypes (GI-1, GI-3, GI-4, GI-8, and GI-9) and eight GII genotypes (GII-2, GII-3, GII-4, GII-6, GII-7, GII-12, GII-16, and GII-17) of NoV were identified in acute gastroenteritis patients in 2008. CONCLUSIONS: The genetic characteristics of norovirus and the epidemiologic patterns of a viral pathogen from acute gastroenteritis patients may give potentially effective data for epidemiological studies in Seoul, Korea.

Detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in Seoul, Korea.

BACKGROUND: Human enteroviruses (HEVs) are a major cause of herpangina, HFMD (hand, foot, and mouth disease), and other neurological diseases in Seoul, Korea. METHODS: A total of 56 specimens from hospitalized patients collected from February to December 2009 (37 females and 19 males) in Seoul were tested for HEV from stool, throat swab, and vesicle swab samples taken from patients with herpangina or HFMD using cell culture and RT-PCR in 2009. By the 1D gene, encoding the VP1 capsid protein, seven different HEV genotypes were detected with Coxsackievirus A2, A4, A5, A9, A16 (CA), Coxsackievirus B1 (CB), and Enterovirus 71 (EV71). The most prevalent genotype was CA16 (6, 10.7%), followed by CA2 (4, 7.1%), CA5 (4, 7.1%), EV71 (2, 3.6%), CA4 (1, 1.8%), CA9 (1, 1.8%), and CB1 (1, 1.8%). The 1D gene sequences of two EV71 strains were closely related with one another (98.5% nucleotide similarity) and belonged to the C4 genotype. CONCLUSIONS: It is important to continuously survey the genetic characteristics of EV71 and CA16 from patients, which will provide useful data that aids in our understanding of HFMD infections in Seoul, Korea and may contribute to future control.

Differential Stability of miR-9-5p and miR-9-3p in the Brain Is Determined by Their Unique Cis- and Trans-Acting Elements.

microRNAs (miRs) are fundamental regulators of protein coding genes. In the CNS, miR-9 is highly enriched and critical for neuronal development and function. Mature miRs are derived from a duplex precursor, and the -5p strand ("guide") is preferentially incorporated into an RNA-induced silencing complex (RISC) to exert its regulatory functions, while the complementary -3p strand ("passenger") is thought to be rapidly degraded. By contrast, both strands of the miR-9 duplex have unique functions critical for neuronal physiology, yet their respective degradation rates and mechanisms governing degradation are not well understood. Therefore, we determined the degradation kinetics of miR-9-5p and miR-9-3p and investigated the cis and trans elements that affected their stability in the brain. Using a combination of homogeneous neuronal/astrocyte cell models and heterogeneous brain tissue lysate, we demonstrate the novel finding that miR-9-3p was more stable than the miR-9-5p guide strand in all models tested. Moreover, the degradation kinetics of both miR-9-5p and miR-9-3p were brain-region specific, suggesting that each brain region was differentially enriched for specific degradation factors. We also determined that the 3' nucleotides harbor important cis elements required to not only maintain stability, but also to recruit potential protein degradation factors. We used mass spectrometry to assess the miR-9 interacting proteins and found that the -5p and -3p strands were associated with functionally distinct proteins. Overall, these studies revealed unique miR-9-5p and miR-9-3p degradation kinetics in the brain and proposed critical nucleotide sequences and protein partners that could contribute to this differential stability.

A Brownian energy depot model of the basilar membrane oscillation with a braking mechanism.

High auditory sensitivity, sharp frequency selectivity, and spontaneous otoacoustic emissions are signatures of active amplification of the cochlea. The human ear can also detect very large amplitude sounds without being damaged, as long as the exposed time is not too long. The outer hair cells are believed to be the best candidate for the active force generator of the mammalian cochlea. In this paper, we propose a new model for the basilar membrane oscillation which describes both an active and a protective mechanism by employing an energy depot concept and a critical velocity of the basilar membrane. The compressive response of the basilar membrane at the characteristic frequency and the dynamic response to the stimulation are consistent with the experimental results. Although our model displays a Hopf bifurcation, our braking mechanism results in a hyper-compressive response to intense stimuli which is not generically observed near a Hopf bifurcation. Asymmetry seen in experimental recordings between the onset and the offset of the basilar membrane response to a sound burst is also observed in this model.

Optimized fiber optic bioprobe with high spectral contrast exploiting laser-induced fluorescence for malignancy diagnosis.

A high spectral contrast is expected to be very important when laser-induced fluorescence (LIF) is employed for cancer diagnosis. We developed a LIF optical fiber sensor to achieve a very high spectral contrast between normal and malignant tissues. A comprehensive experimental investigation was carried out to study the role of two critically important parameters for sensor design, namely, the excitation-collection geometry and the excitation wavelength, and their effect on the autofluorescence spectral contrast. An optimum sensing configuration was determined in order to enhance the small, but consistent, spectral difference between the normal and the malignant tissue for improving the accuracy of LIF-based cancer diagnosis. With the optimum sensor configuration, we realized a spectral contrast of more than 22 times between normal and malignant tissue sample spectra.

Prognostic factors influencing the development of an iatrogenic pneumothorax for computed tomography-guided radiofrequency ablation of upper renal tumor.

BACKGROUND: Percutaneous radiofrequency (RF) ablation of upper renal tumors is considered a minimally invasive treatment, but this technique may cause pneumothorax. PURPOSE: To assess retrospectively the prognostic factors influencing the development of iatrogenic pneumothorax for RF ablation of upper renal tumors. MATERIAL AND METHODS: Computed tomography (CT)-guided RF ablation was performed in 24 patients (21 men, three women; age range 31-77 years, mean age 53.3 years) with 28 upper renal tumors. Various factors for pneumothorax-complicated (PC) upper renal tumors and non-pneumothoracic (NP) upper renal tumors were compared during RF ablation to determine which of the factors were involved in the development of pneumothorax. RESULTS: Among 28 upper renal tumors in 24 patients, a pneumothorax occurred accidentally in six patients with eight tumors and intentionally in two patients with two tumors. This complication was treated with conservative management, instead of tube drainage. PC upper renal tumors had shorter distance from the lung or from the costophrenic line to the tumor, a larger angle between the costophrenic line and the tumor, and a higher incidence of intervening lung tissue than NP upper renal tumors (P<0.01). Intervening lung tissue was more frequently detected on CT images obtained with the patient in the prone position than on CT images obtained with the patient in the supine position. CONCLUSION: The presence of intervening lung tissue and the close proximity between an upper renal tumor and the lung are high risk factors for developing an iatrogenic pneumothorax. Pre-ablation CT scan should be performed in the prone position to exactly evaluate intervening lung tissue.

Isolated tubal torsion: specific signs on preoperative computed tomography and magnetic resonance imaging.

Isolated torsion of the fallopian tube is a rare cause of lower abdominal pain and commonly occurs after menarche. Prompt identification of this entity can prevent irreversible vascular damage, but the diagnosis is rarely made before surgery due to nonspecific clinical and imaging features. We report a case of isolated tubal torsion with specific imaging features on preoperative computed tomography and magnetic resonance imaging.

Spontaneous rupture of pheochromocytoma: computed tomography-pathologic features and correlation.

Spontaneous rupture is a rare complication of pheochromocytoma. Its preoperative diagnosis is of great importance in determining treatment and prognosis. We describe computed tomography pathologic findings and correlate their features in a case with ruptured pheochromocytoma.

Structural and functional characteristics of oestrogen receptor ß splice variants: Implications for the ageing brain.

Oestrogen receptor (ER)ß is a multifunctional nuclear receptor that mediates the actions of oestrogenic compounds. Despite its well defined role in mediating the actions of oestrogens, a substantial body of evidence demonstrates that ERß has a broad range of physiological functions independent of those normally attributed to oestrogen signalling. These functions can partly be achieved by the activity of several alternatively spliced isoforms that have been identified for ERß. This short review describes structural differences between the ERß splice variants that are known to be translated into proteins. Moreover, we discuss how these alternative structures contribute to functional differences in the context of both healthy and pathological conditions. Our review also describes the principal factors that regulate alternative RNA splicing. The alternatively spliced isoforms of ERß are differentially expressed according to brain region, age and hormonal milieu, emphasising the likelihood that there are precise cell-specific mechanisms regulating ERß alternative splicing. However, despite these correlative data, the molecular factors regulating alternative ERß splicing in the brain remain unknown. We also review the basic mechanisms that regulate alternative RNA splicing and use that framework to make logical predictions about ERß alternative splicing in the brain.