Recovery from Cranial Nerve Symptoms after Flow Diversion without Coiling for Unruptured Very Large and Giant ICA Aneurysms.

BACKGROUND AND PURPOSE: Cranial nerve symptoms, including visual impairment and ophthalmoplegia, are one of the most common presentations of very large and giant (≥15 mm) ICA aneurysms. In this study, we evaluated the treatment outcomes of flow diversion and conventional coiling in terms of recovery from cranial nerve symptoms and postoperative complications. MATERIALS AND METHODS: Seventy-nine patients with unruptured ICA aneurysms of >15 mm who were treated with flow diversion or conventional coiling between December 2009 and December 2020 were retrospectively evaluated. We compared the radiologic and clinical outcomes, including recovery from cranial nerve symptoms, between the 2 groups. RESULTS: Twenty-eight of 49 patients (57.1%) treated with flow diversion and 10 of 30 patients (33.3%) treated with conventional coiling initially presented with cranial nerve symptoms (P = .068). In the clinical follow-up, the symptom recovery rate was significantly higher in those treated with flow diversion (15 [50%] versus 3 [25%] with conventional coiling, P = .046). Multivariate logistic regression analysis demonstrated that flow diversion was significantly associated with symptom recovery (OR, 7.425; 95% CI, 1.091-50.546; P = .040). The overall postoperative complication rate was similar (flow diversion, 10 [20.4%]; conventional coiling, 6 [20.0%], P = .965), though fatal hemorrhagic complications occurred only in patients with intradurally located aneurysms treated with flow diversion (4 [8.2%] versus 0 [0.0%] with coiling, P = .108). CONCLUSIONS: Flow diversion without coiling for very large and giant ICA aneurysms yielded a higher rate of recovery from cranial nerve symptoms, but it may be related to an increased hemorrhagic complication rate, especially for intradurally located aneurysms.

Predictors of the Effects of Flow Diversion in Very Large and Giant Aneurysms.

BACKGROUND AND PURPOSE: The treatment paradigm for very large and giant aneurysms has recently changed to flow diversion, in light of the results of the Pipeline for Uncoilable or Failed Aneurysms trial. However, the effects of flow diversion were definitely unknown. We explored this topic and identified the predictors of such effects. MATERIALS AND METHODS: We retrospectively reviewed 51 patients with unruptured aneurysms admitted to our institution for flow diversion between February 2014 and August 2019. Patients were categorized into an effect group (no filling or remnant entry) and a no-effect group (subtotal or total filling). We evaluated the aneurysm size and shape, incorporation vessel, parent artery stenosis and curvature, stagnation of contrast medium within the aneurysm, use of balloon angioplasty, and intra-aneurysm thrombus as potential predictors of the effects of flow diversion. RESULTS: The effect group comprised 34 patients (66.7%, 34/51; no filling, 35.3%, 18/51; and remnant entry, 31.4%, 16/51). The no-effect group comprised 17 patients (33.3%, 17/51; subtotal filling, 29.4%, 15/51; and total filling, 3.9%, 2/51). An incorporation vessel and balloon angioplasty were independent risk factors for the no-effect group in multivariate logistic regression analyses (OR = 0.13 and 0.05; 95% confidence intervals, 0.02-0.62 and 0.00-0.32; P values, .021 and .004, respectively). CONCLUSIONS: Flow diversion is effective for very large and giant aneurysms, but the outcomes require further improvement. The results of this study show that an incorporated vessel and excessive balloon angioplasty might compromise flow diversion. This finding can help improve the outcomes of flow diversion.

Intraprocedural Flat Panel Detector Rotational Angiography and an Image Fusion Technique for Delivery of a Microcatheter into the Targeted Shunt Pouch of a Dural Arteriovenous Fistula.

The accurate and safe delivery of a microcatheter to a targeted shunt pouch is essential for successful transvenous embolization of intracranial dural arteriovenous fistulas. However, complex anatomy and variations in head and neck veins and occluded sinuses can hinder intraprocedural microcatheter delivery. In this study, we introduce an intraprocedural flat panel detector rotational angiography and image fusion technique to aid precise navigation inside the veins and proper placement of the microcatheter in the targeted shunt pouch.

Landscape of Elderly Suicide in South Korea: Its Trend According to Age, Gender, and Educational Attainment.

South Korea has one of the highest suicide rates in the world, and the most alarming suicide rate is among its elders. This study aims to understand the social, historical, and cultural context of the Korean older adults and examine suicide trends based on that understanding. The results show that the suicide risk increases with age, the male suicide rate outweighs that of females, and the suicide rate decreases with educational attainment. In addition, several suggestions for reducing elderly suicide rate are addressed, including differentiating the existing social services for elders by age and expanding suicide prevention programs beyond schools to communities so that all people in need can access them.

The Fate of Unruptured Intracranial Vertebrobasilar Dissecting Aneurysm with Brain Stem Compression According to Different Treatment Modalities.

BACKGROUND AND PURPOSE: Unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression are difficult to treat. In the present study, the clinical and radiologic outcomes of unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression based on different treatment modalities were evaluated. MATERIALS AND METHODS: This study included 28 patients with unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression treated from January 2009 to December 2017. Treatment methods were observation (n = 6), stent-assisted coil embolization (n = 9), parent artery occlusion (n = 6), and flow diversion (n = 7). The data of baseline characteristics, change of aneurysm size, retreatment rate, stroke occurrence, and alteration of the mRS score were obtained from retrospective chart review. RESULTS: The initial size of dissecting aneurysms was largest in the flow diversion group (22.5 ± 7.7 mm), followed by parent artery occlusion (20.3 ± 8.4 mm), stent-assisted coil embolization (11.7 ± 2.2 mm), and observation (17.8 ± 5.5 mm; P = .01) groups. The reduction rate of aneurysm size was highest in the parent artery occlusion group (26.7 ± 32.1%), followed by flow diversion (14.1% ± 28.7%), stent-assisted coil embolization (-17.9 ± 30.3%), and observation (-31.5 ± 30.8%; P = .007) groups. Additional treatment was needed in the observation (4/6, 66.7%) and stent-assisted coil embolization (3/9, 33.3%; P = .017) groups. Improvement of the mRS score on follow-up was observed in the flow diversion (6/7, 85.7%) and parent artery occlusion (4/6, 66.7%) groups but not in the stent-assisted coil embolization and observation groups. A worsened mRS score was most common in the observation group (4/6, 66.7%), followed by stent-assisted coil embolization (3/9, 33.3%), parent artery occlusion (2/6, 33.3%), and flow diversion (0/7, 0%) groups. CONCLUSIONS: When treating intracranial vertebrobasilar dissecting aneurysms with brain stem compression, parent artery occlusion and flow diversion should be considered to reduce aneurysm size and improve the mRS score.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. METHODS: The serum SPD level was measured in patients with AERD (n = 336), those with aspirin-tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated. RESULTS: The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P = .002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD. CONCLUSION: The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.

Seven-year Follow-up of Resin Infiltration Treatment on Noncavitated Proximal Caries.

The purpose of this case report is to present success and failure outcomes of seven-year follow-up of resin infiltration treatment (RIT) used for the proximal caries of maxillary premolars. Although resin infiltration can be a good option for micro-invasive treatment, long-term follow-up data are not sufficient, and the outcome of this technique can be affected by factors such as technique sensitivity of procedure, patient's caries risk, and depth of caries progression. Therefore, careful case selection, application, and follow-up are needed.

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma.

BACKGROUND: Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. OBJECTIVES: We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). METHODS: Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). RESULTS: Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = -0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin-exacerbated respiratory disease.

BACKGROUND: To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. METHODS: An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. RESULTS: A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4 /PGF2 α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4 /PGF2 α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). CONCLUSIONS AND CLINICAL RELEVANCE: Serum metabolite level of LTE4 and LTE4 /PGF2 α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease.

BACKGROUND: Clinical presentation of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (NERD) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes. METHODS: We performed two-step cluster analysis using urticaria, chronic rhinosinusitis (CRS), and atopy, in a NERD cohort comprising 302 patients. Asthma exacerbation was defined as receiving at least one burst of intravenous steroid treatment and/or at least two bursts of oral steroid use (≥ 45 mg/3 days) per year. The possession rate of anti-asthmatic medications was estimated during the follow-up period. RESULTS: There were four subtypes: subtype 1 (NERD with CRS/atopy and no urticaria), subtype 2 (NERD with CRS and no urticaria/atopy), subtype 3 (NERD without CRS/urticaria), and subtype 4 (NERD with urticaria). Significant differences were found between the four subtypes in the female proportion, baseline FEV1%, serum total IgE level, and sputum/peripheral eosinophil count. A higher frequency of asthma exacerbations was noted in subtype 1 compared to subtype 3. The possession rates of medium- to high-dose inhaled corticosteroids/long-acting beta2 -agonists showed significant differences among the four subtypes. Metabolomic analysis showed that the four subtypes of NERD had a higher serum leukotriene E4 (LTE4) level than those with aspirin-tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE4 level than those with subtype 2. CONCLUSION: We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD.

The prevalence of causative organisms of community-acquired urethritis in an age group at high risk for sexually transmitted infections in Korean Soldiers.

OBJECTIVES: This study was designed to evaluate the causative organisms in young male soldiers with clinical signs and symptoms after sexual contact that suggests a diagnosis of urethritis. METHODS: Between June 2012 and January 2015, male patients with urethritis symptoms that had resulted from sexual contact within 3 months participated in this study. All patients were evaluated using urinalysis and were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), Mycoplasma hominis (MH), herpes simplex virus (HSV) type II and Trichomonas vaginalis (TV) using multiplex PCR (mPCR) assay in order to detect sexually transmitted infections (STI) or pathogens. RESULTS: A total of 436 male patients aged 18-28 years were included in the study. The median age was 22.0 years. The prevalence of STI pathogens were as follows: NG in 19.0%, CT in 36.6%, UU in 24.0%, MG in 21.5%, MH in 6.1%, HSV type II in 1.6%, TV in 0.2% and indeterminate STI pathogens in 9.4%. Coinfection of NG with non-NG was detected in 5.7% of the participants, while the coinfection rates for STI pathogens were: with CT in 3.4%, with UU in 2.7%, with MG in 0.2% and with MH in 0.2%. CONCLUSIONS: CT was the most prevalent STI pathogen and coinfections of NG with non-NG appeared less frequently. The young male soldiers with urethritis should be administered suitable antibiotics for STI pathogens that were found by mPCR results, rather than an experimental combination of antibiotics for coinfections.

Risk factors for peri-anaesthetic dental injury.

In this retrospective case-control study, we evaluated peri-operative dental injury risk factors following tracheal intubation. Ninety-four of 290,415 patients experienced dental injury following tracheal intubation over a 10-y period. A control group was matched for surgery type and intubating anaesthetist. The incidence of dental injury was 0.03%. Univariate analysis revealed that previous and current difficult intubation, male gender, hepatitis, neurological disease, anticonvulsant use, pre-existing poor dentition and the use of airway devices (other than a laryngoscope) were associated with dental injury. Multivariate analysis revealed that predictors of dental injury were: history of hepatitis, odds ratio (95% CI) 10.1 (1.02-100.3); poor dentition, 8.8 (3.9-20.0); alternative airway device use, 3.1 (1.2-8.0); and intubation difficulty, 3.7 (1.0-13.3). As well as confirming previously reported risk factors for dental injury during tracheal intubation, this study also suggests hepatitis and the use of alternative airway devices as additional risk factors.

Combined blockade of the histamine H1 and H4 receptor suppresses peanut-induced intestinal anaphylaxis by regulating dendritic cell function.

BACKGROUND: Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis. OBJECTIVES: The objective of this study was to determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy. METHODS: Balb/c mice were sensitized and challenged with peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120. Bone marrow-derived DCs (BMDCs) were adoptively transferred to nonsensitized WT mice. Symptoms, intestinal inflammation, and mesenteric lymph node and intestine mucosal DCs were assessed. Effects of the drugs on DC chemotaxis, calcium mobilization, and antigen-presenting cell function were measured. RESULTS: Treatment with loratadine or JNJ7777120 individually partially suppressed the development of diarrhea and intestinal inflammation and decreased the numbers of DCs in the mesenteric lymph nodes and lamina propria. Combined treatment with both drugs prevented the development of diarrhea and intestinal inflammation. In vitro, the combination suppressed DC antigen-presenting cell function to T helper cells and DC calcium mobilization and chemotaxis to histamine. CONCLUSION: Blockade of both H1R and H4R in the challenge phase had additive effects in preventing the intestinal consequences of peanut sensitization and challenge. These effects were mediated through the limitation of mesenteric lymph node and intestinal DC accumulation and function. Identification of this histamine H1R/H4R-DC-CD4+ T-cell axis provides new insights into the development of peanut-induced intestinal allergic responses and for prevention and treatment of peanut allergy.

Undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a young soldier.

We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a 21-year-old male soldier. Soldiers live in close quarters, and have a regimented lifestyle that may not allow for frequent voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in acute urinary retention.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

BACKGROUND AND PURPOSE: The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. MATERIALS AND METHODS: Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. RESULTS: The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P < .05). No differences in cortical thickness were found in all group contrasts. CONCLUSIONS: Resting-state functional connectivity and WM alterations might be useful imaging biomarkers for identifying changes in patients with Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. The functional and microstructural substrates may topographically differ depending on the rate of cognitive decline in these patients.

Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target.

BACKGROUND: Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the pathogenesis of severe asthma. OBJECTIVE: We compared autophagy in the sputum granulocytes, peripheral blood cells (PBCs) and peripheral blood eosinophils (PBEs) between patients with severe asthma and those with non-severe asthma and investigated the functional effects of autophagy. METHODS: We enrolled 36 patients with severe asthma, 14 with non-severe asthma and 23 normal healthy controls in this study. Sputum granulocytes, PBCs and PBEs were isolated from each subject. Autophagy was evaluated based on the expression of microtubule-associated protein light chain 3 (LC3) by Western blot, confocal microscopy, transmission electron microscopy and flow cytometry. IL-8 levels were measured by ELISA. To induce autophagy, HL-60 cells, human primary small airway epithelial cells (SAECs) and A549 cells were treated with IL-5, IL-1ß and TNF-α. To inhibit autophagy, PI3K inhibitors (LY29400 and 3-methyladenine [3-MA]) and hydroxychloroquine (HCQ) were used. Knockdown of ATG5 and Beclin-1 was performed in A549 cells, and the therapeutic effects of dexamethasone were evaluated. RESULTS: Higher autophagy levels were noted in sputum granulocytes, PBCs and PBEs from patients with severe asthma than from patients with non-severe asthma and healthy controls (P < 0.05 for all). IL-5 increased autophagy levels in both PBCs and PBEs (P < 0.05). 3-MA attenuated the increased expression of LC3-II and eosinophil cationic protein in HL-60 cells induced by IL-5 (P = 0.034 for both). Dexamethasone did not affect autophagy levels in PBEs. IL-1ß increased LC3-II expression and IL-8 production (P < 0.01) in SAECs, and this was attenuated by LY294002, 3-MA, HCQ and knockdown of ATG5 and Beclin-1 (in A549 cells) (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy-resistant severe asthma.

Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?

Classical Galactosaemia is a rare disorder of carbohydrate metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). The disease is life-threatening in the neonate, and the only treatment option is life-long dietary restriction of galactose. However, long-term complications persist in treated patients including cognitive impairments, speech and language abnormalities and premature ovarian insufficiency in females. Microarray analysis of T-lymphocytes from treated adult patients identified systemic dysregulation of numerous gene pathways, including the glycosylation, inflammatory and inositol pathways. Analysis of gene expression in patient-derived dermal fibroblasts of patients exposed to toxic levels of galactose, with immunostaining, has further identified the susceptibility of the glycosylation gene alpha-1,2-mannosyltransferase (ALG9) and the inflammatory gene annexin A1 (ANXA1) to increased galactose concentrations. These data suggest that Galactosaemia is a multi-system disorder affecting numerous signalling pathways.

Graft-bending angle and femoral tunnel length after single-bundle anterior cruciate ligament reconstruction: comparison of the transtibial, anteromedial portal and outside-in techniques.

We used immediate post-operative in vivo three-dimensional computed tomography to compare graft bending angles and femoral tunnel lengths in 155 patients who had undergone single-bundle reconstruction of the anterior cruciate ligament using the transtibial (n = 37), anteromedial portal (n = 72) and outside-in (n = 46) techniques. The bending angles in the sagittal and axial planes were significantly greater but the coronal-bending angle was significantly less in the transtibial group than in the anteromedial portal and outside-in groups (p < 0.001 each). The mean length of the femoral tunnel in all three planes was significantly greater in the transtibial group than the anteromedial portal and outside-in groups (p < 0.001 each), but all mean tunnel lengths in the three groups exceeded 30 mm. The only significant difference was the coronal graft- bending angle in the anteromedial portal and outside-in groups (23.5° vs 29.8°, p = 0.012). Compared with the transtibial technique, the anteromedial portal and outside-in techniques may reduce the graft-bending stress at the opening of the femoral tunnel. Despite the femoral tunnel length being shorter in the anteromedial portal and outside-in techniques than in the transtibial technique, a femoral tunnel length of more than 30 mm in the anteromedial portal and outside-in techniques may be sufficient for the graft to heal.

Gene expression and localization of 20α-hydroxysteroid dehydrogenase (HSD) in reproductive tissues during early pregnancy of cattle.

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone, and this enzyme has an important role in the regulation of luteal function in mammals. It has previously been determined that the 20α-HSD gene is primarily expressed by large luteal cells during the late stage of the estrous cycle. In the present study, the amounts of mRNA were determined in cultured cells of the corpus luteum (CL) cells. The localization of 20α-HSD was also determined in ovaries, placenta, and endometrium during early pregnancy. The amount of 20α-HSD mRNA in cultured luteal cells increased with time and by treatment with the luteolysis agent prostaglandin F2α (PGF2α). Immunofluorescence assays detected increased protein in cultured luteal cells. The 20α-HSD mRNA and protein were present in the ovaries, placenta, and endometrium on Days 30, 60, and 90 of pregnancy. In particular, gene expression was much greater in the ovary than in the placenta and endometrium. Immuno-histochemical analysis indicated that bovine 20α-HSD was primarily localized in ovarian large luteal cells, placental cytotrophoblast villus, and glandular epithelial cells of the endometrium during early pregnancy. Furthermore, in situ analyses demonstrated colocalization of 20α-HSD mRNA and protein. Taken together, results of the present study indicate that 20α-HSD mRNA and protein are co-localized in large luteal cells, the placenta, and the endometrium during early pregnancy, suggesting that 20α-HSD regulates mechanisms involved in the maintenance of early pregnancy.