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There is increasing evidence that shore platforms and other elements of rock coasts may be inherited, at least in part, from interglacial stages when sea level was similar to today's. Most of this evidence, which includes ancient beaches and datable terrestrial deposits, has been obtained from areas of resistant, slowly eroding rock, where the platforms often appear to be much too wide to have developed since the sea reached its present level. It is much more difficult to demonstrate that inheritance has occurred in areas of weaker rock, which generally lack any datable material. The coast of western Galicia in northwestern Spain has shore platforms in igneous and metamorphic rocks that were deeply weathered during the Tertiary. These platforms are closely associated with ancient beaches from the last interglacial stage, and associated periglacial and fluvio-nival deposits that covered and fossilized most of the Eemian platforms and cliffs during the late middle and late Weichselian glacial stage. The sedimentary processes and the thickness and facies of the sediments were determined by the height, aspect and gradient of the coastal mountains, and their distance from the coast. Radiocarbon dating, sedimentary analysis and platform morphology indicate that the shore platforms of Galicia have been inherited from at least the last interglacial stage. They were fossilized in places beneath thick Weichselian deposits and then exhumed during the Holocene transgression. The abundant evidence for inheritance in Galicia has important implications for other coasts in fairly weak rocks where such evidence is generally lacking. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity., (© 2022 Japanese Dermatological Association.)

Rapid diagnosis of blood infections requires fast and efficient separation of bacteria from blood. We have developed spinning hollow disks that separate bacteria from blood cells via the differences in sedimentation velocities of these particles. Factors affecting separation included the spinning speed and duration, and disk size. These factors were varied in dozens of experiments for which the volume of separated plasma, and the concentration of bacteria and red blood cells (RBCs) in separated plasma were measured. Data were correlated by a parameter of characteristic sedimentation length, which is the distance that an idealized RBC would travel during the entire spin. Results show that characteristic sedimentation length of 20 to 25 mm produces an optimal separation and collection of bacteria in plasma. This corresponds to spinning a 12-cm-diameter disk at 3,000 rpm for 13 s. Following the spin, a careful deceleration preserves the separation of cells from plasma and provides a bacterial recovery of about 61 ± 5%., (© 2019 American Institute of Chemical Engineers.)

Background: Some chronic inflammatory skin diseases, such as psoriasis, have been associated with an increased prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, this prevalence in hidradenitis suppurativa (HS) has not been assessed to date., Objectives: To determine the prevalence of NAFLD in patients with HS and the risk factors associated with this disorder., Methods: This case-control study enrolled 70 HS patients and 150 age- and gender-matched controls who were evaluated by hepatic ultrasonography (US) and transient elastography (TE) after excluding other secondary causes of chronic liver disease. The diagnosis of NAFLD was established if US and/or TE were altered., Results: The prevalence of NAFLD was significantly increased in patients with HS compared to controls (72.9% vs. 24.7%: P < 0.001). In the multivariable regression model adjusted for age, sex and classic metabolic risk factors for NAFLD, HS was significantly and independently associated with the presence of NAFLD [OR 7.75 confidence interval (CI) 2.54-23.64; P < 0.001]., Conclusions: Our results show a high prevalence of NAFLD in HS patients independent of classic metabolic risk factors. Therefore, we suggest HS patients to be evaluated for NAFLD and managed accordingly., (© 2019 European Academy of Dermatology and Venereology.)

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA 2 DS 2 VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA 2 DS 2 VASc=1) (or women with CHA 2 DS 2 VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA 2 DS 2 VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA 2 DS 2 VASc=0, CHA 2 DS 2 VASc=1, females with a CHA 2 DS 2 VASc=2, and CHA 2 DS 2 VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA 2 DS 2 VASc ≥2 patients (84.2%), those with a CHA 2 DS 2 VASc=0 (60.3%), 1 (69.9%), and females with a CHA 2 DS 2 VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P<0.0001). Stroke rates were low overall and ranged from 0 per 100 patient-years in those with CHA 2 DS 2 VASc=0, 0.8 (95% confidence interval [CI] [0.5-1.2]) in those with CHA 2 DS 2 VASc=1, 0.8 (95% CI [0.4-1.6]) in females with a CHA 2 DS 2 VASc score=2, and 1.7 (95% CI [1.6-1.9]) in CHA 2 DS 2 VASc ≥2. All-cause mortality (per 100 patient-years) was highest in females with a CHA 2 DS 2 VASc score=2 (1.4) (95% CI [0.8-2.3]), compared with patients with a CHA 2 DS 2 VASc=0 (0.2) (95% CI [0.1-1.0]), and CHA 2 DS 2 VASc=1 (1.0) (95% CI [0.7-1.4]), but lower than patients with a CHA 2 DS 2 VASc ≥2 (5.7) (95% CI [5.4-6.0]). Conclusion The majority of CHA 2 DS 2 VASc=0-1 patients are treated with oral anticoagulation. In addition, the absolute risks of death and stroke/transient ischemic attack were low among both male and females CHA 2 DS 2 VASc=0-1 as well as among females with a CHA 2 DS 2 VASc score=2. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01701817.

Purpose: To investigate the feasibility, effectiveness and acceptability of using prosthetic occluding contact lenses (OCLs) to treat moderate amblyopia in adults and of the role of the multifocal visual evoked potential (mfVEP) as a predictor of postamblyopic therapy., Methods: A comparative, prospective, interventional, case series pilot study with amblyopic adults (mean age: 40 years, range 20-50 years) allocated into two intervention groups: eye patching and OCL. The primary outcome variable was logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and secondary outcomes were mfVEP amplitude and latency and patients' health-related quality of life National Eye Institute Visual Function Questionnaire (NEI VFQ-25)., Results: Significant improvements in pre- to postamblyopic therapy BCVA were seen at 1.5 months in the OCL group [0.29 logMAR, 95% confidence interval (CI): 0.10-0.47 versus 0.11 logMAR, 95% CI: 0.02-0.19; p < 0.001] and eye patching group (0.29 logMAR, 95% CI: 0.17-0.40 versus 0.18 logMAR, 95% CI: 0.12-0.23; p < 0.01). Post-treatment BCVA was inversely related to age (R: 0.009, 95% CI: -0.02 to -0.001; p = 0.04) and the presence of strabismus (R: -0.3, 95% CI: -0.434 to -0.17; p = 0.001). No significant changes in the number and size of the abnormal mfVEP amplitude and latency defects were observed after occlusion. The NEI VFQ-25 composite score showed significant improvement in the OCL users at 12 months compared to eye patching., Conclusion: Significant vision improvement can be achieved, making occlusion with OCLs an effective and more acceptable therapy for adults with amblyopia., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that affects the apocrine gland-bearing areas of the body., Objective: We aimed to determine the prevalence of IR in patients with HS., Methods: This cross-sectional, case-control study enrolled 137 subjects, 76 patients with HS and 61 age- and gender-matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA-IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels., Results: The median (IQR) HOMA-IR value in HS patients was significantly higher [2.0 (1.0-3.6)] than in controls [1.5 (0.9-2.3)] (P = 0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (P = 0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA-IR [2.51 (0.18) vs 1.92(0.21); P = 0.04]. The HOMA-IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease., Conclusion: Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly., (© 2018 European Academy of Dermatology and Venereology.)

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, the etiology of which can be dependent on the interactions of multiple genes. We previously reported haplotype associations for polymorphic variants of interferon regulatory factor 6 (IRF6), msh homeobox 1 (MSX1), bone morphogenetic protein 4 (BMP4), and transforming growth factor beta 3 (TGFB3) in Chile. Here, we analyzed the haplotype-based gene-gene interaction for markers of these genes and NSCL/P risk in the Chilean population. We genotyped 15 single nucleoptide polymorphisms (SNPs) in 152 Chilean patients and 164 controls. Linkage disequilibrium (LD) blocks were determined using the Haploview software, and phase reconstruction was performed by the Phase program. Haplotype-based interactions were evaluated using the multifactor dimensionality reduction (MDR) method. We detected two LD blocks composed of two SNPs from BMP4 (Block 1) and three SNPs from IRF6 (Block 2). Although MDR showed no statistical significance for the global interaction model involving these blocks, we found four combinations conferring a statistically significantly increased NSCL/P risk (Block 1-Block 2): T-T/T-G C-G-T/G-A-T; T-T/T-G C-G-C/C-G-C; T-T/T-G G-A-T/G-A-T; and T-T/C-G G-A-T/G-A-T. These findings may reflect the presence of a genomic region containing potential causal variants interacting in the etiology of NSCL/P and may contribute to disentangling the complex etiology of this birth defect., (© 2017 Eur J Oral Sci.)

The aim of the present study was to determine if the use of the anti-tumor necrosis factor (TNF)-α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m 2 or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow-mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty-nine patients were studied. Anti-TNF-α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti-TNF-α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis., (© 2016 Japanese Dermatological Association.)

The high morbidity and mortality rate of bloodstream infections involving antibiotic-resistant bacteria necessitate a rapid identification of the infectious organism and its resistance profile. Traditional methods based on culturing the blood typically require at least 24 h, and genetic amplification by PCR in the presence of blood components has been problematic. The rapid separation of bacteria from blood would facilitate their genetic identification by PCR or other methods so that the proper antibiotic regimen can quickly be selected for the septic patient. Microfluidic systems that separate bacteria from whole blood have been developed, but these are designed to process only microliter quantities of whole blood or only highly diluted blood. However, symptoms of clinical blood infections can be manifest with bacterial burdens perhaps as low as 10 CFU/mL, and thus milliliter quantities of blood must be processed to collect enough bacteria for reliable genetic analysis. This review considers the advantages and shortcomings of various methods to separate bacteria from blood, with emphasis on techniques that can be done in less than 10 min on milliliter-quantities of whole blood. These techniques include filtration, screening, centrifugation, sedimentation, hydrodynamic focusing, chemical capture on surfaces or beads, field-flow fractionation, and dielectrophoresis. Techniques with the most promise include screening, sedimentation, and magnetic bead capture, as they allow large quantities of blood to be processed quickly. Some microfluidic techniques can be scaled up. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:823-839, 2016., (© 2016 American Institute of Chemical Engineers.)

Infant and young child feeding has been recognised as an essential element to improve growth of children, especially in developing countries where malnutrition among children and its dire consequences are very prevalent. However, little attention has been paid on the influence of fathers on child feeding practices, although fathers are very important in raising well-adjusted, happy and successful children. Therefore, this study aimed to assess the influence of fathers' child feeding knowledge and practice on children's dietary diversity. A community-based comparative cross-sectional study was conducted among 850 eligible urban and rural households with children of 6-23 months. The father and mother of the child were interviewed on children's dietary diversity and fathers' knowledge and practice of child feeding. Nearly half (46%) of the children in the rural district did not meet the minimum dietary diversity, and in the urban district, the rate was even worse (72%). Grains were the common food group given to the children in both districts, whereas flesh food was the least commonly consumed food group. Additionally, low vitamin A-rich food and other fruit and vegetable consumption seem to be a problem in both districts. Almost all dimensions of fathers' knowledge and practice were significantly related to children's minimum dietary diversity; especially, fathers' knowledge of food groups was an important predictor (P-value < 0.001) in both districts. Interventions that focus on the fathers' knowledge of child feeding, especially about food groups, are recommended to improve children's dietary diversity in the study communities., (© 2014 John Wiley & Sons Ltd.)

Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity., (© 2015 Japanese Dermatological Association.)

Background: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis., Objective: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients., Methods: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6., Results: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 μg/mL, vs. 35.6 ± 29.9 μg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed., Conclusion: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis., (© 2015 European Academy of Dermatology and Venereology.)

Background: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases., Objective: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy., Methods: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6., Results: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen., Conclusion: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity., (© 2015 European Academy of Dermatology and Venereology.)

Objective: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis., Methods: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6., Results: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable)., Conclusion: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis., (© 2014 European Academy of Dermatology and Venereology.)

We present a novel ultrasound-guided regional anaesthetic technique that may achieve complete paraesthesia of the hemithorax. This technique may be a viable alternative to current regional anaesthetic techniques such as thoracic paravertebral and central neuraxial blockade, which can be technically more challenging and have a higher potential side-effect profile. We performed the serratus block at two different levels in the midaxillary line on four female volunteers. We recorded the degree of paraesthesia obtained and performed fat-suppression magnetic resonance imaging and three-dimensional reconstructions of the spread of local anaesthetic in the serratus plane. All volunteers reported an effective block that provided long-lasting paraesthesia (750-840 min). There were no side-effects noted in this initial descriptive study. While these are preliminary findings, and must be confirmed in a clinical trial, they highlight the potential for the serratus plane block to provide analgesia following surgery on the thoracic wall. We suggest that this novel approach appears to be safe, effective, and easy to perform, and is associated with a low risk of side-effects., (© 2013 The Association of Anaesthetists of Great Britain and Ireland.)

Objectives/hypothesis: To develop a robotic surgery training regimen integrating objective skill assessment for otolaryngology and head and neck surgery trainees consisting of training modules of increasing complexity leading up to procedure-specific training. In particular, we investigated applications of such a training approach for surgical extirpation of oropharyngeal tumors via a transoral approach using the da Vinci robotic system., Study Design: Prospective blinded data collection and objective evaluation (Objective Structured Assessment of Technical Skills [OSATS]) of three distinct phases using the da Vinci robotic surgical system in an academic university medical engineering/computer science laboratory setting., Methods: Between September 2010 and July 2011, eight otolaryngology-head and neck surgery residents and four staff experts from an academic hospital participated in three distinct phases of robotic surgery training involving 1) robotic platform operational skills, 2) set up of the patient side system, and 3) a complete ex vivo surgical extirpation of an oropharyngeal tumor located in the base of tongue. Trainees performed multiple (four) approximately equally spaced training sessions in each stage of the training. In addition to trainees, baseline performance data were obtained for the experts. Each surgical stage was documented with motion and event data captured from the application programming interfaces of the da Vinci system, as well as separate video cameras as appropriate. All data were assessed using automated skill measures of task efficiency and correlated with structured assessment (OSATS and similar Likert scale) from three experts to assess expert and trainee differences and compute automated and expert assessed learning curves., Results: Our data show that such training results in an improved didactic robotic knowledge base and improved clinical efficiency with respect to the set up and console manipulation. Experts (e.g., average OSATS, 25; standard deviation [SD], 3.1; module 1, suturing) and trainees (average OSATS, 15.9; SD, 3.9; week 1) are well separated at the beginning of the training, and the separation reduces significantly (expert average OSATS, 27.6; SD, 2.7; trainee average OSATS, 24.2; SD, 6.8; module 3) at the conclusion of the training. Learning curves in each of the three stages show diminishing differences between the experts and trainees, which is also consistent with expert assessment. Subjective assessment by experts verified the clinical utility of the module 3 surgical environment, and a survey of trainees consistently rated the curriculum as very useful in progression to human operating room assistance., Conclusions: Structured curricular robotic surgery training with objective assessment promises to reduce the overhead for mentors, allow detailed assessment of human-machine interface skills, and create customized training models for individualized training. This preliminary study verifies the utility of such training in improving human-machine operations skills (module 1), and operating room and surgical skills (modules 2 and 3). In contrast to current coarse measures of total operating time and subjective assessment of error for short mass training sessions, these methods may allow individual tasks to be removed from the trainee regimen when skill levels are within the standard deviation of the experts for these tasks, which can greatly enhance overall efficiency of the training regimen and allow time for additional and more complex training to be incorporated in the same time frame., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX., Methods: A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented., Results: Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events., Conclusion: The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile., (Copyright © 2011 by the American College of Rheumatology.)

Based on association and sequencing studies, investigators have postulated muscle segment homeobox 1 (MSX1) as a strong candidate gene involved in the causation of nonsyndromic cleft lip with or without cleft palate (NSCLP). Parent-of-origin effects have been suggested for some NSCLP candidate genes but not for MSX1. The aims of the present study were to test for allele/haplotype associations applying the transmission disequilibrium test (TDT) and the transmission asymmetry test (TAT) to evaluate the possible parent-of-origin effects of MSX1 in Chilean patients with NSCLP. We analyzed five SNPs (rs6446693/c.-425G>T/c.-35G>A/rs3775261/rs12532) located from 6.3 kb upstream to 3' UTR in a sample of 150 unrelated NSCLP case-parent trios. Four haplotypes showed overtransmission from parents to affected progeny, but individual SNPs did not. Two haplotypes presented allele combination C-G-A-G (P = 0.035) and two T-G-C-A (P = 0.044) (SNP order rs6446693/c.-35G>A/rs3775261/rs12532). The rs12532 A allele had a 2.08-fold increase in the risk of NSCLP when inherited from the father (95% CI: 1.10-4.02; P = 0.025), but not from the mother. These results could indicate epigenetic control by imprinting in the role of MSX1 in NSCLP. Different authors have proposed that some genes that play a role in NSCLP depend on parental origin. Our findings and those previously reported by our group show that a variety of factors appears to be involved in the association between MSX1 and NSCLP. The full mechanism of MSX1 in the development of NSCLP has not been fully understood.

EGFR [EGF (epidermal growth factor) receptor] overexpression correlates with poor prognosis and bad outcomes in different tumours. However, evidence for EGFR contribution in melanoma immunobiology is limited. We have expressed the full-length human EGFR gene in a murine melanoma cell line. EGFR protein expression in stably trnasfected B16 cells in culture was defined by immunoblotting, immunohistochemistry and FACS. Additionally, transfected cells became sensitive to the lysis induced with an anti-EGFR monoclonal antibody in the presence of complement. Exogenous human EGF addition induced cell proliferation, validating the transfected receptor functionality. Thus we have developed a system to express a functional EGFR in order to evaluate the potential contribution of EGFR expression in melanoma biology and its resulting relevance as a target for immunointerventions in nonepithelial tumours.

With the use of the whole-cell voltage-clamp technique, we have recorded the currents induced by ionotropic glutamate receptor agonists on isolated axonless horizontal cells (HC) of rabbit retina. Bath application of the non-N-methyl-D-aspartate receptor agonists: kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and L-glutamate (GLU) produced an increase in the conductance for non-selective cations. All the isolated horizontal cells responded to GLU, AMPA and KA. Responses elicited by GLU and AMPA but not KA exhibited a concentration-dependent desensitization. Application of N-methyl-D-aspartate (NMDA) evoked no responses. The rank order affinities of the agonists as estimated from EC50 values were AMPA > GLU > KA. Whereas KA had the lowest affinity of the agonists tested, it produced the largest currents. Hill coefficients of the concentration-response data were near 1 for AMPA, and 2 for KA and GLU. Coapplication of AMPA with cyclothiazide (CTZ) blocks AMPA receptor desensitization, and enhanced its effects on conductance. However, CTZ did not change the KA -induced conductances. In all cells tested, 6,7-dinitroquinoxaline (DNQX) completely and reversibly blocked the effects of KA and AMPA. The KA- and AMPA-induced currents were also completely blocked by 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a selective AMPA receptor antagonist. These results indicate that the responses to glutamate agonists in HC were mediated almost exclusively by AMPA receptors. Our study indicates that AMPA receptors play a fundamental role in mediating the synaptic input into rabbit horizontal cells.

Objective: To assess the features and therapeutic response of visual manifestations and cerebrovascular accidents (CVA) in giant cell (temporal) arteritis (GCA) and to identify the predictors for permanent visual loss (VL) and CVA in GCA., Methods: Two hundred thirty-nine patients with biopsy-proven GCA were included in a retrospective multicenter study. Data on demographic, clinical, and laboratory features were collected. The predictors were identified by a forward stepwise nonconditional logistic regression analysis., Results: Visual involvement was observed in 69 patients, and 34 had permanent VL. The diagnostic delay since the onset of visual symptoms was longer in the 11 patients with bilateral VL. The interval to involvement of the second eye was 5 days. The predictors of permanent VL were transient VL, jaw claudication, normal levels of liver enzymes, and absence of constitutional syndrome. Partial improvement of visual acuity was observed in 8 patients. After adjustment for the treatment regimen (intravenous pulse methylprednisolone versus oral prednisone), early treatment (within the first day of VL) was the only predictor of improvement. CVA, observed in 8 patients, involved the vertebral-basilar territory in 4. CVA was more frequent in patients with visual symptoms, appearing shortly after VL (median 7 days) and despite appropriate therapy. Predictors of CVA were permanent VL and jaw claudication., Conclusion: In GCA, the risk of permanent VL is increased in patients with transient VL and/or jaw claudication, and decreased in those with elevated liver enzyme levels and/or constitutional syndrome. Partial therapeutic success is more probable if treatment is started within the first day of VL. CVA is more likely in patients with permanent VL and/or jaw claudication, often developing despite appropriate corticosteroid therapy.

Objective: To assess the possible differences between children (< or = 20 years) and adults (> 20 years) with Henoch-Schönlein purpura (HSP)., Methods: A retrospective study of an unselected population of patients with HSP who presented to our teaching hospital between 1975 and 1994. Patients were classified as having HSP according to the criteria proposed by Michel et al., Results: Following the above-mentioned criteria, 162 white patients (113 male and 49 female) were classified as having HSP; 46 of the patients were adults (mean +/- SD age 53.2 +/- 16.9 years) and 116 were children (6.9 +/- 3.1 years). We were unable to identify any precipitating event in 72% of the adults and 66% of the children. The frequency of previous drug treatment, primarily antibiotics or analgesics, was similar in both groups, whereas previous upper respiratory tract infection was more frequent among the children (P < 0.02). At symptom onset, cutaneous lesions were the main clinical manifestation in both groups. However, adults had a lower frequency of abdominal pain (P < 0.008) and fever (P < 0.01), and a higher frequency of joint symptoms (P < 0.001). During the clinical course, adults had more frequent (P < 0.001) and severe renal involvement. An increased erythrocyte sedimentation rate was also more frequent in the adults (P < 0.001). Adults required more aggressive therapy, consisting of steroids (P < 0.002) and/or cytotoxic agents (P < 0.001). The outcome was relatively good in both age groups, with complete recovery in 107 children (93.9%) and in 33 adults (89.2%) after a mean +/- SD followup of 19.4 +/- 27.7 (median 12) and 21.8 +/- 33.5 (median 15) months, respectively., Conclusion: In adulthood, HSP, as defined by the criteria proposed by Michel et al, represents a more severe clinical syndrome, with a higher frequency of renal involvement. However, the final outcome of HSP is equally good in patients of both age groups.

Objective: To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA)., Methods: A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single-therapy disease-modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen., Results: Four of the 43 patients (9.3%) who had been receiving long-term, well-tolerated treatment with MTX (mean +/- SD 375.5 +/- 159.5 days, range 227-561 days) developed AFTR shortly (mean +/- SD 25.7 +/- 13.6 days, range 17-46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 +/- 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR., Conclusion: The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single-drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.

From dental casts of 94 parent-offspring and 127 full-sib pairs, sampled from two Chilean populations, shovelling indices are computed to measure the degree of shovelling of maxillary central incisors quantitatively. Genetic correlations are computed to determine the role of genetic factors in explaining the variation in this trait. Assuming only hereditary factors to be responsible for the transmission of shovel shape, 68% of total variability is ascribed to the additive effect of genes.