Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer.

BACKGROUND/AIM: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy. MATERIALS AND METHODS: Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary human cells from fresh tumor specimens. RESULTS: All cell lines showed reliable growth in all cell culture methods. The spheroids showed significant delay of growth and/or necrosis compared to control groups when exposed to current standard chemotherapeutic regimens. Single 3D spheroids ready for therapy susceptibility testing could be generated from actual tumor specimens after enzymatic and mechanical separation. CONCLUSION: In its current form, this single spheroid-based in vitro assay was able to test individual therapy susceptibility to current standard therapy regimens or, potentially, for testing new targeted drugs in HNSCC treatment. With recent discoveries regarding tumor heterogeneity and individual mutation status, a reliable assay is a prerequisite for personalized therapy in head and neck cancer.

Corrigendum to "Nutritional Risk Factors for Age-Related Macular Degeneration".

[This corrects the article DOI: 10.1155/2014/413150.].

Exploratory study of long-term health-related quality of life in patients with surgically treated primary parotid gland cancer.

BACKGROUND: Health-related quality of life (HRQOL) has received more and more attention as an outcome in cancer therapy. In this exploratory study, we assessed the long-term HRQOL among 77 surgically treated patients with parotid gland cancer. METHODS: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaires were used in a cross-sectional design. The mean time-lag between initial diagnosis and completion of the questionnaire was 89.7 months. RESULTS: The HRQOL significantly increased with the time-lag to surgery and decreased with the patients' age. Factors with clinically significant effects in several areas of long-term HRQOL (ie, more than 4 scores) were age, type of neck dissection, preoperative facial nerve palsy, and postoperative radiation therapy. CONCLUSION: In parotid gland cancer surgery, factors, such as sex, age, type of surgery, facial nerve palsy, and radiation therapy, seem to be associated with clinically meaningful differences in long-term HRQOL scores.

Impact of xylomethazoline on eustachian tube function in healthy participants.

INTRODUCTION: The use of decongestants is common in otitis media eustachian tube (ET) dysfunction. However, the underlying mechanism and the type of action on the complex middle ear pressure equalization system are poorly understood. Here, by use of the pressure chamber, we investigated the impact of intranasal decongestive therapy (xylomethazoline) on ET function. MATERIALS AND METHODS: Thirty healthy participants (60 ears) were exposed to a predetermined profile of phases of compression and decompression in a hypobaric and hyperbaric pressure chamber. ET opening pressure, ET opening duration, ET opening frequency, and ET closing pressure were determined before and after intranasal application of xylomethazoline. RESULTS: A significantly higher number of ET openings (ET opening frequency) in passive equalization condition could be measured after application of decongestants than before. No significant difference could be found in the values of ET opening pressure, ET opening duration, and ET closing pressure parameters before in comparison with the values after application of xylomethazoline. CONCLUSION: We conclude that xylomethazoline might only have a minor effect during active and passive middle ear pressure equalization. Larger cohorts and targeted application of decongestants should be tested to confirm these preliminary data and to find new evidence on the effects of decongestants.

Characterizing the active opening of the eustachian tube in a hypobaric/hyperbaric pressure chamber.

OBJECTIVE: Active and passive opening of the Eustachian tube (ET) enables direct aeration of the middle ear and a pressure balance between middle ear and the ambient pressure. The aim of this study was to characterize standard values for the opening pressure (ETOP), the opening frequency (ETOF), and the opening duration (ETOD) for active tubal openings (Valsalva maneuver, swallowing) in healthy participants. DESIGN/PARTICIPANTS: In a hypobaric/hyperbaric pressure chamber, 30 healthy participants (19 women, 11 men; mean age, 25.57 ± 3.33 years) were exposed to a standardized profile of compression and decompression. The pressure values were recorded via continuous impedance measurement during the Valsalva maneuver and swallowing. Based on the data, standard curves were identified and the ETOP, ETOD, and ETOF were determined. RESULTS: Recurring patterns of the pressure curve during active tube opening for the Valsalva maneuver and for active swallowing were characterized. The mean value for the Valsalva maneuver for ETOP was 41.21 ± 17.38 mbar; for the ETOD, it was 2.65 ± 1.87 seconds. In the active pressure compensation by swallowing, the mean value for the ETOP was 29.91 ± 13.07 mbar; and for the ETOD, it was 0.82 ± 0.53 seconds. CONCLUSION: Standard values for the opening pressure of the tube and the tube opening duration for active tubal openings (Valsalva maneuver, swallowing) were described, and typical curve gradients for healthy subjects could be shown. This is another step toward analyzing the function of the tube in compression and decompression.

Electrocochleography in children with auditory synaptopathy/neuropathy: diagnostic findings and characteristic parameters.

INTRODUCTION: The early diagnosis of AS/AN in children remains challenging because it exclusively relies on the detection of OAE and/or CM, while ABR are pathologically changed or missing. The aim of our study was to ensure the diagnosis of AS/AN, demarcate it to an outer hair cell damage and possibly differentiate between pre- and postsynaptic pathologies. METHODS: We retrospectively evaluated the transtympanic ECochG results of ten children with AS/AN and compared them to a matched group with SNHL and without any signs of AS/AN. We analyzed the thresholds, latencies and - as a new parameter - the amplitude ratio between CAP and SP. RESULTS: CM and SP thresholds were significantly lower than CAP thresholds in AS/AN patients and significantly lower than SP and CM thresholds in SNHL patients with comparable CAP thresholds. The CAP/SP ratio of amplitudes in SNHL children was more than three times (significantly) higher than in AS/AN children. The cutoff value was set at 1.0 in order to differentiate between both groups with a 80-90% sensitivity and specificity. It was not possible to differentiate between a pre- and postsynaptic type of AS/AN in our collective. SUMMARY AND CONCLUSION: The ECochG can add valuable information for a precise differential diagnosis of AS/AN, especially in babyhood. We identified the CAP/SP ratio as a new parameter for differentiation between AS/AN and SNHL. When the CAP/SP ratio falls below 1.0, patients can be diagnosed AS/AN with high specificity and sensitivity. Significantly smaller SPL are needed to evoke SP and CM in the AS/AN group, thus showing the preserved hair cell function.

Post-chemotherapy cognitive impairment in patients with B-cell non-Hodgkin lymphoma: a first comprehensive approach to determine cognitive impairments after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or rituximab and bendamustine.

To assess the effects of chemoimmunotherapy on post-chemotherapy cognitive impairments (PCCI) in patients with B-cell non-Hodgkin lymphoma (NHL), we used objective and subjective measures of cognitive functions in combination with serum parameters and neuroelectric recordings. Self-perceived status of cognition, fatigue and emotional functioning were reduced in patients (n=30) compared to healthy controls (n=10). Cognitive performance was impaired in patients with NHL compared to controls and a norm sample (n=1179). PCCI was more severe in patients treated with rituximab and bendamustine (BR) than in patients who received R in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) polychemotherapy (R-CHOP). Individual alpha peak frequency and serum brain-derived neurotrophic factor (BDNF) levels in patients with NHL correlated with accuracy in the objective cognition test. Higher serum interleukin-6 (IL-6) concentrations were associated with higher fatigue levels. Patients with NHL and especially those who were treated with BR were affected by PCCI. BDNF and IL-6 might be involved in the pathogenesis of PCCI and fatigue.

Validation of the German version of the Schedule of Attitudes Toward Hastened Death (SAHD-D) with patients in palliative care.

OBJECTIVE: Reliable and validated instruments are needed in order to study the desire for hastened death (DHD). As there is no instrument in the German language to measure DHD, our aim was to validate a German version of the Schedule of Attitudes Toward Hastened Death (SAHD-D). METHOD: The SAHD was translated following guidelines promulgated by the European Organization for Research and Treatment of Cancer (EORTC). In eligible patients (clinical situation adequate, MMSE ≥21), the following instruments were employed: a symptom checklist (HOPE), the HADS-D (Hospital Anxiety and Depression Scale), the EORTC-QLQ-PAL15, and the SAHD-D, as well as an external estimation of DHD provided by the attending physician. A high level of DHD was defined as the mean plus one standard deviation (SD). RESULTS: Of the 869 patients assessed, 92 were eligible for inclusion (66% females, mean age of 64.5 years). The SAHD-D total score ranged from 0 to 18, with a mean of 5 and a standard deviation (SD) of 3.7. A high level of DHD was found in 20% (n = 19). For discriminant validity, significant correlations were found between the SAHD-D and depression (r rho = 0.472), anxiety (r rho = 0.224), and clinical state (r rho = 0.178). For criterion validity, the external estimate of DHD showed a low significant correlation with patient score (r rho = 0.290). Factor analysis of the SAHD-D identified two factors. SIGNIFICANCE OF RESULTS: Validation of the SAHD-D illustrated good discriminant validity, confirming that a desire to hasten death is a construct separate from depression, anxiety, or physical state. The unidimensionality of the SAHD could not be reproduced. Our findings support the multifactorial interdependencies on DHD and suggest that the SAHD-D should be refined by considering actual wishes, general attitudes, and options of patients.

Self-rating makes the difference: identifying palliative care needs of patients feeling severely affected by multiple sclerosis.

OBJECTIVE: People feeling severely affected by multiple sclerosis (MS) comprise a heterogeneous group, and this heterogeneity leads to very distinct needs and makes planning for needs difficult. To provide optimal care, it is important to identify specific needs in specific subgroups. Our objective was to identify the specific palliative care (PC) needs of patients who felt severely affected by the disease by analyzing their feeling (1) more or (2) less severely affected and their possible differences in expressed care needs. METHOD: A self-report questionnaire with 25 needs categories including 7 categories pertaining to care was applied to patients who felt severely affected by MS. An additional single question identified patients feeling more (≥7, median-split) and less (<7) severely affected. Differences were analyzed by chi-squared and Mann-Whitney U tests. The sample (N = 573) was composed of respondents who replied to an invitation by the German Multiple Sclerosis Society to participate in a survey on unmet needs of severely affected patients. RESULTS: Of 573 patients (median age 51), 358 (62.48%) felt more severely affected. Compared to patients feeling less severely affected, they found the stress on their next of kin to be higher (p < 0.001), were in greater need of home visitation (p < 0.001), did not have permanent neurologists (p = 0.016), and felt that they visited them too rarely (p < 0.0001). They also needed more emotional support from their nursing care service (p = 0.006). SIGNIFICANCE OF RESULTS: A self-rating scale can identify two groups of patients with different care needs. These data may help shaping patient-centered support structures. Palliative care, with its multidisciplinary approach, might be one further option to meet the specific needs of patients and their relatives.

Comparison of three noninvasive methods for hemoglobin screening of blood donors.

BACKGROUND: To prevent phlebotomy of anemic individuals and to ensure hemoglobin (Hb) content of the blood units, Hb screening of blood donors before donation is essential. Hb values are mostly evaluated by measurement of capillary blood obtained from fingerstick. Rapid noninvasive methods have recently become available and may be preferred by donors and staff. The aim of this study was to evaluate for the first time all different noninvasive methods for Hb screening. STUDY DESIGN AND METHODS: Blood donors were screened for Hb levels in three different trials using three different noninvasive methods (Haemospect [MBR Optical Systems GmbH & Co. KG], NBM 200 [LMB Technology GmbH], Pronto-7 [Masimo Europe Ltd]) in comparison to the established fingerstick method (CompoLab Hb [Fresenius Kabi GmbH]) and to levels obtained from venous samples on a cell counter (Sysmex [Sysmex Europe GmbH]) as reference. The usability of the noninvasive methods was assessed with an especially developed survey. RESULTS: Technical failures occurred by using the Pronto-7 due to nail polish, skin color, or ambient light. The NBM 200 also showed a high sensitivity to ambient light and noticeably lower Hb levels for women than obtained from the Sysmex. The statistical analysis showed the following bias and standard deviation of differences of all methods in comparison to the venous results: Haemospect, -0.22 ± 1.24; NBM, 200 -0.12 ± 1.14; Pronto-7, -0.50 ± 0.99; and CompoLab Hb, -0.53 ± 0.81. CONCLUSION: Noninvasive Hb tests represent an attractive alternative by eliminating pain and reducing risks of blood contamination. The main problem for generating reliable results seems to be preanalytical variability in sampling. Despite the sensitivity to environmental stress, all methods are suitable for Hb measurement.

Increased rate of parental postpartum depression and traumatization in moderate and late preterm infants is independent of the infant's motor repertoire.

BACKGROUND: Moderately and late preterm infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. Parents of preterm infants are at risk of postpartal depression (PPD) and posttraumatic stress disorder (PTSD), and preterm infants are at risk of developmental impairment. AIM: This study aimed to assess (1) the incidence of parental PPD and PTSD in moderate to late preterm infants in comparison to full-term infants and (2) the influence of infants' motor repertoire assessed by Prechtl's general movements and illness severity on parental PPD and PTSD. SUBJECTS: We studied 60 mothers and 56 fathers of 69 preterm infants (born at 32 to 37 weeks of gestation) and 32 mothers and 29 fathers of 34 full-term infants. OUTCOME MEASURES: We assessed the incidence of parental PPD, PTSD and perceived social support as well as infants' illness severity and motor repertoire at birth, term and 3 months corrected age. RESULTS: Preterm mothers and fathers had significant higher depression scores after birth compared to full-term parents (p=0.033 and 0.021). Preterm fathers also had higher traumatization scores compared to full-term fathers (p=0.007). Probable or possible PPD/PTSD was not associated with infant's illness severity or quality of motor repertoire. No differences in motor development were found between preterm and full-term infants. CONCLUSION: Moderate to late preterm infants' parents are at increased risk for PPD irrespective of infants' motor repertoire or illness severity.

Blood sampling via a peripheral artery catheter decreases cerebral oxygenation index in very low-birthweight infants.

AIM: This study evaluated the impact of blood sampling via peripheral arterial catheters on cerebral oxygenation and blood volume as a function of blood sampling velocity. METHODS: Near-infrared spectroscopy was applied to 20 very low-birthweight infants during peripheral arterial blood sampling. Changes in cerebral oxygenated, deoxygenated and total haemoglobin, cerebral blood volume and cerebral oxygenation index were recorded. Heart rate and oxygen saturation were measured continuously. To assess the impact of blood sampling velocity, both fast 40-sec and slow 70-sec sampling procedures were performed in a crossover study design, in which the order of sampling velocities was randomised for each patient. RESULTS: Both fast and slow blood sampling procedures resulted in a significant decrease in cerebral oxygenation index (fast, p = 0.002, slow, p = 0.008), and an increase in mean heart rate (both p = 0.02) and mean blood pressure (p = 0.02 and 0.04). Oxygenated and total haemoglobin and cerebral blood volume only decreased significantly after slow blood sampling (p < 0.001). CONCLUSION: Blood sampling from peripheral arterial catheters leads to significant fluctuations in cerebral oxygenation independent of the sampling velocity. Changes are comparable to those reported from umbilical blood sampling. We advise that blood sampling should be restricted as much as possible.

Nutritional risk factors for age-related macular degeneration.

PURPOSE: To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). METHODS: Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). RESULTS: In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10(-6); 2-6x/week: OR: 1.67, P = 7.98 × 10(-5)) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2-6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. CONCLUSION: Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD.

Nongenetic risk factors for neovascular age-related macular degeneration.

PURPOSE: To create a risk model for neovascular age-related macular degeneration (nAMD) based on nongenetic factors. METHODS: In this case-control study, 1459 individuals were included, 445 patients showed nAMD and 1014 were healthy controls. Participants were randomly assigned into a training set (containing two-thirds of individuals) and a validation set. Stepwise logistic regression analysis was performed for 25 environmental risk factors in the training set. The risk model with the remaining factors was then validated in the validation set using receiver operating characteristics (ROC) curve and Hosmer-Lemeshow-Test. Additionally, a genetic risk model including variants in the complement factor H gene (CFH, rs1061170) and the age-related maculopathy susceptibility 2 gene (ARMS2, rs10490924) was generated. RESULTS: The environmental risk model with the factors age, alcohol use, allergy, education, sunlight exposure, fish consumption, and physical exercise showed an AUC of 0.80 (95% confidence interval [CI] 0.76-0.84) in the training set. Validation of the model showed adequate calibration (Hosmer-Lemeshow P = 0.81). The AUC for the genetic model was 0.77 (95% CI 0.730-0.808), for the combined environmental and genetic model 0.92 (95% CI 0.887-0.947). CONCLUSIONS: Seven nongenetic factors are able to provide equivalent discrimination between nAMD patients and controls to genetic risk models. Most of them are modifiable and give the opportunity for counseling patients.

Head shadow, squelch, and summation effects with an energetic or informational masker in bilateral and bimodal CI users.

PURPOSE: The objective of the study was to investigate the influence of noise (energetic) and speech (energetic plus informational) maskers on the head shadow (HS), squelch (SQ), and binaural summation (SU) effect in bilateral and bimodal cochlear implant (CI) users. METHOD: Speech recognition was measured in the presence of either a competing talker or modulated speech-shaped noise in 10 bimodal and 10 bilateral adult CI users. HS, SQ, and SU effects were calculated. The interfering signals were manipulated with respect to F0 to consider the influence of different speaker voices. RESULTS: The effects HS, SQ, and SU differed depending on the type of masker. A detailed analysis of errors was used to dissociate energetic and informational masking effects. The analysis showed a release from energetic than from informational masking. CONCLUSION: Noise interferers are not sufficient to reflect difficulties experienced with speech understanding in noise for bilateral and bimodal CI users.

Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial.

OBJECTIVES: To assess the influence of an infusion of clonidine 1 µg/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. DESIGN: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. SETTING: Twenty-eight level 3 German PICUs/neonatal ICUs. PATIENTS: Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). INTERVENTIONS: Patients received clonidine 1 µg/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 µg/kg/hr, placebo: 3.2 ± 3.1 µg/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 µg/kg/hr, placebo: 180.2 ± 204.0 µg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. CONCLUSIONS: Clonidine 1 µg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

Genetic and environmental risk factors for age-related macular degeneration in persons 90 years and older.

PURPOSE: We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in nonagenarians with age-related macular degeneration (AMD). METHODS: This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by multiple logistic regression analysis, including genetic and environmental risk factors (smoking, hypertension, body mass index, diabetes) for different age groups (<70, 70-79, 80-89, ≥ 90 years [nonagenarians]). RESULTS: In nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] = 1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 × 10(-13); OR, 70-79 years = 2.70, P = 1.00 × 10(-13); OR, 80-89 years = 3.11, P = 6.56 × 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P = 1.80 × 10(-11); 70-79 years OR = 1.89, P = 4.48 × 10(-13); 80-89 years OR = 2.71, P = 1.28 × 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P = 0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs) for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P = 0.009; ARMS2 0.44 vs. 0.29, P = 2.97 × 10(-5)), while the MAFs in controls were not significantly different. The genetic risk score revealed the lowest discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658 for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years = 0.704, <70 years = 0.682), while no significant difference was seen for the environmental risk score (AUC < 70 years = 0.579, 70-79 years = 0.567, 80-89 years = 0.600, >90 years = 0.608). CONCLUSIONS: Risk alleles in CFH and ARMS2 have a significantly smaller effect on AMD development in nonagenarians, while environmental factors retain a similar effect.

Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.

Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56 × 10(-7)), AMD phenotype (p = 1.15 × 10(-11)) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6)), higher body mass index (p = 1.00 × 10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60 × 10(-6)) in CFH, rs4151667 (p = 1.01 × 10(-5)) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.

Do the blinds smell better?

If people lose a sense organ, there is thought to be an increase in the remaining sensory functions. Previous studies showed ambiguous results on this topic. In a prospective matched pair case-control study on 46 blind and 46 normal-sighted subjects, the olfactory performance was examined using the Sniffin' Sticks Test [threshold-discrimination-identification (TDI) test], determining the olfactory threshold, the identification and the discrimination performance. There was no significant difference between the groups. Neither the overall olfactory performance (TDI score) nor any of its subtests did correlate with the vision or with the duration of blindness. The study could not detect any superior smell abilities of blind subjects as compared to sighted subjects.