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PURPOSE: [177Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [177Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [161Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of 161Tb- and 177Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice. METHODS: Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the 177Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study. RESULTS: The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the 161Tb- and 177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities. CONCLUSION: Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [161Tb]Tb-DOTA-LM3 and [161Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective 177Lu-based analogues.
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OBJECTIVES: The risk of Post-COVID-19 condition (PCC) under hybrid immunity remains unclear. METHODS: Using data from the German National Cohort (NAKO Gesundheitsstudie), we investigated risk factors for self-reported post-infection symptoms (any PCC is defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms). RESULTS: Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4-12 months after infection; among them 23% reported nine or more symptoms. Individuals, who did not develop PCC after their first infection, had a strongly reduced risk for PCC after their second infection (50%) and a temporary risk reduction, which waned over 9 months after the preceding infection. The risk of developing PCC strongly depended on the virus variant. Within variants, there was no effect of the number of preceding vaccinations, apart from a strong protection by the fourth vaccination compared to three vaccinations for the Omicron variant (odds ratio = 0.52; 95% confidence interval 0.45-0.61). CONCLUSIONS: Previous infections without PCC and a fourth vaccination were associated with a lower risk of PCC after a new infection, indicating diminished risk under hybrid immunity. The two components of risk reduction after a preceding infection suggest different immunological mechanisms.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/immunology , Germany/epidemiology , Male , Female , SARS-CoV-2/immunology , Middle Aged , Adult , Risk Factors , Aged , Cohort Studies , Post-Acute COVID-19 Syndrome , Vaccination/statistics & numerical data , Young Adult , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosageABSTRACT
Due to the demographic changes, the number of older patients in ophthalmological practices and clinics, including those with diplopia, is increasing. Some of the patients report not only horizontally shifted double images but also or only vertically shifted double images. Vertical double vision often causes significant diagnostic problems for ophthalmologists. The underlying condition could urgently require further neurological, neuroradiological and/or internal medical diagnostics (e.g., skew deviation, 4th nerve palsy, myasthenia, Graves' orbitopathy, orbital floor fracture, orbital mass, 3rd nerve palsy) but the cause of diplopia could also be a condition in which overdiagnosis should be avoided (e.g., sagging eye syndrome, the prevalence of which significantly increases with increasing age; decompensated strabismus due to inferior oblique muscle overaction, myopia-associated vertical tropia). For some diseases early diagnosis is important for a better prognosis, e.g., tumor diagnosis, Graves' disease and stroke. This article presents an overview of the most common and most important differential diagnoses of vertical tropia in patients over 50 years of age.
Subject(s)
Diplopia , Strabismus , Humans , Diagnosis, Differential , Strabismus/diagnosis , Aged , Diplopia/diagnosis , Diplopia/etiology , Middle Aged , Aged, 80 and over , Male , FemaleABSTRACT
BACKGROUND: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. METHODS: Data from the baseline assessment of the German National Cohort (NAKO) were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between childhood and adolescence factors and risk of MS. Analyses stratified by sex were conducted. RESULTS: Among a total of 204,273 participants, 858 reported an MS diagnosis. Male sex was associated with a decreased MS risk (HR 0.48; 95% CI 0.41-0.56), while overweight (HR 2.03; 95% CI 1.41-2.94) and obesity (HR 1.89; 95% CI 1.02-3.48) at 18 years of age compared to normal weight were associated with increased MS risk. Having been breastfed for ≤ 4 months was associated with a decreased MS risk in men (HR 0.59; 95% CI 0.40-0.86) compared to no breastfeeding. No association with MS risk was observed for the remaining factors. CONCLUSIONS: Apart from overweight and obesity at the age of 18 years, we did not observe considerable associations with MS risk. The proportion of cases that can be explained by childhood and adolescence factors examined in this study was low. Further investigations of the association between the onset of overweight and obesity in childhood and adolescence and its interaction with physical activity and MS risk seem worthwhile.
Subject(s)
Multiple Sclerosis , Pediatric Obesity , Humans , Adolescent , Male , Adult , Overweight/epidemiology , Multiple Sclerosis/epidemiology , ExerciseSubject(s)
Ileal Neoplasms , Neuroendocrine Tumors , Receptors, Somatostatin , Humans , Male , Ileal Neoplasms/diagnostic imaging , Neoplasm Metastasis , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Organometallic Compounds/therapeutic use , Radiopharmaceuticals , Receptors, Somatostatin/metabolism , Receptors, Somatostatin/antagonists & inhibitors , AgedABSTRACT
BACKGROUND: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. METHODS: To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data were collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from >2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. RESULTS: Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. LIMITATIONS: The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometric data. CONCLUSIONS: In summary, our results suggest a strong link between post-COVID depression and fatigue, highlighting the need for integrative treatment approaches.
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COVID-19 , Sleep Wake Disorders , Humans , Quality of Life , Depression/epidemiology , Depression/therapy , Cross-Sectional Studies , Prospective Studies , Cohort Studies , COVID-19/complications , COVID-19/epidemiology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy , Fatigue/epidemiology , Fatigue/etiologyABSTRACT
PURPOSE: The prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism. METHOD: In this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents). RESULTS: The results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents. CONCLUSION: The results confirm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly self-directed socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.
Subject(s)
Burnout, Professional , Parents , Child , Humans , Burnout, Psychological , Socialization , Burnout, Professional/epidemiologyABSTRACT
BACKGROUND: Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood. METHODS: Data from 156 807 NAKO Health Study participants were analyzed by means of logistic regressions, with adjustment for age, sex, years of education, and study site. The Childhood Trauma Screener differentiated between no/minor (n = 115 891) and moderate/severe childhood trauma (n = 40 916). The outcome variables were medical diagnoses of five somatic and two mental health conditions as stated in the clinical history. RESULTS: Persons with childhood trauma were more likely to bear a diagnosis of all of the studied conditions: cancer (odds ratio [OR] = 1.10; 95% confidence interval: [1.05; 1.15]), myocardial infarction (OR = 1.13 [1.03; 1.24]), diabetes (OR = 1.16, [1.10; 1.23]), stroke (OR = 1.35 [1.23; 1.48]), chronic obstructive pulmonary disease (OR = 1.45 [1.38; 1.52]), depression (OR = 2.36 [2.29; 2.43]), and anxiety disorders (OR = 2.08 [2.00; 2.17]). All of these associations were stronger in younger persons, regardless of the nature of childhood trauma. Differences between the sexes were observed only for some of these associations. CONCLUSION: Childhood trauma was associated with a higher probability of developing mental as well as somatic illness in adulthood. As childhood trauma is an element of individual history that the victim has little to no control over, and because the illnesses that can arise in adulthood in association with it are a heavy burden on the affected persons and on society, there is a need for research on these associations and for the development of preventive measures.
Subject(s)
Adverse Childhood Experiences , Diabetes Mellitus , Mental Disorders , Humans , Mental Disorders/epidemiology , Anxiety DisordersABSTRACT
The COVID-19 pandemic and the ongoing lockdowns might have had a strong impact on mental health of mothers and their infants/toddlers. For example, families had to deal with health issues and social isolation, which might have affected mental health and parent-child interactions. The aim of this study is to evaluate differences in (1) infantile regulatory disorders, (2) maternal mental health, (3) the impact of maternal mental health on infantile regulatory disorders, and (4) alterations in the mother-child interaction for participants recruited before versus after the onset of the first German lockdown. For this reason, mother-child dyads have been divided into two groups and were compared by analyzing clinical interviews on psychopathology of mother and child (M.I.N.I. & DC:05) and mother-child-interactions (Emotional Availability Scales). Results showed that (1) differences in infantile sleeping disorders emerged (phi = 0.243; p = 0.016) compared to the pre-lockdown group, while (2) the occurrence of maternal panic and anxiety increased in the post-lockdown group (phi = 0.229; p = 0.022). Moreover, there was (3) an association for maternal panic and child's sleep disorder, and (4) specific associations with maternal non-hostility in the mother-child-interaction. In conclusion, the present study highlights the differences of maternal mental health occurrences and infants' regulatory problems, as well as the possible effects of the COVID-19 pandemic for infants. In the pre-lockdown group, maternal non-hostility might have acted as a promotive factor against regulatory disorders, while this mechanism was mitigated in the post-lockdown group.
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BACKGROUND: The aim of this study was to investigate the mediating role of the Big 5 personality traits (extraversion, neuroticism, openness, agreeableness, conscientiousness) in the association between early traumatization and depressive symptoms in early adulthood (20-25-year-olds) in a German population-based sample. METHODS: A total of 3176 participants from the German National Cohort (NAKO) baseline with an age between 20 and 25 years were included in this investigation. The sum score of the 9-item-version of the Patient Health Questionnaire was used for assessment of depressive symptoms. A structural equation model was built to test the paths between childhood trauma, Big 5 personality traits and depressive symptoms. RESULTS: Overall, 10.7 % of the young adult sample had a PHQ-9 sum score of ten or higher. The final mediation model fitted well for young adults. We found evidence for a partial mediating effect of Big 5 personality traits. LIMITATIONS: We only adjusted for age, sex, and year of data collection and did not include biological factors in the model. CONCLUSION: Young adults with early trauma experiences have a risk for developing depressive symptoms in young adulthood. Personality traits, especially neuroticism, partially mediated the association between early trauma and depressive symptoms for young adults and should be recognized in preventive strategies.
Subject(s)
Adverse Childhood Experiences , Depression , Young Adult , Humans , Adult , Depression/epidemiology , Personality , NeuroticismABSTRACT
Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro.
Subject(s)
COVID-19 , Humans , Animals , Mice , Caco-2 Cells , HEK293 Cells , Leukocytes, Mononuclear , SARS-CoV-2 , Antiviral Agents , RNA, Messenger , Antigens, Neoplasm , Biomarkers, TumorABSTRACT
Introduction: Family history of depression and childhood maltreatment are established risk factors for depression. However, how these factors are interrelated and jointly influence depression risk is not well understood. The present study investigated (i) if childhood maltreatment is associated with a family history of depression (ii) if family history and childhood maltreatment are associated with increased lifetime and current depression, and whether both factors interact beyond their main effects, and (iii) if family history affects lifetime and current depression via childhood maltreatment. Methods: Analyses were based on a subgroup of the first 100,000 participants of the German National Cohort (NAKO), with complete information (58,703 participants, mean age = 51.2 years, 53% female). Parental family history of depression was assessed via self-report, childhood maltreatment with the Childhood Trauma Screener (CTS), lifetime depression with self-reported physician's diagnosis and the Mini-International Neuropsychiatric Interview (MINI), and current depressive symptoms with the depression scale of the Patient Health Questionnaire (PHQ-9). Generalized linear models were used to test main and interaction effects. Mediation was tested using causal mediation analyses. Results: Higher frequencies of the childhood maltreatment measures were found in subjects reporting a positive family history of depression. Family history and childhood maltreatment were independently associated with increased depression. No statistical interactions of family history and childhood maltreatment were found for the lifetime depression measures. For current depressive symptoms (PHQ-9 sum score), an interaction was found, with stronger associations of childhood maltreatment and depression in subjects with a positive family history. Childhood maltreatment was estimated to mediate 7%-12% of the effect of family history on depression, with higher mediated proportions in subjects whose parents had a depression onset below 40 years. Abuse showed stronger associations with family history and depression, and higher mediated proportions of family history effects on depression than neglect. Discussion: The present study confirms the association of childhood maltreatment and family history with depression in a large population-based cohort. While analyses provide little evidence for the joint effects of both risk factors on depression beyond their individual effects, results are consistent with family history affecting depression via childhood maltreatment to a small extent.
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(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to "only-children", HRs for second- or later-born individuals were 0.70 (95% CI = 0.50-0.96) and 0.65 (95% CI = 0.45-0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults' T1D risk assessment for early detection.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Adolescent , Adult , Birth Order , Cesarean Section/adverse effects , Child , Cohort Studies , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/etiology , Diabetes Mellitus, Type 2/complications , Female , Humans , PregnancyABSTRACT
PURPOSE: To investigate (1) the bias in effect estimation due to heaping or digit preference, (2) the association between age at hypertension diagnosis and risk of cardiovascular comorbidities, and (3) the influence of heaping on risk estimates. METHODS: We performed a simulation study with various scenarios, binary outcome, and normal or lognormal distributed covariables. We calculated mean logistic coefficients under the original and heaped data and their relative deviation. The association of age at hypertension diagnosis and risk of ≥1 cardiovascular comorbidity was investigated using logistic regression among 50,858 participants in the NAKO Gesundheitsstudie (German National Cohort) who reported such diagnosis. We assessed the proportion of heaped observations and to what extent heaping may have influenced risk estimates. RESULTS: Based on the simulation study and assuming 50% of observations in the variable of interest to be heaped, relative bias was <6%. In NAKO, a 5-year younger age at hypertension diagnosis was associated with a 15% increased risk of having ≥1 cardiovascular comorbidity. Observed heaping in age at hypertension diagnosis was 12.6%, and bias of the risk estimate was 0.14%. CONCLUSIONS: Bias in effect estimation due to heaping is low in most common scenarios. Younger age at hypertension diagnosis is associated with a higher risk of cardiovascular comorbidities.
Subject(s)
Hypertension , Bias , Cohort Studies , Comorbidity , Computer Simulation , Humans , Hypertension/diagnosis , Hypertension/epidemiologyABSTRACT
Background: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Methods: COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742). Findings: In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6-12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience. Interpretation: PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions. Funding: The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).
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PURPOSE: To evaluate the effect of Prism adaptation test (PAT) on the angle of squint in decompensated esophoria (decEPH) and decompensated microesotropia (decMET). METHODS: In this single-center retrospective study we reviewed the medical records of patients with the diagnosis of decEPH or decMET, aged at least 12 years, who were treated by strabismus surgery for the first time. The maximum Angle of squint (AOS) for far (F) and near (N) fixation and PAT results before surgery, as well as AOS (F) and AOS (N) after surgery and results of binocular function tests were considered. PAT included wearing a prism based on the largest angle for over 60 min. RESULTS: 100 patients (mean age 37 ± 17 years) were included in the decEPH group, 82 patients (mean age 30 ± 13 years) in the decMET group. For decEPH, before surgery AOS was 25.5 ± 8.8 pdpt (F) and 23.5 ± 9.8 pdpt (N). During PAT the AOS increased significantly by 2.7 ± 4.3 to 28.2 ± 8.6 pdpt (F) and by 4.9 ± 4.5 to 28.3 ± 9.5 pdpt (N). Altogether, in 82% of decEPH patients AOS (F) and/ or AOS (N) in- or decreased by at least 3 pdpt. For decMET, before surgery AOS was 28.6 ± 10.8 pdpt for far (F) and 30.9 ± 11.8 pdpt for near fixation (N). During PAT the AOS increased significantly by 4.2 ± 5.8 to 32.5 ± 9.5 pdpt (F) and by 3.7 ± 6.1 to 34.4 ± 9.5 pdpt (N). Altogether, in 51% of decMET patients, AOS (F) and/ or AOS (N) increased by at least 10 pdpt, therefore more than 5° which would have been maximally expected from mictrotropia, or decreased by at least 3 pdpt. CONCLUSIONS: The Prism adaptation test (PAT) showed remarkable changes in AOS in both decEPH and decMET. In patients with decEPH, the preoperative assessment of the "true AOS" under PAT reflects a pivotal requirement for successful strabismus surgery, as 82% had dose relevant angle changes ≥ 3 pdpt. For patients with decMET the preoperative prism adaptation test is especially of diagnostic value, but also 51% of decMET patients had changes in AOS beyond the expected microtropic angle (≥ 10 pdpt) or even a dose relevant angle decrease (≥ 3pdpt).
Subject(s)
Esotropia , Strabismus , Adaptation, Ocular , Adolescent , Adult , Humans , Middle Aged , Oculomotor Muscles/surgery , Retrospective Studies , Strabismus/diagnosis , Strabismus/surgery , Young AdultABSTRACT
Gut enzymes can metabolize plant defense compounds and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence feeding preference is largely unknown. We studied the metabolization of taraxinic acid ß-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We have demonstrated that TA-G is rapidly deglucosylated and conjugated to glutathione in the insect gut. A broad-spectrum M. melolontha ß-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglucosylation. Using cross-species RNA interference, we have shown that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference of M. melolontha larvae for TA-G-deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense compound. Our work illustrates the multifaceted roles of insect digestive enzymes as mediators of plant-herbivore interactions.
Plants produce certain substances to fend off attackers like plant-feeding insects. To stop these compounds from damaging their own cells, plants often attach sugar molecules to them. When an insect tries to eat the plant, the plant removes the stabilizing sugar, 'activating' the compounds and making them toxic or foul-tasting. Curiously, some insects remove the sugar themselves, but it is unclear what consequences this has, especially for insect behavior. Dandelions, Taraxacum officinale, make high concentrations of a sugar-containing defense compound in their roots called taraxinic acid ß-D-glucopyranosyl ester, or TA-G for short. TA-G deters the larvae of the Maybug a pest also known as the common cockchafer or the doodlebug from eating dandelion roots. When Maybug larvae do eat TA-G, it is found in their systems without its sugar. However, it is unclear whether it is the plant or the larva that removes the sugar. A second open question is how the sugar removal process affects the behavior of the Maybug larvae. Using chemical analysis and genetic manipulation, Huber et al. investigated what happens when Maybug larvae eat TA-G. This revealed that the acidity levels in the larvae's digestive system deactivate the proteins from the dandelion that would normally remove the sugar from TA-G. However, rather than leaving the compound intact, larvae remove the sugar from TA-G themselves. They do this using a digestive enzyme, known as a beta-glucosidase, that cuts through sugar. Removing the sugar from TA-G made the compound less toxic, allowing the larvae to grow bigger, but it also increased TA-G's deterrent effects, making the larvae less likely to eat the roots. Any organism that eats plants, including humans, must deal with chemicals like TA-G in their food. Once inside the body, enzymes can change these chemicals, altering their effects. This happens with many medicines, too. In the future, it might be possible to design compounds that activate only in certain species, or under certain conditions. Further studies in different systems may aid the development of new methods of pest control, or new drug treatments.
Subject(s)
Coleoptera/enzymology , Glucosides/metabolism , Herbivory , Insect Proteins/metabolism , Lactones/metabolism , Sesquiterpenes/metabolism , Taraxacum/metabolism , beta-Galactosidase/metabolism , Animals , Coleoptera/embryology , Coleoptera/genetics , Digestion , Glucosides/toxicity , Glutathione/metabolism , Hydrolysis , Inactivation, Metabolic , Insect Proteins/genetics , Lactones/toxicity , Larva/enzymology , Larva/genetics , Secondary Metabolism , Sesquiterpenes/toxicity , Taraxacum/toxicity , beta-Galactosidase/geneticsABSTRACT
BACKGROUND: Participation in epidemiologic studies has been declining over the last decades. In addition to postal invitations and phone calls, home visits can be conducted to increase participation. The aim of this study was therefore to evaluate the effects of home visits in terms of response increase and composition of the additionally recruited and final sample. METHODS: In the framework of the German National Cohort (NAKO) recruitment process, two of 18 study centers, Halle (Saale) and Berlin-Center, performed home visits as additional recruitment step after postal invitation and reminders. Response increase was calculated and differences between participants recruited via home visits and standard recruitment were examined. Proportions are presented as percentages with 95%-confidence intervals. RESULTS: In the general population in Halle, 21.3-22.8% participated after postal invitation and two reminders in the five assessed recruitment waves. The increase of the overall response was 2.8 percentage points (95%confidence interval: 1.9-4.0) for home visits compared to 2.4 percentage points (95%CI: 1.7-3.3) for alternatively sent third postal reminder. Participants recruited via home visits had similar characteristics to those recruited via standard recruitment. Among persons of Turkish descent in Berlin-Center site of the NAKO, home visits conducted by native speakers increased the participation of women, persons living together with their partner, were born in Turkey, had lower German language skills, lower-income, lower education, were more often smokers and reported more often diabetes and depression to a degree which changed overall estimates for this subsample. CONCLUSIONS: As an additional recruitment measure in the general population, home visits increased response only marginally, and the through home visits recruited participants did not differ from those already recruited. Among persons with migration background, home visits by a native speaker increased participation of persons not reached by the standard recruitment, but the effects of using a native speaker approach could not be separated from the effect of home visits.
Subject(s)
House Calls , Cohort Studies , Cross-Sectional Studies , Female , Germany , HumansABSTRACT
Infantile nystagmus syndrome (INS) denominates early-onset, involuntary oscillatory eye movements with different etiologies. Nystagmus is also one of the symptoms in oculocutaneus albinism (OCA), a heterogeneous disease mainly caused by defects in melanin synthesis or melanosome biogenesis. Dopachrome tautomerase (DCT, also called TYRP2) together with tyrosinase (TYR) and tyrosin-related protein 1 (TYRP1) is one of the key enzymes in melanin synthesis. Although DCT´s role in pigmentation has been proven in different species, until now only mutations in TYR and TYRP1 have been found in patients with OCA. Detailed ophthalmological and orthoptic investigations identified a consanguineous family with two individuals with isolated infantile nystagmus and one family member with subtle signs of albinism. By whole-exome sequencing and segregation analysis, we identified the missense mutation c.176G > T (p.Gly59Val) in DCT in a homozygous state in all three affected family members. We show that this mutation results in incomplete protein maturation and targeting in vitro compatible with a partial or total loss of function. Subsequent screening of a cohort of patients with OCA (n = 85) and INS (n = 25) revealed two heterozygous truncating mutations, namely c.876C > A (p.Tyr292*) and c.1407G > A (p.Trp469*), in an independent patient with OCA. Taken together, our data suggest that mutations in DCT can cause a phenotypic spectrum ranging from isolated infantile nystagmus to oculocutaneous albinism.