Evaluation of Anti-PT Antibody Response after Pertussis Vaccination and Infection: The Importance of Both Quantity and Quality

Pertussis toxin (PT) is considered the main virulence factor causing whooping cough or pertussis. The protein is widely studied and its composition was revealed and sequenced already during the 1980s. The human immune system creates a good response against PT when measured in quantity. However, the serum anti-PT antibodies wane rapidly, and only a small amount of these antibodies are found a few years after vaccination/infection. Therefore, multiple approaches to study the functionality (quality) of these antibodies, e.g., avidity, neutralizing capacity, and epitope specificity, have been investigated. In addition, the long-term B cell memory (Bmem) to PT is crucial for good protection throughout life. In this review, we summarize the findings from functional PT antibody and Bmem studies. These results are discussed in line with the quantity of serum anti-PT antibodies. PT neutralizing antibodies and anti-PT antibodies with proper avidity are crucial for good protection against the disease, and certain epitopes have been identified to have multiple functions in the protection. Although PT-specific Bmem responses are detectable at least five years after vaccination, long-term surveillance is lacking. Variation of the natural boosting of circulating Bordetella pertussis in communities is an important confounding factor in these memory studies.

Keratoconus Diagnosis: Validation of a Novel Parameter Set Derived from IOP-Matched Scenario

Purpose. Considering that intraocular pressure (IOP) is an important confounding factor in corneal biomechanical evaluation, the notion of matching IOP should be introduced to eliminate any potential bias. This study aimed to assess the capability of a novel parameter set (NPS) derived from IOP-matched scenario to diagnose keratoconus. Methods. Seventy samples (training set; 35 keratoconus and 35 normal corneas; pairwise matching for IOP) were used to determine NPS by forward logistic regression. A large validation dataset comprising 62 matching samples (31 keratoconus and 31 normal corneas) and 203 unmatching samples (112 keratoconus and 91 normal corneas) was used to evaluate its clinical significance. To further assess its diagnosis capability, NPS was compared with the other two prior biomechanical indexes. Results. NPS was comprised of three biomechanical parameters, namely, DA Ratio Max 1 mm (DRM1), the first applanation time (AT1), and an energy loading parameter (Eload). NPS was successfully applied to the validation dataset, with a higher accuracy of 96.8% and 95.6% in the IOP-matched and -unmatched scenarios, respectively. More surprisingly, accuracy of NPS was 95.5% in the combined validation, an improvement compared to the two prior biomechanical indexes. Conclusions. This is the first study taking IOP bias into consideration to determine a biomechanical parameter set. Our study shows that NPS indeed offers comparable performance in keratoconus diagnosis. Translational Relevance. Determining a parameter set after eliminating the influence from IOP is useful in revealing the essential differences between keratoconus and normal corneas and possibly facilitating further progress in keratoconus diagnosis.

Creating cartoons to represent habitual leg movements

Many people have a habit of moving their legs and believe that this behavior is due to the restless legs syndrome (RLS), a highly prevalent neurological condition that greatly impairs the quality of life of affected individuals. This behavioral pattern, characterized by the habit of moving one’s legs and feet, may be an important confounding factor in the diagnosis of RLS. Objective: To describe the main movements associated with this benign behavioral state to characterize a possible clinical condition that can contribute to the differential diagnosis of RLS. Methods: Experienced sleep specialists, who primarily see RLS patients listed the most frequent movements people without RLS report while describing their suspected RLS. We first compiled a list of the lower-limb movements described by the specialists. Then, one of the authors (KC) carried out all movements of the list on camera to obtain a video footage. This footage was sent to one of the authors, EPC, who, alongside a group of students, drew graphic representations (cartoons) of the recorded movements. Results: The panel of sleep experts described 13 leg movements commonly reported by their patients. The experts reported 11 simple movements and two combined movements. Conclusion: In this study we developed an instrument that allows us to oppose and distinguish a pathological condition (RLS) from a behavioral phenomenon. This state of behavioral leg fidgeting needs to be better characterized and may eventually be recognized as a clinical entity per se.

Diabetes mellitus is not a risk factor for osteoarthritis

BackgroundAssociation between diabetes mellitus (DM) and risk of osteoarthritis (OA) can be confounded by body mass index (BMI), a strong risk factor for both conditions. We evaluate the association between DM or hyperglycaemia with OA using systematic review and meta-analysis.MethodsWe searched PubMed and Web of Science databases in English for studies that gave information on the association between DM and OA. Two meta-analysis models were conducted to address: (1) risk of DM comparing subjects with and without OA and (2) risk of OA comparing subjects with and without DM. As far as available, risk estimates that adjusted for BMI were used.Results31 studies with a pooled population size of 295 100 subjects were reviewed. 16 and 15 studies reported positive associations and null/ negative associations between DM and OA. 68.8% of positive studies had adjusted for BMI, compared with 93.3% of null/negative studies. In meta-analysis model 1, there was an increase prevalence of DM in subjects with OA compared with those without (OR 1.56, 95% CI 1.28 to 1.89). In meta-analysis model 2, there was no increased risk of OA (OR 1.14, 95% CI 0.98 to 1.33) in subjects with DM compared with those without, regardless of gender and OA sites. Comparing subjects with DM to those without, an increased risk of OA was noted in cross-sectional studies, but not in case-control and prospective cohort studies.ConclusionsThis meta-analysis does not support DM as an independent risk factor for OA. BMI was probably the most important confounding factor.

Parasitic infection: a buffer against ocean acidification?

Recently, there has been a concerted research effort by marine scientists to quantify the sensitivity of marine organisms to ocean acidification (OA). Empirical data generated by this research have been used to predict changes to marine ecosystem health, biodiversity and productivity that will be caused by continued acidification. These studies have also found that the effects of OA on marine organisms can be significantly modified by additional abiotic stressors (e.g. temperature or oxygen) and biotic interactions (e.g. competition or predation). To date, however, the effects of parasitic infection on the sensitivity of marine organisms to OA have been largely ignored. We show that parasitic infection significantly altered the response of a marine gastropod to simulated OA conditions by reducing the mortality of infected individuals relative to uninfected conspecifics. Without the inclusion of infection data, our analysis would not have detected the significant effect of pH on host mortality. These results strongly suggest that parasitic infection may be an important confounding factor in OA research and must be taken into consideration when assessing the response of marine species to OA.

Married to Intolerance: Attitudes toward Intermarriage in Germany, 1900–2006

We analyze under what conditions intermarriage can be used as an indicator of tolerance, and whether such tolerant attitudes persisted in Germany during the twentieth century. We find strong evidence for the persistence of tolerant attitudes towards intermarriage with Jews. At the same time, our empirical analysis also cautions against using intermarriage as a simple proxy for tolerance: The size of Jewish communities in the early twentieth century is an important confounding factor.

Is executive impairment associated with schizophrenic syndromes? A meta-analysis

BackgroundA key neuropsychological proposal in schizophrenia is that negative and disorganization symptoms are associated with different patterns of impairment on executive tasks.MethodStudies reporting correlations between positive, negative or disorganization symptoms and any type of executive test were meta-analysed. The influence of moderating factors was also examined, including age, treatment and stage of illness and whether symptoms were relapsing or persistent. The magnitudes of the correlations were compared with those for general intellectual impairment.ResultsPooled correlations between executive impairment and both negative symptoms and disorganization were significant in the small-to-moderate range. That for positive symptoms (‘reality distortion’), however, was close to zero. The pattern of correlations among different executive tests differed significantly for negative symptoms and disorganization. Patients with stable clinical pictures showed significantly higher correlations with executive impairment than those with relapsing and remitting illnesses. Both negative symptoms and disorganization also correlated significantly with general intellectual function as indexed by current IQ.ConclusionsMeta-analysis supports the view that negative symptoms and disorganization are associated with partially dissociable patterns of executive impairment. However, co-existent general intellectual impairment has been an important confounding factor in the studies to date.