X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses.</p> <p>Methods</p> <p>The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed.</p> <p>Results</p> <p>2 patients previously diagnosed with CVID associated with virtual absence of CD19⁺B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. <b>Patient 1</b>, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). <b>Patient 2</b>, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA</p> <p>Conclusion</p> <p>These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19⁺B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.</p

Comparison of breast cancer-related lymphedema (Upper Limb Swelling) prevalence estimated using objective and subjective criteria and relationship with quality of life

This study aimed to investigate lymphedema prevalence using three different measurement/diagnostic criterion combinations and explore the relationship between lymphedema and quality of life for each, to provide evaluation of rehabilitation. Cross-sectional data from 617 women attending review appointments after completing surgery, chemotherapy, and radiotherapy included the Morbidity Screening Tool (MST; criterion: yes to lymphedema); Lymphedema and Breast Cancer Questionnaire (LBCQ; criterion: yes to heaviness and/or swelling); percentage limb volume difference (perometer: %LVD; criterion: 10%+ difference); and the Functional Assessment of Cancer Therapy breast cancer-specific quality of life tool (FACT B+4). Perometry measurements were conducted in a clinic room. Between 341 and 577 participants provided sufficient data for each analysis, with mean age varying from 60 to 62 (SD 9.95-10.03) and median months after treatment from 49 to 51. Lymphedema prevalence varied from 26.2% for perometry %LVD to 20.5% for the MST and 23.9% for the LBCQ; differences were not significant. Limits of agreement analysis between %LVD and the subjective measures showed little consistency, while moderate consistency resulted between the subjective measures. Quality of life differed significantly for women with and without lymphedema only when subjective measurements were used. Results suggest that subjective and objective tools investigate different aspects of lymphedema. 2013 Catherine Bulley et al.sch_phy2013pub3233pub80756

The association of Social Anxiety Disorder, Alcohol Use Disorder and reproduction: Results from four nationally representative samples of adults in the USA.

Social Anxiety Disorder (SAD) and Alcohol Use Disorder (AUD) are highly prevalent and frequently co-occur. The results of population studies suggest that SAD tends to precede AUD, and the results of laboratory studies suggest that alcohol use facilitates social behaviors in socially anxious individuals. Therefore, we posited that, in a modern context, a tendency to consume alcohol may be positively selected for among socially anxious individuals by its effect on the likelihood of finding a partner and reproducing. We tested the hypothesis that a higher proportion of individuals with a lifetime diagnosis of SAD and AUD reproduce (i.e., have at least one child) relative to individuals with SAD absent AUD in an individual participant meta-analysis based on over 65,000 adults derived from four nationally representative cross-sectional samples. We then cross-validated these findings against the results of a 10-year follow up of one of these surveys. Lifetime history of SAD was not associated with reproduction whereas lifetime history of AUD was positively associated with reproduction. There was no statistically detectable difference in the proportion of individuals with a lifetime history of SAD with or without AUD who reproduced. There was considerable heterogeneity in all of the analyses involving SAD, suggesting that there are likely to be other pertinent variables relating to SAD and reproduction that should be delineated

ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.

Pulmonary arterial (PA) smooth muscle cells (PASMC) generate vascular tone in response to agonists coupled to Gq-protein receptor signaling. Such agonists stimulate oscillating calcium waves, the frequency of which drives the strength of contraction. These Ca2+ events are modulated by a variety of ion channels including voltage-gated calcium channels (CaV1.2), the Tmem16a or Anoctamin-1 (ANO1)-encoded calcium-activated chloride (CaCC) channel, and Ca2+ release from the sarcoplasmic reticulum through inositol-trisphosphate receptors (IP3R). Although these calcium events have been characterized, it is unclear how these calcium oscillations underly a sustained contraction in these muscle cells. We used smooth muscle-specific ablation of ANO1 and pharmacological tools to establish the role of ANO1, CaV1.2, and IP3R in the contractile and intracellular Ca2+ signaling properties of mouse PA smooth muscle expressing the Ca2+ biosensor GCaMP3 or GCaMP6. Pharmacological block or genetic ablation of ANO1 or inhibition of CaV1.2 or IP3R, or Ca2+ store depletion equally inhibited 5-HT-induced tone and intracellular Ca2+ waves. Coimmunoprecipitation experiments showed that an anti-ANO1 antibody was able to pull down both CaV1.2 and IP3R. Confocal and superresolution nanomicroscopy showed that ANO1 coassembles with both CaV1.2 and IP3R at or near the plasma membrane of PASMC from wild-type mice. We conclude that the stable 5-HT-induced PA contraction results from the integration of stochastic and localized Ca2+ events supported by a microenvironment comprising ANO1, CaV1.2, and IP3R. In this model, ANO1 and CaV1.2 would indirectly support cyclical Ca2+ release events from IP3R and propagation of intracellular Ca2+ waves

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment

Purpose: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. Methods: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post-surgery. Results: Breast cancer patients’ experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. Conclusions: bWell, a novel app for arm and shoulder exercises was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. Implications for Cancer Survivors: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care

Ascorbate Biosynthesis during Early Fruit Development Is the Main Reason for Its Accumulation in Kiwi

Background: Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. Methodology/Principal Findings: We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in large

Registered Replication Report: Dijksterhuis and van Knippenberg (1998)

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender

Registered Replication Report: Dijksterhuis and van Knippenberg (1998)

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164\ua0Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models