HAART in hand: The change in Kaposi’s sarcoma presentation in KwaZulu-Natal, South Africa

Background. HIV/AIDS-related Kaposi’s sarcoma (HIV-KS) is a public health problem in South Africa (SA). It is AIDS defining. There have been no studies evaluating its prevalence since the national roll-out of highly active antiretroviral therapy (HAART).Objective. To evaluate the effect of HAART on the disease profile of HIV-KS in KwaZulu-Natal Province (KZN), SA.Methods. Charts of patients with histologically confirmed HIV-KS were reviewed at an oncology clinic in KZN. The significance of associations of HAART with age, gender, CD4 count, urban/rural residence, fungating lesions, ulceration and lymphoedema, and treatment delay, was determined by t-tests for normally distributed continuous variables and χ2 tests for categorical variables. Logistic regression models were used to analyse the association of HAART with CD4 count.Results. Of 198 patients, 194 were documented as HIV-positive; 168 (86.6%) were on HAART at the time of their KS diagnosis. The mean CD4 count of 266 cells/μL was higher than that in previous studies at this site. The mean age at presentation was 36.6 (standard deviation 10.1) years. Females presented at a younger mean age than males (p<0.001). The mean age of females on HAART was 34.7 years and that of males 39.0 years (p=0.003). HAART-naive patients were three times more likely than those receiving HAART (15.4% v. 4.8%) to have visceral involvement (p=0.03).Conclusions. HAART use has resulted in outcome improvement. Mean age at presentation has increased in the group as a whole and for females in particular. The trend in mean CD4 counts has shown positive growth. Females no longer shoulder a disproportionate burden of disease

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance

Apoptosis, a genetically programmed cell death, allows for homeostasis and tissue remodelling during development of all multi-cellular organisms. Phagocytes swiftly recognize, engulf and digest apoptotic cells. Yet, to date the molecular mechanisms underlying this phagocytic process are still poorly understood. To delineate the molecular mechanisms of apoptotic cell clearance in Drosophila, we have carried out a deficiency screen and have identified three overlapping phagocytosis-defective mutants, which all delete the fly homologue of the ced-12 gene, known as Dmel\ced12. As anticipated, we have found that Dmel\ced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmel\ced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmel\ced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, which encodes a member of the TRPP channel family, is also required for phagocytosis of apoptotic cells, thereby demonstrating a novel role for PKD2 in this process. We have also observed genetic interactions between pkd2, simu, drpr, rya-r44F, and retinophilin (rtp), also known as undertaker (uta), a gene encoding a MORN-repeat containing molecule, which we have recently found to be implicated in calcium homeostasis during phagocytosis. However, we have not found any genetic interaction between Dmel\ced-12 and simu. Based on these genetic interactions and recent reports demonstrating a role for the mammalian pkd-2 gene product in ER calcium release during store-operated calcium entry, we propose that PKD2 functions in the DRPR/RTP pathway to regulate calcium homeostasis during this process. Similarly to its C. elegans homologue, Dmel\Ced-12 appears to function in a genetically distinct pathway

Treatment of distal humeral fractures using conventional implants. Biomechanical evaluation of a new implant configuration

<p>Abstract</p> <p>Background</p> <p>In the face of costly fixation hardware with varying performance for treatment of distal humeral fractures, a novel technique (U-Frame) is proposed using conventional implants in a 180° plate arrangement. In this in-vitro study the biomechanical stability of this method was compared with the established technique which utilizes angular stable locking compression plates (LCP) in a 90° configuration.</p> <p>Methods</p> <p>An unstable distal 3-part fracture (AO 13-C2.3) was created in eight pairs of human cadaveric humeri. All bone pairs were operated with either the "Frame" technique, where two parallel plates are distally interconnected, or with the LCP technique. The specimens were cyclically loaded in simulated flexion and extension of the arm until failure of the construct occurred. Motion of all fragments was tracked by means of optical motion capturing. Construct stiffness and cycles to failure were identified for all specimens.</p> <p>Results</p> <p>Compared to the LCP constructs, the "Frame" technique revealed significant higher construct stiffness in extension of the arm (P = 0.01). The stiffness in flexion was not significantly different (P = 0.16). Number of cycles to failure was found significantly larger for the "Frame" technique (P = 0.01).</p> <p>Conclusions</p> <p>In an in-vitro context the proposed method offers enhanced biomechanical stability and at the same time significantly reduces implant costs.</p

Marking Embryonic Stem Cells with a 2A Self-Cleaving Peptide: A NKX2-5 Emerald GFP BAC Reporter

Fluorescent reporters are useful for assaying gene expression in living cells and for identifying and isolating pure cell populations from heterogeneous cultures, including embryonic stem (ES) cells. Multiple fluorophores and genetic selection markers exist; however, a system for creating reporter constructs that preserve the regulatory sequences near a gene's native ATG start site has not been widely available.Here, we describe a series of modular marker plasmids containing independent reporter, bacterial selection, and eukaryotic selection components, compatible with both Gateway recombination and lambda prophage bacterial artificial chromosome (BAC) recombineering techniques. A 2A self-cleaving peptide links the reporter to the native open reading frame. We use an emerald GFP marker cassette to create a human BAC reporter and ES cell reporter line for the early cardiac marker NKX2-5. NKX2-5 expression was detected in differentiating mouse ES cells and ES cell-derived mice.Our results describe a NKX2-5 ES cell reporter line for studying early events in cardiomyocyte formation. The results also demonstrate that our modular marker plasmids could be used for generating reporters from unmodified BACs, potentially as part of an ES cell reporter library

Air Pollution, Urgent Asthma Medical Visits and the Modifying Effect of Neighborhood Asthma Prevalence

Background: Social and environmental stressors, may modify associations between environmental pollutants and asthma symptoms. We examined if neighborhood asthma prevalence (higher: HAPN vs. lower: LAPN), a surrogate for underlying risk factors for asthma, modified the relationship between pollutants and urgent asthma visits. Methods: Through zip code, home addresses were linked to New York City Community Air Survey’s land use regression model for street-level, annual average nitrogen dioxide (NO2), particulate matter (PM2.5), elemental carbon (EC); summer average ozone (O3); winter average sulfur dioxide (SO2) concentrations. Poisson regression models were fit to estimate the association (prevalence ratio, PR) between pollutant exposures and seeking urgent asthma care. Results: All pollutants, except O3 were higher in HAPN than LAPN (P0.05). Conclusions: Relationships between modeled street-level pollutants and urgent asthma were stronger in LAPN compared to HAPN. Social stressors that may be more prevalent in HAPN than LAPN, could play a greater role in asthma exacerbations in HAPN versus pollutant exposure alone

Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Impairments in executive function and language processing are characteristic of both schizophrenia and bipolar disorder. Their functional neuroanatomy demonstrate features that are shared as well as specific to each disorder. Determining the distinct pattern of neural responses in schizophrenia and bipolar disorder may provide biomarkers for their diagnoses.</p> <p>Methods</p> <p>104 participants underwent functional magnetic resonance imaging (fMRI) scans while performing a phonological verbal fluency task. Subjects were 32 patients with schizophrenia in remission, 32 patients with bipolar disorder in an euthymic state, and 40 healthy volunteers. Neural responses to verbal fluency were examined in each group, and the diagnostic potential of the pattern of the neural responses was assessed with machine learning analysis.</p> <p>Results</p> <p>During the verbal fluency task, both patient groups showed increased activation in the anterior cingulate, left dorsolateral prefrontal cortex and right putamen as compared to healthy controls, as well as reduced deactivation of precuneus and posterior cingulate. The magnitude of activation was greatest in patients with schizophrenia, followed by patients with bipolar disorder and then healthy individuals. Additional recruitment in the right inferior frontal and right dorsolateral prefrontal cortices was observed in schizophrenia relative to both bipolar disorder and healthy subjects. The pattern of neural responses correctly identified individual patients with schizophrenia with an accuracy of 92%, and those with bipolar disorder with an accuracy of 79% in which mis-classification was typically of bipolar subjects as healthy controls.</p> <p>Conclusions</p> <p>In summary, both schizophrenia and bipolar disorder are associated with altered function in prefrontal, striatal and default mode networks, but the magnitude of this dysfunction is particularly marked in schizophrenia. The pattern of response to verbal fluency is highly diagnostic for schizophrenia and distinct from bipolar disorder. Pattern classification of functional MRI measurements of language processing is a potential diagnostic marker of schizophrenia.</p

Stressed out symbiotes:hypotheses for the influence of abiotic stress on arbuscular mycorrhizal fungi

Abiotic stress is a widespread threat to both plant and soil communities. Arbuscular mycorrhizal (AM) fungi can alleviate effects of abiotic stress by improving host plant stress tolerance, but the direct effects of abiotic stress on AM fungi are less well understood. We propose two hypotheses predicting how AM fungi will respond to abiotic stress. The stress exclusion hypothesis predicts that AM fungal abundance and diversity will decrease with persistent abiotic stress. The mycorrhizal stress adaptation hypothesis predicts that AM fungi will evolve in response to abiotic stress to maintain their fitness. We conclude that abiotic stress can have effects on AM fungi independent of the effects on the host plant. AM fungal communities will change in composition in response to abiotic stress, which may mean the loss of important individual species. This could alter feedbacks to the plant community and beyond. AM fungi will adapt to abiotic stress independent of their host plant. The adaptation of AM fungi to abiotic stress should allow the maintenance of the plant-AM fungal mutualism in the face of changing climates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00442-016-3673-7) contains supplementary material, which is available to authorized users