Functional Relaxation and Guided Imagery as Complementary Therapy in Asthma: A Randomized Controlled Clinical Trial

Background: Asthma is a frequently disabling and almost invariably distressing disease that has a high overall prevalence. Although relaxation techniques and hypnotherapeutic interventions have proven their effectiveness in numerous trials, relaxation therapies are still not recommended in treatment guidelines due to a lack of methodological quality in many of the trials. Therefore, this study aims to investigate the efficacy of the brief relaxation technique of functional relaxation (FR) and guided imagery (GI) in adult asthmatics in a randomized controlled trial. Methods: 64 patients with extrinsic bronchial asthma were treated over a 4-week period and assessed at baseline, after treatment and after 4 months, for follow-up. 16 patients completed FR, 14 GI, 15 both FR and GI (FR/GI) and 13 received a placebo relaxation technique as the control intervention (CI). The forced expiratory volume in the first second (FEV 1) as well as the specific airway resistance (sR(aw)) were employed as primary outcome measures. Results: Participation in FR, GI and FR/GI led to increases in FEV 1 (% predicted) of 7.6 +/- 13.2, 3.3 +/- 9.8, and 8.3 +/- 21.0, respectively, as compared to -1.8 +/- 11.1 in the CI group at the end of the therapy. After follow-up, the increases in FEV 1 were 6.9 +/- 10.3 in the FR group, 4.4 +/- 7.3 in the GI and 4.5 +/- 8.1 in the FR/GI, compared to -2.8 +/- 9.2 in the CI. Improvements in sR(aw) (% predicted) were in keeping with the changes in FEV 1 in all groups. Conclusions: Our study confirms a positive effect of FR on respiratory parameters and suggests a clinically relevant long-term benefit from FR as a nonpharmacological and complementary therapy treatment option. Copyright (C) 2009 S. Karger AG, Base

The clonal structure and dynamics of the human T cell response to an organic chemical hapten

Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis, and is used in treatment of warts, melanoma and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals, and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage, and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a Dynamic Bayesian Network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens

Mixed Theileria infections in free-ranging buffalo herds : implications for diagnosing Theileria parva infections in Cape buffalo (Syncerus caffer)

Buffalo-adapted Theileria parva causes Corridor disease in cattle. Strict control measures therefore apply to the movement of buffalo in South Africa and include mandatory testing of buffalo for the presence of T. parva. The official test is a realtime hybridization PCR assay that amplifies the V4 hypervariable region of the 18S rRNA gene of T. parva, T. sp. (buffalo) and T. sp. (bougasvlei). The effect that mixed T. parva and T. sp. (buffalo)-like infections have on accurate T. parva diagnosis was investigated in this study. In vitro mixed infection simulations indicated PCR signal suppression at 100 to 1000-fold T. sp. (buffalo) excess at low T. parva parasitaemia. Suppression of PCR signal was found in field buffalo with mixed infections. The T. parva-positive status of these cases was confirmed by selective suppression of T. sp. (buffalo) amplification using a locked nucleic acid clamp and independent assays based on the p67, p104 and Tpr genes. The incidence of mixed infections in the Corridor disease endemic region of South Africa is significant, while the prevalence in buffalo outside the endemic area is currently low. A predicted increase of T. sp. (buffalo)-like infections can affect future diagnoses where mixed infections occur, prompting the need for improvements in current diagnostics.This project was funded by OVI project numbers 15/08/ 1P01 and OV21/03/C148 (Department of Agriculture, Forestry and Fisheries contract).http://journals.cambridge.org/action/displayJournal?jid=pa

The Hybrid II assay : a sensitive and specific real-time hybridization assay for the diagnosis of Theileria parva infection in Cape buffalo (Syncerus caffer) and cattle

Corridor disease is an acute, fatal disease of cattle caused by buffalo-adapted Theileria parva. This is a nationally controlled disease in South Africa and strict control measures apply for the movement of buffalo, which includes mandatory testing for the presence of T. parva and other controlled diseases. Accurate diagnosis of the T. parva carrier state in buffalo using the official real-time hybridization PCR assay (Sibeko et al. 2008), has been shown to be affected by concurrent infection with T. sp. (buffalo)-like parasites.We describe the Hybrid II assay, a real-time hybridization PCR method, which compareswell with the official hybridization assay in terms of specificity and sensitivity. It is, however, not influenced by mixed infections of T. sp. (buffalo)-like parasites and is as such a significant improvement on the current hybridization assay.This project was funded by OVI project numbers 15/08/ 1P01 and OV21/03/C148 (Department of Agriculture, Forestry and Fisheries contract).http://journals.cambridge.org/action/displayJournal?jid=parab201

The association between psychological distress, alcohol use and physical non-communicable diseases in a nationally representative sample of South Africans

This study examines the associations between symptoms of mental disorders and diabetes and hypertension in a nationally representative sample of South Africans. We examined unadjusted and adjusted associations of socio-demographic characteristics, alcohol use and psychological distress with diabetes and hypertension. Multivariate logistic regression revealed that hypertension is significantly associated with age, while diabetes is significantly associated with age, population group and psychological distress. The association between psychological distress and diabetes found here suggests the usefulness of additional research using more detailed measures of psychiatric disorders in local studies and reinforces clinical calls for attention to psychiatric screening in patients with diabetes.IS

Geographic patterns of genetic variation in a broadly distributed marine vertebrate: new insights into loggerhead turtle stock structure from expanded mitochondrial DNA sequences

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (~800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology

The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST).

BACKGROUND: [68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called 'wild-type' GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST. AIMS: To investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST. METHODS: [68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study. RESULTS: [68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST. CONCLUSIONS: Our data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST

Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1–2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines