Effectiveness of a home-based pulmonary rehabilitation programme in pulmonary function and health related quality of life for patients with pulmonary tuberculosis: a pilot study

Background: Patients with Pulmonary Tuberculosis (PTB) often develop impairment in pulmonary function due to anatomical changes secondary to the illness. Physiotherapy in the form of pulmonary rehabilitation has been advocated.Objective: The aim of the study was to determine whether adherence to a six-week home-based pulmonary rehabilitation programme (PRP) improved the baseline measurements of lung function, exercise tolerance and health-related quality of life (HRQoL) in patients receiving out-patient treatment for PTB.Method: A single blinded randomized control study design was used to assess the effects of a six-week home- based PRP in patients receiving treatment for PTB at a local clinic in Khayelitsha, Western Cape. We evaluated lung function by spirometry (MINATO AUTOSPIRO-model no. AZ-505), exercise tolerance using the 6-min-walk test (6MWT), the Borg exercise exertion scale and HRQoL using the EQ-5 D questionnaire in an intervention group (n=34) and a control group (n=33). The trend of the effects of the PRP on lung function was towards increases, but there was no statistical difference between the intervention and control groups at the end of the sixth week in the values of FVC (p=0.2; 95% CI -0.9 to 0.51) as well as FEV1 (p=0.1; 95% CI -0.07 to 0.51). Similar trend was observed for exercise tolerance, and there was no significant difference in HRQoL (p=0.789).Conclusion: The outcome of the study provides motivation for further consideration and implementation of a pulmonary rehabilitation programme for patients with PTB.Keywords: Pulmonary rehabilitation, pulmonary tuberculosi

Research paper: Wh-questions' expression in persianspeaking children: A comparison between spontaneous and elicited probes

Objectives: Studies have shown that most children before the age of 5 are capable to comprehend and express wh-questions in daily conversations. This study aimed at comparing the ability of wh-questions' production in 4-6-year-old children in spontaneous and elicited conditions. Methods: In this descriptive-analytic study, 72 (n=72) 4-6-year-old Persian-speaking children were selected randomly from kindergartens of Hamadan, Iran. Three different probes were used to evaluate the spontaneous and elicited conditions in the expression of questions with "what, where, who, why, and when". In the first probe, children were encouraged to ask questions spontaneously about experimental pictures. While in the second probe, the verbal prompt was presented about wh-questions, and wh-words were provided as key-words in the third probe. Repeated measures analysis of variance test with between-subjects' factors of sex (male, female) and age group (4-5 years, 5-6 years) and within-subjects' factor of the method (I, II, III) was performed in the study. Results: There was a main effect of probes in "where, who, and when" questions and the mean scores of the II and III probes were significantly higher than those of probe I. Children in probe I received higher scores for why questions than the other probes. "What" questions were expressed more by children in probe II. "Why, when, and where" scores were significantly higher for 5-6 years group than for 4-5 years group. There was no significant effect on all wh-questions. Discussion: The higher accuracy of wh-questions in probe II and III compared to probe I suggested that this competence is significantly developed by the use of elicited procedures (verbal prompt or providing wh-words as key-words) in comparison with no elicitation. © 2020 University of Social Welfare and Rehabilitation Sciences

Pulmonary hypertension in adults completing tuberculosis treatment

Background Pulmonary hypertension (PH) after tuberculosis (TB) is typically not included among the chronic lung diseases causing PH (group 3 PH), with few data available to support the inclusion. Objectives To determine the prevalence of PH in an adult population completing TB treatment. Methods. This single-centre, cross-sectional study only included patients with their first documented episode of TB, and who were in the second half of treatment or had recently completed treatment. PH was assessed using transthoracic echocardiography. Questionnaires were also completed and spirometry and a 6-minute walk test were performed. Results One hundred patients were enrolled, with a mean age of 37.1 years, of whom 58% were male and 46% HIV positive. The median time since initiation of TB treatment was 22 weeks. The mean (standard deviation) measured right ventricular systolic pressure (RVSP) was 23.6 (6.24) mmHg. One participant had PH (defined as RVSP ≥40 mmHg; 95% confidence interval (CI) 0.0 - 3.0) and a further 3 had possible PH (RVSP ≥35 and <40 mmHg), with a combined PH prevalence of 4% (95% CI 0.2 - 7.8). Airflow obstruction on spirometry was found in 13.3% of 98 patients, while 25.5% had a reduced forced vital capacity. There was no association between RVSP or PH/possible PH and sex, age, HIV status, systemic hypertension, spirometry measurements or 6-minute walking distance. Smoking status was associated with RVSP, but not with the presence of PH/possible PH. Conclusion There was a significant prevalence of PH in this preliminary study of predominantly young patients completing treatment for a first episode of TB. Larger and more detailed studies are warranted

Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer

International audienceIntroduction: Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.Methods: By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.Results: Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.Conclusions: A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy

RET PLCγ Phosphotyrosine Binding Domain Regulates Ca2+ Signaling and Neocortical Neuronal Migration

The receptor tyrosine kinase RET plays an essential role during embryogenesis in regulating cell proliferation, differentiation, and migration. Upon glial cell line-derived neurotrophic factor (GDNF) stimulation, RET can trigger multiple intracellular signaling pathways that in concert activate various downstream effectors. Here we report that the RET receptor induces calcium (Ca2+) signaling and regulates neocortical neuronal progenitor migration through the Phospholipase-C gamma (PLCγ) binding domain Tyr1015. This signaling cascade releases Ca2+ from the endoplasmic reticulum through the inositol 1,4,5-trisphosphate receptor and stimulates phosphorylation of ERK1/2 and CaMKII. A point mutation at Tyr1015 on RET or small interfering RNA gene silencing of PLCγ block the GDNF-induced signaling cascade. Delivery of the RET mutation to neuronal progenitors in the embryonic ventricular zone using in utero electroporation reveal that Tyr1015 is necessary for GDNF-stimulated migration of neurons to the cortical plate. These findings demonstrate a novel RET mediated signaling pathway that elevates cytosolic Ca2+ and modulates neuronal migration in the developing neocortex through the PLCγ binding domain Tyr1015

“We have been working overnight without sleeping”: traditional birth attendants’ practices and perceptions of post-partum care services in rural Tanzania

Background: In many low-income countries, formal post-partum care utilization is much lower than that of skilled delivery and antenatal care. While Traditional Birth Attendants (TBAs) might play a role in post-partum care, research exploring their attitudes and practices during this period is scarce. Therefore, the aim of this study was to explore TBAs’ practices and perceptions in post-partum care in rural Tanzania. Methods: Qualitative in-depth interview data were collected from eight untrained and three trained TBAs. Additionally, five multiparous women who were clients of untrained TBAs were also interviewed. Interviews were conducted in February 2013. Data were digitally recorded and transcribed verbatim. Qualitative content analysis was used to analyze data. Results: Our study found that TBAs take care of women during post-partum with rituals appreciated by women. They report lacking formal post-partum care training, which makes them ill-equipped to detect and handle post-partum complications. Despite their lack of preparation, they try to provide care for some post-partum complications which could put the health of the woman at risk. TBAs perceive that utilization of hospital-based post-partum services among women was only important for the baby and for managing complications which they cannot handle. They are poorly linked with the health system. Conclusions: This study found that the TBAs conducted close follow-ups and some of their practices were appreciated by women. However, the fact that they were trying to manage certain post-partum complications can put women at risk. These findings point out the need to enhance the communication between TBAs and the formal health system and to increase the quality of the TBA services, especially in terms of prompt referral, through provision of training, mentoring, monitoring and supervision of the TBA servic

Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development

Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and β-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development

Effects of IKAP/hELP1 Deficiency on Gene Expression in Differentiating Neuroblastoma Cells: Implications for Familial Dysautonomia

Familial dysautonomia (FD) is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype