Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa.

Background: South Africa shows one of the highest global burdens of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Since 2002, MDR-TB in South Africa has been treated by a standardized combination therapy, which until 2010 included ofloxacin, kanamycin, ethionamide, ethambutol and pyrazinamide. Since 2010, ethambutol has been replaced by cycloserine or terizidone.

Pili contribute to biofilm formation in vitro in Mycobacterium tuberculosis.

Organized bacterial communities, or biofilms, provide an important reservoir for persistent cells that are inaccessible or tolerant to antibiotics. Curli pili are cell-surface structures produced by certain bacteria and have been implicated in biofilm formation in these species. In order to determine whether these structures, which were suggested to be encoded by the Rv3312A (mtp) gene, have a similar role in Mycobacterium tuberculosis, we generated a Δmtp mutant and a mtp-complemented strain of a clinical isolate of M.

Plant microRNAs display differential 3' truncation and tailing modifications that are ARGONAUTE1 dependent and conserved across species.

Plant small RNAs are 3' methylated by the methyltransferase HUA1 ENHANCER1 (HEN1). In plant hen1 mutants, 3' modifications of small RNAs, including oligo-uridylation (tailing), are associated with accelerated degradation of microRNAs (miRNAs). By sequencing small RNAs of the wild type and hen1 mutants from Arabidopsis thaliana, rice (Oryza sativa), and maize (Zea mays), we found 3' truncation prior to tailing is widespread in these mutants.

AIDS-related progressive multifocal leukoencephalopathy (PML): a retrospective study from Pretoria, South Africa.

Introduction And Objectives: Progressive multifocal leukoencephalopathy (PML), caused by the John Cunningham (JC) virus, results from lytic infection of predominantly oligodendrocytes. Following the HIV pandemic, the incidence of PML has risen sharply, but has rarely been reported in Africa. An increasing number of PML cases were seen recently in a tertiary South African hospital, and this study describes their clinical and radiological features.

Promoting change through political consciousness: a South African speech-language pathology response to the World Report on Disability.

In the context of the World Report on Disability, Wylie, McAllister, Davidson, and Marshall (2013) question how speech-language pathologists (SLPs) change practices to benefit under-served people with communication disability. This commentary provides a South African response premised on Political Consciousness. In South Africa, a grossly unequal society, the under-served population is not only those with communication disability but also include those who are at a communication disadvantage due to disabling conditions.

Can the subaltern speak? Visibility of international migrants with communication and swallowing disabilities in the World Report on Disability.

Wylie, McAllister, Davidson, and Marshal (2013) argued that the speech-language pathology profession must be encouraged to consider novel ways to deliver equitable services to people with communication disorders. People with communication disorders include the world's 215 million international migrants who deserve unique commentary when considering disability in the world. Hence, this paper focuses on invisibility of international migrants with communication or swallowing disorders in the World Report on Disability.

Synthesis and antitubercular activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides.

A series of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides 7-13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT-IR, NMR ((1)H and (13)C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay.

Sirenomelia: case reports and current concepts of pathogenesis.

We present 2 cases of sirenomelia and highlight the recent theories about its pathogenesis. Both cases had a large aberrant abdominal umbilical artery (AAUA) arising from the aorta, suggesting vascular steal as the pathophysiology. However, the bilateral upper limb defects noted in 1 case, the reported 10% association of holoprosencephaly and anencephaly, and the reports of sirenomelia with normal umbilical arteries point to the alternative caudal dysgenesis (CD) theory.

Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months.

Novel polycyclic 'cage'-1,2-diamines as potential anti-tuberculosis agents.

A series of polycyclic 'cage' derivatives of N-geranyl-1,2 diamines were synthesized and screened for their anti-mycobacterial activity against H(37)Rv, multidrug resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis. By substituting the adamantyl skeleton of SQ109 with trishomocubanyl (9), oxa-pentacycloundecyl (14, 16), pentacycloundecyl, PCU, (10, 15) and azapentacycloundecyl (22, 23), the effect of other polycyclic "cage" skeletons could be investigated. Compound 9 (trishomocubanyl moiety) proved to be the most active (MICs: 0.

Mycobacterium tuberculosis isolates grown under oxygen deprivation invade pulmonary epithelial cells.

Mycobacterium tuberculosis has the ability to adapt to and survive under different environmental conditions, including oxygen deprivation. To better understand the pathogenesis of M. tuberculosis, we studied the invasion of human alveolar (A549) and human bronchial (BBM) epithelial cell lines by M.

Population structure of multi- and extensively drug-resistant Mycobacterium tuberculosis strains in South Africa.

Genotyping of multidrug-resistant (MDR) Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in four South African provinces (Western Cape, Eastern Cape, KwaZulu-Natal, and Gauteng) revealed a distinct population structure of the MDR strains in all four regions, despite the evidence of substantial human migration between these settings. In all analyzed provinces, a negative correlation between strain diversity and an increasing level of drug resistance (from MDR-TB to extensively drug-resistant TB [XDR-TB]) was observed. Strains predominating in XDR-TB in the Western and Eastern Cape and KwaZulu-Natal Provinces were strongly associated with harboring an inhA promoter mutation, potentially suggesting a role of these mutations in XDR-TB development in South Africa.

Emergence and treatment of multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in South Africa.

Drug resistant tuberculosis (TB) has reached alarming proportions in South Africa, draining valuable resources that are needed to fight drug susceptible TB. It is currently estimated that 9.6% of all TB cases have multi-drug resistant (MDR)-TB, thereby ranking South Africa as one of the highest MDR-TB burden countries in the world.

Total synthesis of a depsidomycin analogue by convergent solid-phase peptide synthesis and macrolactonization strategy for antitubercular activity.

Depsidomycin is a cyclic heptadepsi-peptide isolated from the cultured broth of Streptomyces lavendofoliae MI951-62F2. It exhibits significant antimicrobial and immunosuppressive activity. The total synthesis of a depsidomycin analogue in which 1,2-piperazine-3-carboxylic acid was substituted with proline is described.

Configurations of self-identity formations of adults who stutter.

It is important for clinicians to understand how adults who stutter construct who they are, i.e. their self-identity, in order to offer personally meaningful interventions.

Autism Spectrum Conditions--enhancing Nurture and Development (ASCEND): an evaluation of intervention support groups for parents.

There is relatively little evidence about the effectiveness of parent-training programmes for children with autism spectrum conditions (ASCs). Here we evaluate a programme developed to fill a gap in the provision of parent interventions after EarlyBird, which is only available for parents of pre-school ASC children. This programme (ASCEND) has now been running for five years.

Adhesion to and invasion of pulmonary epithelial cells by the F15/LAM4/KZN and Beijing strains of Mycobacterium tuberculosis.

Globally, specific genotypes of Mycobacterium tuberculosis have been shown to dominate in patients, suggesting that these are more successful pathogens. One such genotype, the F15/LAM4/KZN (KZN) family of M. tuberculosis, has predominated in KwaZulu-Natal, South Africa, since the early 1990s.

Nosocomial transmission of the F15/LAM4/KZN genotype of Mycobacterium tuberculosis in patients on tuberculosis treatment.

Setting: King George V (KGV) Hospital has the largest tuberculosis (TB) facility in KwaZulu-Natal (KZN), the province with the highest prevalence of TB-HIV (human immunodeficiency virus) co-infection in South Africa. During the study, KGV was the only provincial referral hospital for patients with drug-resistant TB.

Objective: To determine the role of nosocomial transmission in patients infected with a new strain of Mycobacterium tuberculosis during treatment.

Sedation in ICU: are we achieving goals?

Objective: The purpose of this study was to examine whether sedation goals, utilizing a validated sedation assessment scale, the Riker Sedation-Agitation Scale (SAS), and a standardized sedation protocol, were achieved in Intensive Care Unit (ICU) patients.

Design: This is a nested prospective cohort study

Setting: The study was conducted in a tertiary care medical-surgical ICU.

Patients: All mechanically ventilated adult patients who were judged by their treating intensivists to require intravenous sedation for more than 24 hours, were included in the study.

Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa.

The KZN strain family of Mycobacterium tuberculosis is a highly virulent strain endemic to the KwaZulu-Natal region of South Africa, which has recently experienced an outbreak of extensively-drug resistant tuberculosis. To investigate the causes and evolution of drug-resistance, we determined the DNA sequences of several clinical isolates--one drug-susceptible, one multi-drug resistant, and nine extensively drug-resistant--using whole-genome sequencing. Analysis of polymorphisms among the strains is consistent with the drug-susceptibility profiles, in that well-known mutations are observed that are correlated with resistance to isoniazid, rifampicin, kanamycin, ofloxacin, ethambutol, and pyrazinamide.

Pentacyclo-undecane derived cyclic tetra-amines: synthesis and evaluation as potent anti-tuberculosis agents.

As part of an ongoing effort to develop highly potent anti-tuberculosis agents, fourteen pentacyclo-undecane (PCU) tetra-amine compounds were synthesized and screened for their in vitro anti-mycobacterial activity against two TB strains, H37Rv and XDR 194 [an extensively drug-resistant strain of tuberculosis]. Using the broth macrodilution method, nitrofuranylamide based compounds (6a and 6b) showed almost similar activities against the H37Rv strain of Mycobacterium tuberculosis when compared with the control drug, ethambutol. N-Geranyl piperazine PCU (8a) and trans-trans farnesyl piperazine PCU (8b) were 3.

The homogeneity of audibility and prosody of Zulu words for speech reception threshold (SRT) testing.

The aim of this investigation was to determine which of 58 preselected Zulu words developed by Panday et al. (2007) could be used for Speech Reception Threshold (SRT) testing. To realize this aim the homogeneity of audibility of 58 bisyllabic Zulu low tone verbs was measured, followed by an analysis of the prosodic features of the selected words.

Exogenous reinfection as a cause of multidrug-resistant and extensively drug-resistant tuberculosis in rural South Africa.

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are now major threats in areas of South Africa with a high prevalence of TB and human immunodeficiency virus (HIV) infection. The role of exogenous reinfection as a cause of MDR and XDR TB in these settings has not been determined.

Methods: We reviewed data from patients with culture-positive TB who later developed MDR or XDR TB in Tugela Ferry, KwaZulu-Natal, South Africa during 2005-2006.

Distinct size distribution of endogeneous siRNAs in maize: Evidence from deep sequencing in the mop1-1 mutant.

Small RNAs from plants are known to be highly complex and abundant, with this complexity proportional to genome size. Most endogenous siRNAs in Arabidopsis are dependent on RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) for their biogenesis. Recent work has demonstrated that the maize MEDIATOR OF PARAMUTATION1 (mop1) gene is a predicted ortholog of RDR2.