A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism

We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller 'intermediate' genome dataset from 1998 to 1999 and a 'modern' genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor ("X4 tropism"); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53/80) of subtype D env sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in env, suggesting recombination and selection have acted to remove subtype D env from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism

The Transit Phase of Migration: Circulation of Malaria and Its Multidrug-Resistant Forms in Africa

In the third article in a six-part <I>PLoS Medicine</I> series on Migration & Health, Cally Roper and Caroline Lynch use a case study of migration and anti-malarial drug resistance in Uganda to discuss the specific health risks and policy needs associated with the transit phase of migration

The effect of multitasking on the communication skill and clinical skills of medical students

Abstract Background Mental workload is an abstract concept that perceives cognition as the brain having a small and finite capacity to process information, with high levels of workload associated with poor performance and error. While an individual may be able to complete two different tasks individually, a combination of tasks may lead to cognitive overload and poor performance. In many high-risk industries, it is common to measure mental workload and then to redesign tasks until cognitive overload is avoided. This study aimed to measure the effect of multitasking on the mental workload and performance of medical students completing single and combined clinical tasks. Methods Medical students who had completed basic clinical skills training in a single undergraduate Medical School completed four standardised tasks for a total of four minutes each, consisting of: inactivity, listening, venepuncture and a combination of listening and venepuncture. Task performance was measured using standard binary checklists and with mental workload measured using a secondary task method. Results The tasks were successfully completed by 40 subjects and as expected, mental workload increased with task complexity. Combining the two tasks showed no difference in the associated mental workload and performance at venepuncture (p = 0.082) However, during the combined task, listening appeared to deteriorate (p < 0.001). Conclusions If staff are expected to simultaneously complete multiple tasks then they may preferentially shed communication tasks in order to maintain their performance of physical tasks, leading to the appearance of poor communication skills. Although this is a small-scale study in medical students it suggests that the active assessment and management of clinician workload in busy clinical settings may be an effective strategy to improve doctor-patient communication

Role of TNFα in pulmonary pathophysiology

Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death

Cellular therapies for treating pain associated with spinal cord injury

Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Sex Differences in Dietary Intake in British Army Recruits undergoing Phase One training

Background: British Army Phase One training exposes men and women to challenging distances of 13.5 km·d⁻¹ vs. 11.8 km·d⁻¹ and energy expenditures of ~4000 kcal·d⁻¹ and ~3000 kcal·d⁻¹, respectively. As such, it is essential that adequate nutrition is provided to support training demands. However, to date, there is a paucity of data on habitual dietary intake of British Army recruits. The aims of this study were to: (i) compare habitual dietary intake in British Army recruits undergoing Phase One training to Military Dietary Reference Values (MDRVs), and (ii) establish if there was a relative sex difference in dietary intake between men and women. Method: Researcher led weighed food records and food diaries were used to assess dietary intake in twenty-eight women (age 21.4 ± 3.0 yrs., height: 163.7 ± 5.0 cm, body mass 65.0 ± 6.7 kg), and seventeen men (age 20.4 ± 2.3 yrs., height: 178.0 ± 7.9 cm, body mass 74.6 ± 8.1 kg) at the Army Training Centre, Pirbright for 8-days in week ten of training. Macro and micronutrient content were estimated using dietary analysis software (Nutritics, Dublin) and assessed via an independent sample t-test to establish if there was a sex difference in daily energy, macro or micronutrient intakes. Results: Estimated daily energy intake was less than the MDRV for both men and women, with men consuming a greater amount of energy compared with women (2846 ± 573 vs. 2207 ± 585 kcal·day⁻¹, p0.030, ES=0.67). There were no differences in dietary fat intake between men and women (1.5 ± 0.2 vs. 1.5 ± 0.5 g·kg⁻¹·day⁻¹, p=0.483, ES=0.00). Conclusions: Daily EI in men and women in Phase One training does not meet MDRVs. Interventions to increase macronutrient intakes should be considered along with research investigating the potential benefits for increasing different macronutrient intakes on training adaptations