Sepsis: precision-based medicine for pregnancy and the puerperium

Sepsis contributes significantly to global morbidity and mortality, particularly in vulnerable populations. Pregnant and recently pregnant women are particularly prone to rapid progression to sepsis and septic shock, with 11% of maternal deaths worldwide being attributed to sepsis. The impact on the neonate is considerable, with 1 million neonatal deaths annually attributed to maternal infection or sepsis. Pregnancy specific physiological and immunological adaptations are likely to contribute to a greater impact of infection, but current approaches to the management of sepsis are based on those developed for the non-pregnant population. Pregnancy-specific strategies are required to optimise recognition and management of these patients. We review current knowledge of the physiology and immunology of pregnancy and propose areas of research, which may advance the development of pregnancy-specific diagnostic and therapeutic approaches to optimise the care of pregnant women and their babies

Gastro-intestinal helminths of pigeons (Columba livia) in Gujarat, India

A study was conducted to assess the prevalence of helmith parasites of domestic wild and zoo pigeons in Gujarat, India by faecal sampling and postmortem examination. Qualitative examination of 78 faecal samples revealed 71 (91%) with parasitic infections of nematodes (85%), cestodes (31%) and Eimeria sp (77%). There were 200-1600 nematode eggs per gram during the monsoon season, which was high compared to the 200-1000 eggs per gram in winter and summer. In post-mortems 85% had parasitic infections, of nematodes (75%), cestodes (69%) and Eimeria sp (58%). Two species of nematodes (Ascaridia columbae and Capillaria obsignata) and five species of three genera of cestodes (Raillietina echinobothridia, R. tetragona, R. cesticillus, Cotugnia digonophora and Hymenolepis sp) were identified. Despite their parasitic infections, not a single pigeon revealed any alarming clinical signs

Wilderness medicine at high altitude: recent developments in the field.

Travel to high altitude is increasingly popular. With this comes an increased incidence of high-altitude illness and therefore an increased need to improve our strategies to prevent and accurately diagnose these. In this review, we provide a summary of recent advances of relevance to practitioners who may be advising travelers to altitude. Although the Lake Louise Score is now widely used as a diagnostic tool for acute mountain sickness (AMS), increasing evidence questions the validity of doing so, and of considering AMS as a single condition. Biomarkers, such as brain natriuretic peptide, are likely correlating with pulmonary artery systolic pressure, thus potential markers of the development of altitude illness. Established drug treatments include acetazolamide, nifedipine, and dexamethasone. Drugs with a potential to reduce the risk of developing AMS include nitrate supplements, propagators of nitric oxide, and supplemental iron. The role of exercise in the development of altitude illness remains hotly debated, and it appears that the intensity of exercise is more important than the exercise itself. Finally, despite copious studies demonstrating the value of preacclimatization in reducing the risk of altitude illness and improving performance, an optimal protocol to preacclimatize an individual remains elusive

Maternal sepsis update: current management and controversies

•Sepsis is a leading cause of maternal morbidity and mortality, globally and in the UK. •In pregnancy and the puerperium, women may be more susceptible to rapid deterioration of illness following an infection. •Sepsis has a complex pathophysiology and the immunological and cardiovascular adaptations of normal pregnancy may have an adverse impact on the maternal response to infection. Furthermore, physiological changes of pregnancy, which mimic those of sepsis, often delay optimal management. •‘Bedside’ identification of pathogens and their antibiotic resistance patterns may help to improve clinical outcomes. •Recent updates in sepsis management, areas of controversy and the importance of translational research and clinical trials for pregnancy and the puerperium are discussed

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007-2012

BACKGROUND: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. METHODS: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. RESULTS: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old. CONCLUSION: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required

Human labour is associated with altered regulatory T cell function and maternal immune activation

During human pregnancy, regulatory T cell (Treg) function is enhanced and immune activation is repressed allowing the growth and development of the feto–placental unit. Here, we have investigated whether human labour is associated with a reversal of the pregnancy‐induced changes in the maternal immune system. We tested the hypothesis that human labour is associated with a decline in Treg function, specifically their ability to modulate Toll‐like receptor (TLR)‐induced immune responses. We studied the changes in cell number, activation status and functional behaviour of peripheral blood, myometrial (myoMC) and cord blood mononuclear cells (CBMC) with the onset of labour. We found that Treg function declines and that Treg cellular targets change with labour onset. The changes in Treg function were associated with increased activation of myoMC, assessed by their expression of major histocompatibility complex (MHC) class II molecules and CBMC inflammatory cells. The innate immune system showed increased activation, as shown by altered monocyte and neutrophil cell phenotypes, possibly to be ready to respond to microbial invasion after birth or to contribute to tissue remodelling. Our results highlight changes in the function of the adaptive and innate immune systems that may have important roles in the onset of human labour

In vitro Anti-proliferative and Apoptotic Activities of Eurycoma longifolia Jack (Simaroubaceae) on HL-60 Cell Line

Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells.Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia roots, at different doses andtime points. The anti-proliferative activity of E. longifolia was assessed via cell counting and trypan blue exclusion. Apoptosis was evaluated via Annexin-V FITC/IP and Hoechst staining. Flow cytometry and Wright staining were used to assess its differentiation activities.Results: F1 showed unremarkable growth inhibition rate while F2 and F3 showed growth inhibitory effects with median inhibitory concentration (IC50) values of 15.2 and 28.6 ìg/ml, respectively. Treatment with F2 and F3 (100 ìg/ml) for 96 h increased cell death from 3.3 to 95.5 and 76.3 %,respectively. Treatment with F2 (50 ìg/ml) induced apoptosis by 14, 19.5 and 25 % after 24, 48 and 72 h, respectively. No differentiation activity was observed, as indicated by absence of myeloid maturation and a non-significant CD14 positivity (p &gt; 0.05).Conclusion: E. longifolia extract (F2) showed promising anti-leukemic activity and can be a candidate for the development of a drug for the treatment of acute promyelocytic leukemia (APL).Keywords: Acute promyelocytic leukemia (APL), HL-60 cells, Eurycoma longifolia, Apoptosis, Antiproliferation, Differentiatio