Chlamydiae as pathogens: new species and new issues.

The recognition of genital chlamydial infection as an important public health problem was made first by the recognition of its role in acute clinical syndromes, as well as in serious reproductive and ocular complications, and secondly by our awareness of its prevalence when diagnostic tests became widely accessible. The recent availability of effective single dose oral antimicrobial therapy and sensitive molecular amplification tests that allow the use of noninvasive specimens for diagnosis and screening is expected to have a major impact in reducing the prevalence of disease in the next decade. Clinical manifestations associated with Chlamydia pneumoniae infection continue to emerge beyond respiratory illness. In particular, its association with atherosclerosis deserves further investigation. Chlamydia pecorum, a pathogen of ruminants, was recently recognized as a new species. The continued application of molecular techniques will likely elucidate an expanding role for chlamydiae in human and animal diseases, delineate the phylogenetic relationships among chlamydial species and within the eubacteria domain, and provide tools for detection and control of chlamydial infections

Investment case for eliminating mother-to-child transmission of syphilis: promoting better maternal and child health and stronger health systems

Mother-to-child transmission (MTCT) of syphilis (commonly referred to as “congenital syphilis”) is relatively simple to eliminate and it is inexpensive to detect and treat, making it a possible “easy win” in terms of cost, feasibility and speed of scale-up. Investing in screening and treatment for syphilis in pregnant women ranks as one of the most cost-effective antenatal interventions. Screening all pregnant women, using simple and low-cost technologies, is feasible, even in low-resource settings. Syphilis is easily cured with penicillin, and MTCT of syphilis is easily prevented when pregnant mothers with syphilis infection are identified early and treated promptly. Penicillin is off patent, widely available, on the World Health Organization (WHO) list of essential medicines and, above all, inexpensive

Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews.

OBJECTIVES: Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection. METHODS: PubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers. RESULTS: The performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection. CONCLUSIONS: Although current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach

Iron supplementation and altitude: Decision making using a regression tree

[No abstract available

Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure

Purpose : To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2–4 weeks of moderate altitude exposure.Methods :Hematological data collected from 178 athletes (98 males, 80 females) exposed to moderate altitude (1,350–3,000 m) were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII) and blood iron parameters [ferritin and transferrin saturation (TSAT)]. Results :Altitude exposure (mean ± s: 21 ± 3 days) increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d) = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d) = -2.87 [-3.88, -1.66]). Conclusion :Oral iron supplementation during 2–4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores

"Particle Informatics": Advancing Our Understanding of Particle Properties through Digital Design

We introduce a combination of existing and novel approaches to the assessment and prediction of particle properties intrinsic to the formulation and manufacture of pharmaceuticals. Naturally following on from established solid form informatics methods, we return to the drug lamotrigine, re-evaluating its context in the Cambridge Structural Database (CSD). We then apply predictive digital design tools built around the CSD-System suite of software, including Synthonic Engineering methods that focus on intermolecular interaction energies, to analyze and understand important particle properties and their effects on several key stages of pharmaceutical manufacturing. We present a new, robust workflow that brings these approaches together to build on the knowledge gained from each step and explain how this knowledge can be combined to provide resolutions at decision points encountered during formulation design and manufacturing processes

Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

BACKGROUND: The chemokine CCL2 has an important role in the recruitment of inflammatory cells into the central nervous system (CNS). A transgenic mouse model that overexpresses CCL2 in the CNS shows an accumulation of leukocytes within the perivascular space surrounding vessels, and which infiltrate into the brain parenchyma following the administration of pertussis toxin (PTx). METHODS: This study used contrast-enhanced magnetic resonance imaging (MRI) to quantify the extent of blood–brain barrier (BBB) disruption in this model pre- and post-PTx administration compared to wild-type mice. Contrast-enhanced MR images were obtained before and 1, 3, and 5 days after PTx injection in each animal. After the final imaging session fluorescent dextran tracers were administered intravenously to each mouse and brains were examined histologically for cellular infiltrates, BBB leakage and tight junction protein. RESULTS: BBB breakdown, defined as a disruption of both the endothelium and glia limitans, was found only in CCL2 transgenic mice following PTx administration and seen on MR images as focal areas of contrast enhancement and histologically as dextrans leaking from blood vessels. No evidence of disruption in endothelial tight junctions was observed. CONCLUSION: Genetic and environmental stimuli were needed to disrupt the integrity of the BBB in this model of neuroinflammation

Iron status and the acute post-exercise hepcidin response in athletes

This study explored the relationship between serum ferritin and hepcidin in athletes. Baseline serum ferritin levels of 54 athletes from the control trial of five investigations conducted in our laboratory were considered; athletes were grouped according to values 100 mg/L (SF\u3e100). Data pooling resulted in each athlete completing one of five running sessions: (1) 8x3 min at 85% vVO2peak; (2) 5x4 min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous at 75% vVO 2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each running session were represented amongst all four groups; hence, the mean exercise duration and intensity were not different (p\u3e0.05). Venous blood samples were collected pre-, post- and 3 h post-exercise, and were analysed for serum ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise serum ferritin levels were different between groups (p0.05). Post-exercise IL-6 was significantly elevated compared to baseline within each group (p100;

Sprint cycling rate of torque development associates with strength measurement in trained cyclists

Purpose: A cyclist’s rate of force/torque development (RFD/RTD) and peak force/torque can be measured during single-joint or whole-body isometric tests, or during cycling. However, there is limited understanding of the relationship between these measures, and of the mechanisms that contribute to each measure. Therefore, we examined the: (i) relationship between quadriceps central and peripheral neuromuscular function with RFD/RTD in isometric knee extension, isometric mid-thigh pull (IMTP), and sprint cycling; and (ii) relationship among RFD/RTD and peak force/torque between protocols. Methods: Eighteen trained cyclists completed two familiarisation and two experimental sessions. Each session involved an isometric knee extension, IMTP, and sprint cycling protocol, where peak force/torque, average and peak RFD/RTD, and early (0 – 100 ms) and late (0–200 ms) RFD/RTD were measured. Additionally, measures of quadriceps central and peripheral neuromuscular function were assessed during the knee extension. Results: Strong relationships were observed between quadriceps early EMG activity (EMG50/M) and knee extension RTD (r or ρ = 0.51 – 0.65) and IMTP late RFD (r = 0.51), and between cycling early or late RTD and peak twitch torque (r or ρ = 0.70 – 0.75). Strong-to-very strong relationships were observed between knee extension, IMTP, and sprint cycling for peak force/torque, early and late RFD/RTD, and peak RFD/RTD (r or ρ = 0.59 – 0.80). Conclusion: In trained cyclists, knee extension RTD or IMTP late RFD are related to measures of quadriceps central neuromuscular function, while cycling RTD is related to measures of quadriceps peripheral neuromuscular function. Further, the strong associations among force/torque measures between tasks indicate a level of transferability across tasks