Effect of early detection and treatment on malaria related maternal mortality on the north-western border of Thailand 1986-2010

Introduction

Maternal mortality is high in developing countries, but there are few data in high-risk groups such as migrants and refugees in malaria-endemic areas. Trends in maternal mortality were followed over 25 years in antenatal clinics prospectively established in an area with low seasonal transmission on the north-western border of Thailand.

Methods and Findings

All medical records from women who attended the Shoklo Malaria Research Unit antenatal clinics from 12^th May 1986 to 31^st December 2010 were reviewed, and maternal death records were analyzed for causality. There were 71 pregnancy-related deaths recorded amongst 50,981 women who attended antenatal care at least once. Three were suicide and excluded from the analysis as incidental deaths. The estimated maternal mortality ratio (MMR) overall was 184 (95%CI 150–230) per 100,000 live births. In camps for displaced persons there has been a six-fold decline in the MMR from 499 (95%CI 200–780) in 1986–90 to 79 (40–170) in 2006–10, p<0.05. In migrants from adjacent Myanmar the decline in MMR was less significant: 588 (100–3260) to 252 (150–430) from 1996–2000 to 2006–2010. Mortality from P.falciparum malaria in pregnancy dropped sharply with the introduction of systematic screening and treatment and continued to decline with the reduction in the incidence of malaria in the communities. P.vivax was not a cause of maternal death in this population. Infection (non-puerperal sepsis and P.falciparum malaria) accounted for 39.7 (27/68) % of all deaths.

Conclusions

Frequent antenatal clinic screening allows early detection and treatment of falciparum malaria and substantially reduces maternal mortality from P.falciparum malaria. No significant decline has been observed in deaths from sepsis or other causes in refugee and migrant women on the Thai–Myanmar border.     

Validation of a new method for testing provider clinical quality in rural settings in low- and middle-income countries: the observed simulated patient

Background

Assessing the quality of care provided by individual health practitioners is critical to identifying possible risks to the health of the public. However, existing assessment methods can be inaccurate, expensive, or infeasible in many developing country settings, particularly in rural areas and especially for children. Following an assessment of the strengths and weaknesses of the existing methods for provider assessment, we developed a synthesis method combining components of direct observation, clinical vignettes, and medical mannequins which we have termed “Observed Simulated Patient” or OSP. An OSP assessment involves a trained actor playing the role of a ‘mother’, a life-size doll representing a 5-year old boy, and a trained observer. The provider being assessed was informed in advance of the role-playing, and told to conduct the diagnosis and treatment as he normally would while verbally describing the examinations.

Methodology/Principal Findings

We tested the validity of OSP by conducting parallel scoring of medical providers in Myanmar, assessing the quality of their diagnosis and treatment of pediatric malaria, first by direct observation of true patients and second by OSP. Data were collected from 20 private independent medical practitioners in Mon and Kayin States, Myanmar between December 26, 2010 and January 12, 2011. All areas of assessment showed agreement between OSP and direct observation above 90% except for history taking related to past experience with malaria medicines. In this area, providers did not ask questions of the OSP to the same degree that they questioned real patients (agreement 82.8%).

Conclusions/Significance

The OSP methodology may provide a valuable option for quality assessment of providers in places, or for health conditions, where other assessment tools are unworkable.     

Rho GTPase controls invagination and cohesive migration of the Drosophila salivary gland through Crumbs and Rho-kinase

Coordinated cell movements shape simple epithelia into functional tissues and organs during embryogenesis. Regulators and effectors of the small GTPase Rho have been shown to be essential for epithelial morphogenesis in cell culture; however, the mechanism by which Rho GTPase and its downstream effectors control coordinated movement of epithelia in a developing tissue or organ is largely unknown. Here, we show that Rho1 GTPase activity is required for the invagination of Drosophila embryonic salivary gland epithelia and for directed migration of the internalized gland. We demonstrate that the absence of zygotic function of Rho1 results in the selective loss of the apical proteins, Crumbs (Crb), Drosophila atypical PKC and Stardust during gland invagination and that this is partially due to reduced crb RNA levels and apical localization. In parallel to regulation of crb RNA and protein, Rho1 activity also signals through Rho-kinase (Rok) to induce apical constriction and cell shape change during invagination. After invagination, Rho-Rok signaling is required again for the coordinated contraction and dorsal migration of the proximal half of the gland. We also show that Rho1 activity is required for proper development of the circular visceral mesoderm upon which the gland migrates. Our genetic and live-imaging analyses provide novel evidence that the proximal gland cells play an essential and active role in salivary gland migration that propels the entire gland to turn and migrate posteriorly.     

Studies of iron-uptake mechanisms in two bacterial species of the shewanella genus adapted to middle-range (Shewanella putrefaciens) or antarctic (Shewanella gelidimarina) temperatures

Iron(III)-uptake mechanisms in bacteria indigenous to the Antarctic, which is the most Fe-deficient continent on Earth, have not been extensively studied. The cold-adapted, Antarctic bacterium, Shewanella gelidimarina, does not produce detectable levels of the siderophore, putrebactin, in the supernatant of Fe(III)-deprived cultures. This is distinct from the putrebactin-producing bacterium from the same genus, Shewanella putrefaciens, which is adapted to middle-range temperatures. The production of putrebactin by S. putrefaciens is optimal, when the pH value of the medium is 7.0. According to the strong positive response from whole cells in the Chrome Azurol S (CAS) agar diffusion assay, Shewanella gelidimarina appears to produce cell-associated siderophores. In the RP-HPLC trace of an Fe(III)-loaded extract from the cell-associated components of S. gelidimarina cultured in media with [Fe(III)] ca. 0 microM, a peak appears at [MeCN] ca. 77%, which decreases in intensity in a parallel experiment in which [Fe(III)] ca. 5 microM, and is barely detectable in Fe(III)-replete media ([Fe(III)] ca. 20 microM). The Fe(III)-dependence of this peak suggests that the attendant species, which is significantly more hydrophobic than putrebactin (RP-HPLC elution: [MeCN] ca. 14%), is associated with Fe(III)-management in S. gelidimarina. This study highlights the diversity in Fe(III)-uptake mechanisms in Shewanella species adapted to different environmental and thermal niches.     

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients

BackgroundThis study aimed to evaluate short term clinical outcomes of accelerated hypofractionated radiotherapy (AHR T) regarding locoregional response (LRR), symptoms relief and acute toxicities in non-small cell lung cancer (NSCLC) patients. The radical treatment for inoperable NSCLC is intolerable for some patients. An alternative RT regime should be considered for them.Materials and methodsInoperable NSCLC patients who could not tolerate radical treatment were treated with AHRT (45 Gy in 15 fractions over three weeks) by using the 3-dimensional conformal (RT) technique. The LRR was assessed by chest computed tomography (CT) performed before and 6 weeks after RT. Relief of symptoms such as cough, dyspnoea and chest pain was evaluated during RT and 6 and 12 weeks after RT, compared with the status before RT. Treatment-related acute toxicities such as dysphagia and radiation dermatitis were observed during and 6 and 12 weeks after RT.ResultsTotal 65 patients (seven patients of stage II and fifty-eight patients of stage III) were included. Partial response was seen in 70.8% of patients, and stable disease was seen in 29.2% while there was neither complete response nor progressive disease after RT. Statistically significant associations were found between tumour response vs. pre-treatment tumour size and tumour response vs. performance status of the patients. Satisfactory symptom relief was found after RT, but severe acute dysphagia and radiation dermatitis (more than grade 3) were not observed.ConclusionSatisfactory LRR, symptom relief and acute toxicities were achieved by this regime. Long term studies are recommended to evaluate late toxicities and survival outcome further.Trial registration noTCTR20200110001     

Neuroscience goes on a chip

Advances in microelectronics, microfluidics, polymers and microfabrication have enabled the creation of disposable lab-on-a-chips (LOCs) as the new tools for neuroscience research. The LOCs have been applied for a wide range of neurobiology studies, including cellular and molecular biochemical experimentations, morphological observations and electrophysiological investigations. The integration of miniaturised components leads to analytical instrumentations with unprecedented automation, speed of analysis, and flexibility. These features make LOCs capable enough to replace their bulky and expensive bench-top counterparts. LOCs can be useful for genomic, proteomic, epigenomic, peptidomic, connectomic and electrophysiological studies and also as effective tools for reductionist neuroscientists. Moreover, they can be applied at higher level studies such as developmental neurobiology and behavioural investigations. This work provides an in-depth review of LOC platforms for neuroscience research. First, we review the essential bench-top neuroscience instrumentation as per their functions and features. Next, we present LOC counterparts for those bench-top instrumentations. Finally, we offer perspectives on persistent challenges and our perception of opportunities based on LOC instrumentations in neuroscience research.     

Dermatoglyphics of Down's syndrome patients in Malays--a comparative study

There has been no recent report on the dermatoglyphics of the Malays (normal population as well as patients with Down's syndrome). A study on the frequencies of the dermal patterns (dermatoglyphics) of the digits, palms and hallucal areas was done therefore in 40 Malay patients with Down's syndrome and 200 unrelated normal controls. Only the patients with the standard 21 trisomy karyotype were included in the study. Comparison was made with the published data on studies done in various racial groups. Significant differences of the dermal patterns were found not only between the controls but also among patients of different races.     

An Endocytosed TGN38 Chimeric Protein Is Delivered to the TGN after Trafficking through the Endocytic Recycling Compartment in CHO Cells

To examine TGN38 trafficking from the cell surface to the TGN, CHO cells were stably transfected with a chimeric transmembrane protein, TacTGN38. We used fluorescent and ¹²⁵I-labeled anti-Tac IgG and Fab fragments to follow TacTGN38''s postendocytic trafficking. At steady-state, anti-Tac was mainly in the TGN, but shortly after endocytosis it was predominantly in early endosomes. 11% of cellular TacTGN38 is on the plasma membrane. Kinetic analysis of trafficking of antibodies bound to TacTGN38 showed that after short endocytic pulses, 80% of internalized anti-Tac returned to the cell surface (t _1/2 = 9 min), and the remainder trafficked to the TGN. When longer filling pulses and chases were used to load anti-Tac into the TGN, it returned to the cell surface with a t _1/2 of 46 min. Quantitative confocal microscopy analysis also showed that fluorescent anti-Tac fills the TGN with a 46-min t _1/2. Using the measured rate constants in a simple kinetic model, we predict that 82% of TacTGN38 is in the TGN, and 7% is in endosomes. TacTGN38 leaves the TGN slowly, which accounts for its steady-state distribution despite the inefficient targeting from the cell surface to the TGN.     

Effects of pH indicators on various activities of chromatophroes of Rhodospirillum rubrum.

1. The effects of pH indicators on activities for ATP hydrolysis in the dark and ATP-Pi exchange in the dark were examined with chromatophores from Rhodospirillum rubrum. Of thirty-one pH indicators tested, eleven (metanil yellow, 2, 4-dinitrophenol, ethyl orange, bromocresol green, resazurin, neutral red, bromthymol blue, alpha-naphtholphthalein, o-cresolphthalein, phenolphthalein, and alizarin yellow G) almost completely inhibited the activities for ATP formation and ATP-Pi exchange at concentrations of 1 mM, and were studied in detail. 2. Of the eleven pH indicators, those other than alpha-naptholphthalein, o-cresolphthalein and phenolphthalein, when assayed at appropriate concentrations, inhibited ATP-Pi exchange, but not ATP hydrolysis. In ATP-Pi exchange, these eight pH indicators at the concentrations described above were competitive against Pi, and non-competitive against ATP. The remaining three kinds of pH indicators were non-competitive against either Pi or ATP, when assayed at concentrations of the dyes that inhibited both activities. 3. The amounts of pH indicators bound with chromatophores were measured. No correlation was found between the amounts of the bound dyes and the extents of their inhibition of either ATP formation or ATP-Pi exchange. 4. Ethyl orange (pKa=4.1) and 2, 4-dinitrophenol (pKa=3.9) stimulated ATP hydrolysis to the greatest extent. The latter dye was hardly bound with chromatophores. 5. The stimulatory effects of pH indicators on ATP hydrolysis were hardly affected by extraction of quinones from chromatophores. 6. Most of the pH indicators stimulated both succinate-cytochrome c2 and NADH-cytochrome c2 reductions in the dark. 7. The mechanism of uncoupling of the electron transfer system and the phosphorylation system by pH indicators and the mechanism of the coupling are discussed.