Contact allergens in African countries: A review of published patch test studies.

Only few studies on contact allergy in African countries have been published. The aim of the present study was to provide an overview of the most common contact allergens identified by the use of patch tests in African countries based on a review of the existing literature. A total of twenty-four publications from eight African countries were initially identified by search in PubMed. The abstracts and method sections were screened, and 15 studies in which patch tests were actually used to identify the allergen causing the allergic contact dermatitis (ACD) were finally selected. Nickel, cobalt, chromium, fragrance mix and p-tert-butylphenol-formaldehyde resin were the dominating contact allergens responsible for 40%-90% of the positive patch test reactions. This study indicates that a targeted effort directed towards prevention, avoidance and regulation of reliably identified contact allergens could reduce the disease burden of ACD considerable in some African countries.

Aerobic bacterial methane synthesis.

Reports of biogenic methane (CH4) synthesis associated with a range of organisms have steadily accumulated in the literature. This has not happened without controversy and in most cases the process is poorly understood at the gene and enzyme levels. In marine and freshwater environments, CH4 supersaturation of oxic surface waters has been termed the "methane paradox" because biological CH4 synthesis is viewed to be a strictly anaerobic process carried out by O2-sensitive methanogens. Interest in this phenomenon has surged within the past decade because of the importance of understanding sources and sinks of this potent greenhouse gas. In our work on Yellowstone Lake in Yellowstone National Park, we demonstrate microbiological conversion of methylamine to CH4 and isolate and characterize an Acidovorax sp. capable of this activity. Furthermore, we identify and clone a gene critical to this process (encodes pyridoxylamine phosphate-dependent aspartate aminotransferase) and demonstrate that this property can be transferred to Escherichia coli with this gene and will occur as a purified enzyme. This previously unrecognized process sheds light on environmental cycling of CH4, suggesting that O2-insensitive, ecologically relevant aerobic CH4 synthesis is likely of widespread distribution in the environment and should be considered in CH4 modeling efforts.

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. METHODS: Six months to fourteen years old children presenting with acute uncomplicated malaria (n = 115) were enrolled in two hospitals and a Health Centre in Ghana's Greater Accra region and treated with artemether-lumefantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. RESULTS: Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had > 10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with > 10% ring survival rates. CONCLUSIONS: The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.

An evaluation of the reading the mind in the eyes test's psychometric properties and scores in South Africa-cultural implications.

The 'Reading the Mind in the Eyes' test (RMET) has been translated and tested in many cultural settings. Results indicate that items show variability in meeting the original psychometric testing criteria. Individuals from non-Western cultures score differently on the RMET. As such, questions arise as to the cross-cultural validity of the RMET. This study tested the English version of the RMET, that consists almost exclusively of White faces, at a large South African university to determine its validity in a culturally diverse context. A total of 443 students from a range of different demographic backgrounds completed the instrument. Students were selected using simple random sampling. 30 out of the 36 items continued to show satisfactory psychometric properties. Further evidence shows significant differences based on race and home language in both overall scores and item level scores. Black race and African home language respondents show lower RMET scores and different item level perspectives on certain mental states. The current RMET is not inclusive. It requires stimuli reflecting more races and cultures. This lack of diversity is likely to be influencing and biasing results and psychometric properties. The continued exclusion of racial stimuli such as Black race is also promoting a systemic discriminatory instrument. These results have cultural implications for how we interpret and use the RMET.

In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria.

Severe malaria is mostly caused by Plasmodium falciparum, resulting in considerable, systemic inflammation and pronounced endothelial activation. The endothelium forms an interface between blood and tissue, and vasculopathy has previously been linked with malaria severity. We studied the extent to which the endothelial glycocalyx that normally maintains endothelial function is involved in falciparum malaria pathogenesis by using incident dark-field imaging in the buccal mucosa. This enabled calculation of the perfused boundary region, which indicates to what extent erythrocytes can permeate the endothelial glycocalyx. The perfused boundary region was significantly increased in severe malaria patients and mirrored by an increase of soluble glycocalyx components in plasma. This is suggestive of a substantial endothelial glycocalyx loss. Patients with severe malaria had significantly higher plasma levels of sulfated glycosaminoglycans than patients with uncomplicated malaria, whereas other measured glycocalyx markers were raised to a comparable extent in both groups. In severe malaria, the plasma level of the glycosaminoglycan hyaluronic acid was positively correlated with the perfused boundary region in the buccal cavity. Plasma hyaluronic acid and heparan sulfate were particularly high in severe malaria patients with a low Blantyre coma score, suggesting involvement in its pathogenesis. In vivo imaging also detected perivascular hemorrhages and sequestering late-stage parasites. In line with this, plasma angiopoietin-1 was decreased while angiopoietin-2 was increased, suggesting vascular instability. The density of hemorrhages correlated negatively with plasma levels of angiopoietin-1. Our findings indicate that as with experimental malaria, the loss of endothelial glycocalyx is associated with vascular dysfunction in human malaria and is related to severity.

Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx.

BACKGROUND: Plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. Endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. It was investigated if the cellular glycocalyx affects the binding of P. falciparum-infected erythrocytes to CD36 in vitro. METHODS: Glycocalyx growth was followed in vitro by using azido sugars and cationized ferritin detecting O-glycoproteins and negatively charged proteoglycans, respectively. P. falciparum (clone FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1-4 days after seeding was quantified by using a static binding assay. RESULTS: The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2-4 days. CONCLUSION: The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has previously been ignored. The previously reported loss of glycocalyx during experimental malaria may play an important role in the pathogenesis of malaria complications by allowing the close interaction between infected erythrocytes and endothelial receptors.

Crowdsourced 'R&D' and medical research.

INTRODUCTION OR BACKGROUND: Crowdsourced R&D, a research methodology increasingly applied to medical research, has properties well suited to large-scale medical data collection and analysis, as well as enabling rapid research responses to crises such as disease outbreaks. SOURCES OF DATA: Multidisciplinary literature offers diverse perspectives of crowdsourced R&D as a useful large-scale medical data collection and research problem-solving methodology. AREAS OF AGREEMENT: Crowdsourced R&D has demonstrated 'proof of concept' in a host of different biomedical research applications. AREAS OF CONTROVERSY: A wide range of quality and ethical issues relate to crowdsourced R&D. GROWING POINTS: The rapid growth in applications of crowdsourced R&D in medical research is predicted by an increasing body of multidisciplinary theory. AREAS FOR TIMELY RESEARCH: Further research in areas such as artificial intelligence may allow better coordination and management of the high volumes of medical data and problem-solving inputs generated by the crowdsourced R&D process.

Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania.

BACKGROUND: Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1-4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria. METHODS: Study participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay. RESULTS: Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria. CONCLUSION: Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings.

Hot springs viruses at Yellowstone National Park have ancient origins and are adapted to thermophilic hosts.

Geothermal springs house unicellular red algae in the class Cyanidiophyceae that dominate the microbial biomass at these sites. Little is known about host-virus interactions in these environments. We analyzed the virus community associated with red algal mats in three neighboring habitats (creek, endolithic, soil) at Lemonade Creek, Yellowstone National Park (YNP), USA. We find that despite proximity, each habitat houses a unique collection of viruses, with the giant viruses, Megaviricetes, dominant in all three. The early branching phylogenetic position of genes encoded on metagenome assembled virus genomes (vMAGs) suggests that the YNP lineages are of ancient origin and not due to multiple invasions from mesophilic habitats. The existence of genomic footprints of adaptation to thermophily in the vMAGs is consistent with this idea. The Cyanidiophyceae at geothermal sites originated ca. 1.5 Bya and are therefore relevant to understanding biotic interactions on the early Earth.

A Hybrid Anchoring Technology Composed of Reinforced Flexible Shells for a Knee Unloading Exosuit.

Soft robotic wearables have emerged as an ergonomic alternative to rigid robotic wearables, commonly utilizing tension-based actuation systems. However, their soft structure's natural tendency to buckle limits their use for compression bearing applications. This study presents reinforced flexible shell (RFS) anchoring, a compliant, low-profile, ergonomic wearable platform capable of high compression resistance. RFS anchors are fabricated with soft and semirigid materials that typically buckle under compressive loads. Buckling is overcome using the wearer's leg as a support structure, reinforcing the shells with straps, and minimizing the space between the shells and the wearer's skin-enabling force transmission orders of magnitude larger. RFS anchoring performance was evaluated comparatively by examining the shift-deformation profiles of three identically designed braces fabricated with different materials: rigid, strapped RFS, and unstrapped RFS. The unstrapped RFS severely deformed before 200 N of force could be applied. The strapped RFS successfully supported 200 N of force and exhibited a nearly identical transient shift-deformation profile with the rigid brace condition. RFS anchoring technology was applied to a compression-resistant hybrid exosuit, Exo-Unloader, for knee osteoarthritis. Exo-Unloader utilizes a tendon-driven linear sliding actuation system that unloads the medial and lateral compartments of the knee. Exo-Unloader can deliver 200 N of unloading force without deforming, as indicted by its similar transient shift-deformation profile with a rigid unloader baseline. Although rigid braces effectively withstand and transmit high compressive loads, they lack compliance; RFS anchoring technology expands the application of soft and flexible materials to compression-based wearable assistive systems.

Identification of Single-Nucleotide Polymorphisms in the Mitochondrial Genome and Kelch 13 Gene of Plasmodium falciparum in Different Geographical Populations.

The emergence of artemisinin-resistant Plasmodium falciparum parasites in Southeast Asia threatens malaria control and elimination. The interconnectedness of parasite populations may be essential to monitor the spread of resistance. Combining a published barcoding system of geographically restricted single-nucleotide polymorphisms (SNPs), mainly mitochondria of P. falciparum with SNPs in the K13 artemisinin resistance marker, could elucidate the parasite population structure and provide insight regarding the spread of drug resistance. We explored the diversity of mitochondrial SNPs (bp position 611-2825) and identified K13 SNPs from malaria patients in the districts of India (Ranchi), Tanzania (Korogwe), and Senegal (Podor, Richard Toll, Kaolack, and Ndoffane). DNA was amplified using a nested PCR and Sanger-sequenced. Overall, 199 K13 sequences (India: N = 92; Tanzania: N = 48; Senegal: N = 59) and 237 mitochondrial sequences (India: N = 93; Tanzania: N = 48; Senegal: N = 96) were generated. SNPs were identified by comparisons with reference genomes. We detected previously reported geographically restricted mitochondrial SNPs (T2175C and G1367A) as markers for parasites originating from the Indian subcontinent and several geographically unrestricted mitochondrial SNPs. Combining haplotypes with published P. falciparum mitochondrial genome data suggested possible regional differences within India. All three countries had G1692A, but Tanzanian and Senegalese SNPs were well-differentiated. Some mitochondrial SNPs are reported here for the first time. Four nonsynonymous K13 SNPs were detected: K189T (India, Tanzania, Senegal); A175T (Tanzania); and A174V and R255K (Senegal). This study supports the use of mitochondrial SNPs to determine the origin of the parasite and suggests that the P. falciparum populations studied were susceptible to artemisinin during sampling because all K13 SNPs observed were outside the propeller domain for artemisinin resistance.

Phylogeny and diversity of alkane-degrading enzyme gene variants in the laurentian great lakes and western atlantic.

Many aquatic environments are at risk for oil contamination and alkanes are one of the primary constituents of oil. The alkane hydroxylase (AlkB) is a common enzyme used by microorganisms to initiate the process of alkane-degradation. While many aspects of alkane bioremediation have been studied, the diversity and evolution of genes involved in hydrocarbon degradation from environmental settings is relatively understudied. The majority of work done to-date has focused on the marine environment. Here we sought to better understand the phylogenetic diversity of alkB genes across marine and freshwater settings using culture-independent methods. We hypothesized that there would be distinct phylogenetic diversity of alkB genes in freshwater relative to the marine environment. Our results confirm that alkB has distinct variants based on environment while our diversity analyses demonstrate that freshwater and marine alkB communities have unique responses to oil amendments. Our results also demonstrate that in the marine environment, depth is a key factor impacting diversity of alkB genes.

Photopic pupillometry-guided laser in situ keratomileusis for hyperopic presbyopia.

PURPOSE: To evaluate a method of surgically treating presbyopia in hyperopic patients having laser in situ keratomileusis (LASIK) by selecting excimer ablation optical zone diameters based on the photopic pupil. SETTING: Private practice, Beverly Hills, California, USA. METHODS: This prospective analysis comprised 46 patients having hyperopic LASIK for presbyopia. The distance-dominant eye was treated with a standard 6.0 mm optical and 9.0 mm outer zone for full distance correction with no nomogram adjustment from the final preoperative manifest refraction. In the nondominant eye, an algorithm was used to select the optical and blend zone diameters and the optical zone size-dependent programmed amount of correction augmentation. Variables evaluated at the 6-month postoperative visit included preoperative and postoperative manifest refractive spherical equivalent (MRSE), refractive cylinder, and monocular and binocular near and distance uncorrected visual acuities. Patient satisfaction and spectacle dependence were also evaluated. RESULTS: In the near-corrected eye, the mean preoperative and postoperative MRSE was +1.10 diopters (D) +/- 1.20 (SD) and -1.30 +/- 0.56 D, respectively, and the mean refractive cylinder, -0.76 +/- 0.91 D and -0.36 +/- 0.33 D, respectively (P<.05). The mean uncorrected near acuity in the near-corrected eye was J10 preoperatively and J1 postoperatively (P<.0001) and the binocular mean uncorrected near acuity, J10 and J1, respectively (P<.0001). The mean uncorrected logMAR distance acuity in the near-corrected eye was +0.38 +/- 0.31 (20/50) preoperatively and +0.36 +/- 0.25 (20/50) postoperatively (P>.05). The mean binocular uncorrected logMAR distance acuity was +0.30 +/- 0.30 (20/40) and +0.01 +/- 0.08 (20/20) (P<.0001), respectively. The mean overall patient satisfaction score was 8.8 (scale 1 to 10). After LASIK, no patient reported using spectacles full time for near or distance and 15% reported part-time use. CONCLUSION: Photopic pupillometry-guided LASIK may be an effective option when considering surgical treatment of presbyopia in hyperopic patients.

Mechanical modeling of fluid-driven polymer lenses.

A finite-element model (FEM) is employed to study the pressure response of deformable elastic membranes used as tunable optical elements. The model is capable of determining in situ both the modulus and the prestrain from a measurement of peak deflection versus pressure. Given accurate values for modulus and prestrain, it is shown that the two parameters of a standard optical shape function (radius of curvature and conic constant) can be accurately predicted. The effects of prestrain in polydimethylsiloxane (PDMS) membranes are investigated in detail. It was found that prestrain reduces the sensitivity of the membrane shape to the details of the edge clamping. It also reduces the variation of the conic constant with changes in curvature. Thus the ability to control the prestrain as well as thickness and modulus is important to developing robust optical designs based on fluid-driven polymer lenses.

Treatment options for anisohyperopia.

PURPOSE: To investigate the success of conventional methods in the treatment of anisohyperopic amblyopia. METHODS: A retrospective chart review of all patients with anisohyperopic amblyopia seen at the UCSD/ Ratner Children's Eye Center during a 42-month period was performed. The charts of 35 patients aged 3 to 14 years (mean age, 6.8 years) with 1.5 to 6.5 diopters of anisohyperopia were reviewed. Main outcome measures were the difference in refractive error and the pre- and post-treatment Snellen equivalent distance acuities. Treatment consisted of one or a combination of the following: spectacles, contact lenses, patching, and atropine. Binocularity was determined using the Titmus test. Compliance to treatment also was rated. RESULTS: Thirteen (37.1%) patients were treated with spectacles alone, 11 (31.5%) were treated with a combination of atropine and patching, 8 (22.8%) were treated with patching alone, 2 (5.7%) received blurring contact lenses, and 1 (2.9%) patient was treated with atropine alone. The average pretreatment visual acuity was 20/108, with an improvement to an average of 20/27 at the termination of treatment. Ninety-four percent of the patients obtained a visual acuity of 20/40 or better. CONCLUSIONS: Conventional methods of treatment are effective in improving vision and binocular status in anisohyperopia. Depending on the patient, only spectacles may be required.

Disaster management, crowdsourced R&D and probabilistic innovation theory: Toward real time disaster response capability.

General agreement exists effective disaster management faces constraints related to knowledge sharing and a need for real-time research responses. Extreme case examples of disasters especially vulnerable to these challenges are global pandemics, or disease outbreaks, in which data required for research response are only available after the start of an outbreak. This paper argues the developing field of probabilistic innovation (innovation increasing probability of solving societal problems through radically increasing coordination of volumes of problem-solving inputs and analysis), and its methodologies, such as those drawing from crowdsourced R&D and social media, may offer useful insights into enabling real time research capabilities, with important implications for disaster and crisis management. Three paradigms of disaster research are differentiated, as literature is related to theory offered by post normal science, Kuhnian 'normal science' and Lakatosian 'structural science,' and the goal of achieving real time research problem solving capacity in disaster crisis situations. Global collaborative innovation platforms and large-scale investments in emerging crowdsourced R&D and social media technologies together with synthesis of appropriate theory may contribute to improved real time disaster response and resilience across contexts, particularly in instances where data required to manage response is only available after disasters unfold.

Botulinum A toxin injection for restrictive myopathy of thyroid-related orbitopathy: effects on intraocular pressure.

PURPOSE: To study the effect of extraocular muscle injections of botulinum A toxin on intraocular pressure in patients with thyroid-related orbitopathy. DESIGN: Retrospective observational case series. METHODS: The medical records of eight consecutive patients with restrictive myopathy secondary to thyroid related orbitopathy (TRO) who underwent botulinum A toxin injection from December 1997 to December 1998 were reviewed and analyzed retrospectively. All patients were seen at the University of California, San Diego (UCSD) Thyroid Eye Center, a university-based tertiary referral center. The main outcome measure was intraocular pressure (IOP) readings taken before and after injection in both primary gaze and upgaze (involving one eye in seven of the patients and both eyes in one patient). Intraocular pressure readings were measured by an unmasked physician using a Goldmann applanation tonometer. RESULTS: A statistically significant decrease in IOP in upgaze was noted 2 to 6 weeks following botulinum A toxin injection and in both fields of gaze (primary and upgaze) after 2 to 4 months. The mean IOP before injection was 21.4 +/- 3.0 mm Hg in primary gaze and 29.9 +/- 9.7 mm Hg in upgaze. The mean IOP, following injection at 2 to 6 weeks, was 19.2 +/- 4.2 mm Hg (P <.095) in primary gaze and 25.1 +/- 5.9 mm Hg (P <.023) in upgaze. At 2 to 4 months following injection, the mean IOP was 19.3 +/- 3.9 mm Hg (P <.044) in primary gaze and 27.7 +/- 8.5 mm Hg (P <.024) in upgaze. Six patients indicated improved ocular deviation, which was associated with a lowering of IOP. Two patients indicated no change in IOP or strabismic deviation following botulinum A toxin injection. CONCLUSIONS: Botulinum A toxin injections cause a secondary effect to lower IOP in patients with restrictive strabismus associated with thyroid-related orbitopathy.

Vision testing in the pediatric population.

The goal of office testing of the child remains the same as it is for the adult--to gather as much information as efficiently as possible. Clinical testing of the child requires familiarity with the limitations available tests. Perhaps most important is the ability choose the proper test to use at every development stage. Cooperation may be surprisingly good in to hands of experienced examiners, though very young children can be unpredictable. The general ophthalmologist should not fear having young patients but rather take joy in the interaction with them. Armed with as many tools as possible, the challenge of testing children can be converted to the reward of helping families.