DNA barcoding of herbal supplements on the US commercial market associated with the purported treatment of COVID-19.

INTRODUCTION: The COVID-19 pandemic was associated with an increased global use of traditional medicines, including Ayurvedic herbal preparations. Due to their growing demand, their processed nature, and the complexity of the global supply chain, there is an increased risk of adulteration in these products. OBJECTIVES: The objective of this study was to assess the use of DNA barcoding for species identification in herbal supplements on the US market associated with the Ayurvedic treatment of respiratory symptoms. METHODS: A total of 54 commercial products containing Ayurvedic herbs were tested with four DNA barcoding regions (i.e., rbcL, matK, ITS2, and mini-ITS2) using two composite samples per product. Nine categories of herbs were targeted: amla, ashwagandha, cinnamon, ginger, guduchi, tribulus, tulsi, turmeric, and vacha. RESULTS: At least one species was identified in 64.8% of products and the expected species was detected in 38.9% of products. Undeclared plant species, including other Ayurvedic herbs, rice, and pepper, were detected in 19 products, and fungal species were identified in 12 products. The presence of undeclared plant species may be a result of intentional substitution or contamination during harvest or processing, while fungal DNA was likely associated with the plant material or the growing environment. The greatest sequencing success (42.6-46.3%) was obtained with the matK and rbcL primers. CONCLUSION: The results of this study indicate that a combination of genetic loci should be used for DNA barcoding of herbal supplements. Due to the limitations of DNA barcoding in identification of these products, future research should incorporate chemical characterization techniques.

Assessing the dynamics of CO adsorption on Cu(110) using the vdW-DF2 functional and artificial neural networks.

In this work, we revisit the dynamics of carbon monoxide molecular chemisorption on Cu(110) by using quasi-classical trajectory calculations. The molecule-surface interaction is described through an atomistic neural network approach based on Density Functional Theory calculations using a nonlocal exchange-correlation (XC) functional that includes the effect of long-range dispersion forces: vdW-DF2 [Lee et al. Phys. Rev. B, 82, 081101 (2010)]. With this approach, we significantly improve the agreement with experiments with respect to a similar previous study based on a semi-local XC functional. In particular, we obtain excellent agreement with molecular beam experimental data concerning the dependence of the initial sticking probability on surface temperature and impact energy at normal incidence. For off-normal incidence, our results also reproduce two trends observed experimentally: (i) the preferential sticking for molecules impinging parallel to the [1̄10] direction compared to [001] and (ii) the change from positive to negative scaling as the impact energy increases. Nevertheless, understanding the origin of some remaining quantitative discrepancies with experiments requires further investigations.

Labeling compliance and online claims for Ayurvedic herbal supplements on the U.S. market associated with the purported treatment of COVID-19.

During the COVID-19 pandemic, many consumers increased their use of supplements that claimed to support immune health, including Ayurvedic preparations. The goal of this study was to analyze labeling compliance and online claims for Ayurvedic herbal supplements associated with the purported treatment of COVID-19. The physical product labels for 51 herbal supplements labeled as ginger, tulsi/holy basil, amla, vacha/calamus root, guduchi/giloy, cinnamon, ashwagandha, tribulus, or turmeric were assessed for U.S. regulatory compliance. Disease claims, structure/function claims, and general well-being claims were also examined. The online listings for products purchased online (n = 42) were examined for claims and for the presence of the required legal disclaimer. Collectively, 61% of products had at least one instance of noncompliance on the physical label. The most common violations included missing/noncompliant disclaimer (33%), noncompliant "Supplement Facts" label (29%), noncompliant statement of identity (27%) and noncompliant domestic mailing address or phone number (25%). Structure/function claims occurred more frequently in the online product listings (average of 5 claims per product) compared to the physical labels (average of 2 claims per product). Disease claims were observed for 38% of online product listings and on 8% of physical labels. The use of disease claims on herbal supplements is a significant concern for public health because it may lead consumers to delay seeking professional treatment for life-threatening diseases. Overall, this study revealed a lack of labeling compliance among Ayurvedic herbal supplements and a need for greater scrutiny and monitoring of online product listings.

Mathematical assessment of the impact of human-antibodies on sporogony during the within-mosquito dynamics of Plasmodium falciparum parasites.

We develop and analyze a deterministic ordinary differential equation mathematical model for the within-mosquito dynamics of the Plasmodium falciparum malaria parasite. Our model takes into account the action and effect of blood resident human-antibodies, ingested by the mosquito during a blood meal from humans, in inhibiting gamete fertilization. The model also captures subsequent developmental processes that lead to the different forms of the parasite within the mosquito. Continuous functions are used to model the switching transition from oocyst to sporozoites as well as human antibody density variations within the mosquito gut are proposed and used. In sum, our model integrates the developmental stages of the parasite within the mosquito such as gametogenesis, fertilization and sporogenesis culminating in the formation of sporozoites. Quantitative and qualitative analyses including a sensitivity analysis for influential parameters are performed. We quantify the average sporozoite load produced at the end of the within-mosquito malaria parasite's developmental stages. Our analysis shows that an increase in the efficiency of the ingested human antibodies in inhibiting fertilization within the mosquito's gut results in lowering the density of oocysts and hence sporozoites that are eventually produced by each mosquito vector. So, it is possible to control and limit oocysts development and hence sporozoites development within a mosquito by boosting the efficiency of antibodies as a pathway to the development of transmission-blocking vaccines which could potentially reduce oocysts prevalence among mosquitoes and hence reduce the transmission potential from mosquitoes to human.

Atrial matrix remodeling in atrial fibrillation patients with aortic stenosis.

BACKGROUND: This study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. METHODS: A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to aortic valve replacement surgery in a tertiary hospital were selected. RESULTS: Fibrosis was significantly increased in the AF group when compared to sinus rhythm (SR) patients (p = 0.024). Moreover, cardiomyocyte area was significantly higher in AF patients versus SR patients (p = 0.008). Conversely, collagen III gene expression was increased in AF patients (p = 0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p = 0.006). TIMP1 (p = 0.004) and TIMP2 (p = 0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p = 0.0159) and mean (p = 0.031) gradients demonstrated a negative association with serum TIMP1. CONCLUSIONS: Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.

On a three-stage structured model for the dynamics of malaria transmission with human treatment, adult vector demographics and one aquatic stage.

A modelling framework that describes the dynamics of populations of the female Anopheles sp mosquitoes is used to develop and analyse a deterministic ordinary differential equation model for dynamics and transmission of malaria amongst humans and varying mosquito populations. The framework includes a characterization of the gonotrophic cycle of the female mosquito. The epidemiological model also captures a novel feature whereby treated human's blood can become mosquitocidal to the questing mosquitoes upon the successful ingestion of the treated human's blood. Analysis of the disease free system, that is the model in the absence of infection in the human and mosquito populations, reveals the presence of a basic offspring number, N, whose size determines the existence and stability of a thriving mosquito population in the sense that when N≤1 we have only the mosquito extinction steady state which is globally asymptotically stable, while for N > 1 we have the persistent mosquito population steady state which is also globally asymptotically stable for these range of values of N. In the presence of disease, N still strongly affects the properties of the epidemiological model in the sense that for N≤1 the only steady state for the system is the mosquito extinction steady state, which is globally and asymptotically stable. As N increases beyond unity in the epidemiological model, we obtained the epidemiological basic reproduction number, R0. For R0 < 1, the disease free equilibrium, with both healthy thriving susceptible human and mosquito populations, is globally asymptotically stable. Both N and R0 are studied for control purposes and our study highlights that multiple control schemes would have a stronger impact on reducing both N and R0 to values small enough for a possible disease vector control and disease eradication. Our model further illustrates that newly emerged mosquitoes that are infected with the malaria parasite during their first blood meal play an important and strong role in the malaria disease dynamics. Additionally, mosquitoes at later gonotrophic cycle stages also impact the dynamics but their contributions to the total mosquito population size decreases with increasing number of gonotrophic cycles. The size of the contribution into the young mosquito population is also dependent on the length of the gonotrophic cycles, an important bionomic parameter, as well as on how the mosquitoes at the final gonotrophic cycles are incorporated into the modelling scheme.

The Impact of Recruitment on the Dynamics of an Immune-Suppressed Within-Human-Host Model of the Plasmodium falciparum Parasite.

A model is developed and used to study within-human malaria parasite dynamics. The model integrates actors involved in the development-progression of parasitemia, gametocytogenesis and mechanisms for immune response activation. Model analyses under immune suppression reveal different dynamical behaviours for different healthy red blood cell (HRBC) generation functions. Existence of a threshold parameter determines conditions for HRBCs depletion. Oscillatory dynamics reminiscent of malaria parasitemia are obtained. A dependence exists on the type of recruitment function used to generate HRBCs, with complexities observed for a more nonlinear function. An upper bound that delimits the size of feasible parasitized steady-state solution exists for a logistic function but not a constant function. The upper bound is completely characterized and is affected by parameters associated with HRBCs recruitment, parasitized red blood cells generation and the release and time-to-release of free merozoites. A stable density size for mature gametocytes, the bridge to invertebrate hosts, is derived.

Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance.

We develop an age-structured ODE model to investigate the role of intermittent preventive treatment (IPT) in averting malaria-induced mortality in children, and its related cost in promoting the spread of antimalarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to reduce malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spread. Our mathematical model is used to explore IPT effects on drug resistance and deaths averted in holoendemic malaria regions. The model includes drug-sensitive and drug-resistant strains as well as human hosts and mosquitoes. The basic reproduction, and invasion reproduction numbers for both strains are derived. Numerical simulations show the individual and combined effects of IPT and treatment of symptomatic infections on the prevalence of both strains and the number of lives saved. Our results suggest that while IPT can indeed save lives, particularly in high transmission regions, certain combinations of drugs used for IPT and to treat symptomatic infection may result in more deaths when resistant parasite strains are circulating. Moreover, the half-lives of the treatment and IPT drugs used play an important role in the extent to which IPT may influence spread of the resistant strain. A sensitivity analysis indicates the model outcomes are most sensitive to the reduction factor of transmission for the resistant strain, rate of immunity loss, and the natural clearance rate of sensitive infections.

Correction to: Satellite Images Combined with Field Data Reveal Negative Changes in the Distribution of Babassu Palms after Clearing off Amazonian Forests.

The original article has been corrected.

Satellite Images Combined with Field Data Reveal Negative Changes in the Distribution of Babassu Palms after Clearing off Amazonian Forests.

When the Amazonian rain forest is cut to create pasture, some of the original vegetal species survive clearing, even expressing their ability to invade agro-systems. It is true of the babassu palm, which can be considered, paradoxically, a natural resource by the "Interstate Movement of Babassu Fruit Breaker Women" or as native weed by land owners-farmers. To manage potential conflict of land uses, we study here the current density of this palm tree in different habitats, based on a combination of field data and remote sensing data. Firstly, we checked that the field survey methodology (i.e., counting free-trunk palm trees over 20 cm in circumference) provides density values compatible with those stemming from satellite images interpretation. We can see then that, a PA-Benfica Brazilian territory revealed an average density of the babassu lower in pastures (2.86 ind/ha) than in the dense forest (4.72 ind/ha) from which they originate and than in fallow land (4.31 ind/ha). We analyze in detail density data repartition in three habitats and we discuss results from the literature on the density of this palm tree versus its resilience at different developmental stages after forest clearing, depending on anthropogenic-or not-factors, including solar radiation, fire, weeding, clear cutting, burying fruit, and competition with forage grass. All these results can be exploited for the design of future management plans for the babassu palm and we think that the linked methodology and interdisciplinary approach can be extended to others palms and trees species in similar problematic issues.

Evolutionary implications for the determination of gametocyte sex ratios under fecundity variation for the malaria parasite.

We investigate sex ratio determination strategies for the Malaria parasite based on putative changes in its male fecundity over the lifetime of an infection, and how such strategies might have evolved. We model fitness using the incomplete fertilization limit developed in Teboh-Ewungkem and Yuster (2010). We divide the infection lifetime of a strain into two periods, assume each human is infected by two different strains, and assume that there are two different strategies present among the many strains in the general malaria parasite population. A unique parameter dependent ESS exists for all parameter values in both of our main models, with many such strategies unbeatable. These strategies produce both male and female biased population sex ratios with female bias predominating over most of the parameter space. The first model (SKM) suggests that strains without the ability to detect characteristics of other strains present could still have evolved strategies to vary sex ratio over their lifetimes, and the second model (DKM) suggests strains with detection abilities might have evolved after that. Our analysis suggests that once the ability to detect the population sizes and fecundities of other strains has developed, detection of their sex ratio choices confers no additional selective advantage in that a DKM ESS is still an ESS among sex ratio detecting strategies. The sex ratio choices for each DKM ESS are given by the equilibrium values of the parameter equivalent sex ratio detecting strategy described in Teboh-Ewungkem and Wang (2012), in the case where two strains employing that strategy encounter each other.

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

AIMS: To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. METHODS AND RESULTS: Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. CONCLUSIONS: Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. SIGNIFICANCE AND IMPACT OF THE STUDY: These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV.

Distribution and Sources of Petroleum Hydrocarbons in Recent Sediments of the Imo River, SE Nigeria.

The distribution of aliphatic and aromatic hydrocarbons in surface sediments of the lower course of the Imo River (Nigeria) was investigated to determine the sources and fate of these compounds. The aliphatic fraction is characterized by a widespread contribution of highly weathered/biodegraded hydrocarbon residues (reflected in the absence of prominent n-alkane peaks coupled with the presence of 17α(H),21ß(H)-25-norhopane, an indicator of heavy hydrocarbon biodegradation) of Nigerian crude oils (confirmed by the occurrence of 18α(H)-oleanane, a compound characteristic of oils of deltaic origin). The concentrations of polycyclic aromatic hydrocarbons (PAHs) ranging from 48 to 117 ng/g dry weight (dw; ∑13PAHs) indicate a moderate pollution, possibly lowered by the sandy lithology and low organic carbon (OC) content of the sediments. Concentrations slightly decrease towards the estuary of the river, probably due to the fact that these stations are affected by tidal flushing of pollutants adsorbed on sediment particles and carried away by occasional storm to the Atlantic Ocean. A number of PAH ratios, including parent/alkylated and isomeric compounds, indicates a predominance of petrogenic sources, with a low contribution of pyrolytic inputs, particularly of fossil fuel combustion. On the basis of OC/ON (>10) and Per/ΣPAHpenta- (>10) values, a diagenetic terrigenous OC was proposed as a source of perylene to the river.

Risk assessment of human exposure to polycyclic aromatic hydrocarbons via shrimp (Macrobrachium felicinum) consumption along the Imo River catchments, SE Nigeria.

Shrimp species (Macrobrachium felicinum) collected from estuarine mangrove area of the Imo River is an important route of exposure to polycyclic aromatic hydrocarbons (PAHs). The estuarine associated sediment (EAS) composited sample showed higher TPAH, ΣAlkyl, ΣPAHcarc and ΣPAHEPA concentrations (550.84, 172.36, 413.17 and 482.11 ng/g dry weight-dw) than their mean concentrations in shrimp samples (509.39 ± 354.21, 31.38 ± 18.49, 52.10 ± 1.35 and 460.06 ± 330.76 ng/g wet weight-ww), respectively. Among the individual PAHs congeners, phenanthrene was the dominant species detected in the EAS accounting for 21.02 % of the total PAH load and the decreasing order of 3- > 2- > 5- > 4- > 6-ring contamination was found. A different pattern predominated by naphthalene was observed for the shrimp species, suggesting that the organisms have different selectivity for a range of PAHs congeners. These variations may be attributed to different degree of bioavailability of these compounds, characteristic sandy lithology of the EAS and the protective capacity of soot particles associated with liquid fossil fuel combustion masking the uptake of high molecular weight PAHs by the organisms. Cancer risk associated with consumption of shrimps in the region was assessed using estimated daily intake (EDI) and compared with standards. The EDI values for naphthalene, benzo(a)pyrene and ∑PAHcarc were lower than the USEPA benchmarks and EFSA levels of concern values for adult and children population, suggesting low probability of developing cancer.

[Vascular interventional radiology: a fundamental procedure for the management of paediatric trauma]. / Radiología vascular intervencionista: un arma para el tratamiento del niño politraumatizado. Experiencia en un centro de Trauma Pediátrico.

INTRODUCTION: The management of active bleeding with haemodinamic lability in the paediatric trauma patient is difficult and generally leads to damage control surgery. Vascular Interventional Radiology (VIR) techniques are useful for the diagnosis as for the definitive treatment. AIM: The aim of our study was to describe our experience and evaluate effectiveness of VIR in the management of the paediatric trauma patient with active bleeding signs. METHODS: Retrospective analysis (2003-2014) of politraumatic patients who showed contrast blush on computed tomography and then treated by VIR techniques. RESULTS: In the reported study period 16 patients underwent VIR procedures. Medium age was 13 years (5-17). The most frequent lesion mechanism was traffic accident (8 out of 17) and 93,75% were blunt traumas. Findings on initial Computed Tomography were 12 contrast blushes and 2 absences of arterial flow. In 2 cases the contrast blush appeared 48 hours after the accident. Arteriography allowed us to localize the bleeding vessels in all the cases, performing selective or supraselective renal (7), pelvic (5), hepatic (3), splenic (1) and intercostal (1) embolization. One patient required an endoprothesis for renal revascularization. Two cases needed additional surgical procedures (2 nephrectomies) because of complete section of the renal artery (1) and disruption of the ureteropelvic junction (1). One case required hemofiltration in relation to rhabdomyolysis. CONCLUSION: In our experience VIR is a valuable diagnostic and therapeutic procedure for the management of paediatric trauma patients, with high effectiveness and a low complication rate.

INTRODUCCION: El tratamiento del sangrado activo en niños politraumatizados con labilidad hemodinámica es difícil y generalmente obliga a realizar una cirugía de control de daños. La aplicación de técnicas de Radiología Vascular Intervencionista (RVI) ayuda al diagnóstico y tratamiento definitivo. OBJETIVO: Describir nuestra experiencia y valorar la eficacia de la RVI en el tratamiento del paciente traumático pediátrico con signos de sangrado activo. MATERIAL Y METODO: Análisis retrospectivo (2003-2014) de los pacientes politraumatizados tratados mediante RVI en los cuales la AngioTC mostraba fuga de contraste o ausencia de captación. RESULTADOS: En el periodo de estudio se trataron 16 pacientes, con una media de edad de 13 años (5-17). El mecanismo lesional más frecuente fue el accidente de tráfico. El 93,75% fueron traumatismos cerrados. Los hallazgos de la angioTC inicial fueron 12 sangrados activos, 2 ausencias de flujo arterial. Dos sangrados se produjeron a las 48 horas del trauma. La arteriografía permitió localizar los vasos sangrantes, realizándose embolización selectiva o supraselectiva a nivel renal (7), pélvico (5), hepático (3), esplénico (1) e intercostal (1). Un paciente preciso revascularización renal con endoprótesis. Un paciente requirió nefrectomía urgente tras la angiografía por avulsión arterial completa y en 1 caso se realizó nefrectomía a las 48 horas por fuga de contraste y disrupción de la unión pieloureteral. En un caso se observó rabdomiólisis como complicación que requirió hemofiltración. CONCLUSION: La RVI constituye un procedimiento diagnóstico y terapéutico en el abordaje del paciente pediátrico traumático, con alta efectividad y escasas complicaciones, siendo una herramienta fundamental en un centro de trauma pediátrico.

Mathematical assessment of the effect of traditional beliefs and customs on the transmission dynamics of the 2014 Ebola outbreaks.

BACKGROUND: Ebola is one of the most virulent human viral diseases, with a case fatality ratio between 25% to 90%. The 2014 West African outbreaks are the largest and worst in history. There is no specific treatment or effective/safe vaccine against the disease. Hence, control efforts are restricted to basic public health preventive (non-pharmaceutical) measures. Such efforts are undermined by traditional/cultural belief systems and customs, characterized by general mistrust and skepticism against government efforts to combat the disease. This study assesses the roles of traditional customs and public healthcare systems on the disease spread. METHODS: A mathematical model is designed and used to assess population-level impact of basic non-pharmaceutical control measures on the 2014 Ebola outbreaks. The model incorporates the effects of traditional belief systems and customs, along with disease transmission within health-care settings and by Ebola-deceased individuals. A sensitivity analysis is performed to determine model parameters that most affect disease transmission. The model is parameterized using data from Guinea, one of the three Ebola-stricken countries. Numerical simulations are performed and the parameters that drive disease transmission, with or without basic public health control measures, determined. Three effectiveness levels of such basic measures are considered. RESULTS: The distribution of the basic reproduction number ([Formula: see text]) for Guinea (in the absence of basic control measures) is such that [Formula: see text], for the case when the belief systems do not result in more unreported Ebola cases. When such systems inhibit control efforts, the distribution increases to [Formula: see text]. The total Ebola cases are contributed by Ebola-deceased individuals (22%), symptomatic individuals in the early (33%) and latter (45%) infection stages. A significant reduction of new Ebola cases can be achieved by increasing health-care workers' daily shifts from 8 to 24 hours, limiting hospital visitation to 1 hour and educating the populace to abandon detrimental traditional/cultural belief systems. CONCLUSIONS: The 2014 outbreaks are controllable using a moderately-effective basic public health intervention strategy alone. A much higher (>50%) disease burden would have been recorded in the absence of such intervention. 2000 Mathematics Subject Classifications 92B05, 93A30, 93C15.

Persistent oscillations and backward bifurcation in a malaria model with varying human and mosquito populations: implications for control.

We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number Rm, and the disease basic reproduction number R0, whose size can be reduced by reducing Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito's demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of Rm and R0, threshold quantities to be taken into consideration when designing control strategies. Both Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito's birth constant λm and the mosquito's feeding success probability pw. Control of λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter R0 is shown to be highly sensitive to pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes.

Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species.

Candida invasive infections have increased in frequency during the last decades. Such infections are often associated to medical indwelling devices like central venous catheter. The recurrent nature and difficulties in the treatment of these infections are often related to biofilm formation. The objective of this study was to investigate the anti-biofilm activity of low-molecular weight chitosan hydrogel (LMWCH), a natural biopolymer obtained from the N-deacylation of crustacean chitin, upon clinical relevant Candida species. The in vitro ability of LMWCH to impair biofilm formation and to disorganize a preformed biofilm was tested in polystyrene microplates and quantified by the semi quantitative XTT assay and by the crystal violet assay. LMWCH in vivo efficacy as a coating for medical indwelling devices was evaluated for the first time for Candida parapsilosis, using a mouse subcutaneous foreign body model using polyurethane catheter segments. Scanning electron microscopy was used to access biofilm architecture after LMWCH treatment. We found that LMWCH efficiently impaired biofilm formation of all Candida species, also promoting biofilm disaggregation. Most importantly, LMWCH was able to significantly inhibit biofilm formation by C. parapsilosis in an in vivo catheter mouse model. SEM images showed biofilm collapsed cells compatible with membrane damage, suggesting that this could be one of the possible mechanisms underlying biofilm impairment. LMWCH revealed to be a promising compound for treatment of candidiasis or its prevention through medical device coating.

The effect of intermittent preventive treatment on anti-malarial drug resistance spread in areas with population movement.

BACKGROUND: The use of intermittent preventive treatment in pregnant women (IPTp), children (IPTc) and infant (IPTi) is an increasingly popular preventive strategy aimed at reducing malaria risk in these vulnerable groups. Studies to understand how this preventive intervention can affect the spread of anti-malarial drug resistance are important especially when there is human movement between neighbouring low and high transmission areas. Because the same drug is sometimes utilized for IPTi and for symptomatic malaria treatment, distinguishing their individual roles on accelerating the spread of drug resistant malaria, with or without human movement, may be difficult to isolate experimentally or by analysing data. A theoretical framework, as presented here, is thus relevant as the role of IPTi on accelerating the spread of drug resistance can be isolated in individual populations and when the populations are interconnected and interact. METHODS: A previously published model is expanded to include human movement between neighbouring high and low transmission areas, with focus placed on the malaria parasites. Parasite fitness functions, determined by how many humans the parasites can infect, are used to investigate how fast resistance can spread within the neighbouring communities linked by movement, when the populations are at endemic equilibrium. RESULTS: Model simulations indicate that population movement results in resistance spreading fastest in high transmission areas, and the more complete the anti-malarial resistance the faster the resistant parasite will tend to spread through a population. Moreover, the demography of infection in low transmission areas tends to change to reflect the demography of high transmission areas. Additionally, when regions are strongly connected the rate of spread of partially resistant parasites (R1) relative to drug sensitive parasites (RS), and fully resistant parasites (R2) relative to partially resistant parasites (R1) tend to behave the same in both populations, as should be expected. CONCLUSIONS: In fighting anti-malarial drug resistance, different drug resistance monitoring and management policies are needed when the area in question is an isolated high or low transmission area, or when it is close and interacting with a neighbouring high or low transmission area, with human movement between them.

On a reproductive stage-structured model for the population dynamics of the malaria vector.

A reproductive stage-structured deterministic differential equation model for the population dynamics of the human malaria vector is derived and analysed. The model captures the gonotrophic and behavioural life characteristics of the female Anopheles sp. mosquito and takes into consideration the fact that for the purposes of reproduction, the female Anopheles sp. mosquito must visit and bite humans (or animals) to harvest necessary proteins from blood that it needs for the development of its eggs. Focusing on mosquitoes that feed exclusively on humans, our results indicate the existence of a threshold parameter, the vectorial reproduction number, whose size increases with increasing number of gonotrophic cycles, and is also affected by the female mosquito's birth rate, its attraction and visitation rate to human residences, and its contact rate with humans. A stability analysis of the model indicates that the mosquito can establish itself in the environment if and only if the value of the vectorial reproduction number exceeds unity and that mosquito eradication is possible if the vectorial reproduction number is less than unity, since, then, the trivial steady state which always exist is unique and is globally and asymptotically stable. When a persistent vector population steady state exists, it is locally and asymptotically stable for a range of reproduction numbers, but can also be driven to instability via a Hopf bifurcation as the reproduction number increases further away from unity. The model derivation identifies and characterizes control parameters relating to activities such as human-mosquito contact and the mosquito's survival chances between blood meals and egg laying. Our results show that the total mosquito population size increases with increasing number of gonotrophic cycles. Therefore understanding the fundamental aspects of the mosquito's behaviour provides a pathway for the study of human-mosquito contact and mosquito population control. Control of the mosquito population densities would ultimately lead to malaria control.