Changes in metabolic phenotypes of Plasmodium falciparum in vitro cultures during gametocyte development.

BACKGROUND: Gametocytes are the Plasmodium life stage that is solely responsible for malaria transmission. Despite their important role in perpetuating malaria, gametocyte differentiation and development is poorly understood. METHODS: To shed light on the biochemical changes that occur during asexual and gametocyte development, metabolic characterization of media from in vitro intra-erythrocytic Plasmodium falciparum cultures was performed throughout gametocyte development by applying 1H nuclear magnetic spectroscopy, and using sham erythrocyte cultures as controls. Spectral differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods. RESULTS: Clear parasite-associated changes in metabolism were observed throughout the culture period, revealing differences between asexual parasites and gametocyte stages. With culture progression and development of gametocytes, parasitic release of the glycolytic end products lactate, pyruvate, alanine, and glycerol, were found to be dramatically reduced whilst acetate release was greatly increased. Also, uptake of lipid moieties CH(2), CH(3), and CH = CH-CH(2)-CH(2) increased throughout gametocyte development, peaking with maturity. CONCLUSIONS: This study uniquely presents an initial characterization of the metabolic exchange between parasite and culture medium during in vitro P. falciparum gametocyte culture. Results suggest that energy metabolism and lipid utilization between the asexual stages and gametocytes is different. This study provides new insights for gametocyte-specific nutritional requirements to aid future optimization and standardization of in vitro gametocyte cultivation, and highlights areas of novel gametocyte cell biology that deserve to be studied in greater detail and may yield new targets for transmission-blocking drugs

Assessing the quality of care at primary health care level in two pilot regions of Albania

The quality of care (QoC) of primary health care (PHC) services in Albania faces challenges on multiple levels including governance, access, infrastructure and health care workers. In addition, there is a lack of trust in the latter. The Health for All Project (HAP) funded by the Swiss Agency for Development and Cooperation therefore aimed at enhancing the population's health by improving PHC services and implementing health promotion activities following a multi-strategic health system strengthening approach. The objective of this article is to compare QoC before and after the 4 years of project implementation. A cross-sectional study was implemented at 38 PHC facilities in urban and rural locations in the Diber and Fier regions of Albania in 2015 and in 2018. A survey measured the infrastructure of the different facilities, provider-patient interactions through clinical observation and patient satisfaction. During clinical observations, special attention was given to diabetes and hypertensive patients. Infrastructure scores improved from base- to endline with significant changes seen on national level and for rural facilities (p < 0.01). Facility infrastructure and overall cleanliness, hygiene and basic/essential medical equipment and supplies improved at endline, while for public accountability/transparency and guidelines and materials no significant change was observed. The overall clinical observation score increased at endline overall, in both areas and in rural and urban setting. However, infection prevention and control procedures and diabetes treatment still experienced relatively low levels of performance at endline. Patient satisfaction on PHC services is generally high and higher yet at endline. The changes observed in the 38 PHC facilities in two regions in Albania between 2015 and 2018 were overall positive with improvements seen at all three levels assessed, e.g., infrastructure, service provision and patient satisfaction. However, to gain overall improvements in the QoC and move toward a more efficient and sustainable health system requires continuous investments in infrastructure alongside interventions at the provider and user level

The consequences of compromising the EU's free movement of persons principle on Swiss research: how to survive constrained access to regional funding

Between 2014 and 2016, Switzerland's access to some of the EU funding was limited after a referendum against mass immigration was accepted and the country refused to sign the free movement accord to the EU's newest member, Croatia. It is well documented that Switzerland has suffered from a drop in participation, funding and a decrease in consortium lead positions. However, there is no account of the consequences on institutional level. We therefore aimed at describing the immediate- and longer-term impact of the partial association status to the Swiss Tropical and Public Health Institute (Swiss TPH) and to identify key strategies for minimizing institutional damage during a limited access period to a key regional funding source. A quantitative analysis of the institute's grants database, from 2007 to 2019, did not show any clear trends related to the partial association status of Switzerland for funding and projects awarded. The qualitative outcomes changed along the timeline assessed; whereas in 2014 a range of negative effects were stated by Swiss TPH researchers, a survey conducted in 2019 with Swiss TPH applicants and project partners to Horizon 2020, revealed that most project leaders felt that the partial association did neither affect their external partners' willingness to collaborate nor Swiss TPH's role in the proposal or consortium. On the other hand, the institutional strategic goal of taking on consortia leads was delayed by several years as a direct consequence of the partial association. Also, the exclusion from European research networks and the lack of consultation of expertise by the European partner institutions was widely seen as damaging. A policy of favouring long-term partnerships over ad-hoc collaborations, along with constant and trustful communication, as immediate mitigation measure, helped averting some of the reputational and access damage. Moreover, the Swiss TPH business model based on a three-way strategy of research, education and services has proven highly viable allowing to build a large pool of potential funding sources internationally, resulting in relative resilience in terms of income lost

Planetary Gearbox Prototype Development and Manufacturing

Goal of this research was to develop and manufacture planetary gearbox prototype using rapid prototyping technology (additive manufacturing). Developed prototype was used to visually analyse the design of the planetary gearbox. Also, it was used to improve and innovate education of students on several courses at Mechanical Design study program at Faculty of Mechanical Engineering. It is shown that low cost rapid prototyping technology can be used to manufacture prototypes of complex machines and machine elements. Prototypes manufactured using this technology have same functionality like the real one. Main limitation is the fact that they cannot sustain real world loads and stresses. This paper shows opportunities which low cost rapid prototyping technology is offering in improvement and innovation of education process at engineering schools and faculties. All complex and heavy machines can be manufactured using this type of technology and on that way more precisely presented to the students

Some Slaughter and Carcass Traits of the Lambs of Dalmatian Pramenka Reared in Three Different Fattening Systems

In order to determine the impact of different fattening system (I - milk, pasture; II - indoors, milk, grains, III - milk, pasture, concentrate) on slaughter value and carcass quality of the lambs of Dalmatian Pramenka, 18 lambs (100 ± 5 days old), 6 in each group, were slaughtered. Lambs of one group were from the same flock and selected by birth weight (2.00 ± 0.20 kg). After slaughtering and cutting the carcasses into halves, in order to determine the share of legs and shoulders as well as certain tissues in the halves, the legs and shoulders were separated from the halves and total dissection was made. The significant differences (P<0.05) of slaughter weight (I - 21.17 kg, II - 23.25 kg, III - 26.25 kg) and hot carcass weight (I - 9.98 kg, II - 11.92 kg, III - 12.92 kg) among three groups were found. The legs II (1.65 kg) and III (1.71 kg) were significantly heavier (P<0.001) than legs I (1.32 kg), as well as shoulders (I - 0.52 kg, II - 0.65 kg, III - 0.69 kg; P<0.01). Total dissection of the halves established these tissues ratio: muscle 51.25 %, fat 10.18 %, connective 13.93%, bone 23.04% and other tissues 2.32%. The biggest quantity of muscle tissue was found in halves III (3.27 kg) what was more (P<0.05) than in halves II (2.83 kg) and I (2.50 kg). However, the biggest quantity of fat was found in halves II (0.85 kg) what was more (P<0.01) than in halves I (0.33 kg) and III (0.52 kg). Therefore, the addition of concentrate in pasture fattening system (III) increased the muscularity, without significantly increasing the amount of fat in the lamb carcass

The Effect of Acoustic Forcing on Instabilities and Breakdown in Swept-Wing Flow over a Backward-Facing Step

Instability interaction and breakdown were experimentally investigated in the flow over a swept backward-facing step. Acoustic forcing was used to excite the Tollmien-Schlichting (TS) instability and to acquire phase-locked results. The phase-averaged results illustrate the complex nature of the interaction between the TS and stationary cross flow instabilities. The weak stationary cross flow disturbance causes a distortion of the TS wavefront. The breakdown process is characterized by large positive and negative spikes in velocity. The positive spikes occur near the same time and location as the positive part of the TS wave. Higher-order spectral analysis was used to further investigate the nonlinear interactions between the TS instability and the traveling cross flow disturbances. The results reveal that a likely cause for the generation of the spikes corresponds to nonlinear interactions between the TS, traveling cross flow, and stationary cross flow disturbances. The spikes begin at low amplitudes of the unsteady and steady disturbances (2-4% U (sub e) (i.e. boundary layer edge velocity)) but can achieve very large amplitudes (20-30 percent U (sub e) (i.e. boundary layer edge velocity)) that initiate an early, though highly intermittent, breakdown to turbulence

Usability of Two New Interactive Game Sensor-Based Hand Training Devices in Parkinson's Disease.

This pilot cross-sectional study aimed to evaluate the usability of two new interactive game sensor-based hand devices (GripAble and Smart Sensor Egg) in both healthy adults as well as in persons with Parkinson's Disease (PD). Eight healthy adults and eight persons with PD participated in this study. Besides a standardised usability measure, the state of flow after one training session and the effect of cognitive abilities on flow were evaluated. High system usability scores (SUS) were obtained both in healthy participants (72.5, IQR = 64.375-90, GripAble) as well as persons with PD (77.5, IQR = 70-80.625, GripAble; 77.5, IQR = 75-82.5, Smart Sensor Egg). Similarly, high FSSOT scores were achieved after one training session (42.5, IQR = 39.75-50, GripAble; 50, IQR = 47-50, Smart Sensor Egg; maximum score 55). Across both groups, FSSOT scores correlated significantly with SUS scores (r = 0.52, p = 0.039). Finally, MoCA did not correlate significantly with FSSOT scores (r = 0.02, p = 0.9). The present study shows high usability for both interactive game sensor-based hand training devices, for persons with PD and healthy participants

Consumer perception on purchase decision factors and health indicators related to the quality and safety of meat sold in dibiteries in Dakar, Senegal

Accelerated socio-economic and demographic changes have led to the transformation of eating habits in sub-Saharan African cities including Dakar, Senegal. The result is the proliferation of informal fast-food establishments, such as the 'dibiteries' serving braised sheep meat. However, owing to poor hygiene practices, consumption of dibiterie meat poses a public health concern. It was unclear how the dibiterie meat quality and safety were perceived among customers who define their own purchasing social norms. A total of 165 meat consumers were randomly selected and interviewed, from 165 dibiteries sampled by convenience in the Dakar region using a structured questionnaire. Results showed that purchase decisions were guided by trust in the salesperson's expertise, the taste of the product, perceived risk of meat contamination, tenderness, price, the nutritional value, the smell and the colour and freshness of the meat. The perceived quality and safety of dibiterie meat was expressed by the 'organoleptic quality', 'environment and service' and 'price and trust of the product's safety' factors. The majority of consumers (61%) were 'less concerned' about the safety of dibiterie meat, and the acceptable price range of the product was between $5.08 and$7.62. As this food product is gaining popularity in Dakar and the majority of our participating consumers do not show high levels of concern, we suggest stricter standards

Species composition and insecticide resistance in malaria vectors in Ellibou, southern Côte d'Ivoire and first finding of; Anopheles arabiensis; in Côte d'Ivoire

Background Knowing the species composition and insecticide resistance status of the target vector population is important to guide malaria vector control. The aim of this study was to characterize the malaria vector population in terms of species composition, insecticide susceptibility status and potential underlying resistance mechanisms in Ellibou, southern Côte d'Ivoire. Methods A 1-year longitudinal entomological survey was conducted using light traps and pyrethroid spray catches to sample adult mosquitoes in combination with larval sampling. The susceptibility status of Anopheles gambiae sensu lato (s.l.) to bendiocarb, deltamethrin, DDT and malathion was assessed using the World Health Organization insecticide susceptibility test. Additionally, An. gambiae specimens were screened for knockdown (kdr) and acetylcholineesterase (ace1) target site resistance alleles, and the expression levels of eight metabolic resistance genes, including seven cytochrome P450 monooxygenases (P450s) and one glutathione S-transferase (GST), measured with reverse transcription quantitative real-time polymerase chain reaction (qPCR). Results Overall, 2383 adult mosquitoes from 12 different taxa were collected with Culex quinquefasciatus and An. gambiae being the predominant taxa. Molecular identification of An. gambiae s.l. revealed the presence of Anopheles arabiensis, Anopheles coluzzii, An. gambiae sensu stricto (s.s.) and Anopheles coluzzii/An. gambiae s.s. hybrids. Anopheles gambiae mosquitoes were resistant to all insecticides except malathion. PCR diagnostics revealed the presence of ace1-G280S and the kdr L995F, L995S and N1570Y target-site mutations. Additionally, several genes were upregulated, including five P450s (i.e., CYP6P3, CYP6M2, CYP9K1, CYP6Z1, CYP6P1) and GSTE2. Conclusion This is the first documented presence of An. arabiensis in Côte d'Ivoire. Its detection - together with a recent finding further north of the country - confirms its existence in the country, which is an early warning sign, as An. arabiensis shows a different biology than the currently documented malaria vectors. Because the local An. gambiae population was still susceptible to malathion, upregulation of P450s, conferring insecticide resistance to pyrethroids, together with the presence of ace1, suggest negative cross-resistance. Therefore, organophosphates could be an alternative insecticide class for indoor residual spraying in the Ellibou area, while additional tools against the outdoor biting An. arabiensis will have to be considered