Depicted simulation model for removal of second-generation antipsychotic drugs adsorbed on Zn-MOF: adsorption locator assessment.

CONTEXT: Electronic durable behavior on the material surface was accompanied by a class of antipsychotic drugs (APD) to describe the surface modification in the designed adsorption model. Hierarchically Zn-MOF system was utilized for estimating its capacity for drug molecule removal. Geometrically optimized strategy on the studied systems was performed using DFT/GGA/PBE. FMOs analysis was depicted based on the same level of calculations, and molecular electrostatic potential surface (MEP) was generated for unadsorbed and adsorbed systems to illustrate the variation in the surface-active sites. By interpreting the electronic density of states (DOS), the atomic orbital can be identified as a major or minor electronic distribution by PDOS graph. Adsorption locating behavior was considered to detect the significant surface interaction mode between APD and Zn-MOF surface based on lower adsorption energy. The stability of the adsorbed model was best described through dynamic simulation analysis with time through elevated temperatures. The non-covalent interactions were described using RDG/NCI analysis to show the major favorable surface interaction predicting the highly stable adsorption system. METHODS: The most accurate geometrical computations were performed using the materials studio software followed by surface cleavage and vacuum slab generation. The first principle of DFT was used to apply CASTEP module with GGA/PBE method for band structure and DOS calculations. Three systems of antipsychotic drugs were computationally studied using CASTEP simulation package and adsorbed on an optimized Zn-MOF surface. Adsorption locator module predicted the preferred adsorption mechanistic models, in which the first model was arranged to be more stable, to confirm the occurrence of some interactions in the adsorption mechanism.

Cost and quality of operational larviciding using drones and smartphone technology.

BACKGROUND: Larval Source Management (LSM) is an important tool for malaria vector control and is recommended by WHO as a supplementary vector control measure. LSM has contributed in many successful attempts to eliminate the disease across the Globe. However, this approach is typically labour-intensive, largely due to the difficulties in locating and mapping potential malarial mosquito breeding sites. Previous studies have demonstrated the potential for drone imaging technology to map malaria vector breeding sites. However, key questions remain unanswered related to the use and cost of this technology within operational vector control. METHODS: Using Zanzibar (United Republic of Tanzania) as a demonstration site, a protocol was collaboratively designed that employs drones and smartphones for supporting operational LSM, termed the Spatial Intelligence System (SIS). SIS was evaluated over a four-month LSM programme by comparing key mapping accuracy indicators and relative costs (both mapping costs and intervention costs) against conventional ground-based methods. Additionally, malaria case incidence was compared between the SIS and conventional study areas, including an estimation of the incremental cost-effectiveness of switching from conventional to SIS larviciding. RESULTS: The results demonstrate that the SIS approach is significantly more accurate than a conventional approach for mapping potential breeding sites: mean % correct per site: SIS = 60% (95% CI 32-88%, p = 0.02), conventional = 18% (95% CI - 3-39%). Whilst SIS cost more in the start-up phase, overall annualized costs were similar to the conventional approach, with a simulated cost per person protected per year of $3.69 ($0.32 to $15.12) for conventional and $3.94 ($0.342 to $16.27) for SIS larviciding. The main economic benefits were reduced labour costs associated with SIS in the pre-intervention baseline mapping of habitats. There was no difference in malaria case incidence between the three arms. Cost effectiveness analysis showed that SIS is likely to provide similar health benefits at similar costs compared to the conventional arm. CONCLUSIONS: The use of drones and smartphones provides an improved means of mapping breeding sites for use in operational LSM. Furthermore, deploying this technology does not appear to be more costly than a conventional ground-based approach and, as such, may represent an important tool for Malaria Control Programmes that plan to implement LSM.

Malaria elimination in Zanzibar: where next?

In 2018, Zanzibar developed a national malaria strategic plan IV (2018-2023) to guide elimination of malaria by 2023. We assessed progress in the implementation of malaria activities as part of the end-term review of the strategic plan. The review was done between August and October 2022 following the WHO guideline to assess progress made towards malaria elimination, effectiveness of the health systems in delivering malaria case management; and malaria financing. A desk review examined available malaria data, annual work plans and implementation reports for evidence of implemented malaria activities. This was complemented by field visits to selected health facilities and communities by external experts, and interviews with health management teams and inhabitants to authenticate desk review findings. A steady increase in the annual parasite incidence (API) was observed in Zanzibar, from 2.7 (2017) to 3.6 (2021) cases per 1,000 population with marked heterogeneity between areas. However, about 68% of the detected malaria cases were imported into Zanzibar. Malaria case follow-up and investigation increased from <70% in 2017 to 94% and 96% respectively, in 2021. The review noted a 3.7-fold increase of the health allocation in the country's budget, from 31.7 million USD (2017/18) to 117.3 million USD (2022/23) but malaria allocation remained low (<1%). The varying transmission levels in the islands suggest a need for strategic re-orientation of the elimination attempts from a national-wide to a sub-national agenda. We recommend increasing malaria allocation from the health budget to ensure sustainability of malaria elimination interventions.

Ultrasound assessment of the brachial plexus nerve root cross-sectional areas in asymptomatic patients with type 2 diabetes.

Type 2 diabetes mellitus (T2D) is one of the most common metabolic diseases and is often associated with cervical radiculoplexus neuropathies. Magnetic resonance imaging is the modality of choice for evaluating the brachial plexus, however, the use of ultrasound for its evaluation has increased and has been shown to be an additional reliable method. We aimed to compare the cross-sectional areas of the C5, C6, and C7 nerve roots of the brachial plexus, at the interscalene groove, in asymptomatic patients with T2D to that of an asymptomatic control cohort without T2D. A total of 25 asymptomatic patients with T2D were recruited from outpatient clinics. A total of 18 asymptomatic subjects without T2D were also recruited from hospital staff volunteers to form the control cohort. High-resolution ultrasound imaging of the bilateral C5, C6, and C7 nerve roots of the brachial plexus was performed in the short axis, at the level of the interscalene grooves. The nerve root cross-sectional areas were recorded and compared. In the patients with T2D, HbA1c and fasting blood glucose (FBG) levels were obtained as well as the duration of T2D in years and correlated with cross-sectional areas. The cross-sectional areas of C6 and C7 were significantly smaller in the T2D cohort. Additionally, HbA1c, and FBG levels as well as the duration of T2D were negatively correlated with the C5, C6, and C7 cross-sectional areas. Our study demonstrated smaller brachial plexus nerve root cross-sectional areas in asymptomatic patients with T2D which negatively correlated with HbA1c, and FBG levels as well as the duration of T2D.

Comparative Assessment of Medicinal Plant Utilization among Balti and Shina Communities in the Periphery of Deosai National Park, Pakistan.

Traditional ecological knowledge, linguistic, and sociocultural perspectives are key contributors to environmental sustainability. Therefore, it is essential to identify and preserve this biocultural heritage, especially that of indigenous communities and minorities. We conducted an ethnobotanical survey to document the plant species used by the Balti and Shina communities living in the buffer zone of Deosai National Park (DNP), western Himalayas, Pakistan. A combination of random and purposive sampling techniques was adapted, targeting middle- and old-aged informants. A total of 46 semi-structured interviews were conducted and the gathered data were evaluated using relative frequency of citation (RFC) and through comparison with the ethnomedicinal literature. In total, 47 medicinal plant species belonging to 42 genera and 23 families were recorded. Baltis and Shinas cited 42 and 38 plant species, respectively, that were used to treat various diseases. About 60% of species were common among both communities, but 27.7% and 12.8% were exclusive to Baltis and Shinas, respectively. Considerable heterogeneity was noted in vernacular names, plant part(s) used, preparation, and administration. Ribes alpestre, Aconitum violaceum, Delphinium brunonianum, Thymus linearis, and Swertia petiolata were highly utilized species having RFCs > 50. In addition, 46% of medicinal uses, specifically that of Allardia tomentosa, A. tridactylites, Jurinea dolomiaea, and Gallium boreale, were reported for the first time from the region. Cross-cultural analysis revealed sociocultural gaps between both groups. Relatively, Baltis retained more ethnomedicinal knowledge and their traditional medicinal system is more closely associated with traditional Tibetan medicine. Generally, Balti and Shina communities retain substantial biocultural and ethnological diversity, which has been reflected in the present study. Our findings underline the importance and need for sustainable utilization of natural resources, specifically the plant species of this region. However, an in-depth ethnobotanical investigation may underpin the holistic comparative medical ethnobotany of the entire region.

Cost effectiveness of bariatric surgery in patients with obesity related comorbidities: A retrospective study.

Background and Aim: Bariatric surgery has been reported to be an effective but expensive method for obesity management. This study aimed to determine the economic benefit for patients who underwent bariatric surgery. Methodology: We conducted a retrospective chart review of patients who underwent bariatric surgery and was on medications for obesity-related comorbidities at the Obesity Research Center in King Khalid University Hospital, Riyadh, Saudi Arabia. Data on the use and cost of medications before and after bariatric surgery were collected. Results: A total of 266 patients, 107 males (40.23%), and 159 Females (59.77%) with a mean age of 41.06 years were included in the study. There was a reduction in the mean number of medications used by patients before and 1-year post-op (before: 1.84, after: 0.52), with a significant reduction in the cost of medications (SAR5152.24 before, and SAR1695.36 after, 67% reduction, P < 0.001). Patients < 32 years old had the most reduction in medications cost (76.64% reduction). No significant difference in the cost reduction after surgery between genders (P = 0.971). There were significant reductions in numbers of out-patient clinic visits (2.26 ± 2.43 to 1.57 ± 1.42) and in-patient hospitalizations (0.31 ± 0.57 to 0.10 ± 0.36) after surgery (P < 0.001 and P < 0.001, respectively). Conclusion: Bariatric surgery can be considered as a cost-effective treatment for patients with obesity-related comorbidities. A significant reduction has been found in post-operative medications cost, out-patient clinic visits and in-patient hospitalizations after bariatric surgery.

Formulation of Curcumin-ß-cyclodextrin-polyvinylpyrrolidone supramolecular inclusion complex: experimental, molecular docking, and preclinical anti-inflammatory assessment.

This research planned to ameliorate an aqueous solubility and dissolution of Curcumin (CUR) by the formulation of inclusion complex with ß-cyclodextrin (ß-CD) and polyvinylpyrrolidone (PVP). The phase solubility study was performed to assess the solubility of CUR. The prepared CUR complex assessed for dissolution study, physicochemical evaluation, in-vitro antioxidant activity, molecular modeling, and anti-inflammatory assessment. The pivotal findings of phase-solubility studies demonstrate apparent stability constant (Kc) and complexation efficiency (CE) values for CUR-ß-CD and CUR-ß-CD-PVP complex was 175.4 M -1, 1.15% and 833.3.2 M -1 and 5.21%, respectively. The characterization results revealed amorphization of crystalline state (CUR) into amorphous state. The maximum drug release found with the ternary CUR complex (F7), i.e. 45.41 ± 3.78% in 6 h study. The chemical shift in the NMR supports that the aromatic ring of CUR is completely complexed inside the ß-CD cavity. The antioxidant activity of pure CUR was found to be 58.02 ± 2.21% and CUR ternary complex (F7) showed significantly higher activity to 96.02 ± 2.46%. The in-vivo effect of CUR complex (F7) was also found significantly higher than that of pure CUR. The molecular modeling study depicted that PVP increased the stability of the ternary complex by forming the link between CUR and ß-CD. Thus, the ternary inclusion complex of CUR-ß-CD-PVP could contribute as an innovative outcome in the enhancement of solubility and in-vivo activity.

Taking local ownership: government and household contribution to indoor residual spraying in Zanzibar and mainland Tanzania.

BACKGROUND: While donor funding is instrumental in initiation and implementation of malaria control efforts, national government contributions are key to local ownership and sustainability. This study explored in-kind contributions of local government and households towards the cost of indoor residual spraying (IRS) interventions in Tanzania. METHODS: Data were collected through interviews with local government officials and technical teams in the IRS project. Household contribution was based on provision of water for IRS. Government contributions included government-provided warehouse and office space, vehicles, and staff labour. In-kind contributions were aggregated at the district, regional and national level. Calculations were based on proportion of total costs of IRS from 2010 to 2012. RESULTS: The mainland government provided larger amounts of in-kind contribution in absolute value (mean of US$454 200) compared to Zanzibar (US$89 163). On average, in-kind contribution was 5.5% of total costs in Zanzibar and 2.9% in mainland. The proportion of government in-kind contribution was higher in Zanzibar versus the mainland (86% vs 50%) while household contribution was higher in mainland compared to Zanzibar (50% vs 14%). CONCLUSION: Government involvement, particularly through budgetary allocations and increased in-kind contribution, needs to be encouraged for malaria control efforts to be locally owned, managed and sustained.

The dynamics of pyrethroid resistance in Anopheles arabiensis from Zanzibar and an assessment of the underlying genetic basis.

BACKGROUND: The emergence of pyrethroid resistance in the malaria vector, Anopheles arabiensis, threatens to undermine the considerable gains made towards eliminating malaria on Zanzibar. Previously, resistance was restricted to the island of Pemba while mosquitoes from Unguja, the larger of the two islands of Zanzibar, were susceptible. Here, we characterised the mechanism(s) responsible for resistance on Zanzibar using a combination of gene expression and target-site mutation assays. METHODS: WHO resistance bioassays were conducted using 1-5d old adult Anopheles gambiae s.l. collected between 2011 and 2013 across the archipelago. Synergist assays with the P450 inhibitor piperonyl-butoxide were performed in 2013. Members of the An. gambiae complex were PCR-identified and screened for target-site mutations (kdr and Ace-1). Gene expression in pyrethroid resistant An. arabiensis from Pemba was analysed using whole-genome microarrays. RESULTS: Pyrethroid resistance is now present across the entire Zanzibar archipelago. Survival to the pyrethroid lambda-cyhalothrin in bioassays conducted in 2013 was 23.5-54.3% on Unguja and 32.9-81.7% on Pemba. We present evidence that resistance is mediated, in part at least, by elevated P450 monoxygenases. Whole-genome microarray scans showed that the most enriched gene terms in resistant An. arabiensis from Pemba were associated with P450 activity and synergist assays with PBO completely restored susceptibility to pyrethroids in both islands. CYP4G16 was the most consistently over-expressed gene in resistant mosquitoes compared with two susceptible strains from Unguja and Dar es Salaam. Expression of this P450 is enriched in the abdomen and it is thought to play a role in hydrocarbon synthesis. Microarray and qPCR detected several additional genes putatively involved in this pathway enriched in the Pemba pyrethroid resistant population and we hypothesise that resistance may be, in part, related to alterations in the structure of the mosquito cuticle. None of the kdr target-site mutations, associated with pyrethroid/DDT resistance in An. gambiae elsewhere in Africa, were found on the islands. CONCLUSION: The consequences of this resistance phenotype are discussed in relation to future vector control strategies on Zanzibar to support the ongoing malaria elimination efforts on the islands.

Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability.

BACKGROUND: The need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations. METHODS: DNA was extracted from two RDT devices (Paracheck-Pf® and SD Bioline Malaria Pf/Pan®), seeded in vitro with 10-fold dilutions of cultured 3D7 P. falciparum parasites diluted in malaria negative whole blood. The level of P. falciparum detection was determined for each extraction method and RDT device with multiple nested-PCR and real-time PCR assays. The field applicability was tested on 855 paired RDT (Paracheck-Pf) and filter paper (Whatman® 3MM) blood samples (734 RDT negative and 121 RDT positive samples) collected from febrile patients in Zanzibar 2010. RDT positive samples were genotyped at four key single nucleotide polymorphisms (SNPs) in pfmdr1 and pfcrt as well as for pfmdr1 copy number, all associated with anti-malarial drug resistance. RESULTS: The P. falciparum DNA detection limit varied with RDT device and extraction method. Chelex-100 extraction performed best for all extraction matrixes. There was no statistically significant difference in PCR detection rates in DNA extracted from RDTs and filter paper field samples. Similarly there were no significant differences in the PCR success rates and genotyping outcomes for the respective SNPs in the 121 RDT positive samples. CONCLUSIONS: The results support RDTs as a valuable source of parasite DNA and provide evidence for RDT-DNA extraction for improved malaria case detection, molecular drug resistance surveillance, and RDT quality control.

Assessing the cost-benefit effect of a Plasmodium falciparum drug resistance mutation on parasite growth in vitro.

Plasmodium falciparum mutations associated with antimalarial resistance may be beneficial for parasites under drug pressure, although they may also cause a fitness cost. We herein present an in vitro model showing how this combined effect on parasite growth varies with the drug concentration and suggest a calculated drug-specific cost-benefit index, indicating the possible advantage for mutated parasites. We specifically studied the D-to-Y change at position 1246 encoded by the pfmdr1 gene (pfmdr1 D1246Y) in relation to amodiaquine resistance. Susceptibilities to amodiaquine, desethylamodiaquine, and chloroquine, as well as relative fitness, were determined for two modified isogenic P. falciparum clones differing only in the pfmdr1 1246 position. Data were used to create a new comparative graph of relative growth in relation to the drug concentration and to calculate the ratio between the benefit of resistance and the fitness cost. Results were related to an in vivo allele selection analysis after amodiaquine or artesunate-amodiaquine treatment. pfmdr1 1246Y was associated with decreased susceptibility to amodiaquine and desethylamodiaquine but at a growth fitness cost of 11%. Mutated parasites grew less in low drug concentrations due to a predominating fitness cost, but beyond a breakpoint concentration they grew more due to a predominating benefit of increased resistance. The cost-benefit indexes indicated that pfmdr1 1246Y was most advantageous for amodiaquine-exposed parasites. In vivo, a first drug selection of mutant parasites followed by a fitness selection of wild-type parasites supported the in vitro data. This cost-benefit model may predict the risk for selection of drug resistance mutations in different malaria transmission settings.

System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania.

BACKGROUND: Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. METHODS: Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. RESULTS: The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). CONCLUSIONS: Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain high effective coverage, there is need for complimentary distribution strategies between mass distribution campaigns. Considering the community's preferences prior to a mass distribution and addressing the communities concerns through information, education and communication, may improve the LLIN usage.