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Environmental Health Insights 2019Barrier insecticide treatments have a long history in mosquito control programs but have been used more frequently in the United States in recent years for control of... (Review)
Review
BACKGROUND AND PURPOSE
Barrier insecticide treatments have a long history in mosquito control programs but have been used more frequently in the United States in recent years for control of invasive "backyard" species (eg, ) and increases in incidence of vector-borne diseases (eg, Zika).
METHODS
We reviewed the published literature for studies investigating barrier treatments for mosquito control during the last 74 years (1944-2018). We searched databases such as PubMed, Web of Science, and Google Scholar to retrieve worldwide literature on barrier treatments.
RESULTS
Forty-four studies that evaluated 20 active ingredients (AIs) and 21 formulated products against multiple mosquito species are included. Insecticides investigated for efficacy included organochlorines (dichlorodiphenyltrichloroethane [DDT], β-hexachlorocyclohexane [BHC]), organophosphates (malathion), and pyrethroids (bifenthrin, deltamethrin, permethrin, lambda-cyhalothrin) as AIs. Study design varied with multiple methods used to evaluate effectiveness of barrier treatments. Barrier treatments were effective at lowering mosquito populations although there was variation between studies and for different mosquito species. Factors other than AI, such as exposure to rainfall and application equipment used, also influenced control efficacy.
CONCLUSIONS
Many of the basic questions on the effectiveness of barrier insecticide applications have been answered, but several important details still must be investigated to improve precision and impact on vector-borne pathogen transmission. Recommendations are made to assist future evaluations of barrier treatments for mosquito control and to limit the potential development of insecticide resistance.
PubMed: 31263373
DOI: 10.1177/1178630219859004 -
Molecular Systems Biology Jun 2021The ability to switch a gene from off to on and monitor dynamic changes provides a powerful approach for probing gene function and elucidating causal regulatory...
The ability to switch a gene from off to on and monitor dynamic changes provides a powerful approach for probing gene function and elucidating causal regulatory relationships. Here, we developed and characterized YETI (Yeast Estradiol strains with Titratable Induction), a collection in which > 5,600 yeast genes are engineered for transcriptional inducibility with single-gene precision at their native loci and without plasmids. Each strain contains SGA screening markers and a unique barcode, enabling high-throughput genetics. We characterized YETI using growth phenotyping and BAR-seq screens, and we used a YETI allele to identify the regulon of Rof1, showing that it acts to repress transcription. We observed that strains with inducible essential genes that have low native expression can often grow without inducer. Analysis of data from eukaryotic and prokaryotic systems shows that native expression is a variable that can bias promoter-perturbing screens, including CRISPRi. We engineered a second expression system, Z EB42, that gives lower expression than Z EV, a feature enabling conditional activation and repression of lowly expressed essential genes that grow without inducer in the YETI library.
Topics: Gene Library; Genes, Essential; Plasmids; Promoter Regions, Genetic; Saccharomyces cerevisiae
PubMed: 34096681
DOI: 10.15252/msb.202110207 -
Applied Drug Research, Clinical Trials... 2022A major goal of the Clinical and Translational Science Award programs is to build and grow clinical and translational research, including the need to ensure that study...
BACKGROUND
A major goal of the Clinical and Translational Science Award programs is to build and grow clinical and translational research, including the need to ensure that study teams are educated and adhere to best clinical research practices.
OBJECTIVE
One of the primary objectives of the Center for Clinical and Translational Science at the University of Kentucky is to help investigators implement standard operating procedures and provide resources to conduct clinical research that is rigorous, ethical and safe.
METHODS
The University of Kentucky Center for Clinical and Translational Science sought to establish a Quality Assurance/Quality Improvement program for Principal Investigator (PI) initiated clinical research studies using Center for Clinical and Translational Science services. Initiated in 2011, this program's goal was to improve research design quality and from the start of the project, "find it, fix it", leading to improved PI education, without being viewed as punitive.
RESULTS
Since the initiation of our Quality Assurance/Quality Improvement program, PI acceptance has been good and we have expanded its footprint and adjusted our review style to better match the needs of our PIs. This article discusses our experiences with Quality Assurance/Quality Improvement program development and growth.
CONCLUSION
A Quality Assurance/Quality Improvement program can be developed that is efficient, effective, educational and well accepted by all clinical research stakeholders.
PubMed: 36619690
DOI: 10.2174/2667337109666220615125134 -
BMJ Global Health Apr 2021Despite considerable improvements in vaccination coverage over the last decade, half of the world's unvaccinated and undervaccinated children are located in Africa. The...
INTRODUCTION
Despite considerable improvements in vaccination coverage over the last decade, half of the world's unvaccinated and undervaccinated children are located in Africa. The role of institutional trust in explaining vaccination gaps has been highlighted in several qualitative reports but so far has only been quantified in a small number of high-income countries.
METHODS
We matched information on child vaccination status from the Demographic Health Surveys with information on institutional trust from the Afrobarometer surveys at the subnational level. A total of 166 953 children from 41 surveys administered in 22 African countries covering 216 subnational regions were used. Based on a principal component analysis, we constructed an institutional mistrust index that combined the level of mistrust in the head of state, parliament, electoral system, courts and local government. Associations between institutional mistrust and child vaccination uptake were assessed with multivariable fixed effects logistic regressions that controlled for time-invariant subnational region characteristics and various child, caregiver, household and community characteristics.
RESULTS
A 1 SD increase in the institutional mistrust index was associated with a 10% (95% CI of ORs: 1.03 to 1.18) increase in the likelihood that a child had not received any of eight basic vaccines and with a 6% decrease in the likelihood a child had received all of the basic vaccines (95% CI: 0.92 to 0.97). Institutional mistrust was negatively associated with the likelihood that a child had received each of the eight basic vaccinations (p<0.05).
CONCLUSIONS
Child vaccination rates in Africa are considerably lower in areas in which the local population displays high levels of mistrust towards local authorities. Institutional mistrust is an important dimension of vaccine hesitancy, considered as one of the most important threats to global health. Empowering local authorities with resources and communication strategies to address institutional mistrust may be needed to close the remaining vaccination gaps in Africa.
Topics: Africa; Child; Humans; Trust; Vaccination; Vaccination Coverage; Vaccines
PubMed: 33926893
DOI: 10.1136/bmjgh-2020-004595 -
Philosophical Transactions. Series A,... Jun 2017Scientific investigations in medicine and beyond increasingly require observations to be described by more features than can be simultaneously visualized. Simply...
Scientific investigations in medicine and beyond increasingly require observations to be described by more features than can be simultaneously visualized. Simply reducing the dimensionality by projections destroys essential relationships in the data. Similarly, traditional clustering algorithms introduce data bias that prevents detection of natural structures expected from generic nonlinear processes. We examine how these problems can best be addressed, where in particular we focus on two recent clustering approaches, Phenograph and Hebbian learning clustering, applied to synthetic and natural data examples. Our results reveal that already for very basic questions, minimizing clustering bias is essential, but that results can benefit further from biased post-processing.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.
Topics: Animals; Bias; Cluster Analysis; Computer Simulation; Epidemiologic Methods; Epidemiologic Studies; Humans; Models, Biological; Models, Statistical
PubMed: 28507238
DOI: 10.1098/rsta.2016.0293 -
Neurobiology of Disease Dec 2020Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB)...
How specific are the conformation-specific α-synuclein antibodies? Characterization and validation of 16 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology.
Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinson's disease (PD) and other synucleinopathies. Therefore, the development of tools and methods to detect and quantify α-syn oligomers has become increasingly crucial for mechanistic studies to understand their role in PD, and to develop new diagnostic methods and therapies for PD and other synucleinopathies. The majority of these tools and methods rely primarily on the use of aggregation state-specific or conformation-specific antibodies. Given the impact of the data and knowledge generated using these antibodies on shaping the foundation and directions of α-syn and PD research, it is crucial that these antibodies are thoroughly characterized, and their specificity or ability to capture diverse α-syn species is tested and validated. Herein, we describe an antibody characterization and validation pipeline that allows a systematic investigation of the specificity of α-syn antibodies using well-defined and well-characterized preparations of various α-syn species, including monomers, fibrils, and different oligomer preparations that are characterized by distinct morphological, chemical and secondary structure properties. This pipeline was used to characterize 18 α-syn antibodies, 16 of which have been reported as conformation- or oligomer-specific antibodies, using an array of techniques, including immunoblot analysis (slot blot and Western blot), a digital ELISA assay using single molecule array technology and surface plasmon resonance. Our results show that i) none of the antibodies tested are specific for one particular type of α-syn species, including monomers, oligomers or fibrils; ii) all antibodies that were reported to be oligomer-specific also recognized fibrillar α-syn; and iii) a few antibodies showed high specificity for oligomers and fibrils but did not bind to monomers. These findings suggest that the great majority of α-syn aggregate-specific antibodies do not differentiate between oligomers and fibrils, thus highlighting the importance of exercising caution when interpreting results obtained using these antibodies. Our results also underscore the critical importance of the characterization and validation of antibodies before their use in mechanistic studies and as diagnostic tools or therapeutic agents. This will not only improve the quality and reproducibility of research and reduce costs but will also reduce the number of therapeutic antibody failures in the clinic.
Topics: Amyloid; Antibodies; Brain; Humans; Lewy Body Disease; Parkinson Disease; alpha-Synuclein
PubMed: 32971232
DOI: 10.1016/j.nbd.2020.105086 -
Netherlands Heart Journal : Monthly... Jun 2022Healthcare expenditure in the Netherlands is increasing at such a rate that currently 1 in 7 employees are working in healthcare/curative care. Future increases in...
BACKGROUND
Healthcare expenditure in the Netherlands is increasing at such a rate that currently 1 in 7 employees are working in healthcare/curative care. Future increases in healthcare spending will be restricted, given that 10% of the country's gross domestic product is spent on healthcare and the fact that there is a workforce shortage. Dutch healthcare consists of a curative sector (mostly hospitals) and nursing care at home. The two entities have separate national budgets (€25 bn + €20 bn respectively) AIM: In a proof of concept, we explored a new hospital-at-home model combining hospital cure and nursing home care budgets. This study tests the feasibility of (1) providing hospital care at home, (2) combining financial budgets, (3) increasing workforces by combining teams and (4) improving perspectives and increasing patient and staff satisfaction.
RESULTS
We tested the feasibility of combining the budgets of a teaching hospital and home care group for cardiology. The budgets were sufficient to hire three nurse practitioners who were trained to work together with 12 home care cardiovascular nurses to provide care in a hospital-at-home setting, including intravenous treatment. Subsequently, the hospital-at-home programme for endocarditis and heart failure treatment was developed and a virtual ward was built within the e‑patient record.
CONCLUSION
The current model demonstrates a proof of concept for a hospital-at-home programme providing hospital-level curative care at home by merging hospital and home care nursing staff and budgets. From the clinical perspective, ambulatory intravenous antibiotic and diuretic treatment at home was effective in safely achieving a reduced length of stay of 847 days in endocarditis patients and 201 days in heart-failure-at-home patients. We call for further studies to facilitate combined home care and hospital cure budgets in cardiology to confirm this concept.
PubMed: 34524621
DOI: 10.1007/s12471-021-01614-2 -
Frontiers in Network Physiology 2022Hearing is one of the human's foremost sensors; being able to hear again after suffering from a hearing loss is a great achievement, under all circumstances. However, in...
Hearing is one of the human's foremost sensors; being able to hear again after suffering from a hearing loss is a great achievement, under all circumstances. However, in the long run, users of present-day hearing aids and cochlear implants are generally only halfway satisfied with what the commercial side offers. We demonstrate here that this is due to the failure of a full integration of these devices into the human physiological circuitry. Important parts of the hearing network that remain unestablished are the efferent connections to the cochlea, which strongly affects the faculty of listening. The latter provides the base for coping with the so-called cocktail party problem, or for a full enjoyment of multi-instrumental musical plays. While nature clearly points at how this could be remedied, to achieve this technologically will require the use of advanced high-precision electrodes and high-precision surgery, as we outline here. Corresponding efforts must be pushed forward by coordinated efforts from the side of science, as the commercial players in the field of hearing aids cannot be expected to have a substantial interest in advancements into this direction.
PubMed: 36926095
DOI: 10.3389/fnetp.2022.868470 -
The Journal of Investigative Dermatology Feb 2024Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to...
Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma.
Topics: Animals; Humans; Mice; Desmoplakins; Desmosomes; Hair; Hair Diseases; Keratoderma, Palmoplantar; Skin; Skin Abnormalities
PubMed: 37716648
DOI: 10.1016/j.jid.2023.02.044 -
International Journal of Environmental... Nov 2021Crawling is recommended for avoiding high heat and toxic fumes and for obtaining more breathable air during evacuations. Few studies have evaluated the effects of...
Crawling is recommended for avoiding high heat and toxic fumes and for obtaining more breathable air during evacuations. Few studies have evaluated the effects of crawling on physical joints and velocity, especially in children. Based on motion capture technology, this study proposes a novel method of using wearable sensors to collect exposure (e.g., mean duration, frequency) on children's joints to objectively quantify the impacts of different locomotion methods on physical characteristics. An on-site experiment was conducted in a kindergarten with 28 children (13 boys and 15 girls) of different ages (4-6 years old) who traveled up to 22 m in three different postures: upright walking (UW), stoop walking (SW), and knee and hand crawling (KHC). The results showed that: (1) The level of joint fatigue for KHC was heavier than bipedal walking ( < 0.05), which was evidenced by higher mean duration and frequency. There was no significant difference between UW and SW ( > 0.05). (2) The physical characteristics of the children in the different postures observed in this study were different ( < 0.05). The ankle was more fatigued than other joints during bipedal walking. Unlike infants, the wrists and hips of the children became fatigued while crawling. The key actions flexion/extension are more likely to induce joint fatigue vs. other actions. (3) Crawling velocity was significantly slower than the bipedal velocities, and UW was 10.6% faster than SW ( < 0.05). The bipedal walking velocity started to decrease after the children had travelled up to 13 m, while the KHC velocity started to decrease after traveling up to 11.6 m. (4) In a severe fire, the adoption of SW is suggested, as the evacuees can both evacuate quickly and avoid overworking their joints. (5) There were no significant differences in the age ( > 0.05) and gender ( > 0.05) of the children on the joints in any of the three postures. To conclude, KHC causes more damage to body joints compared to bipedal walking, as evidenced by higher exposure (mean duration, frequency), whereas UW and SW are similar in terms of the level of joint fatigue. The above findings are expected to provide a useful reference for future applications in the children's risk assessment and in the prevention design of buildings.
Topics: Biomechanical Phenomena; Child; Child, Preschool; Ergonomics; Female; Gait; Humans; Infant; Male; Posture; Walking
PubMed: 34831799
DOI: 10.3390/ijerph182212029