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Sitotroga cerealella is one of the major pests of cereals in the field and storage conditions throughout the world. The main objective was to study the life tables of S. cerealella on wheat, maize and barley and its implications on percent parasitism of Trichogramma chilonis. S. cerealella is reared under lab conditions as its eggs are utilized for rearing T. chilonis. Fresh eggs of S. cerealella were collected and after hatching the neonate larvae of S. cerealella were transferred onto each host plant species for obtaining first (F1) generation (G). Seventy eggs were used for each host and each egg was used as a replicate. Daily observations were made for recording the life-table parameters of the S. cerealella. The data showed that the developmental time of S. cerealella eggs and pupae was maximum (5.68 and 7.75 days) when reared on wheat, while the maximum larval duration (19.77 days) of S. cerealella was recorded on barley. The maximum fecundity (290.30 ± 22.47 eggs/female) was recorded on maize, while minimum fecundity per female was recorded on barley (159.30 eggs/ female). The S. cerealella reared on maize had significantly higher values of finite rate of increase (λ), intrinsic rate of increase (r), and net reproductive rate (Ro) (0.14 ± 0.04 day- 1, 1.16 ± 0.05 day- 1, and 136.85 ± 20.25 eggs/ female) respectively. The mean generation time (T) (35.18 ± 0.61 days) was higher on wheat. Likewise, the gross reproductive rate (GRR) and the age-stage specific reproductive values (vxj) of newly oviposited eggs of S. cerealella were recorded higher (136.85 ± 20.25; 1.160 offspring) on maize. The data regarding the efficacy of T. chilonis for different parameters were recorded higher on maize i.e., percent parasitism (89.00 ± 2.30%), percent adult emergence (81.60 ± 1.20%), adult longevity (3.80 ± 0.10 days) and total adult longevity (9.90 ± 0.20 days) as compared to wheat and barley. Our findings revealed that S. cerealella can be best reared on maize under laboratory conditions as it prefers this host as compared to wheat and barley. Therefore, assigning the most susceptible and favorite host (maize) would help us to improve T. chilonis mass production under laboratory conditions.
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Himenópteros , Mariposas Nocturnas , Avispas , Animales , Femenino , Humanos , Recién Nacido , Grano Comestible , Tablas de Vida , Larva , Triticum , Zea maysRESUMEN
The current study regarding the effects of larval diets on the life table parameters of dengue mosquitoes, Aedes aegypti was conducted under laboratory conditions at 27 ± 2 °C and 60 ± 5% relative humidity at NIFA (Nuclear Institute for Food and Agriculture) Peshawar, Pakistan. The data on life table parameters of Ae. aegypti reared on Diet 1 (replacement diet), Diet 2 (Khan's diet for Anopheles), Diet 3 (Khan's modified diet) and Diet 4 (IAEA diet) were analyzed using the age-stage, two-sex life table software. Diet 4 (IAEA) was used as a control for comparison. The results indicated that significantly maximum percentage of egg hatching of Ae. aegypti was observed when reared on Diet 4 (73.86%) and Diet 3 (72.90%), while less % of egg hatching was recorded in Diet 1 (40.67%) and Diet 2 (55.53%). The data further showed that the Diet 3 had a highest intrinsic rate of increase (r) (0.097 ± 5.68 day-1), finite rate of increase (λ) (1.10 ± 6.26 day-1) and net reproductive rate (R0) (11.99 ± 1.52 eggs/female) followed by Diet 2 and Diet 4. The mean generation time (T) of Ae. aegypti reared on Diet 3 (23.67 ± 0.86 days) and Diet 1 (24.05 ± 0.61 days) was significantly shorter than Diet 2 (26.15 ± 0.71 days) and Diet 4 (26.41 ± 0.38 days). The overall results revealed that Diet 3 showed good results at different life table parameters of Ae. aegypti and can be used as the preferred diet in the Sterile Insect Technique (SIT) where the mass culture of mosquitoes is required.
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Aedes , Dengue , Animales , Femenino , Larva , Tablas de Vida , Dieta , HuevosRESUMEN
BACKGROUND: Breast cancer is rare in men. This population-based study aimed to determine outcomes of male breast cancer in relation to residence and other variables. METHODS: In this retrospective cohort study, men diagnosed with breast cancer in Saskatchewan during 2000-2019 were evaluated. Cox proportional multivariable regression analyses were performed to determine the correlation between survival and clinicopathological and contextual factors. RESULTS: One hundred-eight eligible patients with a median age of 69 years were identified. Of them, 16% had WHO performance status ≥ 2 and 61% were rural residents. The stage at diagnosis was as follows: stage 0, 7%; I, 31%; II, 42%; III, 11%; IV, 8%. Ninety-eight percent had hormone receptor-positive breast cancer. The median disease-free survival of urban patients was 97 (95% CI: 50-143) vs. 64 (46-82) months of rural patients (p = 0.29). The median OS of urban patients was 127 (94-159) vs. 93 (32-153) months for rural patients (p = 0.27). On multivariable analysis, performance status ≥ 2, hazard ratio (HR) 2.82 (1.14-6.94), lack of adjuvant systemic therapy, HR 2.47 (1.03-5.92), and node-positive disease, HR 2.32 (1.22-4.40) were significantly correlated with inferior disease-free survival in early-stage invasive breast cancer. Whereas stage IV disease, HR 7.8 (3.1-19.5), performance status ≥ 2, HR 3.25 (1.57-6.71), and age ≥ 65 years, HR 2.37 (1.13-5.0) were correlated with inferior overall survival in all stages. CONCLUSIONS: Although residence was not significantly correlated with outcomes, rural men had numerically inferior survival. Poor performance status, node-positive disease, and lack of adjuvant systemic therapy were correlated with inferior disease-free survival.
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Smart materials are versatile material systems which exhibit a measurable response to external stimuli. Recently, smart material systems have been developed which incorporate graphene in order to share on its various advantageous properties, such as mechanical strength, electrical conductivity, and thermal conductivity as well as to achieve unique stimuli-dependent responses. Here, a graphene fiber-based smart material that exhibits reversible electrical conductivity switching at a relatively low temperature (60 °C), is reported. Using molecular dynamics (MD) simulation and density functional theory-based non-equilibrium Green's function (DFT-NEGF) approach, it is revealed that this thermo-response behavior is due to the change in configuration of amphiphilic triblock dispersant molecules occurring in the graphene fiber during heating or cooling. These conformational changes alter the total number of graphene-graphene contacts within the composite material system, and thus the electrical conductivity as well. Additionally, this graphene fiber fabrication approach uses a scalable, facile, water-based method, that makes it easy to modify material composition ratios. In all, this work represents an important step forward to enable complete functional tuning of graphene-based smart materials at the nanoscale while increasing commercialization viability.
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This study investigates the electrical heating (also known as Joule heating) characteristics of cementitious composites containing multi-walled carbon nanotubes (CNT) and carbon fibers (CF) as electrically conductive media in an attempt to develop an eco-friendly and sustainable solution to snow and ice removal on roadway pavements during the winter season. Various dosages of CNT and CF between 0 and 1.0% (by weight of cement) were tested to find the optimum mixture proportions that yield high-energy and efficient electrical-heating performance with superior mechanical properties. The electrical properties were characterized by measuring the electrical resistivity and temperature rise when attached to a power source. Furthermore, this study examined how the crack width affects the electrical resistivity of cementitious composites containing CNT and/or CF. Compressive and flexural strengths were also measured at different ages of 1, 3, 7, and 28 days to identify how the additions of CNT and CF affect the mechanical properties. Results have shown that adding CF in combination with CNT substantially reduces the electrical resistivity and, in turn, improves the heating performance, as CFs further densify the electrically conductive network in the hydrated matrix; adding either CNT or CF alone was not an effective option to enhance the electrical characteristics. The findings of this study are expected to provide essential information for the design and construction of an electrically heated concrete pavement system with promoted energy efficiency, which will offer a promising solution to enhance winter road maintenance, improve public safety, and provide substantial social cost savings.
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The current global outbreak of monkeypox (MPX) disease, caused by Monkeypox virus (MPXV), has resulted in 16 thousand infection cases, five deaths, and has been declared a global health emergency of international concern by the World Health Organization. Given current challenges in the safety of existing vaccines, a vaccine to prevent MPX infection and/or onset of symptoms would significantly advance disease management. In this context, a multi-epitope-based vaccine could be a well-suited approach. Herein, we searched a publicly accessible database (Virus Pathogen Database and Analysis Resource) for MPXV immune epitopes from various antigens. We prioritized a group of epitopes (10 CD8+ T cells and four B-cell epitopes) using a computer-aided technique based on desirable immunological and physicochemical properties, sequence conservation criteria, and non-human homology. Three multi-epitope vaccines were constructed (MPXV-1-3) by fusing finalized epitopes with the aid of appropriate linkers and adjuvant (beta-defensin 3, 50S ribosomal protein L7/L12, and Heparin-binding hemagglutinin). Codon optimization and in silico cloning in the pET28a (+) expression vector ensure the optimal expression of each construct in the Escherichia Coli system. Two and three-dimensional structures of the constructed vaccines were predicted and refined. The optimal binding mode of the construct with immune receptors [Toll-like receptors (TLR2, TLR3, and TLR4)] was explored by molecular docking, which revealed high docking energies of MPXV-1-TLR3 (-99.09 kcal/mol), MPXV-2-TLR3 (-98.68 kcal/mol), and MPXV-3-TLR2 (-85.22 kcal/mol). Conformational stability and energetically favourable binding of the vaccine-TLR2/3 complexes were assessed by performing molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). In silico immune simulation suggested that innate, adaptive, and humoral responses will be elicited upon administration of such potent multi-epitope vaccine constructs. The vaccine constructs are antigenic, non-allergen, non-toxic, soluble, topographically exposed, and possess favourable physicochemical characteristics. These results may help experimental vaccinologists design a potent MPX vaccine.
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Epítopos de Linfocito T , Mpox , Humanos , Vacunas de Subunidad , Simulación del Acoplamiento Molecular , Receptor Toll-Like 2 , Receptor Toll-Like 3 , Secuencia de Aminoácidos , Biología Computacional/métodosRESUMEN
The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is the most notorious insect pest of potato globally. Injudicious use of insecticides for management of this pest has resulted in resistance to all major groups of insecticides along with many human, animal health, and environmental concerns. Additionally, the input cost of insecticide development/discovery is markedly increasing because each year thousands of chemicals are produced and tested for their insecticidal properties, requiring billions of dollars. For the management of resistance in insect pests, synergists can play a pivotal role by reducing the application dose of most insecticides. These eco-friendly synergists can be classified into two types: plant-based synergists and RNAi-based synergists. The use of plant-based and RNAi-based synergists in resistance management of insect pests can give promising results with lesser environmental side effects. This review summarizes the resistance status of CPB and discusses the potential advantage of plant-based and RNAi-based synergists for CPB resistance management. It will motivate researchers to further investigate the techniques of using plant- and RNAi-based synergists in combination with insecticides.
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Cadmium (Cd) is one the leading environmental contaminants. The Cd toxicity and its potential stabilization strategies have been investigated in the recent years. However, the combined effects of biochar and microorganisms on the adsorption of Cd and maize plant physiology, still remained unclear. Therefore, this experiment was conducted to evaluate the combined effects of biochar (BC) pyrolyzed from (maize-straw, cow-manure, and poultry-manure, and microorganisms [Trichoderma harzianum (fungus) and Bacillus subtilis (bacteria)], on plant nutrient uptake under various Cd-stress levels (0, 10, and 30 ppm). The highest level of Cd stress (30 ppm) caused the highest reduction in maize plant biomass, intercellular CO2, transpiration rate, water use efficiency, stomatal conductance, and photosynthesis rate as compared to control Cd0 (0 ppm). The sole application of BC and microorganisms significantly improved plant growth, intercellular CO2, transpiration rate, water use efficiency, stomatal conductance, and photosynthesis rate and caused a significant reduction in root and shoot Cd. However, the co-application of BC and microorganisms was more effective than the sole applications. In this regard, the highest improvement in plant growth and carbon assimilation, and highest reduction in root and shoot Cd was recorded from co-application of cow-manure and combined inoculation of Trichoderma harzianum (fungus) + Bacillus subtilis (bacteria) under Cd stress. However, due to the aging factor and biochar leaching alkalinity, the effectiveness of biochar in removing Cd may diminish over time, necessitating long-term experiments to improve understanding of biochar and microbial efficiency for specific bioremediation aims.
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Cancer is the most common cause of mortality worldwide. There is dire need of modern strategies-such as surface modification of nanocarriers-to combat this global illness. Incorporation of active targeting ligands has arisen as a novel platform for specific tumor targeting. The aim of the current study was to formulate PEG-protamine complex (PPC) of doxorubicin (DOX) for treatment of breast cancer (BC). DOX coupling with PEG can enhance cell-penetrating ability: combating resistance in MDA-MB 231 breast cancer cells. Ionic gelation method was adopted to fabricate a pH sensitive nanocomplex. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. In vitro assay was executed to gauge the release potential of nanoformulation. The mean particle size, zeta potential, and polydispersity index (PDI) of the optimized nanoparticles were observed to be 212 nm, 15.2 mV, and 0.264, respectively. Crystallinity studies and Fourier transform infrared (FTIR) analysis revealed no molecular interaction and confirmed the amorphous nature of drug within nanoparticles. The in vitro release data indicate sustained drug release at pH 4.8, which is intracellular pH of breast cancer cells, as compared to the drug solution. PPC loaded with doxorubicin can be utilized as an alternative and effective approach for specific targeting of breast cancer.
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Healthcare workers in Pakistan are still fighting at the frontline to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have been identified as the earliest beneficiaries for COVID-19 vaccination by the health authorities of the country. Besides, the high vaccination rates of frontline healthcare workers (FHWs) are essential to overcome the ongoing pandemic and reduce the vaccines hesitancy among the general population. The current research employed the theory of planned behavior (TPB) to investigate the COVID-19 vaccination behavior among FHWs in Pakistan as well as the predictors of such behavior. Following the epidemic control and prevention policies, a sample of 680 FHWs were accessed to fill in the questionnaire evaluating the components of the TPB. Moreover, the potential role of anticipated regret (AR) and perceived susceptibility (PS) on COVID-19 vaccination behavior was also assessed. The partial least square structural equation modeling (PLS-SEM) results revealed that the TPB components, as well as the AR, have positive associations with the COVID-19 vaccination behavior. The results further confirmed that PS positively affects the anticipated regret, attitude (ATT), and subjective norm (SN) to vaccinate against SARS-CoV-2. The perceived susceptibility also has a positive association with COVID-19 vaccination behavior through the mediation of anticipated regret, ATT, and SN. Our findings highlighted the importance of COVID-19 vaccination among healthcare workers, which can be applied to reduce vaccine hesitancy among the general public.
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This paper reports the fabrication and mechanical properties of macroscale graphene fibers (diameters of 10 to 100 µm with lengths upwards of 2 cm) prepared from a single sheet of single-layer graphene grown via chemical vapor deposition (CVD). The breaking strength of these graphene fibers increased with consecutive tensile test measurements on a single fiber, where fiber fragments produced from a prior test exhibited larger breaking strengths. Additionally, we observed an overall reduction of surface folds and wrinkles, and an increase in their alignment parallel to the tensile direction. We propose that a foundation of this property is the plastic deformations within the fiber that accumulate through sequential tensile testing. Through this cyclic method, our best fiber produced a strength of 2.67 GPa with a 1 mm gauge length.
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BACKGROUND: Serine/threonine kinase 3 (AKT3) is a protein-coding gene that is associated with several cattle immune diseases including different tumors and cancers. The objective of this study was to investigate the differences in structures and functions of AKT3 of cow and buffalo cattle. METHODS: The sequence differences of gene-coding sequence (CDS) and core promoter region of AKT3 in cow and buffalo were analyzed by using bioinformatics tools and PCR sequencing. Also, the functional analysis of promoter regulating gene expression by RT-PCR was performed using 500 Holstein cows and buffalos. And, evaluation of AKT3 inflammatory response to the lipopolysaccharide (LPS)-induced mastitis was performed between both species. RESULTS: The results revealed the variation in 6 exons out of 13 exons of the two species of CDS. Also, 4 different regions in 3-kb promoters of the AKT3 gene were significantly different between cow and buffalo species, in which cow's AKT3 promoter sequence region was started from - 371 to - 1247, while in buffalo, the sequence was started from - 371 to - 969 of the promoter crucial region. Thus, the promoter was overexpressed in cows compared to buffaloes. As a result, significant differences (P < 0.05) between the two species in the AKT3 gene expression level related to the LPS stimulation in their mammary epithelial cell line. CONCLUSIONS: This study emphasized the great importance of the structural differences of AKT3 between the animal species on their different responses against immune diseases like mastitis.
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Glutaraldehyde is a widely used biocide on the market for about 50 years. Despite its broad application, several reports on the emergence of bacterial resistance, and occasional outbreaks caused by poorly disinfection, there is a gap of knowledge on the bacterial adaptation, tolerance, and resistance mechanisms to glutaraldehyde. Here, we analyze the effects of the independent selection of mutations in the transcriptional regulator yqhC for biological replicates of Escherichia coli cells subjected to adaptive laboratory evolution (ALE) in the presence of glutaraldehyde. The evolved strains showed improved survival in the biocide (11-26% increase in fitness) as a result of mutations in the activator yqhC, which led to the overexpression of the yqhD aldehyde reductase gene by 8 to over 30-fold (3.1-5.2 log2FC range). The protective effect was exclusive to yqhD as other aldehyde reductase genes of E. coli, such as yahK, ybbO, yghA, and ahr did not offer protection against the biocide. We describe a novel mechanism of tolerance to glutaraldehyde based on the activation of the aldehyde reductase YqhD by YqhC and bring attention to the potential for the selection of such tolerance mechanism outside the laboratory, given the existence of YqhD homologs in various pathogenic and opportunistic bacterial species.
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INTRODUCTION: This was a comparison of laser trabeculoplasty (LTP) outcomes in eyes with prior Kahook Dual Blade (KDB) goniotomy versus in goniotomy-naive control eyes. METHODS: This was a retrospective matched comparative case series. We identified a cohort of patients undergoing LTP between February 2017 and July 2020 at University of Missouri. Patients were grouped by history of KDB goniotomy versus goniotomy-naivety as a control group. Inclusion criteria included age at least 18 years, minimum of 6 months follow-up after LTP, and minimum period of 6 months between KDB goniotomy and LTP. All KDB procedures were combined with uncomplicated phacoemulsification. Patients who had any additional intraocular pressure (IOP)-lowering procedures between KDB goniotomy and LTP were excluded. Patients in the control group received a single LTP procedure. Primary outcome consisted of the comparison of LTP success, defined as IOP reduction of at least 20% or reduction of glaucoma medications from pre-LTP baseline. Secondary outcomes included IOP and medication reduction from pre-LTP baseline. RESULTS: Twenty-one eyes of 19 patients with history of KDB goniotomy and 42 eyes of 36 control patients without previous angle or laser procedures were included. Baseline characteristics including age, gender, ethnicity, type and severity of glaucoma, baseline IOP, and baseline medications were matched between groups. The LTP success rate was higher in the control group, but was not statistically significant (64% vs 57%, p = 0.58). IOP reduction was only significant in the control eyes (2.50 ± 4.0 mmHg, p = 0.01 vs 2.35 ± 4.7 mmHg, p = 0.08). The number of glaucoma medications was not significantly reduced in either group. CONCLUSION: LTP may have a limited IOP- and medication-lowering effect in eyes with a history of KDB goniotomy compared to goniotomy-naive eyes.
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Extraction and exploration of petroleum hydrocarbons (PHs) to satisfy the rising world population's fossil fuel demand is playing havoc with human beings and other life forms by contaminating the ecosystem, particularly the soil. In the current review, we highlighted the sources of PHs contamination, factors affecting the PHs accumulation in soil, mechanisms of uptake, translocation and potential toxic effects of PHs on plants. In plants, PHs reduce the seed germination andnutrients translocation, and induce oxidative stress, disturb the plant metabolic activity and inhibit the plant physiology and morphology that ultimately reduce plant yield. Moreover, the defense strategy in plants to mitigate the PHs toxicity and other potential remediation techniques, including the use of organic manure, compost, plant hormones, and biochar, and application of microbe-assisted remediation, and phytoremediation are also discussed in the current review. These remediation strategies not only help to remediate PHs pollutionin the soil rhizosphere but also enhance the morphological and physiological attributes of plant and results to improve crop yield under PHs contaminated soils. This review aims to provide significant information on ecological importance of PHs stress in various interdisciplinary investigations and critical remediation techniques to mitigate the contamination of PHs in agricultural soils.
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Petróleo , Contaminantes del Suelo , Biodegradación Ambiental , Ecosistema , Humanos , Hidrocarburos/toxicidad , Petróleo/toxicidad , Suelo , Microbiología del Suelo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidadRESUMEN
BACKGROUND: Although physical activity has been consistently associated with reduced breast cancer mortality, evidence is largely based on data collected at one occasion. We examined how pre- and postdiagnosis physical activity was associated with survival outcomes in high-risk breast cancer patients. METHODS: Included were 1340 patients enrolled in the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) Study, a prospective study of lifestyle and prognosis ancillary to a SWOG clinical trial (S0221). Activity before diagnosis, during treatment, and at 1- and 2-year intervals after enrollment was collected. Patients were categorized according to the Physical Activity Guidelines for Americans as meeting the minimum guidelines (yes/no) and incrementally as inactive, low active, moderately active (meeting the guidelines), or high active. RESULTS: In joint-exposure analyses, patients meeting the guidelines before and 1 year after diagnosis experienced statistically significant reductions in hazards of recurrence (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.42 to 0.82) and mortality (HR = 0.51, 95% CI = 0.34-0.77); associations were stronger at 2-year follow-up for recurrence (HR = 0.45, 95% CI = 0.31 to 0.65) and mortality (HR = 0.32, 95% CI = 0.19 to 0.52). In time-dependent analyses, factoring in activity from all time points, we observed striking associations with mortality for low- (HR = 0.41, 95% CI = 0.24 to 0.68), moderate- (HR = 0.42, 95% CI = 0.23 to 0.76), and high-active patients (HR = 0.31, 95% CI = 0.18 to 0.53). CONCLUSIONS: Meeting the minimum guidelines for physical activity both before diagnosis and after treatment appears to be associated with statistically significantly reduced hazards of recurrence and mortality among breast cancer patients. When considering activity from all time points, including during treatment, lower volumes of regular activity were associated with similar overall survival advantages as meeting and exceeding the guidelines.
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Neoplasias de la Mama/terapia , Quimioterapia , Ejercicio Físico , Recurrencia Local de Neoplasia/terapia , Anciano , Mama/efectos de los fármacos , Mama/patología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
Origami design principles are scale invariant and enable direct miniaturization of origami structures provided the sheets used for folding have equal thickness to length ratios. Recently, seminal steps have been taken to fabricate microscale origami using unidirectionally actuated sheets with nanoscale thickness. Here, we extend the full power of origami-inspired fabrication to nanoscale sheets by engineering bidirectional folding with 4 nm thick atomic layer deposition (ALD) SiNx-SiO2 bilayer films. Strain differentials within these bilayers result in bending, producing microscopic radii of curvature. We lithographically pattern these bilayers and localize the bending using rigid panels to fabricate a variety of complex micro-origami devices. Upon release, these devices self-fold according to prescribed patterns. Our approach combines planar semiconductor microfabrication methods with computerized origami design, making it easy to fabricate and deploy such microstructures en masse. These devices represent an important step forward in the fabrication and assembly of deployable micromechanical systems that can interact with and manipulate micro- and nanoscale environments.
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PURPOSE: Despite reported widespread use of dietary supplements during cancer treatment, few empirical data with regard to their safety or efficacy exist. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes. METHODS: Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cox proportional hazards regression adjusting for clinical and lifestyle variables was used. Recurrence and survival were indexed at 6 months after enrollment using a landmark approach. RESULTS: There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P = .06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P = .14). Relationships with individual antioxidants were weaker perhaps because of small numbers. For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P < .01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P < .01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P < .01) as was use both before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P = .06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes. CONCLUSION: Associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Suplementos Dietéticos , Administración Metronómica , Antioxidantes/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Modelos de Riesgos Proporcionales , Vitaminas/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the genetic factor responsible for causing microcephaly and determine allelic heterogeneity of Abnormal spindle microtubule gene. METHODS: The genetic study was conducted at the Kohat University of Science and Technology, Kohat, and Gomal University, D.I.Khan, Pakistan, during 2017-18, and comprised 5 consanguineous families from South Waziristan, Kurram Agency, Karak, Bannu and Dera Ismail Khan regions of the country's Khyber Pakhtukhwa province. Blood samples from all available and cooperative family members (including normal and affected) were obtained, and molecular analysis was carried out through whole genome single nucleotide polymorphisms genotyping, exome sequencing and Sanger sequencing. RESULTS: Of the 15 patients, 9(60%) were males and 6(40%) were females. Genetic mapping revealed linkage to the MCPH5 locus which harbours the microcephaly-associated abnormal spindle-like microcephaly gene. Mutation analysis of the gene identified missense mutation c.3978G>A (p.Trp1326*) in families A, B and C, a deletion mutation c.7782_7783delGA (p.(Lys2595Serfs*6)) in family D, and a splice site defect c.2936+5G>A in family E. CONCLUSIONS: There was suggestion of strong founder effect of mutation c.3978G>A (p.Trp1326*).