Microneedles: A novel clinical technology for evaluating skin characteristics.

BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment. Non-invasive devices measured skin aging (using high-resolution 3D-imaging in the anti-aging study) or pigmentation (using spectrophotometry in the anti-pigmentation study) at weeks 0 and 4, and adverse skin reactions were monitored. Skin samples were collected with biocompatible microneedle patches. Changes in expression of biomarkers for skin aging and pigmentation were analyzed using qRT-PCR. RESULTS: No adverse events were reported. In the anti-aging study, after 4 weeks, skin roughness significantly improved in 17 out of 20 participants. qRT-PCR showed significantly increased expression of skin-aging related biomarkers: PINK1 in 16/20 participants, COL1A1 in 17/20 participants, and MSN in 16/20 participants. In the anti-pigmentation study, after 4 weeks, skin lightness significantly improved in 16/20 participants. qRT-PCR showed significantly increased expression of skin-pigmentation-related biomarkers: SOD1 in 15/20 participants and Vitamin D Receptor (VDR) in 15/20 participants. No significant change in TFAP2A was observed. CONCLUSION: Skin sampling and mRNA analysis for biomarkers provides a novel, objective, quantitative method for measuring changes in the dermis and evaluating the efficacy of cosmetics. This approach complements existing evaluation methods and has potential application in assessing the effectiveness of medical devices, medications, cosmeceuticals, healthy foods, and beauty devices.

Mosquito Repellents: Efficacy Tests of Commercial Skin-Applied Products in China.

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5-3.88 h landing time and/or 1-5.63 h probing time) and lower prices (13.9-21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents.

Incorporation of electroendocytosis and nanosecond pulsed electric field in electrochemotherapy of breast cancer cells.

The study aimed to evaluate the possibility to perform electrochemotherapy using nanosecond pulsed electric field (nsPEF) and low electric field (LEF) monopolar electrical impulses to alleviate the problems of conventional electroporation. Two types of pulses have been used to treat MCF-7 human breast carcinoma cell line: very low voltage (electric field strength) long trains of short unipolar electric pulses, and low frequencies of extremely intense (40kV/cm), ultra-short (10ns) electric pulses. The electropermeabilization efficiency of the formed endocytotic vesicles was measured using the cloning efficacy test. The cell viability was decreased significantly at a repetition frequency begins from 0.01 Hz by ~35% and reached complete cell loss at 1 Hz of nanosecond pulses for cells treated before with monopolar pulses at 20 V/cm in the presence of BLM with 4 µM concentration. The uptake of non-permeant drugs has been done without plasma membrane permeabilization (classical electroporation), but by endocytosis. Nanosecond electric pulses can disrupt the membrane of endocytotic vesicles and release the cytotoxic drug bleomycin.

Comparative study of rapid ATP bioluminescence assay and conventional plate count method for development of rapid disinfecting activity test.

Antimicrobial activity is tested when developing disinfectants, pharmaceutical products, cosmetics, and many other consumer products. However, the plate count method, the conventional way to count the number of microorganisms, needs several days of culture. Consequently, a means of rapid microbial detection is strongly desired to replace this method. We have already developed a rapid and sensitive microbial adenosine triphosphate (ATP) detection system utilizing ATP bioluminescence, which can quantify microbial ATP within 1 h. To apply this technique to antibacterial activity tests, the ATP method should be proved equal or superior to the conventional method. In this study, we conducted disinfectant activity tests comparing the ATP method and the plate count method, using polyhexamethylene biguanide (PHMB) in different concentrations (0-10 ppm) as a model disinfectant against Staphylococcus aureus and Aspergillus brasiliensis. We found that the log reduction of intracellular ATP had a positive correlation with the log reduction of the plate count. Moreover, the ATP method was able to distinguish different conditions of injured microbial cells that were observed using scanning electron microscopy, whereas colony counting detects only culturable cells. The ATP method is thus a rapid and useful alternative to the conventional method in the field of antimicrobial activity testing.

Artificial dry surface biofilm models for testing the efficacy of cleaning and disinfection.

Dry surface biofilms (DSB) harbouring pathogens are widespread in healthcare settings, are difficult to detect and are resistant to cleaning and disinfection interventions. Here, we describe a practical test protocol to palliate the lack of standard efficacy test methods for DSB. Staphylococcus aureus DSB were produced over a 12-day period, grown with or without the presence of organic matter, and their composition and viability were evaluated. Disinfectant treatment was conducted with a modified ASTM2967-15 test and reduction in viability, transferability and biofilm regrowth post-treatment were measured. Dry surface biofilms produced over a 12-day period had a similar carbohydrates, proteins and DNA content, regardless of the presence or absence of organic matter. The combination of sodium hypochlorite (1000 ppm) and a microfiber cloth was only effective against DSB in the absence of organic load. With the increasing concerns of the uncontrolled presence of DSB in healthcare settings, the development of effective intervention model in the presence of organic load is appropriate for the testing of biocidal products, while the use of three parameters, log10 reduction, transferability and regrowth, provides an accurate and practical measurement of product efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: The widespread presence of biofilms on dry surfaces in healthcare settings has been recently documented. These dry surface biofilms (DSB) present an unprecedented challenge to cleaning and disinfection processes. Here, we describe a practical efficacy protocol based on an in vitro Staphylococcus aureus DSB model. The protocol measures reduction in viability, transferability and biofilm regrowth post-treatment to provide altogether a practical assessment of product efficacy against dry surface biofilms.

Laboratory evaluation of repellency of traditional Czech homemade repellents against Aedes aegypti.

OBJECTIVES: In the Czech Republic, autochtonous transmission of mosquito borne diseases is not common; however, the need for personal protection should not be underestimated. Many people still rely on homemade repellents utilizing recipes based on local folk wisdom that are published annually in local Czech media. Despite minimal disease risk, nuisance biting and potential allergic responses make it essential to evaluate the chemical composition, effect, and duration of four homemade repellents often used and determine the necessity for public health education on application and use of alternative repellent products. METHODS: A review of local web-based media was conducted to identify the most commonly advertised homemade repellent products. The top four products were rosemary (Rosmarinus officinalis), sagebrush (Artemisia absinthium), walnut-tree (Juglans regia) leaves and clove (Syzygium aromaticum). These repellents were then prepared following the published recipes to evaluate their repellency effects, and reveal potential allergen presence. A bioassay against Aedes aegypti was conducted on ten volunteers for each repellent and the chemical composition was detected using gas chromatography. RESULTS: Significant initial repellency effect was found in mixtures of the clove (73.1%) and walnut leaves (49.0%) with ALPATM herbal embrocation after 10 minutes. The efficacy decreased to 46.5% and 34.3 % after 30 minutes, respectively; and, 30.3 and 18.2%, 60 minutes after the application. The remaining two samples, Rosmarinus officinalis and Artemisia absinthium solutions, exhibited no significant effects against Ae. aegypti. The evidence of allergens including cinnamic aldehyde, eugenol and coumarin were detected indicating potential concerns for product safety. CONCLUSION: The homemade repellents reviewed were either ineffective or had unstable repellency effect within one hour. The low efficacy of these products may be appropriate to decrease nuisance biting, but should not be considered for primary prevention against mosquito borne diseases in areas with active disease transmission. Additionally, more research is needed to assess rates of allergic responses to homemade repellent products.

Temperature-mediated absorption of phenylmercuric nitrate on polyethylene and polypropylene containers in chloramphenicol eye drops.

The aim of this work was to find the effect of temperature and manufacturing source of phenylmercuric nitrate (PMN) on PMN absorption on low-density polyethylene (LDPE) and polypropylene containers in chloramphenicol eye drops. Two factorial experiments were designed to study the effect of temperature on PMN assay in chloramphenicol eye drops stored in LDPE and prepared from two different PMN sources. PMN source had no effect on PMN assay at 2-8 °C, however at stress conditions (30 °C/75%RH) for 3 weeks, the effect of PMN source on PMN assay was found significant (p < 0.05) in formulations stored in LDPE bottles. Temperature was the major contributor to decreased PMN assay. In formulations stored in polypropylene containers, PMN source had significant effect on PMN assay at 2-8 °C and 30 °C/75%RH. Overall, new PMN and polypropylene bottles performed better. The eye drops complied with preservative efficacy test both initially and at the end of shelf life. The concentration exponent of PMN is very low and in spite of its high absorption by container/closure, PMN was still able to protect the eye drops at the end of shelf life. It can be inferred that preservative efficacy test is the better indicator of preservative activity.

Evaluation of Swine Protection with Three Commercial Foot-and-Mouth Disease Vaccines against Heterologous Challenge with Type A ASIA/G-VII Lineage Viruses.

Outbreaks caused by foot-and-mouth disease (FMD) A/ASIA/G-VII lineage viruses have often occurred in Middle Eastern and Southeast Asian countries since 2015. Because A/ASIA/G-VII lineage viruses are reported to have distinct antigenic relatedness with available commercial FMD vaccine strains, it is necessary to investigate whether inoculation with vaccines used in Korea could confer cross-protection against A/ASIA/G-VII lineage viruses. In the present study, we conducted two vaccination challenge trials to evaluate the efficacy of three commercial FMD vaccines (O/Manisa + O/3039 + A/Iraq, O/Campos + A/Cruzeiro + A/2001, and O/Primorsky + A/Zabaikalsky) against heterologous challenge with ASIA/G-VII lineage viruses (A/TUR/13/2017 or A/BHU/3/2017 strains) in pigs. In each trial, clinical signs, viremia, and salivary shedding of virus were measured for 7 days after challenge. In summary, the O/Campos + A/Cruzeiro + A/2001 vaccine provided full protection against two A/ASIA/G-VII lineage viruses in vaccinated pigs, where significant protection was observed. Although unprotected animals were observed in groups vaccinated with O/Manisa + O/3039 + A/Iraq or O/Primorsky + A/Zabaikalsky vaccines, the clinical scores and viral RNA levels in the sera and oral swabs of vaccinated animals were significantly lower than those of unvaccinated controls.

Effect of a Single Intrauterine Dose of Human Recombinant Galectin-1 Buffered on Pregnancy Rate in Inseminated Cows.

The objective was to evaluate the efficacy of a single dose of exogenous galectin-1 in improving the pregnancy rate in inseminated cows, comparing the pregnancy rate of the two groups (treatment and control Groups) into 107 contemporary groups (YG) established. An ultrasound exam determined the pregnancy rate performed 25 to 35 days after the fixed-time artificial insemination (FTAI) of breeding beef cows (n = 3469). The pregnancy rate of cows that received a single dose of eGAL-1 (200 ± 10 µg), with an intrauterine administration (n = 1901), was compared with the pregnancy rate of cows inseminated using a conventional AI protocol (n = 1568), both comparing into the same YG. YGs were created considering the grouping of cows belonging to the same farm, with the same nutritional score and management, inseminated by the same inseminator and semen batch, and using the same estrus synchronization protocol). The statistical method used calculated the probability of obtaining pregnancy within each group. The administration of a single dose of eGAL-1 can increase the probability of obtaining pregnancy in beef cows by up to 8.68% (p < 0.0001), suggesting that a single dose of eGAL-1 during the FTAI procedure was reasonable in the beef cattle AI routine and can improve the pregnancy rate considerably.

A Novel Cost-Effective Nanobody against Fumonisin B1 Contaminations: Efficacy Test in Dairy Milk and Chickens.

BACKGROUND: Fumonisin B1 (FB1) is a secondary metabolite produced mainly by Fusarium verticillioides or Fusarium proliferatum. It poses a huge threat to the sustainable animal industry and human health as well via food chains (egg, meat and milk). Although E. coli-expressed nanobodies are documented for diagnostic applications, nanobodies remain elusive as FB1 detoxifiers in feed and food. RESULTS: In the present study, the E. coli-expressed nanobody was assessed to remove FB1 in fresh milk, embryonated eggs and broilers. Firstly, 2 alpacas received intramuscularly FB1-adjuvanted BSA 6 times, and then the variable domain of the heavy-chain antibody (VHH) of fb1 genes were amplified to clone into the pCANTAB 5 E vector in order to generate a VHH-FB1 phage antibody display library, yielding 3.4 × 1010 capacity with 96.7% positivity. Afterwards, 5 anti-FB1 nanobodies were expressed and identified. Furthermore, maximal 43.2% FB1 was removed from milk by 1:2000 concentration of nanobody 5 (Nb5). Furthermore, SPF-embryonated eggs were inoculated into albumens with nanobody-treated FB1. The Nb5 group yielded an 83.3% hatching rate, higher body weight, lower gizzard ulceration and fewer FB1 residuals. In order to warrant the above results, 50 broilers aged 10 days were received orally with 20 ppm of FB1 for 20 days. At the same time, birds were fed orally with 50 µg of Nb5 or bivalent nanobody 11 (BiNb11). Finally, the Nb5 group showed a higher relative body weight gain and lower gastric ulcerations and fewer inflammations in the thymus and bursa. CONCLUSIONS: Based on the above evidence, the Nb5 nanobody may be considered as an additional FB1 detoxifier, contributing to FB1 decontamination.

The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery.

The cancer burden is rapidly increasing in most countries, and thus, new anticancer drugs for effective cancer therapy must be developed. Cancer model systems that recapitulate the biological processes of human cancers are one of the cores of the drug development process. PDCO has emerged as a unique model that preserves the genetic, physiological, and histologic characteristics of original cancer, including inter- and intratumoral heterogeneities. Due to these advantages, the PCDO model is increasingly investigated for anticancer drug screening and efficacy testing, preclinical patient stratification, and precision medicine for selecting the most effective anticancer therapy for patients. Here, we review the prospects and limitations of PDCO compared to the conventional cancer models. With advances in culture success rates, co-culture systems with the tumor microenvironment, organoid-on-a-chip technology, and automation technology, PDCO will become the most promising model to develop anticancer drugs and precision medicine.

Comparison of Different Temperature Conditions for Microbial Enumeration of Aspergillus brasiliensis in the Preservative Efficacy Test.

The preservative efficacy test is an important method for assessing the antimicrobial effect of cosmetic products. In this study, the optimum conditions for the efficient microbial enumeration of Aspergillus brasiliensis were investigated. Cosmetic products, inoculated with A. brasiliensis spore suspensions, were cultivated at 22.5°C, 32.5°C, or 40°C and the detection rate and the number of colonies were determined using the pour culture method. There was no difference in the viable counts of visible colonies among different temperature conditions. However, the viable counts after 3 days of culture were significantly greater for the cultures maintained at 32.5°C or 40°C compared with those maintained at 22.5°C. This effect was attenuated in products containing fatty acids, which could inhibit fungal growth. Overall, these results demonstrate that cultivating A. brasiliensis at 32.5°C reduces the time required for enumeration in the preservative efficacy test. Thus, the results of this study are expected to help improve and expedite microbiological quality control in the cosmetic industry.

Blue light protection, part II-Ingredients and performance testing methods.

BACKGROUND: There are numerous cosmetic ingredients that have been identified to have blue light protection benefits. The urge to learn more about blue light protection claims has led to several substantiation test methods that can be utilized by companies to prove product efficacy. AIMS: Part II of this article provides up-to-date information on cosmetic ingredients that can provide protection from blue light, and methods companies can use to substantiate blue light protection claims. METHODS: An Internet search was completed using the Google Scholar database and a cosmetic ingredient supplier database (UL Prospector) for ingredients and relevant literature. RESULTS: Multiple ingredient categories, for example, algae-derived ingredients, UV filters, botanical extracts, antioxidants, and vitamins, are available on the market to fight against blue light-induced skin damage. There is not a formal standardized method to test for blue light protection; however, spectrophotometers, imaging devices, measuring oxidative stress, and visual evaluations are some of the methods being used today. CONCLUSIONS: The number of ingredients launched for blue light protection and new methods developed to test products for blue light protection claims is expected to increase in the near future as we are learning more about the mechanism of damage that occurs in the skin upon blue light exposure.

Residual Activity of Acaricides for Controlling Spider Mites in Watermelon and Their Impacts on Resident Predatory Mites.

Twospotted spider mite, Tetranychus urticae Koch (Trombidiformes: Tetranychidae), is an important, worldwide pest of watermelon, Citrullus lanatus L. (Thunb.) Matsum. & Nakai (Cucurbitales: Cucurbitaceae). Feeding results in chlorotic spots and leaf necrosis, which can substantially reduce yields. In watermelon, T. urticae is managed solely with acaricides. Issues with acaricide resistance and pesticide label restrictions on number of applications per season require research-based recommendations on products with effective, long-lasting residues. To improve recommendations for T. urticae management in watermelon and to measure possible effects on non-target beneficial mites, we conducted acaricide efficacy trials in two locations in South Carolina, United States. The adulticidal products abamectin, bifenazate, fenpyroximate, and tolfenpyrad and the ovicidal products spiromesifen and etoxazole were tested. We also conducted two bioassays to better determine duration of acaricide residues. In the field trials, all acaricides except tolfenpyrad reduced T. urticae abundance, but all acaricides also reduced abundance of the most common predatory mite, Neoseiulus fallacis (Garman) (Mesostigmata: Phytoseiidae). In the bioassays, abamectin and bifenazate residues caused high adult T. urticae mortality at up to 21 d after treatment, performing better than fenpyroximate and tolfenpyrad. Etoxazole and spiromesifen were longer lasting, with <1 offspring per treated female in the etoxazole treatment at 28 d after treatment. Based on efficacy, abamectin or bifenazate should be rotated with etoxazole for fast knockdown of active stages while reducing reproduction, respectively. However, development and registration of more selective acaricides in watermelon is needed to preserve biological control of T. urticae by predatory mites.

Characterization and In Vitro Efficacy against Listeria monocytogenes of a Newly Isolated Bacteriophage, ɸIZSAM-1.

Listeria monocytogenes is a bacterial pathogen responsible of listeriosis, a disease that in humans is often related to the contamination of ready-to-eat foods. Phages are candidate biodecontaminants of pathogenic bacteria thanks to their ability to lyse prokaryotes while being safe for eukaryotic cells. In this study, ɸIZSAM-1 was isolated from the drain-waters of an Italian blue cheese plant and showed lytic activity against antimicrobial resistant Listeria monocytogenes strains. This phage was subjected to purification and in vitro efficacy tests. The results showed that at multiplicities of infection (MOIs) ≤ 1, phages were able to keep Listeria monocytogenes at low optical density values up to 8 h, with bacterial counts ranging from 1.02 to 3.96 log10 units lower than the control. Besides, ɸIZSAM-1 was further characterized, showing 25 principal proteins (sodium dodecyl sulfate polyacrylamide gel electrophoresis profile) and a genome of approximately 50 kilo base pairs. Moreover, this study describes a new approach to phage isolation for applications in Listeriamonocytogenes biocontrol in food production. In particular, the authors believe that the selection of phages from the same environments where pathogens live could represent a new approach to successfully integrating the control measures in an innovative, cost effective, safe and environmentally friendly way.

Blue Light Protection, Part I-Effects of blue light on the skin.

BACKGROUND: Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight, but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to learn more about this topic is increasing as well. AIMS: Part I of this article provides up-to-date information on the definition of blue light and the negative and positive effects of blue light on the skin. METHODS: An Internet search was completed using the Google scholar database for relevant literature. RESULTS: Blue light can be both harmful and beneficial to the skin, depending on intensity and wavelength. Short-term safety information is more readily available from clinical studies; however, the biological effects of repeated and/or longer-term exposure are not fully understood yet. CONCLUSIONS: Low-energy and low exposure times to high-energy blue light can help prevent skin diseases, while studies have revealed that longer exposure to high-energy blue light can increase the amount of DNA damage, cell and tissue death, and injury, eye damage, skin barrier damage, and photoaging.

3D fluid-dynamic ovarian cancer model resembling systemic drug administration for efficacy assay.

Recently, 3D in vitro cancer models have become important alternatives to animal tests for establishing the efficacy of anticancer treatments. In this work, 3D SKOV-3 cell-laden alginate hydrogels were established as ovarian tumor models and cultured within a fluid-dynamic bioreactor (MIVO®) device able to mimic the capillary flow dynamics feeding the tumor. Cisplatin efficacy tests were performed within the device over time and compared with (i) the in vitro culture under static conditions and (ii) a xenograft mouse model with SKOV-3 cells, by monitoring and measuring cell proliferation or tumor regression, respectively, over time. After one week of treatment with 10 µM cisplatin, viability of cells within the 3D hydrogels cultured under static conditions remained above 80%. In contrast, the viability of cells within the 3D hydrogels cultured within dynamic MIVO® decreased by up to 50%, and very few proliferating Ki67-positive cells were observed through immunostaining. Analysis of drug diffusion, confirmed by computational analysis, explained that these results are due to different cisplatin diffusion mechanisms in the two culture conditions. Interestingly, the outcome of the drug efficacy test in the xenograft model was about 44% of tumor regression after 5 weeks, as predicted in a shorter time in the fluid-dynamic in vitro tests carried out in the MIVO® device. These results indicate that the in vivo-like dynamic environment provided by the MIVO® device allows to better model the 3D tumor environment and predict in vivo drug efficacy than a static in vitro model.

A cleanser formulated with Tris (hydroxymethyl) aminomethane and l-arginine significantly improves facial acne in male Thai subjects.

BACKGROUND: Acne is one of the most common skin problems among human populations. A facial cleanser formulated with alkyl ether carboxylate (AEC) and alkyl carboxylate (AC) can improve acne by cleansing sebum on facial skin but cannot effectively remove keratotic plugs in the skin pores. Recently, we confirmed that Tris (hydroxymethyl) aminomethane and L-arginine (Tris/Arg) is able to reduce sebum levels, disrupt keratotic plugs in vitro and decrease pore size on facial skin. OBJECTIVE: To compare the efficacy of the Tris/Arg-formulated cleanser with the AEC/AC cleanser in Thai subjects with acne. METHODS: We designed a randomized, double-blind, controlled, parallel trial. Thirty-four male Thai subjects with mild to moderate acne were assigned to one of two groups: one group used the Tris/Arg cleanser while the other used the AEC/AC-based cleanser twice a day for 4 weeks. RESULTS: After 4 weeks, significant decreases in noninflammatory acne were observed in both groups, yet significant decreases in inflammatory acne were only observed in the Tris/Arg cleanser group. The sebum level prior to and 30 minutes after facial washing showed no change in either group. The average pore size with keratotic plugs on the cheeks was significantly decreased in the Tris/Arg group. More than half of subjects in both groups observed acne improvement but more subjects in the Tris/Arg group noted pore size improvement. CONCLUSION: The Tris/Arg formulated cleanser has a high efficacy for significantly reducing both noninflammatory and inflammatory acne accompanied by decreases in pore size with keratotic plugs in male Thai subjects.

Effects of long-term indiscriminate use of macrocyclic lactones in cattle: Parasite resistance, clinical helminthosis, and production losses.

Our aims were to describe a case of clinical helminthosis caused by parasite resistance to macrocyclic lactones (MLs) after the long-term frequent use of these drugs in a cattle herd, and to evaluate the production losses prevented by the use of an effective anthelmintic treatment to control these resistant gastrointestinal nematodes (GINs). A case of clinical helminthosis culminating in the death of steers was investigated, the history of the antiparasitic treatments used during an 11-year period in the herd was assessed, and an efficacy test involving seven different drugs was performed. Thereafter, two groups of heifers naturally infected by ML-resistant GINs were formed and strategically treated with either a highly effective (levamisole) or less effective drug (doramectin) over a 9-month period. The heifers were evaluated monthly based on eggs per gram of feces (EPG) counts and liveweights. An evaluation of the history of parasite control in the farm revealed that MLs were used in 96.5% of the treatments aimed at controlling GINs, ticks, and myiasis in the herd. The efficacy test showed the presence of GINs resistance to all the MLs tested. However, levamisole and albendazole sulphoxide were highly effective against these parasites. Heifers treated with levamisole gained 12.1 kg more liveweight on average, compared to those treated with doramectin. Thus, we conclude that indiscriminate and long-term use of MLs in the studied herd led to the failure of GINs control, a critical situation resulting in significant production losses, and a surge of clinical helminthosis in young cattle. In addition, we showed increase in liveweight gain due to using a highly effective drug, in comparison to an ML, during a 9-month period, in heifers naturally infected by ML-resistant GINs.

Patient-derived xenografts as compatible models for precision oncology.

Cancer is a very heterogeneous disease, displaying heterogeneity between patients (inter-tumoral heterogeneity) and heterogeneity within a patient (intra-tumoral heterogeneity). Precision oncology is a diagnostic and therapeutic approach for cancers based on the stratification of patients using genomic and molecular profiling of tumors. To develop diagnostic and therapeutic tools for the application of precision oncology, appropriate preclinical mouse models that reflect tumor heterogeneity are required. Patient-derived xenograft (PDX) models are generated by the engraftment of patient tumors into immunodeficient mice that retain several aspects of the patient's tumor characteristics, including inter-tumoral heterogeneity and intra-tumoral heterogeneity. Therefore, PDX models can be applied in various developmental steps of cancer diagnostics and therapeutics, such as biomarker development, companion diagnostics, drug efficacy testing, overcoming drug resistance, and co-clinical trials. This review summarizes the diverse aspects of PDX models, addressing the factors considered for PDX generation, application of PDX models for cancer research, and future directions of PDX models.