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Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm, Ancylostoma caninum, that is resistant to 3 major classes of anthelmintics is characterized. Various drug assays were used to determine the resistance of BCR to thiabendazole, ivermectin, moxidectin and pyrantel pamoate. When compared to a drug-susceptible isolate of A. caninum, BCR was shown to be significantly resistant to all 4 of the drugs tested. Multiple single nucleotide polymorphisms have been shown to impart benzimidazole resistance, including the F167Y mutation in the ß-tubulin isotype 1 gene, which was confirmed to be present in BCR through molecular analysis. The frequency of the resistant allele in BCR was 76.3% following its first passage in the lab, which represented an increase from approximately 50% in the founding hookworm population. A second, recently described mutation in codon 134 (Q134H) was also detected at lower frequency in the BCR population. Additionally, BCR exhibits an altered larval activation phenotype compared to the susceptible isolate, suggesting differences in the signalling pathways involved in the activation process which may be associated with resistance. Further characterization of this isolate will provide insights into the mechanisms of resistance to macrocyclic lactones and tetrahydropyrimidine anthelmintics.
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Ancylostoma , Anti-Helmínticos , Humanos , Cães , Animais , Ancylostoma/genética , Ancylostomatoidea , Larva/genética , Anti-Helmínticos/farmacologia , Resistência a Múltiplos Medicamentos/genética , Resistência a Medicamentos/genéticaRESUMO
BACKGROUND: Recently, a new cryotherapy device that precisely controls skin temperature was developed. Precision cryotherapy (PC) can be a safe and alternative treatment modality for immune-related skin diseases that are difficult to treat by conventional cryotherapy because of serious adverse events. OBJECTIVE: To evaluate the efficacy and safety of PC in scalp seborrheic dermatitis (SD). METHODS: A single-arm, prospective trial was designed. Twenty-four patients with SD underwent 3 PC interventions 2 weeks apart. At the baseline, Week 6, and Week 8, overall improvements in Physician Global Assessment (PGA) and clinical severity scores were assessed. At each visit, the erythema index (EI) and transepidermal water loss were evaluated. The patients scored 9 subjective symptoms using a visual analog scale (VAS). RESULTS: The itch VAS score decreased by 50.4% at Week 8. Blinded investigators reported improvement of PGA scores from 2.86 ± 0.62 to 1.66 ± 0.61 and clinical severity scores from 4.55 ± 1.30 to 2.45 ± 1.37. The average EI decreased by 19.6% at Week 8 ( p < .05). CONCLUSION: This study not only demonstrated the efficacy and safety of PC in scalp SD but it also revealed insights for PC being a promising treatment modality in immune-related skin diseases.
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Dermatite Seborreica , Humanos , Dermatite Seborreica/terapia , Dermatite Seborreica/induzido quimicamente , Dermatite Seborreica/diagnóstico , Antifúngicos/uso terapêutico , Couro Cabeludo , Estudos Prospectivos , Resultado do Tratamento , Eritema/tratamento farmacológico , Crioterapia/efeitos adversosRESUMO
BACKGROUND/OBJECTIVES: There are scant established data on the cause, distribution, treatment options, and recurrence rate of pediatric keloids in Asian populations. We characterized clinical features by comprehensively categorizing pediatric keloid patients into prepubertal and postpubertal groups at a single tertiary center. METHODS: We searched the database of Kangbuk Samsung Hospital for pediatric patients (< 18 years) with clinically proven keloids who underwent outpatient-based treatment from 2007 to 2021. Clinical features, including demographics, distribution, underlying cause, treatment modality, and recurrence, were analyzed. RESULTS: Of the 93 patients (total 110 keloids), 42 females (45.2%) and 51 males (54.8%), with a mean age of 14.5 ± 4.1 years (range, 1-18 years), were retrospectively analyzed. The mean length of follow-up was 22.0 ± 14.2 months (range, 6-63). Of the 100 keloids with assessable causes, piercing (22%) and acne (19%) were the most common. In the prepubertal group, the lower and upper limbs (n = 7, 28%; n = 6, 24%) were the two most common locations, suggesting that post-traumatic keloids are common during this developmental period. In the postpubertal group, the ear (n = 25, 29.4%) was the most common site, which corresponds to the frequency of cosmetic piercing at this age. No differences were found between the effects of treatment methods on relapse rate. CONCLUSIONS: Understanding the clinical features of pediatric keloids is important in the therapeutic considerations for pediatric keloids. Future studies should analyze a larger number of children with keloids over longer observation periods.
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This study aimed to measure masticatory performance (MP) using ß-carotene gummy jelly to investigate its relationship with skeletal properties in decompensated patients diagnosed with skeletal class III malocclusion. The study included 78 patients (38 men and 40 women) diagnosed with skeletal class III malocclusion without temporomandibular joint disorder and periodontal disease. MP was measured using a new masticatory measuring device and ß-carotene in the gummy jelly. Lateral and posteroanterior cephalograms were obtained, and skeletal properties (Me deviation, ANB, SNB, APDI, Wits, ODI, facial axis, body length, ramus length, SN-GoGn, anterior facial height, posterior facial height, saddle angle, articular angle, and gonial angle) were evaluated. MP differences according to age and sex and the effect of skeletal properties on MP were analyzed using multiple linear regression analysis. The MP of all patients was 3690.55±1428.77 mm², MP of the male group was 4043.05±1498.09 mm², and MP of the female group was 3355.68±1272.19 mm². Among the items investigated, the variable that affected MP was posterior facial height. Posterior facial height showed a positive correlation (P=0.022). There was no significant difference between MP and other skeletal properties (P>0.05). The severity of the hypodivergency in skeletal class III could affect MP. The relationship between facial asymmetry or skeletal relation and MP could not be explained in this study.
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The disruption of thyroid hormones because of chemical exposure is a significant societal problem. Chemical evaluations of environmental and human health risks are conventionally based on animal experiments. However, owing to recent breakthroughs in biotechnology, the potential toxicity of chemicals can now be evaluated using 3D cell cultures. In this study, the interactive effects of thyroid-friendly soft (TS) microspheres on thyroid cell aggregates are elucidated and their potential as a reliable toxicity assessment tool is evaluated. Using state-of-the-art characterization methods coupled with cell-based analysis and quadrupole time-of-flight mass spectrometry, it is shown that TS-microsphere-integrated thyroid cell aggregates exhibit improved thyroid function. Specifically, the responses of zebrafish embryos, which are used for thyroid toxicity analysis, and the TS-microsphere-integrated cell aggregates to methimazole (MMI), a known thyroid inhibitor, are compared. The results show that the thyroid hormone disruption response of the TS-microsphere-integrated thyroid cell aggregates to MMI is more sensitive compared with those of the zebrafish embryos and conventionally formed cell aggregates. This proof-of-concept approach can be used to control cellular function in the desired direction and hence evaluate thyroid function. Thus, the proposed TS-microsphere-integrated cell aggregates may yield new fundamental insights for advancing in vitro cell-based research.
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Glândula Tireoide , Peixe-Zebra , Animais , Humanos , Antitireóideos/farmacologia , Hormônios Tireóideos/farmacologia , Metimazol/toxicidadeRESUMO
Emotional eating or the tendency to eat in response to emotional states can be assessed using self-report measures. The Emotional Eating Scale-II is a commonly used and reliable instrument that measures the desire to eat in response to a range of unpleasant and pleasant emotions. The current study aimed to corroborate the validity of the EES-II and expand its utility by investigating its dimensionality and testing its measurement invariance in samples from English-speaking and non-English-speaking countries. Convergent and predictive validity in respect of food craving, eating, and health indicators were also examined. This cross-national study included a total of 2485 adult participants recruited from Finland, North America, Philippines, United Kingdom, China, Italy, Spain, and South Korea, who completed the EES-II in six different languages. Factor analyses supported a four-factor structure including valence (pleasant, unpleasant) and activation (high, low) for a 12-item English version and slightly modified non-English adaptations. The model exhibited good fit in all samples, and convergent validity was demonstrated. Full invariance of factor loadings and partial invariance of factor loading, intercepts, and error variances was established across samples. Structural equation models revealed that high activation (pleasant and unpleasant) states predicted food cravings and reported eating. Overall findings across multiple samples and countries supported the factorial structure, reliability, invariance, and validity of the resulting Brief Emotional Eating Scale (BEES).
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Fissura , Emoções , Psicometria , Reprodutibilidade dos Testes , Autorrelato , Análise Fatorial , Inquéritos e QuestionáriosRESUMO
We present a rare case of Pacinian corpuscle hyperplasia (PCH) presenting with typical finger pain in a 6-year-old girl. As appendages in children are smaller than those in adults, diagnostic criteria are needed for pathological confirmation of PCH in pediatric patients.
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Corpúsculos de Pacini , Dor , Adulto , Feminino , Humanos , Criança , Corpúsculos de Pacini/patologia , Hiperplasia/diagnóstico , Hiperplasia/patologiaRESUMO
The Korean Pathfinder Lunar Orbiter (KPLO)-MAGnetometer (KMAG) consists of three triaxial fluxgate sensors (MAG1, MAG2, and MAG3) that measure the magnetic field around the Moon. The three sensors are mounted in the order MAG3, MAG2, and MAG1 inside a 1.2 m long boom, away from the satellite body. Before it arrived on the Moon, we compared the magnetic field measurements taken by DSCOVR and KPLO in solar wind to verify the measurement performance of the KMAG instrument. We found that there were artificial disturbances in the KMAG measurement data, such as step-like and spike-like disturbances, which were produced by the spacecraft body. To remove spacecraft-generated disturbances, we applied a multi-sensor method, employing the gradiometer technique and principal component analysis, using KMAG magnetic field data, and confirmed the successful elimination of spacecraft-generated disturbances. In the future, the proposed multi-sensor method is expected to clean the magnetic field data measured onboard the KPLO from the lunar orbit.
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INTRODUCTION: The objective of this study was to evaluate and compare the 3-dimensional (3D) aging changes of the lips among adult skeletal Class I, II, and III malocclusion. METHODS: Female adult orthodontic patients aged 20-50 years with pretreatment cone-beam computed tomography scans were retrospectively classified according to age (20s [20-29 years], 30s [30-39 years], and 40s [40-49 years]) and then subclassified by malocclusion into skeletal Class I, II, and III relationship (9 groups; n = 30 per group). Positional differences in midsagittal and parasagittal soft-tissue landmarks and 3D morphologic aging changes of the lips were evaluated using cone-beam computed tomography scans. RESULTS: Labiale superius and cheilion for patients in their 40s indicated a significant downward and backward position compared with those in their 20s, regardless of skeletal classifications (P <0.05). Accordingly, the upper lip height decreased, and the mouth width increased significantly (P <0.05). For Class III malocclusion, the upper lip vermilion angle was greater for patients in their 40s than those in their 20s (P <0.05), whereas the lower lip vermilion angle was only lower for patients with Class II malocclusion (P <0.05). CONCLUSIONS: Middle-aged adult females (40-49 years) had a lower upper lip height and greater mouth width than those in their 20s, regardless of skeletal malocclusion. However, prominent morphologic aging changes of the lips were noted on the upper lip for skeletal Class III malocclusion and the lower lip for skeletal Class II malocclusion, implying that the underlying skeletal features (or malocclusion) may influence 3D aging changes of the lips.
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Má Oclusão Classe III de Angle , Má Oclusão Classe II de Angle , Má Oclusão , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Lábio/diagnóstico por imagem , Lábio/anatomia & histologia , Face/anatomia & histologia , Estudos Retrospectivos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Cefalometria/métodosRESUMO
Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi jird model of infection. Initially, rifampicin treatment depleted Wolbachia in adult worms and simultaneously impaired female worm fecundity. However, during an 8-month washout period, Wolbachia titers rebounded and embryogenesis returned to normal. Genome sequence analyses of Wolbachia revealed that despite the population bottleneck and recovery, no genetic changes occurred that could account for the rebound. Clusters of densely packed Wolbachia within the worm's ovarian tissues were observed by confocal microscopy and remained in worms treated with rifampicin, suggesting that they may serve as privileged sites that allow Wolbachia to persist in worms while treated with antibiotic. To our knowledge, these clusters have not been previously described and may be the source of the Wolbachia rebound.
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Brugia pahangi/microbiologia , Filariose/microbiologia , Filaricidas/farmacologia , Rifampina/farmacologia , Wolbachia/efeitos dos fármacos , Animais , Feminino , GerbillinaeRESUMO
BACKGROUND AND OBJECTIVES: Transdermally delivered gold nanoparticles (AuNPs) irradiated with near-infrared laser energy can create a photothermal effect within the sebaceous glands (SGs). Photothermal therapy (PTT) can be used clinically to reverse photoaging in SG-rich areas of the skin. Improvements in wrinkles and enlarged pores in Asian skin were assessed following AuNP-mediated PTT with a long-pulsed 755-nm alexandrite laser. STUDY DESIGN/MATERIALS AND METHODS: A single-arm, prospective trial was designed. Twenty Korean patients underwent three gold PTT interventions performed 4 weeks apart at laser hair-removal settings without cooling. At Week 20, changes in the wrinkle index (WI) and pore index (PI), size, and count were calculated using three-dimensional camera analyses. Overall improvements in wrinkles and pores (0-4 scale) were assessed by blinded investigators using standardized photographic comparisons. The subjects scored their satisfaction (0-10 scale) and treatment discomfort (0-10 scale). Safety data were also collected. RESULTS: There were significant reductions in the WI (8.3%, p < 0.01), pore size (23.1%, p = 0.035), and PI (19.9%, p = 0.034) in the periorbital areas at week 20 compared with baseline. The mean reductions in the size (22.5%, p = 0.027), count (16.5%, p = 0.048), and index (22.4%, p = 0.023) of the cheek pores were also significant. Investigators reported average scores of 3.2 ± 0.6 for improved wrinkle appearance, and 3.1 ± 0.7 for improvement in visible pores. Participants were moderately satisfied with the overall results (7.6 ± 1.8). Subjects felt moderate discomfort during treatment (4.7 ± 2.6). No serious or persistent adverse events occurred. CONCLUSIONS: AuNP-mediated PTT showed noticeable efficacy and tolerability in treating wrinkles and pores in Asian skin over a 12 week-follow-up. Further studies with a longer follow-up are needed to confirm the reduction in SG activity at the parameters used.
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Nanopartículas Metálicas , Terapia Fototérmica , Envelhecimento da Pele , Ouro/uso terapêutico , Humanos , Lasers de Estado Sólido/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoRESUMO
ABSTRACT: In the present study, the authors report rare case series with subcutaneous emphysema with or without pneumomediastinum and pneumothorax after orthognathic and facial bone contouring surgery, compare their clinical and radiologic findings, and suggest precautions. Four patients who showed subcutaneous emphysema on follow up chest X-ray and computed tomography after orthognathic and facial bone contouring surgery were included in the study. In all cases post-op subcutaneous emphysema were detected, however, the aspect and mechanisms of post-op air spread were all different. After the conservative management with administering the O 2 by nasal cannula or endotracheal tube, the symptoms were relieved except 1 patient who needed chest tube insertion and further supra-sternal incision. In conclusion, subcutaneous emphysema with or without pneumomediastinum and pneumothorax after orthognathic and facial bone contouring surgery can be occurred by cervical fascia injury or alveolar ruptures. To preventing those complications, traumatic naso-tracheal intubation, excessive positive pressure ventilation, intermaxillary fixation immediate after the surgery, and increase of intra-alveolar pressure of the patients should be avoided.
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Enfisema Mediastínico , Pneumotórax , Enfisema Subcutâneo , Ossos Faciais , Humanos , Intubação Intratraqueal/efeitos adversos , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/terapia , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/terapia , Enfisema Subcutâneo/diagnóstico por imagem , Enfisema Subcutâneo/etiologia , Enfisema Subcutâneo/terapiaRESUMO
Liver and intestinal flukes of the family Fasciolidae cause zoonotic food-borne infections that impact both agriculture and human health throughout the world. Their evolutionary history and the genetic basis underlying their phenotypic and ecological diversity are not well understood. To close that knowledge gap, we compared the whole genomes of Fasciola hepatica, Fasciola gigantica, and Fasciolopsis buski and determined that the split between Fasciolopsis and Fasciola took place â¼90 Ma in the late Cretaceous period, and that between 65 and 50 Ma an intermediate host switch and a shift from intestinal to hepatic habitats occurred in the Fasciola lineage. The rapid climatic and ecological changes occurring during this period may have contributed to the adaptive radiation of these flukes. Expansion of cathepsins, fatty-acid-binding proteins, protein disulfide-isomerases, and molecular chaperones in the genus Fasciola highlights the significance of excretory-secretory proteins in these liver-dwelling flukes. Fasciola hepatica and Fasciola gigantica diverged â¼5 Ma near the Miocene-Pliocene boundary that coincides with reduced faunal exchange between Africa and Eurasia. Severe decrease in the effective population size â¼10 ka in Fasciola is consistent with a founder effect associated with its recent global spread through ruminant domestication. G-protein-coupled receptors may have key roles in adaptation of physiology and behavior to new ecological niches. This study has provided novel insights about the genome evolution of these important pathogens, has generated genomic resources to enable development of improved interventions and diagnosis, and has laid a solid foundation for genomic epidemiology to trace drug resistance and to aid surveillance.
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Evolução Biológica , Fasciolidae/genética , Genoma Helmíntico , Animais , Família MultigênicaRESUMO
BACKGROUND: Previous studies have shown that systemic tranexamic acid reduces bleeding during soft tissue surgeries and reduces postoperative ecchymosis and edema experienced by surgical patients. OBJECTIVE: To evaluate the effect of postoperative tranexamic acid administration on the reduction of ecchymosis and edema after lipoma surgery. MATERIALS AND METHODS: A total of 40 patients who underwent lipoma excision were included in the comparative analysis. In the tranexamic acid group (n = 20), 1 g of tranexamic acid was administered daily for 5 consecutive postoperative days. Tranexamic acid was not administered to the control group (n = 20). The severity of ecchymosis and edema at the first visit after surgery was rated on a 4-point scale by 2 blinded dermatologists. RESULTS: The mean interval of the initial visit after surgery was 1.1 ± 0.5 (range: 1-4) days. Mean ecchymosis scores were significantly lower in the tranexamic acid group (0.5 ± 0.8) than in the control group (1.2 ± 1.0) (p < .05). No statistical difference was seen in mean edema scores between groups (0.5 ± 0.6 in tranexamic acid vs 0.7 ± 0.8 in control). CONCLUSION: We observed that postoperative administration of tranexamic acid significantly decreased ecchymosis in lipoma excision.
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Antifibrinolíticos/uso terapêutico , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Equimose/prevenção & controle , Edema/prevenção & controle , Lipoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Ácido Tranexâmico/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Tela Subcutânea/cirurgiaRESUMO
Becker's nevus (BN) clinically presents as brown patches with hypertrichosis. The risk of pigmentary changes still remains a concern when using lasers to treat Asian patients with BN. We aimed to evaluate the outcomes on reduction of hairs and pigment of BN using the long-pulsed 1064-nm Nd:YAG (LPNY) and/or 755-nm alexandrite (LP-Alex), before treating pigment in earnest. A total of 13 subjects were treated with the LPNY (n = 8), the LP-Alex (n = 4), and both (n = 1). Improvements on hair removal and pigment reduction were assessed using a 5-point global assessment scale. Patient satisfaction was also assessed. Treatment parameters were within those commonly used for the purpose of epilation. The average follow-up period was 19.5 ± 12.3 weeks, and the mean total number of sessions was 2.0. Eleven subjects reported >50% improvement in hair removal (11/13, 86.7%), and pigment reduction of >50% improvement was observed in 9 subjects (9/13, 69.2%). Patient satisfaction showed >50% lesion clearance in 84.6%. Hair removal settings of LPNY and LP-Alex were effective in both hypertrichosis and pigment reduction in the initial strategy of treatment of BN in skin of color.
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Remoção de Cabelo , Hiperpigmentação , Terapia a Laser , Nevo , Neoplasias Cutâneas , Humanos , Hiperpigmentação/etiologia , Hiperpigmentação/radioterapia , Hiperpigmentação/cirurgia , Lasers , Nevo/cirurgia , Pigmentação , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Resultado do TratamentoRESUMO
Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the genomes of Paragonimus westermani, Paragonimus heterotremus, and Paragonimus miyazakii. Immunohistology studies showed that antibodies raised to four recombinant proteins bound to the tegument of adult P. kellicotti worms, at the parasite host interface. Only a known egg antigen was absent from the tegument but present in developing and mature eggs. We evaluated the diagnostic potential of these antigens by Western blot with sera from patients with paragonimiasis (from MO and the Philippines), fascioliasis, and schistosomiasis, and with sera from healthy North American controls. Two recombinant proteins (a cysteine protease and a myoglobin) showed the highest sensitivity and specificity as diagnostic antigens, and they detected antibodies in sera from paragonimiasis patients with early or mature infections. In contrast, antibodies to egg yolk ferritin appeared to be specific marker for patients with adult fluke infections that produce eggs. Our study has identified and localized antigens that are promising for serodiagnosis of human paragonimiasis.
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Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Paragonimíase/diagnóstico , Paragonimus/imunologia , Praziquantel/uso terapêutico , Adulto , Animais , Anti-Helmínticos , Antígenos de Helmintos/metabolismo , Ásia , Gerbillinae , Humanos , Imuno-Histoquímica , Paragonimíase/metabolismo , Paragonimíase/parasitologia , Paragonimus westermani/imunologia , Proteínas Recombinantes , Sensibilidade e Especificidade , Testes SorológicosRESUMO
A lunar vehicle radiation dosimeter (LVRAD) has been proposed for studying the radiation environment on the lunar surface and evaluating its impact on human health. The LVRAD payload comprises four systems: a particle dosimeter and spectrometer (PDS), a tissue-equivalent dosimeter, a fast neutron spectrometer, and an epithermal neutron spectrometer. A silicon photodiode sensor with compact readout electronics was proposed for the PDS. The PDS system aims to measure protons with 10-100 MeV of energy and assess dose in the lunar space environment. The manufactured silicon photodiode sensor has an effective area of 20 mm × 20 mm and thickness of 650 µm; the electronics consist of an amplifier, analog pulse processor, and a 12-bit analog-to-digital converter for signal readout. We studied the responses of silicon sensors which were manufactured with self-made electronics to gamma rays with a wide range of energies and proton beams.
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Dosímetros de Radiação , Silício , Raios gama , Humanos , Nêutrons , Prótons , RadiometriaRESUMO
Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans.
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Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos/genética , Trichostrongyloidea/genética , Tricostrongiloidíase/tratamento farmacológico , Animais , Mapeamento Cromossômico , Variações do Número de Cópias de DNA/genética , Genótipo , Humanos , Ovinos/parasitologia , Trichostrongyloidea/efeitos dos fármacos , Trichostrongyloidea/patogenicidade , Tricostrongiloidíase/genética , Tricostrongiloidíase/parasitologiaRESUMO
Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. hepatica Oregon and related food-borne trematodes are metabolically less constrained than schistosomes and cestodes, taking advantage of the richer millieux offered by the hepatobiliary organs. Protease families differentially expanded between diverse trematodes may facilitate migration and survival within the heterogeneous environments and niches within the mammalian host. Surprisingly, the sequencing of Oregon and Uruguay F. hepatica isolates led to the first discovery of an endobacteria in this species. Two contigs from the F. hepatica Oregon assembly were joined to complete the 859,205 bp genome of a novel Neorickettsia endobacterium (nFh) closely related to the etiological agents of human Sennetsu and Potomac horse fevers. Immunohistochemical studies targeting a Neorickettsia surface protein found nFh in specific organs and tissues of the adult trematode including the female reproductive tract, eggs, the Mehlis' gland, seminal vesicle, and oral suckers, suggesting putative routes for fluke-to-fluke and fluke-to-host transmission. The genomes of F. hepatica and nFh will serve as a resource for further exploration of the biology of F. hepatica, and specifically its newly discovered trans-kingdom interaction with nFh and the impact of both species on disease in ruminants and humans.
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Fasciola hepatica/genética , Genoma Bacteriano , Genoma Helmíntico , Neorickettsia sennetsu/genética , Animais , Proteínas da Membrana Bacteriana Externa/genética , Ehrlichiose/microbiologia , Ehrlichiose/transmissão , Ehrlichiose/veterinária , Fasciola hepatica/isolamento & purificação , Fasciola hepatica/microbiologia , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/transmissão , Cavalos , Humanos , Neorickettsia sennetsu/patogenicidade , Oregon , Ovinos/parasitologia , UruguaiRESUMO
Skin photoaging manifests deeper wrinkles and larger pore size. Various lasers have been tried for rejuvenation of photoaging skin, and the quasi-long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is one promising treatment option. New types of laser device are emerging, including devices operating with picosecond pulse duration combined with a microlens array, which are regarded as a new breakthrough for skin rejuvenation. We aimed to evaluate the clinical effectiveness and safety of the picosecond 1064-nm Nd:YAG laser using a microlens array compared with the quasi-long-pulsed 1064-nm Nd:YAG laser in a split-face design. We designed a split-faced, prospective study and enrolled 25 subjects with photoaging facial wrinkles and enlarged pores. Each facial area was randomly assigned to undergo treatment with either the picosecond 1064-nm Nd:YAG laser (Pico-arm) or the quasi-long-pulsed 1064-nm Nd:YAG laser (Quasi-arm). We performed five laser sessions at 2-week intervals, and final results were assessed after 20 weeks after the initial laser session. We used a five-point global assessment scale, wrinkle and pore index derived from 3D camera analysis. We enrolled a total of 25 subjects (24 females and 1 male) with Fitzpatrick skin types III to IV and a mean age of 63.8 ± 5.7 years. After treatment, 54.2% of subjects in the Pico-arm reported at least moderate improvement in visible pores compared with 41.7% of the Quasi-arm (P = 0.001). A total of 12.5% of subjects in the Pico-arm showed moderate improvement in wrinkles versus 4.2% of the Quasi-arm (P = 0.125). There was a 41.3% reduction in the pore index in the Pico-arm compared to a 3.9% increase in the Quasi-arm (P = 0.048). There was a 16.4% reduction in the wrinkle index in the Pico-arm compared with a 0.5% reduction in the Quasi-arm (P = 0.01). Pain assessment score was higher in the Pico-arm than the Quasi-arm (3.65 ± 1.70 vs 1.28 ± 1.28, P = 0.001). No serious adverse events occurred during the study. Our findings suggest that the picosecond 1064-nm Nd:YAG laser with a microlens array is as effective as the quasi-long-pulsed 1064-nm Nd:YAG laser for treatment of photoaging wrinkles and pores.