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1.
The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.  相似文献   

2.
Precision medicine for inner-ear disease is hampered by the absence of a methodology to sample inner-ear fluid atraumatically. The round window membrane (RWM) is an attractive portal for accessing cochlear fluids as it heals spontaneously. In this study, we report on the development of a microneedle for perilymph sampling that minimizes the size of RWM perforation, facilitates quick aspiration, and provides precise volume control. Here, considering the mechanical anisotropy of the RWM and hydrodynamics through a microneedle, a 31G stainless steel pipe was machined into wedge-shaped design via electrical discharge machining. The sharpness of the needle was evaluated via a surface profilometer. Guinea pig RWM was penetrated in vitro, and 1 μL of perilymph was sampled and analyzed via UV–vis spectroscopy. The prototype wedge shaped needle was successfully fabricated with the tip curvature of 4.5 μm and the surface roughness of 3.66 μm in root mean square. The needle created oval perforation with minor and major diameter of 143 and 344 μm (n?=?6). The sampling duration and standard deviation of aspirated volume were 3 s and 6.8 % respectively. The protein concentration was 1.74 mg/mL. The prototype needle facilitated precise perforation of RWMs and rapid aspiration of cochlear fluid with precise volume control. The needle design is promising and requires testing in human cadaveric temporal bone and further optimization to become clinically viable.  相似文献   

3.
High inflammatory AIRmax mice homozygous for Slc11a1 R and S alleles were produced. AIRmax SS mice showed faster ear tissue regeneration than AIRmax RR mice, suggesting that the S allele favored tissue restoration. Here, we investigated the gene expression profiles and the inflammatory reactions of AIRmax RR and AIRmax SS mice during the initial phase of ear tissue regeneration. We observed superior levels of analysis of wound myeloperoxidase and edema in AIRmax SS mice, although similar cell influx was verified in both lines. Of the genes, 794 were up- and 674 down-regulated in AIRmax RR , while 735 genes were found to be up- and 1616 down-regulated in AIRmax SS mice 48 h after punch. Both mouse lines showed significant over-represented genes related to cell proliferation; however AIRmax SS displayed up-regulation of inflammatory response genes. Quantitative PCR experiments showed higher expressions of Tgfb1, Dap12 and Trem1 genes in AIRmax SS mice. These results indicate that Slc11a1 gene modulated the early inflammatory events of ear tissue regeneration.  相似文献   

4.

Purpose

The purpose of this study was to describe neurovascular structures-at-risk during establishment of five portals for access to distal biceps tendon (DBT) in cubital fossa, and to establish relative safety of these portal sites for such access. We hypothesized that all five portals are safe for endoscopic DBT exploration.

Methods

Ten fresh frozen cadaveric elbows were dissected after placement of portals at five potential sites (four anterior, one posterior). Nine neurovascular structures (CV, cephalic vein; LCN, lateral cutaneous nerve; LV, leash of vessels; RN, radial nerve; SRN, superficial radial nerve; PIN, posterior interosseous nerve; RA, radial artery; BA, brachial artery; MN, median nerve) were dissected, and their distances from portal sites were measured. Statistical analysis was performed to determine relative portal safety, and risk of injury to neurovascular structures in relation to each portal was analyzed.

Results

Structures that were significantly “at risk” were RA (p = 0.006), SRN (p = 0.002), and PIN (p = 0.004). RA was significantly “at risk” of injury from portal 4 (p = 0.009). Similarly, SRN was “at risk” from portal 3 (p = 0.036), and the PIN was “at risk” from portal 2 (p = 0.003).

Conclusions

Portal 1 (parabiceps portal) was safe for all neurovascular structures, however, portals 2–4 were significantly closer to neurovascular structures. RA, SRN, and PIN were significantly “at risk” as compared to other structures amongst the portals studied. Portal 5 was relatively safe for SRN and PIN.

Clinical relevance

Portals 1 (parabiceps portal) and 5 (distal posterior) can be safely placed for endoscopic access to the DBT. Portal 4 (open distal anterior) may be used after careful open dissection and under direct vision. Portals 2 and 3 are not recommended for elbow endoscopy.
  相似文献   

5.
One hundred eighty-one dogs and 26 short-hair cats from suburban areas around Tirana, Albania were examined for ectoparasite infestation. The dogs were examined on several occasions from 2005 through 2009 representing three seasons: winter (December–February), spring (March–May), and summer (June–August); the cats were examined in late autumn (November). In addition, deep ear swab specimens of 30 dogs were examined for ear mites. The arthropod ectoparasite fauna of the dogs included two tick species (Rhipicephalus sanguineus and Ixodes ricinus), three mite species (Sarcoptes scabiei var. canis, Otodectes cynotis, and Demodex canis), three flea species (Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans), and one louse species (Trichodectes canis). In the dogs, rates of infestation were 23.8% for R. sanguineus, 0.6% for I. ricinus, 4.4% for S. scabiei var. canis, 6.7% for O. cynotis, 0.6% for D. canis, 75.7% for C. canis, 5.0% for C. felis, 8.3% for P. irritans, and 6.6% for T. canis. Mixed infestation with two or three species of ectoparasites was recorded on 38.1% of the dogs. Fleas infested 75.7% dogs (geometric mean, 3.96; range, 1–80) and were observed in winter, spring, and summer with increasing prevalences of 64.3%, 75.9%, and 100%. Ticks parasitized 24.3% of the dogs (geometric mean, 0.41; range, 1–331). R. sanguineus ticks were recorded on 34.2% and 50% of the dogs examined in spring and summer, respectively, but were absent on the dogs during winter except for a single I. ricinus specimen observed. Prevalence of infestation with R. sanguineus, S. scabiei var. canis, C. felis, P. irritans, and T. canis did not differ between dogs ≤6 months and dogs >6 months of age; however, prevalence of infestation with C. canis was significantly (p?<?0.01) higher in dogs >6 months old. There was no difference between the sexes for the prevalences of infestation with those parasites. The examination of the cats revealed infestation with only one species of ectoparasite, C. felis (prevalence, 100%; geometric mean, 2.5; range, 1–9).  相似文献   

6.

Purpose

To describe the straight-into-cochlea line that affords the best access for an electrode array to enter via the round window, and how this line relates to the facial nerve, the incus, and mastoid size. The straight-into-cochlea line is important to minimize the cochlear trauma and maximize the likelihood of placement into the scala tympani.

Methods

High-resolution CT scans were obtained for ten craniums with the extremes of large (N = 5) and small (N = 5) mastoid pneumatization; the specimens were from a series of 41 ear normal craniums. Using FIJI, a publicly available software program, the straight-into-cochlea insertion line was determined by defining the xyz coordinates of the middle of the round window and a point 6.0 mm into the cochlea on its centrifugal wall. Then, from the extended straight-into-cochlea insertion line, we determined the shortest perpendicular distance to the middle of the fallopian canal, and from that “fallopian point” to the apex of the posterior process of the incus.

Results

We found good repeatability of measurements. We found the extended straight-into-cochlea insertion lines routinely close to or in the midst of the fallopian canal (50 % ≤ 1.0 mm). We found the lines 4.7–7.8 mm from the apex of the posterior process of the incus. Line positions relative to “fallopian point” and incus showed no relation to mastoid pneumatization. For the distance “fallopian point” to incus, bilateral symmetry was suggested.

Conclusions

Using landmarks registered in an xyz coordinate system, straight-into-cochlea insertion via the round window puts the facial nerve at risk.
  相似文献   

7.
Canine visceral leishmaniasis (CVL) is transmitted through vector, although venereal transmission has been suggested. This study aimed to compare the parasitic loads and inflammatory processes in genital tissues with ear skin from seropositive male dogs. Forty-five seropositive dogs were separated into groups containing symptomatic (n = 23) and asymptomatic (n = 22) animals. The control group (n = 2) healthy animals with seronegative and negative results in direct parasitological test. Samples of ear tip skin, prepuce, glans penis, testis, epididymis, and prostate were collected for evaluation of parasitic load and inflammatory infiltrate. Although ear tip skin was the most intensely parasitized, prepuce and epididymis revealed no difference in parasitism when compared with ear tip skin (P > 0.05). Parasitic loads in testis and prostate were lower than other tissues (P < 0.05). Parasitism in glans penis was high, similar to prepuce and epididymis, but lower than ear tip skin. High parasitism was more frequent in symptomatic dogs than asymptomatic animals. Severe inflammatory processes were more frequent within the symptomatic animals compared with asymptomatic and more predominant in prepuce and epididymis. Ear tip skin and genital tissues presented signs of chronic inflammation. There were weak and moderate positive correlations between parasitic loads and inflammatory processes. Our results demonstrate that, likewise with the ear tip skin, the genital of seropositive dogs can carry a large number of Leishmania infantum amastigotes and this process are more intense in symptomatic animals. These data have important implications for understanding the possibility of venereal transmission of CVL.  相似文献   

8.
Using whole-mount in situ hybridisation techniques, we have examined the expression of major components of the insulin-like growth factor (IGF) axis in early development of the chicken embryo, including both IGF-I and -II, the type 1 IGF receptor (IGFR), and two of the IGF binding proteins, (IGFBP)-2 and -5. We report that these genes fall into two distinct groups with respect to expression pattern, with IGFBP-2 displaying broad overlap of mRNA expression with IGFR and IGF-I during early development, whereas the expression profile of IGFBP-5 most closely resembled that of IGF-II. Comparison between different stages revealed IGFBP-2 mRNA was detected as early as stage 3, whereas IGFBP-5 was first seen at stage 4. In addition, we detected expression domains of IGFBP-5, and to a lesser extent IGFBP-2, which did not overlap with either IGFR or IGF expression patterns. This could indicate IGF independent actions of the IGFBPs during early embryonic development. A striking observation concerning the expression profiles of both IGF-II and IGFBP-5 at early stages of chick embryogenesis is that both these genes are expressed asymmetrically in a pattern similar to that of Sonic Hedgehog (Shh). Furthermore, using cyclopamine, we have demonstrated that IGFBP-5 expression in the early embryo is regulated by Shh. Taken together, these results describe an important role for the IGF system in the very early stages of the developing chicken embryo, and imply that IGFBP-2 and -5 are fundamental developmental factors, with the latter involved in Shh signalling pathways.  相似文献   

9.
Glaser  K. B.  Carlson  R. P.  Sung  A.  Bauer  J.  Lock  Y. -W.  Holloway  D.  Sturm  R.  Hartman  D.  Walter  T.  Woeppel  S.  Howell  R.  Gray  W.  Grimes  D.  Kubrak  D.  Banker  A.  Kreft  A.  Weichman  B. M. 《Inflammation research》1993,39(1):C30-C32
WAY-121,520 inhibited human synovial fluid PLA2 (HSF-PLA2) (IC50=4 μM) using arachidonic acid-labeledE. coli as substrate. Further biochemical characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase (5-LO) activity in the murine macrophage (LTC4, IC50=4nM) and rat PMN (LTB4, IC50=10 nM) and an ability to antagonize LTD4 binding to isolated guinea-pig trachea (pKB=6.0).In vivo anti-inflammatory activity was noted in murine TPA-induced (ED50=91 μg/ear) and arachidonic acid-induced (66% inhibition at 400 μg/ear) ear edema and in leukotriene-dependent antigen-induced bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY-121,520 represents a novel series of indomethacin-based inhibitors of PLA2 with anti-inflammatory activity resulting from a combination of biochemical activities (inhibition of 5-LO and PLA2 and LTD4 antagonism). This agent may provide added therapeutic efficacy over more selective inhibitors.  相似文献   

10.
The WNT family of proteins is composed of several members. In the present study we isolated the full length chick Wnt-6 cDNA and analyzed its expression pattern by in situ hybridization during chick development. Wnt-6 expression is observed in the ectoderm from HH-stage 4 onwards. At HH-stages, 7–16 expression can be seen in the ectoderm overlying the segmental plate and the epithelial somite, while the ectoderm overlying the compartmentalized somite is Wnt-6 negative. Expression is also observed at the heart outflow tract and in the ectoderm overlying the pharyngeal arches. From HH-stages 17 to 27, expression is also observed at limb level, both in the dorsal and ventral ectoderm and a stronger expression in the dorsoventral boundary. Furthermore, expression in the ectoderm delimiting the somitic boundaries in the anteroposterior and mediolateral axis at limb level was observed, as well as in the ventral body wall. Expression becomes evident in the inner ear. From HH-stage 30 onwards, expression is restricted to the feather buds and to the gastrointestinal tract.  相似文献   

11.
12.
A new glucose transport model relying upon diffusion and convection across the capillary membrane was developed, and supplemented with tissue space and lymph flow. The rate of glucose utilization (J util) in the tissue space was described as a saturation function of glucose concentration in the interstitial fluid (C glu,isf), and was varied by applying a scaling factor f to J max. With f = 0, the glucose diffusion ceased within ~20 min. While, with increasing f, the diffusion was accelerated through a decrease in C glu,isf, but the convective flux remained close to resting level. When the glucose supplying capacity of the capillary was measured with a criterion of J util /J max = 0.5, the capacity increased in proportion to the number of perfused capillaries. A consistent profile of declining C glu,isf along the capillary axis was observed at the criterion of 0.5 irrespective of the capillary number. Increasing blood flow scarcely improved the supplying capacity.  相似文献   

13.
The outbreak of bluetongue (BTV-8) in many parts of north-western Europe led to efforts to curb the spread of the disease, particularly in farms with valuable livestock, as on a stud bull farm in Schmergow, Brandenburg, Germany. In the abundance of the putative BT vectors, Palaearctic Culicoides species, several vector control methods were applied in the hope for a reduction of the target insect populations. Insecticide-impregnated ear tags and regular treatments at 6-week intervals of all bulls with deltamethrin pour on were expected to achieve the desired control of the biting midges. Additionally, insecticide-treated mosquito fences circumventing much of the pens were tried for the first time against Culicoides. Two suction black-light traps (BioGents® sentinel traps) helped to monitor the densities of Culicoides and other haematophagous nematocera during the trial period from July to December 2007. Despite all efforts, the densities of Culicoides were not distinctly reduced. Several thousand midges were repeatedly recorded during one-night catches. Examinations of midges and other haematophagous nematocera (Aedes and Anopheles species) revealed high percentages of successful feedings between 10% and 35% for Culicoides and more than 50% for Aedes and Anopheles species. Since all insects were caught inside the pens, the concept of endophily vs exophily or endophagy vs exophagy for some Culicoides species needs to be revised accordingly. Also, stabling of valuable livestock does not reduce the host–vector interface and, hence, the risk of transmission of BT.  相似文献   

14.
Seventeen isolates of Borrelia burgdorferi sensu lato with an unclear genetic characteristic isolated in Russia from various species of Ixodes ticks (I. persulcatus, I. ricinus, and I. pavlovskyi) have been studied by multilocus sequencing analysis. According to the results of typing, these isolates were identified as B. bavariensis (n = 7), B. garinii (n = 6), B. finlandensis (n = 3), and B. spielmanii (n = 1), that is, species that can cause ixodid tick-borne borreliosis diseases in human beings. The allelic polymorphism of five genes (rrs, fla, groEL, recA, and ospA) and spacer rrfArrlB of B. bavariensis and B. garinii isolates was analyzed in comparison with their diversity in the International Nucleotide Sequence Database Collaboration.  相似文献   

15.
We introduce a novel method for fabricating hollow microneedles for transdermal drug delivery using a composite of vertically-aligned carbon nanotubes and polyimide. Patterned bundles of carbon nanotubes are used as a porous scaffold for defining the microneedle geometry. Polyimide resin is wicked through the carbon nanotube scaffold to reinforce the structure and provide the prerequisite strength for achieving skin penetration. The high aspect ratio and bottom-up assembly of carbon nanotubes allow the structure of the microneedles to be created in a single step of nanotube fabrication, providing a simple, scalable method for producing hollow microneedles. To demonstrate the utility of these microneedles, liquid delivery experiments are performed. Successful delivery of aqueous methylene blue dye into both hydrogel and swine skin in vitro is demonstrated. Electron microscopy images of the microneedles taken after delivery confirm that the microneedles do not sustain any structural damage during the delivery process.  相似文献   

16.

Background

Mutations in SLC26A4 cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity). The relationship between mutations in SLC26A4 and Mondini deformity without enlarged vestibular aqueduct has not been studied in any Chinese deaf population. The purpose of this study was to assess whether mutations in the SLC26A4 gene cause Mondini deformity without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese population.

Methods

In total, 144 patients with sensorineural hearing loss were included and subjected to high-resolution temporal bone CT. Among them, 28 patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16 patients with other types of inner ear malformations (IEM group) were identified. The coding exons of SLC26A4 were analyzed in all subjects.

Results

DNA sequence analysis of SLC26A4 was performed in all 144 patients. In the different groups, the detection rate of the SLC26A4 mutation differed. In the isolated MD group, only one single allelic mutation in SLC26A4 was found in one patient (1/28, 3.6%). In the EVA with MD group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. Also, in the EVA group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. These percentages were identical to those in the EVA plus MD group. Only two patients carried monoallelic mutations of the SLC26A4 gene in the IEM group (2/16, 12.5%). There were significant differences in the frequency of SLC26A4 mutation among the groups (P < 0.001). The detection rate of SLC26A4 mutation in the isolated MD group was significantly lower than in the EVA group (with or without MD; P < 0.001), and there was no significant difference in the detection rate of SLC26A4 between the MD group and IEM group (P > 0.5).

Conclusion

Although mutations in the SLC26A4 gene were frequently found in Chinese EVA patients with and without MD, there was no evidence to show a relationship between isolated MD and the SLC26A4 gene in the Chinese population examined. Hearing impairment in patients with isolated MD may be caused by factors other than mutations in the SLC26A4 gene.
  相似文献   

17.
The aim of this review is to provide an update on the plasmids mediating DHA-1 cephalosporinase in Klebsiella pneumoniae. These plasmids have been mainly found in this bacterium but not only. The first was isolated from Salmonella sp. in France in the early 1990s. They are currently reported worldwide. BlaDHA-1 beta-lactamase gene is usually co-expressed with many other antibiotic resistance genes such as extended-spectrum β-lactamases (blaCTX-M-, bla SHV -types), oxacillinases (blaOXA-1, blaOXA-30), penicillinases (bla TEM -type), carbapenemases (bla OXA48 , blaKPC-2), aminoglycosides (aacA, aadA, armA), fluoroquinolones (qnrB4, aac6′-1b-cr), and sulfonamide (sul1) resistance genes. Plasmids carrying DHA-1 cephalosporinase have different sizes (22 to 313 kb), belong to diverse groups of incompatibility (R, L/M, FII(k), FIB, A/C2, HI2, HIB), and are self-transferable or not. The multidrug resistance region consists of a mosaic structure composed of resistance genes, insertion sequences, composite transposon, and integrons.  相似文献   

18.
Epidemiological and epizootiological studies of Rickettsia felis and other Rickettsia spp. are very important, because their natural cycle has not yet been established completely. In total, 315 fleas (Siphonaptera) of 11 species of Ceratophyllidae, Hystrichopsyllidae and Leptopsyllidae families were tested for the presence of Rickettsia species and Coxiella burnetii with conventional and specific quantitative real-time PCR assays. Fleas were collected from five rodent hosts (Myodes glareolus, Apodemus flavicollis, Apodemus agrarius, Microtus subterraneus, Microtus arvalis) and three shrew species (Sorex araneus, Neomys fodiens, Crocidura suaveolens) captured in Eastern and Southern Slovakia. Overall, Rickettsia spp. was found in 10.8 % (34/315) of the tested fleas of Ctenophthalmus agyrtes, Ctenophthalmus solutus, Ctenophthalmus uncinatus and Nosopsyllus fasciatus species. Infected fleas were coming from A. flavicollis, A. agrarius, and M. glareolus captured in Eastern Slovakia. C. burnetii was not found in any fleas. R. felis, Rickettsia helvetica, unidentified Rickettsia, and rickettsial endosymbionts were identified in fleas infesting small mammals in the Ko?ice region, Eastern Slovakia. This study is the first report of R. felis infection in C. solutus male flea collected from A. agrarius in Slovakia.  相似文献   

19.
The cag (cytotoxin-associated gene) pathogenicity island (cagPAI) is one of the major virulence determinants of Helicobacter pylori (H. pylori). The purpose of this study was to investigate the association of the three genes (tnpA, tnpB, and cagA) in H. pylori isolated from Azerbaijani patients with the different gastrointestinal disease. A total of 362 gastric biopsies were collected from hospitals of Tabriz University of Medical Sciences, and were cultured on Brucella agar. The tnpA, tnpB, and cagA genes were detected by PCR. Of the total 264 H. pylori isolates, tnpA, tnpB, and cagA genes were detected in 120 (45.5%), 56 (21.2%) and 172 (65.2%), respectively. A significant association between tnpA and tnpB genes and clinical outcomes were found (P < 0.05). The cagA status was not related to clinical outcomes in our subjects. The predominant genotype among cag-PAI is the cagA. The prevalence of tnpA, tnpB, and cagA genes are high in patients with gastric cancer, and a significant association is revealed between tnpA and tnpB with gastric cancer.  相似文献   

20.
A new nematode species Dichelyne (Cucullanellus) sciaenidicola sp. nov. is described based on specimens collected from the Whitemouth croaker Micropogonias furnieri (Desmarest) and the Argentine croaker Umbrina canosai Berg, from coastal waters of Argentina and Brazil. These nematodes were firstly identified as D. (C.) elongatus (Törnquist, 1931), a commonly reported species from M. furnieri in South American Atlantic waters. However, other species of Dichelyne have so far been reported from this host in the same area, namely D. (C.) rodriguesi (Pinto, Fábio et Noronha, 1970), D. (C.) amaruincai (Freitas, Vicente et Ibañez, 1969) and D. (Dichelyne) micropogonii Pereira et Costa, 1996. A careful re-examination of these parasites, as well as of type specimens of all species reported from M. furnieri, revealed that these nematodes represented a new species. The new species is distinguished from most of its congeners by having papillae 5–7 and 9 forming a subventral line close to cloaca, this feature is shared with other 6 species [D. (C.) dichelyneformis (Szidat, 1950), D. (C.) fraseri (Baylis, 1929), D. (C.) abbreviatus (Rudolphi, 1819), D. (C.) adriaticus (Törnquist, 1931), D. (C.) minutus (Rudolphi, 1819) and D. (C.) mariajuliae Alarcos, Timi, Etchegoin et Sardella, 2006)], which are readily distinguished by their body size, spicules length, distribution patterns of other papillae and position of the excretory pore and deirids. Also, D. (C.) elongatus from Umbrina canariensis (Valenciennes) from West Africa is established as a new species Dichelyne (Cucullanellus) yvonnecampanae sp. nov.; D. (C.) amaruincai from Pacific waters is considered as a valid species, D. (D.) micropogonii is regarded as species inquirendae and D. (C.) rodriguesi is identified as Cucullanus sp.  相似文献   

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