A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma.

BACKGROUND: Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice. METHODS: We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10-20 mm in diameter, we performed survival surgery on each mouse to harvest 90-95% of subcutaneous PDX (incomplete resection), allowing the remaining 5-10% of PDX to continue growing in the same mouse. RESULTS: We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors. CONCLUSIONS: Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.

Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia.

BACKGROUND: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied. METHODS: Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed. RESULTS: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed. CONCLUSIONS: The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.

"Five-point eight-line" anatomic flap design for precise hemitongue reconstruction.

BACKGROUND: Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. METHODS: Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. RESULTS: All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P < .05). CONCLUSIONS: The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.

Multisensory Logic of Infant-Directed Aggression by Males.

Newborn mice emit signals that promote parenting from mothers and fathers but trigger aggressive responses from virgin males. Although pup-directed attacks by males require vomeronasal function, the specific infant cues that elicit this behavior are unknown. We developed a behavioral paradigm based on reconstituted pup cues and showed that discrete infant morphological features combined with salivary chemosignals elicit robust male aggression. Seven vomeronasal receptors were identified based on infant-mediated activity, and the involvement of two receptors, Vmn2r65 and Vmn2r88, in infant-directed aggression was demonstrated by genetic deletion. Using the activation of these receptors as readouts for biochemical fractionation, we isolated two pheromonal compounds, the submandibular gland protein C and hemoglobins. Unexpectedly, none of the identified vomeronasal receptors and associated cues were specific to pups. Thus, infant-mediated aggression by virgin males relies on the recognition of pup's physical traits in addition to parental and infant chemical cues.

The Use of a Honeycomb Technique Combined with Ultrasonic Aspirators and Indocyanine Green Fluorescence Angiography for a Superthin Anterolateral Thigh Flap: A Pilot Study.

BACKGROUND: Harvesting an optimally thinned anterolateral thigh flaps is a challenge in overweight individuals and in the Western population. The authors describe a novel honeycomb technique to achieve a superthin anterolateral thigh flap in overweight patients. METHODS: Forty patients with a body mass index greater than 25 kg/m(2) who required a thinned anterolateral thigh flap for reconstruction were assigned randomly to a honeycomb technique group or a microdissection technique group. The honeycomb technique group underwent flap thinning with the Cavitron Ultrasonic Surgical Aspirator, and flap thinning was performed with a conventional microdissection technique in the microdissection technique group. Perfusion of all flaps was measured by indocyanine green fluorescence angiography before and after thinning. Hypoperfusion was defined as 30 percent. RESULTS: The mean body mass index was 28.6 ± 2.0 kg/m(2) and 27.3 ± 1.9 kg/m(2) in the honeycomb group and the microdissection group, respectively. Flap size, perforator, type of dissection, and initial perfusion were comparable between the two groups. However, significantly more patients (nine of 21) experienced final hypoperfusion in the microdissection group than in the honeycomb group (two of 19) (p = 0.034). In addition, blood loss and final flap thickness were significantly lower in the honeycomb group (p < 0.05), and the duration of thinning was comparable between the two groups. No flap necrosis was found in either group. CONCLUSION: The honeycomb technique in combination with the Cavitron Ultrasonic Surgical Aspirator and indocyanine green angiography was able to remove adipose tissue but protect the integrity of the subcutaneous vascular plexus to reduce potential risk of jeopardizing flap perfusion while obtaining a superthin anterolateral thigh flap in an overweight population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The benefits of being a near-peer teacher.

BACKGROUND: Near-peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored. METHOD: A questionnaire was distributed to the teachers involved in anatomy near-peer teaching at the University of Southampton and Brighton and Sussex Medical School (BSMS). This questionnaire was designed using a rating scale of 0-10 to assess teacher perspectives on their level of knowledge, teaching skills and enjoyment of teaching. Free-text responses determined the teachers' motivation and perceived benefits from the teaching. RESULTS: Twenty-eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS. Long-term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near-peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near-peer teacher in medical school DISCUSSION: There are numerous advantages to being a near-peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies.