Molecular cloning and functional expression of a serotonin receptor from the Southern cattle tick, Boophilus microplus (Acari: Ixodidae)

A full-length cDNA encoding a 5-hydroxytryptamine (5-HT) receptor from the Southern cattle tick, Boophilus microplus, was isolated using a strategy based on sequence homology among G protein-coupled receptors. The deduced amino acid sequence revealed highest identity with Drosophila melanogaster 5HT-dro2A (Z11489, 50.8%) and 5HT-dro2B (Z11490, 49.5%) receptors. The receptor was transiently expressed in mammalian HEK293 cells, and Western blot analysis showed the expected 43.3 kDa band. In these cells, application of 5-HT (10 microm) inhibited forskolin-induced cAMP synthesis by 26%. The results indicate that the tick receptor is an invertebrate 5-HT1-like receptor that couples to Galphai protein.     

Does mental illness stigma contribute to adolescent standardized patients' discomfort with simulations of mental illness and adverse psychosocial experiences?

OBJECTIVE: Adolescent mental illness stigma-related factors may contribute to adolescent standardized patients' (ASP) discomfort with simulations of psychiatric conditions/adverse psychosocial experiences. Paradoxically, however, ASP involvement may provide a stigma-reduction strategy. This article reports an investigation of this hypothetical association between simulation discomfort and mental illness stigma. METHODS: ASPs were randomly assigned to one of two simulation conditions: one was associated with mental illness stigma and one was not. ASP training methods included carefully written case simulations, educational materials, and active teaching methods. After training, ASPs completed the adapted Project Role Questionnaire to rate anticipated role discomfort with hypothetical adolescent psychiatric conditions/adverse psychosocial experiences and to respond to open-ended questions regarding this discomfort. A mixed design ANOVA was used to compare comfort levels across simulation conditions. Narrative responses to an open-ended question were reviewed for relevant themes. RESULTS: Twenty-four ASPs participated. A significant effect of simulation was observed, indicating that ASPs participating in the simulation associated with mental illness stigma anticipated greater comfort with portraying subsequent stigma-associated roles than did ASPs in the simulation not associated with stigma. ASPs' narrative responses regarding their reasons for anticipating discomfort focused upon the role of knowledge-related factors. CONCLUSION: ASPs' work with a psychiatric case simulation was associated with greater anticipated comfort with hypothetical simulations of psychiatric/adverse psychosocial conditions in comparison to ASPs lacking a similar work experience. The ASPs provided explanations for this anticipated discomfort that were suggestive of stigma-related knowledge factors. This preliminary research suggests an association between ASP anticipated role discomfort and mental illness stigma, and that ASP work may contribute to stigma reduction.     

Clinical Surveillance After Macroscopically Complete Surgery for Low-Grade Appendiceal Mucinous Neoplasms (LAMN) with or Without Limited Peritoneal Spread: Long-Term Results in a Prospective Series

Background

Low-grade appendiceal mucinous neoplasm (LAMN) is the most common primary lesion of pseudomyxoma peritonei, a disease whose standard treatment is cytoreduction and hyperthermic intraperitoneal chemotherapy. The optimal management of LAMN is not well defined. This study prospectively assessed a clinical surveillance strategy for LAMN with or without limited peritoneal spread.

Methods

During 2003–2017, the study prospectively enrolled 41 patients treated by macroscopically complete surgery for LAMN with or without limited peritoneal spread (pelvis and right lower quadrant). Follow-up assessment included thoracic-abdomino-pelvic computed tomography scan and serum tumor markers scheduled after surgery, then every 6 months for 5 years, and yearly thereafter. All specimens were reviewed by a dedicated pathologist.

Results

Appendectomy and five right colectomies were performed for 36 patients. Nine patients also underwent macroscopically complete cytoreduction of mucinous peritoneal disease, and four patients had hysterectomy plus bilateral salphingo-oophorectomy. Appendiceal rupture was evaluable in 38 of the 41 patients, being present in 21 patients (51.2%). Mucin, cells, or both outside the appendix were observed in 24 patients (58.5%). The median follow-up period was 58 months (range 9.3–162 months). The 5-year recurrence-free survival rate was 95.1%. Only two patients experienced peritoneal recurrences (4.9%), respectively 18 and 22 months after appendectomy. Their primary lesions were LAMNs with and without appendix wall rupture or extra-appendiceal mucin, respectively. No death occurred.

Conclusion

These findings strongly suggest that radically resected LAMN, even with limited peritoneal spread, carries a low recurrence risk. Furthermore, appendix wall perforation and the presence of mucin, cells, or both outside the appendix were not associated with a higher risk of metachronous peritoneal dissemination. In this setting, clinical and radiologic surveillance is a viable choice.

     

Personalized therapeutic strategies in HER2-driven gastric cancer

Gastric Cancer - Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them...     

FOLFOXIRI-Bevacizumab or FOLFOX-Panitumumab in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Propensity Score-Based Analysis

BackgroundDoublets plus anti‐epidermal growth factor receptors (EGFRs) are the preferred upfront option for patients with left‐sided RAS/BRAF wild‐type metastatic colorectal cancer (mCRC). Initial therapy with FOLFOXIRI‐bevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRI‐bevacizumab versus doublets plus anti‐EGFRs is available in left‐sided RAS/BRAF wild‐type mCRC.Materials and MethodsWe selected patients with left‐sided RAS and BRAF wild‐type mCRC treated with first‐line FOLFOX‐panitumumab or FOLFOXIRI‐bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score‐based analysis was performed to compare FOLFOXIRI‐bevacizumab with FOLFOX‐panitumumab.ResultsA total of 185 patients received FOLFOX‐panitumumab and 132 received FOLFOXIRI‐bevacizumab. Median progression‐free survival (PFS) and median overall survival (OS) were 13.3 and 33.1 months in the FOLFOXIRI‐bevacizumab group compared with 11.4 and 30.3 months in the FOLFOX‐panitumumab group (propensity score‐adjusted hazard ratio (HR) for PFS, 0.82; 95% confidence interval (CI), 0.64–1.04; p = .11; propensity score‐adjusted HR for OS, 0.80; 95% CI, 0.59–1.08; p = .14). No significant differences in overall response rate and disease control rate were observed. A statistically nonsignificant difference in favor of FOLFOXIRI‐bevacizumab was observed for OS after secondary resection of metastases. Chemotherapy‐related adverse events were more frequent in the FOLFOXIRI‐bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001).ConclusionAlthough randomized comparison is lacking, both FOLFOXIRI‐bevacizumab and FOLFOX‐panitumumab are valuable treatment options in left‐sided RAS/BRAF wild‐type mCRC.Implications for PracticeA propensity score‐based analysis of five trials was performed to compare FOLFOX‐panitumumab versus FOLFOXIRI‐bevacizumab in left‐sided RAS/BRAF wild‐type metastatic colorectal cancer (mCRC). No significant differences were observed, but FOLFOXIRI‐bevacizumab achieved numerically superior survival outcomes versus FOLFOX‐panitumumab. Chemotherapy‐related adverse events were more frequent in the FOLFOXIRI‐bevacizumab group. These observations suggest that although doublet chemotherapy plus anti‐EGFRs remains the preferred treatment in patients with left‐sided RAS/BRAF wild‐type mCRC, FOLFOXIRI‐bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients’ preference and potential impact on quality of life.     

Single brain metastases from melanoma: remarks on a series of 84 patients

The authors report on 84 patients with single melanoma brain metastasis surgically treated from 1997 to 2007. There were 46 males and 38 females; mean age was 41 years (range 24–58 years). All patients were surgically treated, and 52 of them received postoperative adjuvant therapy consisting of whole-brain radiation therapy (36), radiosurgery (9), or a combination of these two techniques (7). Brain recurrences were observed in 44 cases, of which 9 were local. Of the latter, seven were re-operated while the remaining two were treated by radiosurgery. At 1-year follow-up, the survival rate was 52% (32 patients) whereas only 12 patients (14%) were still alive after 2 years. None of the patients in which removal was subtotal survived for more than 6 months after surgical treatment. Three years after the onset of the brain metastasis, five patients (6%) were still alive. Survival was significantly influenced by treatment with regard to overall survival reported in other series. A review of literature, together with our own series, suggests that radical surgical treatment of the lesion possibly employing the internal no-touch technique has significantly increased survival in our patients (p < 0.05) and that the association of postoperative radiotherapy and re-operation in the event of recurrent metastatic lesions is advisable even though statistical significance was not reached (p > 0.05).     

Delayed hypersensitivity to 6-methyl-prednisolone in Henoch Schoenlein syndrome

We report a case of allergic reaction to oral 6-methyl-prednisolone in a patient with Henoch Schoenlein syndrome. When this syndrome was first diagnosed the patient was started on 6-methyl-prednisolone orally and after 4 days he developed a pruriginous generalized maculo-papular eruption. The rash disappeared 1 week after withdrawal of 6-methyl-prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6-methyl-prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivaseular infiltrate of lymphocytes, histiocytes and eosinophils.