Purpose Recent studies have demonstrated that short-form Ron (sfRon) kinase drives breast tumor progression and metastasis through robust activation of the PI3K pathway. We reasoned that upfront, concurrent inhibition of sfRon and PI3K might enhance the anti-tumor effects of Ron kinase inhibitor therapy while also preventing potential therapeutic resistance to tyrosine kinase inhibitors (TKIs). Experimental design We used patient-derived breast tumor xenografts (PDXs) as high-fidelity pre-clinical models to determine the efficacy of single agent or dual Ron/PI3K inhibition. We tested the Ron kinase inhibitor ASLAN002 with and without co-administration of the PI3K inhibitor NVP-BKM120 in hormone receptor positive (ER+/PR+) breast PDXs with and without PIK3CA gene mutation. Results Breast PDX tumors harboring wild-type PIK3CA showed a robust response to ASLAN002 as a single agent. In contrast, PDX tumors harboring mutated PIK3CA demonstrated partial resistance to ASLAN002, which was overcome with addition of NVP-BKM120 to the treatment regimen. We further demonstrated that concurrent inhibition of sfRon and PI3K in breast PDX tumors with wild-type PIK3CA provided durable tumor stasis after therapy cessation, whereas discontinuation of either monotherapy facilitated tumor recurrence. Conclusion Our work provides pre-clinical rationale for targeting sfRon in breast cancer patients, with the important stipulation that tumors harboring PIK3CA mutations may be partially resistant to Ron inhibitor therapy. Our data also indicate that tumors with wild type PIK3CA are most effectively treated with an upfront combination of Ron and PI3K inhibitors for the most durable response.

Background:Cutaneous nerves on the dorsum of foot are at risk for iatrogenic damage while performing arthroscopy, local anaesthetic block, surgical approach to the fibula, open reduction and internal fixation of lateral malleolar fractures, application of external fixators, elevation of a fasciocutaneous or fibular flaps for grafting, surgical decompression of neurovascular structures, or miscellaneous surgery on leg, foot and ankle. Hence the present study was undertaken to classify the different patterns of cutaneous innervation on the dorsum of foot of foetuses which will help in minimizing iatrogenic damage to the nerves.Materials and Methods:A total of 40 lower limbs from 20 foetuses were dissected and the branching patterns of nerves were noted and specimens were photographed.Results:Four distinct patterns of innervation with additional subtypes were identified and designated as Type 1 a-g; 2 a-d; 3; 4 a-c.Conclusion:Detailed knowledge about the pattern of cutaneous innervation of dorsum of foot may decrease the damage to these nerves during operative procedures near the foot and ankle.

Introduction: Contraception is a huge matter of concern in India- a developing country with very high and rapid growing population. Thus it is essential to promote contraceptive knowledge and ensure its uptake. The present study’s aim was to evaluate level of awareness of contraception among participants, and assess the factors that influence women’s awareness and choice of contraception. Methodology: The cross sectional study was conducted among premenopausal married females aged 21-45 from Government Lady Goschen Hospital, Mangaluru. A semi structured questionnaire was used to collect information. Data was analyzed using SPSS20. Results: The awareness of contraceptive methods was as follows: condom (90.9%), oral contraception pill (51.5%), tubal ligation (60.63%), intrauterine device (55.85%), natural method (22.87%) and hormonal IUD (24.3%). The most important factor affecting the choice of contraception was Health Care Professionals Advice (51.58%) followed by Partner’s Opinion (43.61%). Among intrinsic factors, the choice of contraception was most influenced by Convenience (30.85%), followed by Side Effects (26.59%), Duration of Action (21.8%), Non Contraceptive Benefits (11.17%), Reversibility (5.31%) and Cost (4.25%). Conclusion: A reassuring trend was noticed in the factors affecting choice of contraception. More than half the study population was aware of the contraceptive methods widely prescribed in Mangaluru.

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