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BACKGROUND Anatomical variations involving the visceral arteries are common. However, variations in coeliac trunk are usually asymptomatic, they may become important in patients undergoing diagnostic angiography for gastrointestinal bleeding or prior to an operative procedure. This study was useful for knowing the possible morphological variations before an upper abdominal surgery. MATERIALS AND METHODS This was a descriptive study done by cadaveric dissection, conducted on thirty cadavers. The coeliac trunk being examined for its origin, branching pattern, distribution, and variations. Results were statistically analysed and compared with the previous studies. RESULTS In our study, 60% of the coeliac trunk shows variations and 40% have normal branching pattern. A complete absence of coeliac trunk was observed in one case. In the present study the Right inferior phrenic artery arising from coeliac trunk in 2 cases (6.6%) and left inferior phrenic artery arising from coeliac trunk in 3 cases (9.9%). Both inferior phrenic arteries are arising from coeliac trunk in 2 cases (6.6%). The common hepatomesenteric trunk and gastro splenic trunk was found in 1 case (3.3%). Hepatosplenic trunk was found in 2 cases (6.6%). In another 2 cases (6.6%) gastric and hepatic artery originate from coeliac trunk but splenic artery has a separate origin from abdominal aorta. An absent trunk was also found in 1 case (3.3%). In 5 cases (16.7%) showed trifurcation with variation in the branching pattern. CONCLUSION The branching pattern and extreme degree variability in coeliac trunk as brought out in the observations of the present study make it obvious that the present study almost falls in description with previous studies.

To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector-based gene therapy for RPE65 mutation-associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2.Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial.Forty subjects who received 1.5×10Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects.End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing.Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 logAfter VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation-associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing.

3^011& at different critical resolved shear stress ratios for the different slip systems. The prediction of the models is correlated with the results of x-ray diffraction measurements. Uniaxial deformation experiments on polycrystalline and single-crystal MgO samples were conducted in situ using white x-ray diffraction with a multielement detector and multianvil high-pressure apparatus at a pressure up to 6 GPa and a temperature of 500 °C. A deformation DIA was used to generate pressure and control at a constant deformation rate. Elastic strains and plastic strains were monitored using x-ray diffraction spectra and x-ray imaging techniques, respectively. The correlation of the data and models suggests that the plastic models need to be used to describe the stress‐strain observations with the presence of plasticity, while the Reuss and Voigt models are appropriate for the elastic region of deformation, before the onset of plastic deformation. The similarity of elastic strains among different lattice planes suggests that the $111% slip system is the most significant slip system in MgO at high pressure and high temperature. © 2004 American Institute of Physics. @DOI: 10.1063/1.1738532#

There is an evolving role for combining radiotherapy (RT) with gene therapy in the management of prostate cancer. However, the clinical results of this combined approach are much needed. The preliminary results addressing the safety of this Phase I-II study combining RT and gene therapy (adenovirus/herpes simplex virus-thymidine kinase gene/valacyclovir with or without hormonal therapy) in the treatment of prostate cancer have been previously reported. We now report the prostate-specific antigen (PSA) response and biopsy data.This trial was composed of three separate arms. Arm A consisted of low-risk patients (Stage T1-T2a, Gleason score7, pretreatment PSA10 ng/mL) treated with combined RT-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated RT. They also received adenovirus/herpes simplex virus-thymidine kinase/valacyclovir gene therapy. Arm B consisted of high-risk patients (Stage T2b-T3, Gleason score6, pretreatment PSA level10 ng/mL) treated with combined RT-gene therapy and hormonal therapy (luteinizing hormone-releasing hormone agonist [30-mg Lupron, 4-month depot] and an antiandrogen [flutamide, 250 mg t.i.d. for 14 days]). Arm C consisted of patients with Stage D1 (positive pelvic lymph nodes) who received the same regimen as Arm B with the addition of 45 Gy to the pelvic lymphatics. PSA determination and biopsy were performed before, during, and after treatment. The American Society for Therapeutic Radiology and Oncology consensus definition (three consecutive rises in PSA level) was used to denote PSA failure.Fifty-nine patients (29 in Arm A, 26 in Arm B, and 4 in Arm C) completed the trial. The median age was 68 years (range, 39-85 years). The median follow-up for the entire group was 13.5 months (range, 1.4-27.8 months). Only Arm A patients were observed to have an increase in PSA on Day 14. The PSA then declined appropriately. All patients in Arm A (median follow-up, 13.4 months) and Arm B (median follow-up, 13.9 months) had biochemical control at last follow-up. Three patients in Arm C (with pretreatment PSA of 335, 19.6, and 2.5 ng/mL and a combined Gleason score of 8, 9, and 9 involving all biopsy cores) had biochemical failure at 3, 3, and 7.7 months. Two patients had distant failure in bone and 1 patient in the para-aortic lymph nodes outside the RT portal. Six to twelve prostate biopsies performed in these 3 patients revealed no evidence of residual carcinoma. In Arm A, biopsy showed no evidence of carcinoma in 66.7% (18 of 27), 92.3% (24 of 26), 91.7% (11 of 12), 100% (8 of 8), and 100% (6 of 6) at 6 weeks, 4 months, 12 months, 18 months, and 24 months after treatment, respectively. In Arm B, no evidence of carcinoma on biopsy was noted in 96% (24 of 25), 90.5% (19 of 21), 100% (14 of 14), 100% (7 of 7), and 100% (2 of 2), respectively, in the same interval after treatment.This is the first reported trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of RT by combining it with in situ gene therapy. The initial transient PSA rise in the Arm A patients may have been a result of local immunologic response or inflammation elicited by in situ gene therapy. Additional investigation to elucidate the mechanisms is needed. Hormonal therapy may have obliterated this rise in Arm B and C patients. The biopsy data were encouraging and appeared to show no evidence of malignancy earlier than historical data. Combined RT, short-course hormonal therapy, and in situ therapy appeared to provide good locoregional control but inadequate systemic control in patients with positive pelvic lymph nodes. Longer term use of hormonal therapy in addition to gene therapy and RT has been adopted for this group of patients to maximize both locoregional and systemic control.

Background: Ovarian tumor and tumor like conditions are seen in women from early childhood to post-menopausal age. The ovaries are a pair of female sex glands responsible for the germ cell maturation, storage and release; cyclically. It also plays an important role in steroidogenesis. The ovaries are a totipotential structure and hence, neoplasms from all 3 germinal layers can be seen arising from it and manifesting clinically as ovarian tumors and tumor like conditions with its occurrence more during the late reproductive life. Ovarian tumors represent about 30% of all cancers of the female genital system. They manifesting in a wide spectrum of clinical, morphological and histological features.Methods: This is retrospective observational study where analysis of all cases which were encountered surgically during the period Mar 2012 to Mar 2017. The cases diagnosed as ovarian tumors were subjected to thorough investigation by CA125, ultrasound (USG) abdomen and pelvis and Computerised Tomography (CT) scan. Emergency presentations with twisted cysts were operated in emergency setting and histopathological examination (HPE) done to identify the nature of tumor. IHC was done wherever necessary to sub classify and confirm the histological diagnosis. Surgeries were done either by conventional laparotomy or by laparoscopy.Results: We have analyzed 175 cases retrospectively after histopathological diagnosis. The commonest lesions were ovarian cysts, out of which 63 cases (36%) were simple serous cyst adenomas followed by mucinous cyst adenomas 30 cases (17.14%). Germ cell tumors with struma ovarii were 34 cases (19.42%). The interesting part of the study was that we had a very high incidence of large endometriomas diagnosed as ovarian cysts before surgery 16 cases (9.4%). Two cases (1.14%) of ovarian malignancy were detected.Conclusions: The above study has revealed a spectrum of ovarian tumors over a wide age range from adolescent to late reproductive to menopausal and late menopausal age group. The incidence of malignancy was (1.14%).

To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer.Arm A: low-risk patients (T1-T2a, Gleason score7, pretreatment PSA10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason scoreor=7, pretreatment PSAor=10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score.Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients (27%) with Grade 1, and 9 patients (30%) with no toxicity. No patient dropped out from the trial or had to withhold treatment because of severe toxicity.This is the first trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of radiotherapy by combining in situ gene therapy. Initial experience has demonstrated the safety of this approach. There is no added toxicity to each therapy used alone. Long-term follow-up and larger cohort studies are warranted to evaluate long-term toxicity and efficacy.

Transgenic mice carrying amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutations develop a motoneuron disease resembling human ALS. c-Jun is a transcription factor frequently induced in injured neurons. In this study we have examined the distribution of c-Jun-immunoreactivity in the brainstem and spinal cord of transgenic SOD1 mice with a glycine 93 alanine (G93A) mutation. In non-transgenic littermates c-Jun immunostaining was predominantly situated in motoneurons. The number of c-Jun immunoreactive motoneuron was reduced in SOD1(G93A) mice due to pronounced loss of motoneurons. In SOD1(G93A) mice, however, c-Jun-immunoreactivity was strongly induced in neurons in the intermediate zone (Rexed's laminae V-VIII and X) of the spinal cord and throughout the brainstem reticular formation. These findings are of interest since increased levels of c-jun also have been found in the intermediate zone of the spinal cord of ALS patients. This c-Jun may be involved in the neurodegenerative processes both in ALS and in motoneuron disease in SOD1(G93A) mice.

[1] Recent developments in high-pressure X-ray studies enable the measurement of the elastic strain anisotropy induced by a macroscopic differential stress in an aggregate sample. Such data are commonly used to constrain the single-crystal elastic moduli under the assumptions of the Reuss-Voigt state. We find this procedure is valid only for samples that have not been plastically deformed. Measured elastic strain anisotropy for MgO at stress levels below the yield point agree well with the Reuss elastic model. Plastic deformation effects a change in the stress field for subpopulations of grains that represent different crystallographic orientations with respect to the applied stress field. Our data for the plastically deformed sample are consistent with the predictions of a self-consistent aggregate model for deforming polycrystals. Such models may be useful as a guide to define the elastic properties in light of the active slip systems. INDEX TERMS: 3902 Mineral Physics: Creep and deformation; 3909 Mineral Physics: Elasticity and anelasticity; 3924 Mineral Physics: High-pressure behavior; 3954 Mineral Physics: X ray, neutron, and electron spectroscopy and diffraction; 3994 Mineral Physics: Instruments and techniques. Citation: Weidner, D. J., L. Li, M. Davis, and J. Chen (2004), Effect of plasticity on elastic modulus measurements, Geophys. Res. Lett., 31, L06621, doi:10.1029/ 2003GL019090.

Combined radiotherapy and gene therapy is a novel therapeutic approach for prostate cancer. There are various potential benefits in combining ionizing radiation with gene therapy to achieve enhanced antitumor effects: A) ionizing radiation improves transfection/ transduction efficiency, transgene integration, and possibly, the “bystander effect” of gene therapy; B) gene therapy, on the other hand, may interfere with repair of radiation-induced DNA damage and increase DNA susceptibility to radiation damage in cancer cells, and C) radiotherapy and gene therapy target at different parts of the cell cycle. Preclinical data have demonstrated the enhanced antitumor effects of this combined approach in local tumor control, prolongation of survival, as well as systemic control. This combined radio-gene therapy is under study in an ongoing clinical trial in prostate cancer. Our study adds gene therapy to the standard of care therapy (radiotherapy). These treatment modalities have different toxicity profiles. The goal of this combined approach is to enhance cancer cure without an increase in treatment-related toxicity. This approach also offers a new paradigm in spatial cooperation, whereby two local therapies are combined to elicit both local and systemic effects. Early clinical results showed the safety of this approach.