Direct contribution of the sensory cortex to the judgment of stimulus duration.

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding.

Primary intestinal-type adenocarcinoma of the vulva. A case report and review of the literature.

Background: Primary non-squamous cell carcinomas of the vulva are rare entities including various tumor types. Among these, primary vulvar intestinal-type adenocarcinoma (vPITA) is extremely rare. Until 2021, less than twenty-five cases have been reported in the literature. Case presentation: We report a case of vPITA in a 63 years old woman with a histopathological diagnosis of signet-ring cell intestinal type adenocarcinoma at vulvar biopsy. Accurate clinical and pathological work-up excluded secondary metastatic localization, and vPITA was diagnosed. The patient was treated with radical vulvectomy and bilateral inguinofemoral dissection. Adjuvant chemo-radiotherapy was performed because of a positive lymph node. At 20 months follow-up the patient was alive and free of disease. Conclusion:  The prognosis of this very rare disease is unclear and optimal treatment is not well established. About 40% of clinical early-stage diseases reported in literature had positive inguinal nodes, more than in vulvar squamous cell carcinomas. A proper histopathologic and clinical diagnosis is mandatory to exclude secondary disease and to recommend an adequate treatment.

Feasibility and Oncological Outcome of Preoperative Chemoradiation With IMRT Dose Intensification for Locally Advanced Esophageal and Gastroesophageal Cancer.

PURPOSE: To explore the feasibility and efficacy of a dose intensification with Intensity Modulated Radiation Therapy and Simultaneous Integrated Boost (IMRT-SIB) in locally advanced esophageal and gastroesophageal cancer (GEJ). METHODS AND MATERIALS: We retrospectively analyzed a series of 69 patients with esophageal or GEJ cancer treated at our Institute, between 2016 and 2019, with preoperative IMRT and SIB up to 52.5-54 Gy in 25 fractions in 5 weeks and concurrent carboplatin (AUC2) and paclitaxel (50 mg/m2), as in the CROSS regimen. RESULTS: All patients completed the planned IMRT-SIB program with a median of four (range 1-5) cycles of concurrent paclitaxel/carboplatin. Compliance to IMRT-SIB was 93%, whereas 54% of patients received four to five cycles and 87% at least three cycles of concurrent carboplatin/paclitaxel. Grade 3 toxicity was reported in 19% of patients. Complete clinical response (cCR) was achieved in 48%, and 13% had disease progression after chemoradiation (CRT). Overall, 49% of patients underwent surgery; reasons for non-operation included cCR in cervical tumor location (10%) or cCR and patient decision (13%). A pathologic complete response (pCR) was achieved in 44% of resected patients. Postoperative complications and mortality rates were 21 and 6%, respectively. At a median follow-up of 12 months (6-25), 2-year overall and progression-free (PFS) survival rates were 81 and 54%, respectively. No difference in PFS by histologic type in operated patients was reported. Non-operated cCR patients had higher PFS, including cervical locations and selected cCR patients who decided for non-operation (75 vs 30%, p < 0.01). CONCLUSION: The study reported favorable results in safety and feasibility of the IMRT-SIB dose intensification in our preoperative CRT program. The toxicity was acceptable, allowing a high compliance to intensified radiation doses with dose reduction of concurrent paclitaxel/carboplatin in some patients. The high rate of cCR and pCR suggested this intensified program is effective in the preoperative CRT and, for selected responsive patients, in the non-operative approach to esophageal and GEJ cancer. The 2-year survival rates were promising. A prospective study is being planned to confirm these observations.

A passive, camera-based head-tracking system for real-time, three-dimensional estimation of head position and orientation in rodents.

Tracking head position and orientation in small mammals is crucial for many applications in the field of behavioral neurophysiology, from the study of spatial navigation to the investigation of active sensing and perceptual representations. Many approaches to head tracking exist, but most of them only estimate the 2D coordinates of the head over the plane where the animal navigates. Full reconstruction of the pose of the head in 3D is much more more challenging and has been achieved only in handful of studies, which employed headsets made of multiple LEDs or inertial units. However, these assemblies are rather bulky and need to be powered to operate, which prevents their application in wireless experiments and in the small enclosures often used in perceptual studies. Here we propose an alternative approach, based on passively imaging a lightweight, compact, 3D structure, painted with a pattern of black dots over a white background. By applying a cascade of feature extraction algorithms that progressively refine the detection of the dots and reconstruct their geometry, we developed a tracking method that is highly precise and accurate, as assessed through a battery of validation measurements. We show that this method can be used to study how a rat samples sensory stimuli during a perceptual discrimination task and how a hippocampal place cell represents head position over extremely small spatial scales. Given its minimal encumbrance and wireless nature, our method could be ideal for high-throughput applications, where tens of animals need to be simultaneously and continuously tracked.NEW & NOTEWORTHY Head tracking is crucial in many behavioral neurophysiology studies. Yet reconstruction of the head's pose in 3D is challenging and typically requires implanting bulky, electrically powered headsets that prevent wireless experiments and are hard to employ in operant boxes. Here we propose an alternative approach, based on passively imaging a compact, 3D dot pattern that, once implanted over the head of a rodent, allows estimating the pose of its head with high precision and accuracy.

Optimizing craniospinal radiotherapy delivery in a pediatric patient affected by supratentorial PNET: a case report.

New advances in radiation therapy for children allow increased conformability and reduced doses to non-target tissues. We report our experience in treating a 4-year-old child with craniospinal tomotherapy after surgery of the primary tumor, a supratentorial primitive neuroectodermal tumor. The tomotherapy plan was compared with conventional craniospinal irradiation, 3D conformal radiation therapy, and intensity-modulated radiation therapy plans. The possible disadvantages of tomotherapy related to the radiation dose to organs at risk, treatment planning, and anesthesia should be carefully considered as the use of the technique is not suggested in a general manner, but selectively, in critical pediatric radiotherapy cases.

Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy.

PURPOSE: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). METHODS: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. RESULTS: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term alpha and the dose per fraction. The estimated values of alpha and OER from data fitting were 0.396 Gy(-1) and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). CONCLUSIONS: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

Thoracic radiation therapy and concomitant low-dose daily paclitaxel in non-small cell lung cancer: a phase I study.

The primary objective of the current study was to determine the maximum tolerated dose of paclitaxel (PTX) that could be added daily to radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). The secondary objective was to achieve a plasma concentration of PTX estimated to exert a radiosensitizing effect. Eighteen patients with locally advanced NSCLC were treated. 60 Gy of RT were given in 2 Gy fractions, 5 days per week. A daily dose of PTX was delivered by 4-h i.v. infusion before RT. The initial dose level of PTX was 9 mg/m2/day, escalated by 1 mg at each additional patient triplet. Two out of 6 patients experienced acute dose limiting toxicity (DLT) at the 12 mg/m2/day PTX dose level. PTX continuously greater than 10 nM, the estimated radiosensitizing condition, was achieved at the PTX dose level of 12 mg/m2/day. PTX at doses up to 11 mg/m2/day may be safely added to a conventional conformal RT course. Both DLT and the estimated radiosensitizing plasma exposure to PTX were encountered at the 12 mg/m(2)/day dose level.

Radiosensitivity in multidrug-resistant and cisplatin-resistant human carcinoma cell lines.

The radiosensitivity of a multidrug-resistant (MDR) clone and a cisplatin-resistant clone was compared with that of their parental chemosensitive cell lines. The LoVo cell line was derived from a human colon carcinoma, and LoVo-R was the MDR clone. The MDR phenotype is attributable to an increased drug efflux mediated by the P-glycoprotein and involves several classes of structurally unrelated drugs. The 2008 cell line was derived from a human ovary carcinoma and C13 was the cisplatin-resistant clone. Reduced cisplatin accumulation and elevated plasma membrane potential partially account for the drug resistance of C13 cells. The chemoresistance of LoVo-R and C13 cells was confirmed by cytotoxicity tests consisting of 24-hour paclitaxel and 1-hour cisplatin incubation, respectively. The radiosensitivity was evaluated by a clonogenic test. The dose-reducing cell survival fraction from 1 to 0.37 (D(0)), the quasi-threshold dose (Dq), and the survival fraction (SF) after 2 or 4 Gy were determined for each cell line. D(0), Dq, and SF(2) were 1.3 +/- 0.4 Gy, 2.1 +/- 0.6 Gy, and 43 +/- 4% for the LoVo cell line and 1.0 +/- 0.2 Gy, 1.7 +/- 0.4 Gy, and 45 +/- 8%, respectively, for the LoVo-R cell line. D(0), Dq, and SF(4) were 1.7 +/- 0.3 Gy, 3.1 +/- 0.4 Gy, and 43 +/- 12% for 2008 cells and 2.6 +/- 0.5 Gy, 4.3 +/- 0.6 Gy, and 53 +/- 11%, respectively for C13 cells. No significant differences were found between LoVo and LoVo-R cells, whereas C13 cells showed a significantly greater D(0,) Dq, and SF(4) than 2008 cells (p <0.05). Incubation of 2008 and C13 cells with subcytotoxic buthionine (BSO) before and after irradiation partially restored C13 radiosensitivity. In fact, D(0) dropped from 2.8 +/- 0.1 to 2.0 +/- 0.3 Gy in C13 cells with and without BSO, whereas it was 1.9 +/- 0.2 Gy in 2008 cells in the absence and presence of BSO. The total glutathione content (GSH) of C13 cells was 1.5-fold higher than that of 2008 cells. BSO treatment caused a partial depletion of GSH in 2008 and C13 cells, but their radiosensitivity did not change accordingly.