Characterization of the currents underlying rhythmic firing in mammalian dopaminergic neurons

A mathematical model of midbrain dopamine neurons has been developed in order to understand the mechanisms underlying two types of calcium-dependent firing patterns that these cells exhibit in vitro. The first is the regular, pacemaker-like firing exhibited in a slice preparation, and the second is a burst firing pattern sometimes exhibited in the presence of apamin. Since both types of oscillations are blocked by nifedipine, we have focused on the slow calcium dynamics underlying these firing modes. The underlying oscillations in membrane potential are best observed when action potentials are blocked by the application of TTX. This converts the regular single-spike firing mode to a slow oscillatory potentials (SOP) and apamin-induced bursting to a slow square-wave oscillation. We hypothesize that the SOP results from the interplay between the L-type calcium current (I\sb{Ca,L}) and the apamin-sensitive calcium-activated potassium current (I\sb{K,Ca,SK}). We further hypothesize that the square-wave oscillation results from the alternating voltage activation and calcium inactivation of I\sb{Ca,L}. Our model consists of two components: (a) a Hodgkin-Huxley-type membrane model, and (b) a fluid compartment model. A material balance on Ca\sp{2+} is provided in the cytosolic fluid compartment, while calcium concentration is considered constant in the extracellular compartment. Model parameters were determined using both voltage-clamp and calcium imaging data from the literature. In addition to modeling the SOP and square-wave oscillations in DA neurons, the model provides reasonable mimicry of the experimentally observed graded modification of the amplitude and frequency of the SOP in response to injected current, as well as the elongation of the plateau duration of the square wave oscillations in response to calcium chelation

Respiratory rhythm generation: A modeling study of the respiratory central pattern generator and the phrenic motor neuron

The respiratory central pattern generator is a collection of medullary neurons that generates the rhythm of respiration. The respiratory central pattern generator feeds phrenic motor neurons, which, in turn, drive the main muscle of respiration, the diaphragm. The purpose of this thesis is to understand the neural control of respiration through mathematical models of the respiratory central pattern generator and phrenic motor neurons. We first designed and validated a Hodgkin-Huxley type model that mimics the behavior of phrenic motor neurons under a wide range of electrical and pharmacological perturbations. This model was constrained physiological data from the literature. Next, we designed and validated a model of the respiratory central pattern generator by connecting four Hodgkin-Huxley type models of medullary respiratory neurons in a mutually inhibitory network. This network was in turn driven by a simple model of an endogenously bursting neuron, which acted as the pacemaker for the respiratory central pattern generator. Finally, the respiratory central pattern generator and phrenic motor neuron models were connected and their interactions studied. Our study of the models has provided a number of insights into the behavior of the respiratory central pattern generator and phrenic motor neurons. These include the suggestion of a role for the T-type and N-type calcium channels during single spikes and repetitive firing in phrenic motor neurons, as well as a better understanding of network properties underlying respiratory rhythm generation. We also utilized an existing model of lung mechanics to study the interactions between the respiratory central pattern generator and ventilation

Advanced Imaging in Multiple Myeloma: New Frontiers for MRI

Plasma cell dyscrasias are estimated to newly affect almost 40,000 people in 2022. They fall on a spectrum of diseases ranging from relatively benign to malignant, the malignant end of the spectrum being multiple myeloma (MM). The International Myeloma Working Group (IMWG) has traditionally outlined the diagnostic criteria and therapeutic management of MM. In the last two decades, novel imaging techniques have been employed for MM to provide more information that can guide not only diagnosis and staging, but also treatment efficacy. These imaging techniques, due to their low invasiveness and high reliability, have gained significant clinical attention and have already changed the clinical practice. The development of functional MRI sequences such as diffusion weighted imaging (DWI) or intravoxel incoherent motion (IVIM) has made the functional assessment of lesions feasible. Moreover, the growing availability of positron emission tomography (PET)–magnetic resonance imaging (MRI) scanners is leading to the potential combination of sensitive anatomical and functional information in a single step. This paper provides an organized framework for evaluating the benefits and challenges of novel and more functional imaging techniques used for the management of patients with plasma cell dyscrasias, notably MM

Measuring and Teaching Confidence Calibration Among Radiologists: A Multi-Institution Study

Our purpose was to assess the calibration of resident, fellow, and attending radiologists on a simple image classification task (presence or absence of an anterior cruciate ligament [ACL] tear based on interpretation of sagittal proton density, fat-saturated MR images) and to assess whether teaching residents could improve their calibration. We created a test containing 30 randomized, sagittal, proton density, fat-saturated MR images of the ACL (15 normal, 15 torn). This test was administered in person to 20 trainees and 3 attendings at one medical center in one state. An online version of the test was given to 23 trainees and 14 attendings from 11 other medical centers in nine other states. Subjects were asked to give their confidence level (0%-100%) that each ACL was torn. Cross-sectional data were collected from 60 radiologists (mean time after medical school = 9.3 years, minimum = 1 year, maximum = 36 years). This demonstrated a statistically significant improvement in calibration as a function of increasing experience (P = .020). Longitudinal data were collected from 12 trainees at the start and end of their musculoskeletal radiology rotation, with an intervening review of the primary and secondary signs of ACL tear on MR. A statistically significant improvement in calibration was noted during the rotation (P = .028). Confidence calibration is a promising tool for quality improvement and radiologist self-assessment. Our study showed that calibration loss improves with experience in radiologists tested on a common and clinically important image classification task. We also demonstrated that calibration can be successfully taught to residents over a relatively short period (2-4 weeks)

Liposarcoma of the thigh with mixed calcification and ossification

Liposarcoma is one of the most common soft-tissue sarcomas. Calcification and ossification can occur in liposarcoma; however, the presence of both ossification and calcification is a very rare entity. We present a case of a partially calcified and ossified dedifferentiated liposarcoma of the thigh in a 76-year-old woman, which contained heterologous elements of chondrosarcoma and rhabdomyosarcoma

Optimal Number of Biopsies andImpact of Testicular Histology on the Outcome of Testicular Sperm Extraction

PURPOSE:To determine the optimal number of biopsies in patients with non-obstructive azoospermia (NOA) who undergo testicular sperm extraction (TESE), and assess the impact of testicular histology on outcome.MATERIALS AND METHODS: Seven hundred and forty-one patients with NOA who underwent TESE in our institution were enrolled in the study. Testicular sperm extraction was performed applying an open surgical technique on the larger testis. The number of biopsies varied according to the presence or absence of spermatozoa. No further biopsies were obtained once spermatozoa were detected. If no spermatozoa were seen, the procedure was continued to a maximum number of 5 biopsies, including a single biopsy of the contralateral testis. RESULTS: Spermatozoa were obtained in 330 (44.5%) patients after a single biopsy. The success rate increased to 381 (51.4%), 416 (56.1%), 433 (58.4%), and 441 (59.5%) after the second, third, fourth, and contralateral sampling, respectively. Multiple sampling increased the success rate; however, success rate did not increase considerably after the third sampling. Performing contralateral testicular biopsy was advantageous in patients with uniform or mixed pattern hypospermatogenesis.CONCLUSION:We recommend performing at least 3 biopsies in patients with NOA who undergo TESE. Further biopsies may also be advantageous when the NOA is a consequence of either uniform or mixed pattern hypospermatogenesis

First Seizure Due to a Ruptured Brain Dermoid Cyst

Introduction: first seizure is an unpleasant experience, the underlying cause and probability of recurrence is critical for the patient. Case: A 72 years old female was brought to our emergency department with a complaint of first seizure. Her daughter stated that she had had a tonic colonic generalized seizure that lasted about 10 seconds. She was complaining of a headache at the time of arrival in the ED, and the seizure had ended. The physical examination was normal and she had no past medical history. Spiral axial brain CT scanning demonstrated a sharp, round lesion with peripheral calcification near the pineal gland which compressed the third ventricle. Multiple nodules with fat density were seen in the subarachnoid space. Phenytoin was started for seizure prophylaxis and a neurosurgery consultation was requested. Tumor was completely reacted. Conclusion: This is a rare case of dermoid cyst near the pineal which compressed the third ventricle and caused midline shift and hydrocephaly. The cause of seizure may be the cyst rupturing. Complete cyst resection is the preferred treatment

Spontaneous hip dislocation secondary to intraarticular neurofibroma: a case report

Spontaneous hip dislocation due to intraarticular neurofibroma in patients with neurofibromatosis type 1 is extremely rare. We describe the imaging features of spontaneous dislocation of hip due to histologically proven intraarticular neurofibroma in young woman with neurofibromatosis type 1, and review the literature.Univ Texas MD Anderson Canc Ctr, Dept Diagnost Imaging, Houston, TX 77030 USAUniv Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USAUniversidade Federal de São Paulo, Escola Paulista Med, Dept Diagnost Posr Imagem, São Paulo, BrazilUniv Texas MD Anderson Canc Ctr, Dept Orthoped Oncol, Houston, TX 77030 USAUniversidade Federal de São Paulo, Escola Paulista Med, Dept Diagnost Posr Imagem, São Paulo, BrazilWeb of Scienc