Combinatorial encoding of odors in the mosquito antennal lobe.

Among the cues that a mosquito uses to find a host for blood-feeding, the smell of the host plays an important role. Previous studies have shown that host odors contain hundreds of chemical odorants, which are detected by different receptors on the peripheral sensory organs of mosquitoes. But how individual odorants are encoded by downstream neurons in the mosquito brain is not known. We developed an in vivo preparation for patch-clamp electrophysiology to record from projection neurons and local neurons in the antennal lobe of Aedes aegypti. Combining intracellular recordings with dye-fills, morphological reconstructions, and immunohistochemistry, we identify different sub-classes of antennal lobe neurons and their putative interactions. Our recordings show that an odorant can activate multiple neurons innervating different glomeruli, and that the stimulus identity and its behavioral preference are represented in the population activity of the projection neurons. Our results provide a detailed description of the second-order olfactory neurons in the central nervous system of mosquitoes and lay a foundation for understanding the neural basis of their olfactory behaviors.

Mosquito Olfactory Response Ensemble enables pattern discovery by curating a behavioral and electrophysiological response database.

Many experimental studies have examined behavioral and electrophysiological responses of mosquitoes to odors. However, the differences across studies in data collection, processing, and reporting make it difficult to perform large-scale analyses combining data from multiple studies. Here we extract and standardize data for 12 mosquito species, along with Drosophila melanogaster for comparison, from over 170 studies and curate the Mosquito Olfactory Response Ensemble (MORE), publicly available at https://neuralsystems.github.io/MORE. We demonstrate the ability of MORE in generating biological insights by finding patterns across studies. Our analyses reveal that ORs are tuned to specific ranges of several physicochemical properties of odorants; the empty-neuron recording technique for measuring OR responses is more sensitive than the Xenopus oocyte technique; there are systematic differences in the behavioral preferences reported by different types of assays; and odorants tend to become less attractive or more aversive at higher concentrations.

Helping medical students to learn pathology more effectively.

CONTEXT: Teaching methods in pathology for undergraduate medical students are not effective. AIMS: To document measures that can be adopted by individual teachers that can excite the interest, participation of the students and help them learn pathology in a clinical reasoning context. SETTINGS AND DESIGN: Medical students in a large international medical school with class sizes of 700-900 were taught the pathology course in a period of sixteen weeks for two cohorts of students each year over a period of twenty years. SUBJECTS AND METHODS: Specific learning objectives were devised to achieve higher levels of cognitive domain including interpretation, analysis and problem solving of clinical data of patients related to the objectives. The teaching sessions were modified to provide for maximum active participation by students with effective feedback at multiple points. Additional learning tools like concept maps, clickers, modified essay questions, flipped classrooms, clinicopathological conferences, directed self-learning activities were included. Learning objectives and assessment tools for professional behavior and communication skills were included. RESULTS: The students actively participated in all the learning activities with enthusiasm and achieved the objectives as reflected in the performance in the in-house examinations and the USMLE step one examination which tests clinical vignette-based problem-solving principles of which around 70% are related to pathology. CONCLUSIONS: The teaching sessions in pathology were useful and effective with adaptation to interactive, clinical reasoning platforms for teaching and assessment.

Management of true lateral infected radicular cyst as well as associated mucosal fenestration that occurred postoperatively through an interdisciplinary approach: A rare case report.

A radicular cyst (RC) is one of the types of inflammatory cyst of odontogenic origin. It is usually associated with nonvital teeth and is mostly observed in males. It is routinely treated by nonsurgical endodontic therapy; however, if the cystic lesion does not respond to endodontic therapy, then surgical intervention with or without regeneration is the treatment of choice, depending upon the size, location of lesion, the bone integrity of the cystic lesion wall, proximity to vital structures and residual bone defect elicit after enucleation, etc., We hereby present successful interdisciplinary management of rare true lateral RC in the interproximal site with respect to teeth number 21 and 22 as well as associated mucosal fenestration that was occurred postoperatively other than its apparent etiology and diagnosis.

Pleomorphic Hyalinizing Angiectatic Tumour: A Rare Case Report and Discussion of Differential Diagnosis.

Pleomorphic Hyalinizing Angiectatic Tumour (PHAT) is one of the rare soft tissue tumour which is non-metastasizing. The origin of this tumour is yet uncertain. It occurs in adults as a slow growing subcutaneous mass mimicking clinically and histologically to various benign and malignant soft tissue tumours such as schwannoma, haemangioma and malignant fibrous histiocytoma. The microscopic features of this tumour include clusters of ectatic, fibrin containing, hyalinized blood vessels with pleomorphic and spindle shaped tumour cells showing intranuclear inclusions, stromal haemosiderin pigment and a variable inflammatory infiltrate. Despite marked pleomorphism, the lesion behaves as a low grade neoplasm, with frequent recurrences, but no metastases. The incidence of this tumour is very rare with less than 100 cases being published. Hence, awareness of this entity is must for proper management of the patient and to avoid misdiagnosis of the lesion. We report a case of pleomorphic hyalinizing angiectatic tumour in a 50-year-old man who presented with a slow growing mass in the left calf region since two years.

Concept map as an adjunct tool to teach pathology.

CONTEXT: Concept maps (CMs) were tested for their effectiveness in teaching pathology in a conceptual manner. AIMS: To correlate the quality of CMs drawn by students with their performance on tests involving clinical problem-solving. SUBJECTS AND METHODS: Students were taught "how, why, and so what" about CMs at the start of the course. Each student drew one CM every week and a minimum of ten throughout the course and submitted them for evaluation and corrections. The course which is offered twice a year (approximately 600 students in each class) generates approximately 12,000-13,000 CMs each year. Two thousand nine hundred CMs from 290 students in one class were included in the study. Each CM was scored by three authors independently. The students' scores on the CMs were correlated with their scores on the midterm and final examinations. STATISTICAL ANALYSIS USED: Wilcoxon signed-rank test and Spearman's rank-order correlation. RESULTS: The mean scores for the CMs at the course's midterm and final were 59% and 69.7%, and the mean scores for the examinations were 76% and 84.2% on the midterm and finals, respectively. There was a highly significant correlation between the CM scores and examination scores (P < 0.0001). CONCLUSION: CMs proved to be a great tool to teach pathology effectively.

Impact of Biosimilar Insulins on Clinical Practice: Meeting Report.

The availability of biosimilar insulins can potentially lead to lower insulin costs and increased access for patients with diabetes, worldwide. However, clinicians and regulatory agencies have raised several concerns regarding the safety and efficacy of these new medications. The European regulatory agencies have established guidelines for market approval of biosimilar insulins; however, many issues remain unresolved. Moreover, although the FDA has developed preliminary pathways for biosimilar protein development and is prepared to review each application on a case-by-case basis, insulins do not fall under this pathway at this time. The development of effective postmarketing surveillance protocols, determination of product interchangeability, and product identification/labeling remain key concerns. Numerous issues surround the development and commercialization of biosimilar insulins; thus, it is important that all stakeholders fully understand the complexity of these issues and how they can potentially affect patient care. Bridging the educational gap among clinicians and regulatory agencies will be challenging but necessary for ensuring patient safety.

Discovery of 3,5-bis(trifluoromethyl)benzyl L-arylglycinamide based potent CCR2 antagonists.

Systematic modification of a screening lead yielded a class of potent glycinamide based CCR2 antagonists. The best compound (55, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-{[2-(1-piperidinyl)ethyl]amino}-2-(3-thienyl)acetamide) displayed good binding affinity (IC50=30 and 39 nM) toward human monocytes and CHO cell expressing human CCR2b, respectively. Functionally, it blocked MCP-1 (CCL2)-induced calcium mobilization (IC50=50 nM) and chemotaxis mediated through the CCR2 receptor (9.6 nM). It is selective against other chemokine receptors tested.

Expression and characterization of the chemokine receptor CCR2B from rhesus monkey.

Species selectivity of chemokine receptor antagonists is a potential deterrent to making preclinical assessments in vivo. To determine if rhesus monkey disease models could support these assessments, we pharmacologically and functionally characterized recombinant rhesus CCR2B receptor. For these studies we obtained the CCR2B coding region by PCR from genomic rhesus DNA and expressed the receptor as stable transfectants in Chinese Hamster Ovary cells. The surface expression of recombinant rhesus CCR2B was detected by flow cytometry using a commercially available monoclonal anti-hCCR2B antibody. This antibody was used to detect rhCCR2B on monocytes in peripheral blood mononuclear cell preparations from rhesus whole blood. The recombinantly expressed CCR2B exhibited similar high affinity binding to the CCR2 chemokine ligands from rhesus and human 125I-rhMCP-1 (K(d)=433+/-14 pM) and 125I-hMCP-1 (K(d)=550+/-256 pM). In competition binding, the receptor exhibited selective high affinity binding to the monocyte chemoattractant protein (MCP) family chemokines with little affinity for most other members of the CC family of chemokines. One exception was eotaxin, a high affinity ligand for CCR3, which bound to rhesus CCR2B receptor (K(i)=1467+/-205 pM). Chemokines which exhibited binding affinity for the receptor were tested for their ability to induce intracellular calcium release. In these experiments the relative potencies of the MCP family of chemokines for rhCCR2B were similar to the observed binding affinities. In contrast, eotaxin was functionally inactive as an antagonist or agonist to this receptor. TAK-799 (N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium chloride), a dual CCR2/CCR5 antagonist, demonstrated high affinity for the rhesus CCR2B in competition with 125I-hMCP-1 binding to the receptor (K(i)=0.5 nM) and also potently blocked the MCP-1 induced calcium mobilization mediated through the receptor.