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Introduction: DENV NS2B-NS3 protease inhibitors were designed based upon the reference molecule, 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl) benzenesulfonamide, reported by our team with the aim to optimize lead compound via rational approach. Top five best scoring molecules with zinc ids ZINC23504872, ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613 bearing 'pyrimidin-4(3H)-one' basic scaffold have been identified as a promising candidate against DENV protease enzyme., Methods: The shape and electrostatic complementary between identified HITs and reference molecules were found to be Tanimotoshape 0.453, 0.690, 0.680, 0.685 & 0.672 respectively and Tanimotoelectrostatic 0.211, 0.211, 0.441, 0.442, 0.442 and 0.442 respectively. The molecular docking studies suggested that the identified HITs displayed the good interactions with active site residues and lower binding energies. The stability of docked complexes was assessed by MD simulations studies. The RMSD values of protein backbone (1.6779, 3.1563, 3.3634, 3.3893 & 3.0960 Å) and protein backbone RMSF values (1.0126, 1.0834, 1.0890, 0.9974 & 1.0080 Å respectively) for all top five HITs were stable and molecules did not fluctuate from the active pocket during entire 100ns MD run., Results: The druggability Dscore below 1 indicate the tightly binding of ligand at the active site. Dscore for ZINC23504872 was found to be 1.084 while for the second class of compounds ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613, 0.503, 0.484, 0.487 and 0.501 Dscores were observed. In-silico ADMET calculations suggested that all five HITs were possessed the drug likeliness properties and did not violate the Lipinski's rule of five., Conclusion: Summing up, these in-silico generated data suggested that the identified molecules bearing pyrimidin-4(3H)-one would be promising scaffold for DENV protease inhibitors. However, experimental results are needed to prove the obtained results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Nonunion of long bones is a difficult clinical problem and challenges the clinical acumen of surgeons. Multiple surgical or nonsurgical modalities have been used to treat nonunions. Noninvasive pulsed electromagnetic stimulation is an entity known to affect the piezoelectric phenomenon of bone forming cells. We conducted a study on 45 long-bone fractures of tibia treated by pulsed electromagnetic stimulation, which are analyzed and reported., Materials and Methods: A total of 45 tibial fractures with established atrophic nonunion were enrolled between 1981 and 1988. All the patients had abnormal mobility and no or minimal gap at fracture site with no evidence of callus formation across the fracture site. The patients' age ranged between 24 and 68 years; 40 were men and 5 were women. All patients having evidence of infection, implant in situ, and gap nonunions were excluded from study. Pulsed electromagnetic stimulation was given using above-knee plaster of Paris cast (0.008 Weber/m2 magnetic field was created for 12 h/day). The average duration for pulsed electromagnetic stimulation (PEMS) therapy was 8.35 weeks, with the range being 6-12 weeks. The cases were evaluated at 6 weeks and subsequently every 6-weekly interval for clinical and radiological union. The withdrawal of therapy was decided as per clinicoradiological evidence of union., Results: All but three patients showed evidence of union. About 35% (n = 16) cases showed union in 10 weeks, and 85%(n = 38) cases showed union in 4 months. The average duration of therapy using PEMS was 8.35+/-0.48 weeks, and the average duration of immobilization was 3.02 +/- 0.22 months. Three cases that did not show evidence of union were poorly compliant for the apparatus of PEMS., Conclusion: PEMS is a useful noninvasive modality of treatment for difficult nonunion of long bones.

Something is definitely wrong with the American health care system. Too many citizens are denied health care, and health care costs continue to rise at an uncomfortable and intolerable rate. Ensuring care for all is a paramount goal. There is no way to simultaneously cover everyone; leave the reimbursement of physicians unrestrained; ensure instantaneous access to every imaginable high-technology service; subsidize the world's costliest and least efficient health bureaucracy; and contain costs. Widespread dissatisfaction in all quarters--physicians, hospitals, third-party payers, regulators and consumers--has led to an avalanche of reform proposals. Rapidly changing social, political, and economic environments; rising fiscal pressure; and an evolving understanding of the major determinants of health have also created pressure for changes. There are some new and hopeful signs that America is facing up to the need for changes in the health care delivery system. The Pan American Uni-Care Health Plan that is described in this article may serve as a reasonable balance among these competing priorities.

A histological and histochemical study of the ovary of Dysdercus koenigii has been carried out to ascertain the origin of protein, lipid and carbohydrate components of the yolk during vitellogenesis. Germaria of the telotrophic ovarioles of this insect comprise mononucleate and binucleate trophocytes, prefollicular cells and oogonia ensheathed in two membranes. The follicular epithelium derived from the prefollicular cells is multilayered in the beginning of the oocyte development but is progressively reduced to one layer in later stages. Chromatin material in the binucleate trophocytes condenses to form DNA-positive blobs. RNA-positive material flowing from the nutritive cords can be seen at the nutritive cord-oocyte junction. Protein bodies appear first in the intercellular spaces of follicular epithelium during the early vitellogenic stages indicating the supply of yolk protein from the haemolymph. Lipids originate as L1 bodies made up of unsaturated phospholipids in the nucleus (germinal vesicle). These bodies by addition of saturated triglycerides from haemolymph change to L2 bodies, which in turn, knock off phospholipid part and change of L3 bodies. Polysaccharides come as extrusions from the germinal vesicle while glycogen is first seen in the intercellular spaces of follicular epithelium and then passes into the oocyte indicating its origin in the haemolymph.

The role of electricity in the promotion of fracture union of long bones in human beings requires further investigation. An electric stimulator was devised through which 15 microamperemeter current was applied to the fractured long bones of 20 patients with delayed union. The best results were obtained in cases where the negative electrode was introduced at the fracture site and the positive electrode was placed proximal to the fracture area. In 90 per cent of cases treated by different methods in this series, union occurred within an average period of 9 1/4 weeks. The rate of infection following introduction of electrodes for electrical stimulation was 20 per cent.

A histomorphologic study was done at intervals up to 10 days after causing a fracture in both hindleg tibiae in dogs and giving direct electrical stimulation in one tibia, the other being used as control (20 microns ampere of direct current were passed in 28 limbs and the current was maintained with the help of a simple regulator developed by the authors). The radiologic and histomorphologic study showed definite evidence of early start and completion of healing processes in the electrically stimulated hindlegs. Negative potentials induced at the fracture sites appeared to be the cause of improved healing. The incidence of infection and focal necrosis at the anode was minimal in this experiment.

The retrocerebral endocrine organs of the adult lemon-butterfly; Papilio demoleus have been described. The organs are subaortic lying closely behind the brain. While the nervi corporis cardiaci I (NCCI) originate from the protocerebrum of the brain, the NCCII seem to take their origin in the tritocerebrum in common with another nerve named earlier as the tegumentary nerve. The corpora cardiaca (CC) and corpora allata (CA) are closely approximated to each other obliterating the nervi corporis allati (NCA) which are conspicuous in the larva of the same species. An intercardiacal bridge (ICB) connects the CC of the two sides and acts as a possible centre of distribution for the neurosecretory material (NSM) to the gut. Histological evidence suggests that the NSM inside the CC remains intraaxonal without being primarily unloaded in the organs for storage. The intrinsic secretory cell of the CC are intimately associated with the neurosecretory fibres from the brain and bear fairly thick axons. No NSM could be detected in the CA of this insect.

Only 14 cases of primary liposarcoma of bones have been reported in the available world literature. This is the first report of its origin from the calvaria. The tumor showed excellent response to deep x-ray therapy.

The retrocerebral endocrine organs, the corpora cardiaca and corpora allata were studied in different developmental stages of the lemon-butterfly. The organs were found to undergo several changes in respect of their position, size, structure and the number of nerves associated with them.

1. Intraarticular hydrocortisone and passive manipulation under general anesthesia does not help mobilize the jaw. 2. Condylectomy gives good results in selected cases, where the duration of ankylosis is minimal. 3. Longer duration requires wide excision of the condyloid as well as coronoid processes. The opposite side also must be operated on in most late cases. A gap of more than 2 cm is left in order to avoid recurrences. 4. Postoperative physiotherapy of the jaw in the form of active and resistive movements of the jaw, if started early, gives good functional results and helps recover the function of the chewing muscles. 5. Functional results are good even without interposition of soft tissues or use of prostheses. 6. Skeletal traction after operation is unnecessary. 7. The results of adequate resection of bone followed by early and adequate physiotherapy are very gratifying to the patient.

The histomorphology of the retrocerebral endocrine organs of the larva of the lemon-butterfly, P. demoleus has been described employing a conventional neurosecretory staining technique. The larval organs lie a little away from the brain and oesophagus and, therefore, are not sub-aortic in position unlike most other insects and the adult of this species itself. There are two long NCCs which innervate other target organs in addition to the CC. The recurrent nerve of the stomatogastric nervous system retains its normal connections with the CC even in absence of the hypocerebral ganglion. Histological evidence suggests that the NSM inside the CC remains intraaxonal without being possibly unloaded in the substance of these organs. Axonal transport of NSM to target organs is also in evidence and though NSM is seen in the NCA, it could not be detected inside the CA.

The neuroendocrine system of the homopteran, Idiocerus atkinsoni has been described, employing a neurosecretory stain. Two groups of medial neurosecretory cells (NSC) of one tinctorial type are present in the pars intercerebralis of the brain. Processes believed to be dendrites of the neurosecretory neurons lie superficially underneath the neurilemma and enclose neurosecretory material (NSM). Both the nervi corporis cardiaci, NCCI and NCCII, are branched. The branches of the former join to form an oesophageal nerve that runs on the oesophageal surface and terminates on the midgut, and those of the latter, innervate the oesophageal dilator muscles. Besides being present in the dendrite-like processes and NSC, the NSM is also seen in the NCCI, anterior part of the aorta and oesophageal nerve but not in the NCCII, corpora cardiaca (CC) and the corpus allatum (CA). It is suggested that the release of NSM into the circulation in this insect occurs through two main routes: the dendrites and the aorta. The evolution of the aorta as an exclusive neurohaemal organ in Hemiptera is discussed.

Unlike many heteropterans, the retrocerebral endocrine organs of the water-bug, Sphaerodema annulatum are not fused with each other or with the hypocerebral ganglion. The NCC I bypass the CC and also innervate the oesophageal dilator muscles, CA and post-allatal pericardial cells in addition to aorta. Terminall, this nerve dilates into an ampulla showing accumulation of NSM and, therefore, regarded as a transitory storage centre. Each CC is divisible into two histological halves; the anterior half being negative and the posterior half positive to AF. The CA are innervated by two NCAs one of which (the NCA I) ramifies to form a NSM containing nerve-net on the surface of the gland regarded as another transitory storage centre. Three qualitatively different secretory factors are recognised in the retrocerebral endocrine-aortal complex of this insect -- of which one, localised in the posterior half of the CC, is regarded as indigenous and the other two present in the CA, aorta and pericardial cell nerves as cerebral in origin. Of the latter, both the factors are transported to the CA while only one to the aorta and pericardial cell nerves.