Antigen distribution pattern of West Nile virus in Culex tritaeniorhynchus,Culex vishnui and Culex pseudovishnui mosquitoes

Distribution of West Nile (WN) virus antigen in different tissues of mosquitoes was studied in three species viz., Culex tritaeniorhynchus, C. vishnui and C. pseudovishnui. Overall per cent positivity was higher in the intra thoracically inoculated as compared to the orally infected mosquitoes, suggesting the existence of a midgut barrier. In a small number of mosquitoes salivary glands were found negative even though fluorescence was seen in the respective head squashes, suggesting salivary gland barrier in these mosquitoes. There was no difference in the per cent salivary gland and salivary gland area positivity between these three species. Presence of virus antigen in the ovaries of these three species on the 3rd post infection day suggests the possibility of transovarial transmission of virus even in the first gonotrophic cycle, which is of epidemiological importance.     

Pelvic limb-salvage surgery for malignant tumors

Thirteen patients with primary malignant tumors of the pelvis underwent internal hemipelvectomy. The diagnoses were: Ewing's sarcoma 7, osteosarcoma 4, chondrosarcoma 1, and malignant fibrous histiocytoma 1. No megaprostheses or massive allografts were used for reconstruction. Six patients underwent resection only with no reconstruction, 5 had strut grafts inserted to restore the pelvic ring, 1 had an autoclaved autograft of the acetabulum and 1 had an ilio-femoral arthrodesis. No patients were lost to follow-up. Nine patients died from their disease after an average of 23 months (range 2 to 72 months). The 4 survivors (3 free of disease) have an average follow-up of 84 months (range 60 to 120 months).     

Simulation and its role in medical education

Medical education is increasingly laying emphasis on a curriculum based on cognitive, psychomotor, and affective domains of learning which were originally proposed nearly 50 years ago. These reforms are framed around best standards of care, error management and patient safety, patient autonomy, and resource allocation. There is a worldwide shift in the method of medical education towards experiential (‘hands-on’) medical learning; however, applying this concept to real patients is less acceptable to society and is subject to legal and ethical issues.     

Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner

The anti-apoptotic BCL-2 family proteins are important targets for cancer chemotherapy. Specific and potent inhibitors of the BCL-2 family, such as ABT-263 (navitoclax) and ABT-199, are only effective against some members of the BCL-2 family but do not target MCL-1, which is commonly amplified in tumors and associated with chemoresistance. In this report, the selectivity and potency of two putative MCL-1 inhibitors, dinaciclib and maritoclax, were assessed. Although both compounds induced Bax/Bak- and caspase-9-dependent apoptosis, dinaciclib was more potent than maritoclax in downregulating MCL-1 and also in inducing apoptosis. However, the compounds induced apoptosis, even in cells lacking MCL-1, suggesting multiple mechanisms of cell death. Furthermore, maritoclax induced extensive mitochondrial fragmentation, and a Bax/Bak- but MCL-1-independent accumulation of mitochondrial reactive oxygen species (ROS), with an accompanying loss of complexes I and III of the electron transport chain. ROS scavengers, such as MitoQ, could not salvage maritoclax-mediated effects on mitochondrial structure and function. Taken together, our data demonstrate that neither dinaciclib nor maritoclax exclusively target MCL-1. Although dinaciclib is clearly not a specific MCL-1 inhibitor, its ability to rapidly downregulate MCL-1 may be beneficial in many clinical settings, where it may reverse chemoresistance or sensitize to other chemotherapeutic agents.     

Reducing toxic reactive carbonyl species in e-cigarette emissions: testing a harm-reduction strategy based on dicarbonyl trapping

Reducing the concentration of reactive carbonyl species (RCS) in e-cigarette emissions represents a major goal to control their potentially harmful effects. Here, we adopted a novel strategy of trapping carbonyls present in e-cigarette emissions by adding polyphenols in e-liquid formulations. Our work showed that the addition of gallic acid, hydroxytyrosol and epigallocatechin gallate reduced the levels of carbonyls formed in the aerosols of vaped e-cigarettes, including formaldehyde, methylglyoxal and glyoxal. Liquid chromatography mass spectrometry analysis highlighted the formation of covalent adducts between aromatic rings and dicarbonyls in both e-liquids and vaped samples, suggesting that dicarbonyls were formed in the e-liquids as degradation products of propylene glycol and glycerol before vaping. Short-term cytotoxic analysis on two lung cellular models showed that dicarbonyl-polyphenol adducts are not cytotoxic, even though carbonyl trapping did not improve cell viability. Our work sheds lights on the ability of polyphenols to trap RCS in high carbonyl e-cigarette emissions, suggesting their potential value in commercial e-liquid formulations.

Reducing the concentration of reactive carbonyl species (RCS) in e-cigarette emissions represents a major goal to control their potentially harmful effects.     

Mild idiopathic lateral cerebral ventricular dilatation in utero: sonographic evaluation

The authors prospectively studied 20 fetuses with mild dilatation of the lateral cerebral ventricles but no other detectable central nervous system abnormality. One case (5%) occurred in a diabetic pregnancy, and three (15%) involved twin pregnancies. Fifteen (75%) fetuses were male, and one (5%) had trisomy 21. Postnatal follow-up at 15-31 months showed a normal outcome in eight cases (40%), an uncertain prognosis in four cases (20%), and death in eight cases (40%). Serial antenatal sonograms were obtained in 17 cases. Among the eight cases with a normal outcome, seven demonstrated no additional sonographic abnormalities and six showed resolution of the ventricular dilatation antenatally. Conversely, all 12 fetuses with demise or an uncertain prognosis demonstrated additional sonographic abnormalities, and six showed stable or progressive ventricular dilatation on follow-up sonograms. Since mild idiopathic lateral ventricular dilatation has a widely variable prognosis, antenatal detection of this finding warrants search for additional findings and follow-up sonography.     

Subthreshold Oscillations Induced By Spinal Nerve Injury In Dissociated Muscle And Cutaneous Afferents Of Mouse DRG

Whole cell patch-clamp recordings were obtained from dissociated mouse lumbar dorsal root ganglion (DRG) neurons. Recordings were made from control neurons and neurons axotomized by transection of the corresponding spinal nerve 1-2 days prior to dissociation. Medium to large muscle and cutaneous afferent neurons were identified by retrograde transport of True Blue or Fluoro-Gold injected into the corresponding peripheral tissue. Action potentials were classified as non-inflected spikes (A(0)) and inflected spikes (A(inf)). High-frequency, low-amplitude subthreshold membrane potential oscillations were observed in 8% of control A(0) neurons, but their incidence increased to 31% in the nerve injury group. Fifty percent of axotomized muscle afferent A(0) cells displayed oscillations, while 26% of axotomized cutaneous afferents exhibited oscillations. Lower-frequency oscillations were also observed in a small fraction (4%) of A(inf) neurons on strong depolarization. Their numbers were increased after the nerve injury, but the difference was not statistically significant. The oscillations often triggered burst firing in distinct patterns of action potential activity. These results indicate that injury-induced membrane oscillations of DRG neurons, previously observed in whole DRG of rats, are present in dissociated DRG neurons of the adult mouse. Moreover, these observations indicate that both muscle and cutaneous afferents in the A(beta) size range give rise to injury-induced membrane oscillations, with muscle afferents being more prone to develop oscillations.