D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum

We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated Gq/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1-D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1-D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIalpha in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity.     

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology,Antibiotic Resistance and Treatment Outcomes: A Study From North India

Background

Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP.

Methods

318 consenting patients with HCAP (n?=?165, aged 16–90 years; median 60 years; 97 males) or HAP (n?=?153; aged 16–85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis.

Results

Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p?=?0.00). The mean APACHE II score was lower in HCAP (17.55?±?6.406, range 30) compared to HAP (19.74?±?8.843, range 37; p?=?0.013). The length of stay?≥?5 days (p?=?0.036) and in-hospital mortality was higher in HAP group (p?=?0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score?≥?17 (OR?=?14, p?=?0.00; HAP: OR?=?10.8, p?=?0.00), and septic shock (OR?=?4.5, p?=?0.00; HAP: OR?=?6.9, p?=?0.00).

Conclusion

The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

     

Case Study of Polyvinylidene Fluoride Doping by Carbon Nanotubes

Modern material science often makes use of polyvinylidene fluoride thin films because of various properties, like a high thermal and chemical stability, or a ferroelectric, pyroelectric and piezoelectric activity. Fibers of this polymer material are, on the other hand, much less explored due to various issues presented by the fibrous form. By introducing carbon nanotubes via electrospinning, it is possible to affect the chemical and electrical properties of the resulting composite. In the case of this paper, the focus was on the further improvement of interesting polyvinylidene fluoride properties by incorporating carbon nanotubes, such as changing the concentration of crystalline phases and the resulting increase of the dielectric constant and conductivity. These changes in properties have been explored by several methods that focused on a structural, chemical and electrical point of view. The resulting obtained data have been documented to create a basis for further research and to increase the overall understanding of the properties and usability of polyvinylidene fluoride fiber composites.     

Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways

BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.AIM To study the hepatoprotective effects of SA against lipopolysaccharide(LPS)/Dgalactosamine(D-GalN)-induced acute liver failure(ALF)in rats.METHODS Experimental ALF was induced with an intraperitoneal(i.p.)administration of 8μg LPS and 800 mg/kg D-GalN in normal saline.SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.RESULTS Data showed that SA ameliorates acute liver dysfunction,decreases serum levels of alanine transaminase(ALT),and aspartate aminotransferase(AST),as well as malondialdehyde(MDA)and NO levels in ALF model rats.However,pretreatment with SA(20 mg/kg and 40 mg/kg)reduced nuclear factor kappalight-chain-enhancer of activated B cells(NF-κB)activation and levels of inflammatory cytokines(tumor necrosis factor-αand interleukin 6).Also,SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.CONCLUSION In conclusion,SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.     

Can simulation measurements be used to predict the irradiated lung volume in the tangential fields in patients treated for breast cancer?

A simple method of estimating the amount of lung irradiated in patients with breast cancer would be of use in minimizing lung complications. To determine whether simple measurements taken at the time of simulation can be used to predict the lung volume in the radiation field, we performed CT scans as part of treatment planning in 40 cases undergoing radiotherapy for breast cancer. Parameters measured from simulator films included: (a) the perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall at the center of the field (CLD); (b) the maximum perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall (MLD); and (c) the length of lung (L) as measured at the posterior tangential field edge on the simulator film. CT scans of the chest were performed with the patient in the treatment position with 1 cm slice intervals, covering lung apex to base. The ipsilateral total lung area and the lung area included within the treatment port were calculated for each CT scan slice, multiplied by the slice thickness, and then integrated over all CT scan slices to give the volumes. The best predictor of the percent of ipsilateral lung volume treated by the tangential fields was the CLD. Employing linear regression analysis, a coefficient of determination r2 = 0.799 was calculated between CLD and percent treated ipsilateral lung volume on CT scan. In comparison, the coefficients for the other parameters were r2 = 0.784 for the MLD, r2 = 0.071 for L, and r2 = 0.690 for CLD x L. A CLD of 1.5 cm predicted that about 6% of the ipsilateral lung would be included in the tangential field, a CLD of 2.5 cm about 16%, and a CLD of 3.5 cm about 26% of the ipsilateral lung, with a mean 90% prediction interval of +/- 7.1% of ipsilateral lung volume. We conclude that the CLD measured at the time of simulation provides a reasonable estimate of the percent of the ipsilateral lung treated by the tangential fields. This information may be of value in evaluating the likelihood of pulmonary complications from such treatment and in minimizing toxicity.     

Clinicopathologic correlation of choroidal folds: secondary to massive cranioorbital hemangiopericytoma.

A 55-year-old woman developed marked choroidal folds in the right eye secondary to a massive tumor in the right orbit. The patient underwent a modified exenteration with debulking of the tumor, thus providing the opportunity to do a clinicopathologic correlation on the choroidal folds. Histopathologically, the orbital tumor proved to be an unusually aggressive malignant hemangiopericytoma. Microscopic examination of the globe showed that the apices of some of the folds were directed toward the retina, whereas the apices of other folds were directed toward the choroid. In contrast to popular concepts, the retinal pigment epithelium was intact at the crests of the folds toward the retinal side, while the retinal pigment epithelium was atrophic in the valleys toward the choroid.     

The Art of Repair in Surgical Hair Restoration—Part II: The Tactics of Repair

BACKGROUND: As patient awareness of new hair transplantation techniques grows, the repair of improperly planned or poorly executed procedures becomes an increasingly important part of surgical hair restoration. OBJECTIVE: Part II of this series is written to serve as a practical guide for surgeons who perform repairs in their daily practices. It focuses on specific repair techniques. METHODS: The repairs are performed by excision with reimplantation and/or by camouflage. Follicular unit transplantation is used for the restorative aspects of the procedure. RESULTS: Using punch or linear excision techniques allows the surgeon to relocate poorly planted grafts to areas that are more appropriate. The key elements of camouflage include creating a deep zone of follicular units, angling grafts in their natural direction, and using forward and side weighting of grafts to increase the appearance of fullness. In special situations, removal of grafts without reimplantation can be accomplished using lasers or electrolysis. CONCLUSION: Meticulous surgical techniques and optimal utilization of a limited hair supply will enable the surgeon to achieve the best possible cosmetic results for patients requiring repairs.