Modulation of Phase Behavior and Microscopic Dynamics in Cationic Vesicles by 1-Decyl-3-methylimidazolium Bromide.

Synthetic cationic lipids have garnered significant attention as promising candidates for gene/DNA transfection in therapeutic applications. The phase behavior of the vesicles formed by these lipids is intriguing, revealing intricate connections to the structure and dynamics of the membrane. These phenomena emerge from the complex interplay between hydrophobic and electrostatic interactions of the lipids. In this study, we explore the impact of an ionic liquid-based surfactant, 1-decyl-3-methylimidazolium bromide (DMIM[Br]), on the structural, dynamical, and phase behavior of cationic dihexadecyldimethylammonium bromide (DHDAB) vesicles. Our investigations indicate that the addition of DMIM[Br] increases the vesicle size while thinning the membrane. Further, DMIM[Br] also induces substantial changes in the membrane phase behavior. At 10 and 25 mol %, DMIM[Br] eliminates the pre-transition from coagel to intermediate crystalline (IC) phase and decreases the onset temperature of the main phase transition to the fluid phase. In the cooling cycle, the addition of DMIM[Br] further induces the formation of an intermediate gel phase. This behavior is reminiscent of the non-synchronous ordering observed in the DODAB membrane, a longer-chain counterpart of DHDAB. Interestingly, at 40 mol % of DMIM[Br], the formation of the intermediate gel phase is largely suppressed. Neutron scattering data provide evidence that the addition of DMIM[Br] enhances lipid mobility in coagel and fluid phases, suggesting that DMIM[Br] acts as a plasticizer, enhancing membrane fluidity across all of the phases. Our findings infer that DMIM[Br] modulates the membrane's phase behavior and fluidity, two essential ingredients for the efficient transport of cargo, by controlling the balance of electrostatic and hydrophobic interactions.

Influence of periodontitis and diabetes on structure and cytokine content of platelet-rich fibrin.

BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate with multiple applications in wound healing and regeneration in both periodontitis and diabetes. However, the three dimensional (3-D) structure and cytokine content of PRF might be altered in patients suffering from either/both of the chronic inflammatory conditions, ultimately influencing the efficacy of PRF as a biomaterial for regenerative medicine. AIM: The aim of the present study was hence to evaluate the effect of both these chronic inflammatory diseases on the 3-D structure of PRF membrane. An attempt was also made to compare the growth factor content between the plasma and RBC ends of the prepared PRF gel. MATERIALS & METHODS: L-PRF was prepared for twenty participants, healthy (5), periodontitis (5), T2DM (5) and T2DM with periodontitis (5). Porosity and fiber diameter of PRF membranes was visualized under FE-SEM and measured using ImageJ Software. PDGF-BB and TGF-ß1 levels in PRF gel were assessed by ELISA. RESULTS: The average diameter of fibrin fibers under FE-SEM was 0.15 to 0.30 micrometers. Porosity was higher at the plasma end (p = 0.042). Red blood cell (RBC) end of the membrane had thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities. Healthy subjects had the least porous PRF compared to subjects with either/both of the chronic conditions. PDGF-BB levels were similar along all the four groups. TGF-ß1 levels were highest in healthy subjects. DISCUSSION: 3-D structure and growth factor content of PRF are influenced by a person's periodontal and/or diabetic status. The RBC end of the PRF membrane, as compared to the plasma end, has thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities, and hence should be favored during periodontal regenerative procedures. CONCLUSION: Both periodontitis and diabetes have a significant influence on the 3-D structure and growth factor content of PRF produced.

Plakophilin-3 Binds the Membrane and Filamentous Actin without Bundling F-Actin.

Plakophilin-3 is a ubiquitously expressed protein found widely in epithelial cells and is a critical component of desmosomes. The plakophilin-3 carboxy-terminal domain harbors nine armadillo repeat motifs with largely unknown functions. Here, we report the 5 Å cryogenic electron microscopy (cryoEM) structure of the armadillo repeat motif domain of plakophilin-3, one of the smaller cryoEM structures reported to date. We find that this domain is a monomer or homodimer in solution. In addition, using an in vitro actin co-sedimentation assay, we show that the armadillo repeat domain of plakophilin-3 directly interacts with F-actin. This feature, through direct interactions with actin filaments, could be responsible for the observed association of extra-desmosomal plakophilin-3 with the actin cytoskeleton directly attached to the adherens junctions in A431 epithelial cells. Further, we demonstrate, through lipid binding analyses, that plakophilin-3 can effectively be recruited to the plasma membrane through phosphatidylinositol-4,5-bisphosphate-mediated interactions. Collectively, we report on novel properties of plakophilin-3, which may be conserved throughout the plakophilin protein family and may be behind the roles of these proteins in cell-cell adhesion.

Nanoparticle mediated cancer immunotherapy.

The versatility and nanoscale size have helped nanoparticles (NPs) improve the efficacy of conventional cancer immunotherapy and opened up exciting approaches to combat cancer. This review first outlines the tumor immune evasion and the defensive tumor microenvironment (TME) that hinders the activity of host immune system against tumor. Then, a detailed description on how the NP based strategies have helped improve the efficacy of conventional cancer vaccines and overcome the obstacles led by TME. Sustained and controlled drug delivery, enhanced cross presentation by immune cells, co-encapsulation of adjuvants, inhibition of immune checkpoints and intrinsic adjuvant like properties have aided NPs to improve the therapeutic efficacy of cancer vaccines. Also, NPs have been efficient modulators of TME. In this context, NPs facilitate better penetration of the chemotherapeutic drug by dissolution of the inhibitory meshwork formed by tumor associated cells, blood vessels, soluble mediators and extra cellular matrix in TME. NPs achieve this by suppression, modulation, or reprogramming of the immune cells and other mediators localised in TME. This review further summarizes the applications of NPs used to enhance the efficacy of cancer vaccines and modulate the TME to improve cancer immunotherapy. Finally, the hurdles faced in commercialization and translation to clinic have been discussed and intriguingly, NPs owe great potential to emerge as clinical formulations for cancer immunotherapy in near future.

1,3 Dialkylated Imidazolium Ionic Liquid Causes Interdigitated Domains in a Phospholipid Membrane.

Amphiphilic imidazolium-based ionic liquids (ILs) have proven their efficacy in altering the membrane integrity and dynamics. The present article investigates the phase-separated domains in a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membrane induced by 1,3 dialkylated imidazolium IL. Isotherm measurements on DPPC monolayers formed at the air-water interface have shown a decrease in the mean molecular area with the addition of this IL. The positive value of the excess Gibbs free energy of mixing indicates an unfavorable mixing of the IL into the lipid. This leads to IL-induced phase-separated domains in the multilayer of the lipid confirmed by the occurrence of two sets of equidistance peaks in the X-ray reflectivity data. The electron density profile along the surface normal obtained by the swelling method shows the bilayer thickness of the newly formed IL-rich phase to be substantially lower (∼34 Å) than the DPPC phase (∼45.8 Å). This IL-rich phase has been confirmed to be interdigitated, showing an enhanced electron density in the tail region due to the overlapping hydrocarbon chains. Differential scanning calorimetry measurements showed that the incorporation of IL enhances the fluidity of the lipid bilayer. Therefore, the study indicates the formation of an interdigitated phase with a lower order compared to the gel phase in the DPPC membrane supplemented with the IL.

Curcumin Accelerates the Lateral Motion of DPPC Membranes.

Curcumin, the main ingredient in turmeric, has attracted attention due to its potential anti-inflammatory, anticancer, wound-healing, and antioxidant properties. Though curcumin efficacy is related to its interaction with biomembranes, there are few reports on the effects of curcumin on the lateral motion of lipids, a fundamental process in the cell membrane. Employing the quasielastic neutron scattering technique, we explore the effects of curcumin on the lateral diffusion of the dipalmotylphosphatidylcholine (DPPC) membrane. Our investigation is also supported by Fourier transform infrared spectroscopy, dynamic light scattering, and calorimetry to understand the interaction between curcumin and the DPPC membrane. It is found that curcumin significantly modulates the packing arrangement and conformations of DPPC lipid, leading to enhanced membrane dynamics. In particular, we find that the presence of curcumin substantially accelerates the DPPC lateral motion in both ordered and fluid phases. The effects are more pronounced in the ordered phase where the lateral diffusion coefficient increases by 23% in comparison to 9% in the fluid phase. Our measurements provide critical insights into molecular mechanisms underlying increased lateral diffusion. In contrast, the localized internal motions of DPPC are barely altered, except for a marginal enhancement observed in the ordered phase. In essence, these findings indicate that curcumin is favorably located at the membrane interface rather than in a transbilayer configuration. Further, the unambiguous evidence that curcumin modulates the membrane dynamics at a molecular level supports a possible action mechanism in which curcumin can act as an allosteric regulator of membrane functionality.

Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

INTRODUCTION: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. METHODS: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. RESULTS: From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5. CONCLUSION: Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.

Oxidative Products of Curcumin Rather Than Curcumin Bind to Helicobacter Pylori Virulence Factor VacA and Are Required to Inhibit Its Vacuolation Activity.

Curcumin is a hydrophobic polyphenol derived from turmeric with potent anti-oxidant, anti-microbial, anti-inflammatory and anti-carcinogenic effects. Curcumin is degraded into various derivatives under in vitro and in vivo conditions, and it appears that its degradation may be responsible for the pharmacological effects of curcumin. The primary risk factor for the cause of gastric cancer is Helicobacter pylori (H. pylori). A virulence factor vacuolating cytotoxic A (VacA) is secreted by H. pylori as a 88 kDa monomer (p88), which can be fragmented into a 33 kDa N-terminal domain (p33) and a 55 kDa C-terminal domain (p55). Recently it has been reported that curcumin oxidation is required to inhibit the activity of another major H.pylori toxin CagA. We performed molecular docking of curcumin and its oxidative derivatives with p33 and p55 domains of VacA. Further, we have examined the effect of the oxidation of curcumin on the vacuolation activity of VacA protein. We observed the binding of curcumin to the p55 domain of VacA at five different sites with moderate binding affinities. Curcumin did not bind to p33 domain of VacA. Remarkably, cyclobutyl cyclopentadione and dihydroxy cyclopentadione, which are oxidized products of curcumin, showed a higher binding affinity with VacA protein at all sites except one as compared to parent curcumin itself. However, cyclobutyl cyclopentadione showed a significant binding affinity for the active site 5 of the p55 protein. Active site five (312-422) of p55 domain of VacA plays a crucial role in VacA-mediated vacuole formation. Invitro experiments showed that curcumin inhibited the vacuolation activity of H. pylori in human gastric cell line AGS cells whereas acetyl and diacetyl curcumin, which cannot be oxidized, failed to inhibit the vacuolation in AGS cells after H. pylori infection. Here our data showed that oxidation is essential for the activity of curcumin in inhibiting the vacuolation activity of H. pylori. Synthesis of these oxidized curcumin derivatives could potentially provide new therapeutic drug molecules for inhibiting H. pylori-mediated pathogenesis.

Deoxycholic Acid (ATX-101) for Fat Reduction.

Excess, unwanted fat in submental and other body areas has been a focus of new modalities in aesthetics. Invasive and, more recently, non-invasive modalities for removal of unwanted fat have been on an increase. ATX-101 (deoxycholic acid injection) is the only injectable drug approved in the United States and Canada for reduction of moderate or severe submental fat in adults, with ongoing trials testing its efficacy in body contouring and lipomas. It has proven efficacy in submental fat reduction with a good safety profile. This article reviews the pharmacology, mechanism of action, clinical effects and adverse effects of ATX-101. It emphasizes on careful patient selection and advises on appropriate volume administration, number of treatments, and injection technique. The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till December 2019 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 2021;20(11):1169-1173. doi:10.36849/JDD.3936.

Resistance, race, and subjectivity in congregation-based community organizing.

Ideas of resistance have become common in media and political discourse in contemporary times where there is growing awareness of racial violence and xenophobia. Calls to "resist" and awakenings to public life prompt questions about the kind of citizenship being cultivated, the social meanings individuals reproduce and create through participation in "resistance," and the changing sense of their positions and agency as they act in the world. Here I examine the citizen-subject that comes into being through "resistance" to racial injustice, drawing on the case of Faith in Action (formerly PICO) and its development of a theological organizing framework, the Theology of Resistance. This study analyzes the discourses and content of two public data sources-The Prophetic Resistance Podcast series and news media about prophetic resistance within the organizing network. These sources offer a means to examine the negotiated nature of political selves that are created through processes that socialize and subjugate as well as through processes wherein subjects produce and sometimes transform social positions. Findings show that centering a racial analytic and prioritizing racial justice outcomes, shifts that were made within FIA, results in the cultivation of a political subject that is reflexive about internal and external subjugating forces, relational as it discards the armor of racial hierarchy and exclusion, and constructive as it creates conditions or contexts for new political subjects through prophetic action. This study contributes to the conceptual development of organizing as a mechanism to generate social change; specifically, it offers the lens of political subjectivity as a meaningful analytic to enrich understandings of this mechanism.

Community organizing: Studying the development and exercise of grassroots power.

There is now wide recognition that grassroots community organizing is a uniquely necessary approach for contending with the persistent and escalating socioeconomic inequities that manifest as disparities across many societal domains, including housing, safety, education, and mental and physical health. The articles in this special issue report findings from studies designed to increase understanding of community organizing processes and produce actionable knowledge that can enhance these and other similar efforts to create more equitable and just cities and regions. These studies examine a variety of community organizing campaigns, initiatives, and networks in North America, as well as one in Bulgaria, and one in South Africa. These groups are building social power and demanding economic, racial, educational, and environmental justice. In this introductory article, we highlight some of the themes that emerge from this set of studies and make recommendations for future roles that research can play in advancing collective understanding and the practical objectives of grassroots organizing initiatives.

Transformation to leadership: Learning about self, the community, the organization, and the system.

Leadership development is an important practice in community organizing. Although this importance is often acknowledged, relatively little scholarship details how leadership development is actually executed, or how concepts of leadership development are applied in organizing practice. This study reports on a thesis conducted by a community organizer utilizing a critical reflexive methodology. Eight active leaders from a community organizing effort in New Orleans, LA were interviewed about their interpretations of their own development as leaders. Leadership development as experienced by leaders is supplemented with observations from the organizer working with these leaders, providing triangulation on developmental processes in practice. Findings demonstrate the potential for transformation among community residents as they work to build collective power for social change.

Aggressive Percutaneous Catheter Drainage Protocol for Necrotic Pancreatic Collections.

BACKGROUND: Percutaneous catheter drainage (PCD) performed pro-actively for collections in acute pancreatitis (AP) is associated with better outcomes. However, there are only a few studies describing this protocol. AIM: We aimed to evaluate an aggressive PCD protocol. METHODS: Consecutive patients with AP who underwent PCD with an aggressive protocol between January 2018 and January 2019 were included. This protocol involved catheter upsizing at a pre-specified interval (every 4-6 days) as well as drainage of all the new collections. The indications and technical details of PCD and clinical outcomes were compared with patients who underwent standard PCD. RESULTS: Out of the 185 patients with AP evaluated during the study period, 110 (59.4%) underwent PCD, all with the aggressive protocol. The historical cohort of standard PCD comprised of 113 patients. There was no significant difference in the indication of PCD and interval from pain onset to PCD between the two groups. The mean number of catheters was significantly higher in the aggressive PCD group (1.86 ± 0.962 vs. 1.44 ± 0.667, p = 0.002). Additional catheters were inserted in 54.2% of patients in aggressive group vs. 36.2% in the standard group (p = 0.006). Length of hospital stay and intensive care unit (ICU) stay were significantly longer in the standard PCD group (34.3 ± 20.14 vs. 27.45 ± 14.2 days, p < 0.001 and 10.46 ± 12.29 vs. 4.12 ± 8.5, p = 0.009, respectively). There was no significant difference in mortality and surgery between the two groups. CONCLUSION: Aggressive PCD protocol results in reduced length of hospital stay and ICU stay and can reduce hospitalization costs.

Efficacy of 2% Lignocaine and 4% Articaine in Oral Surgical Procedure: A Comparative Study.

AIM AND OBJECTIVE: To compare the efficacy of 2% lignocaine and 4% articaine in the extraction of mandibular molars. MATERIALS AND METHODS: This study was conducted on 120 patients requiring surgical removal of tooth. Patients were categorized into 2 groups with 60 samples each. Group I patients were administered 2% lignocaine with 1:50,000 epinephrine and group II patients were administered 4% articaine with 1:100,000 epinephrine for the extraction of mandibular molar. Inferior alveolar nerve, lingual, and buccal nerve block used in both groups to anesthetize the area. RESULTS: The mean onset of action in group I was 85.2 seconds and in group II was 52.6 seconds, duration of anesthesia in group I was 170.2 minutes and in group II was 226.8 minutes, duration of procedure was 30.4 minutes in group I and 32.6 minutes in group II, pain during procedure in group I was 2.75 and in group II was 1.42, pain after procedure was 1.41 in group I and 0.82 in group II, pain during anesthesia insertion was 1.52 in group I and 1.04 in group II. Forty-six (76.7%) patients in group I and 52 (86.7%) patients in group II did not require re-anesthesia, while 12 (20%) in group I and 8 (13.3%) in group II required 1 time re-anesthesia and 2 (3.3%) patients required 2 times re-anesthesia in group I. CONCLUSION: Articaine can be effectively used in oral surgical procedures as there is early onset of action, longer duration of anesthesia, and less need of re-anesthesia. CLINICAL SIGNIFICANCE: Articaine is more effective compared to lignocaine, hence it can be recommended alternatively for tooth extraction and other oral surgical procedures.

Assessment of Dental Caries, Periodontal Status, and Personality Trait among Population of Dehradun, Uttarakhand, India.

AIM AND OBJECTIVE: Assessment of dental caries, periodontitis, and personality trait among population of Dehradun. MATERIALS AND METHODS: This survey was conducted on 480 subjects age ranged 34-45 years of both genders (males-250, females-230). Decayed Missing, Filled Teeth (DMFT) index, periodontal status, and personality trait were recorded. RESULTS: Age group 34-39 years is comprised of 130 males and 140 females and 40-45 years had 120 males and 90 females. Maximum males (120) were laborer and females were housewife (160). Commonly used method of oral hygiene practice was tooth powder by 80 males and 103 females. Maximum subjects of extroversion (180) was seen in age group 40-45 years, maximum females (110) were housewife with extroversion trait, maximum extroversion trait subjects were using tooth powder (113) and datum (100). Mean DMFT score in subjects was 2.52 and community periodontal index of treatment needs (CPITN) score was 3.41. There were 310 extroversion subjects, 120 neuroticism subjects, and 50 combinations of both extroversion and neuroticism. There was a significant difference in mean missing teeth and DMFT in subjects with different personality traits (p < 0.05). The post hoc test showed that mean missing teeth between group E and group E + N was found to be statistically significant (p < 0.05). The post hoc test showed that the mean sextant value for score 2 between group E vs N found to be statistically significant (p < 0.05). Neurotic individuals were found to have poorer periodontal health as compared to extroverts. CONCLUSION: Authors found that personality trait such as psychological factors have greater impact on status of dental caries and periodontitis. Extroverts had less dental caries and better periodontal status when compared to other personality traits. CLINICAL SIGNIFICANCE: Psychological factors have a great impact on status of dental caries and periodontitis. By assessing various psychological factors, the occurrence of both can be avoided. Thus by improving oral health, overall health of an individual can be improved.

Potent Inhibition of Hepatitis E Virus Release by a Cyclic Peptide Inhibitor of the Interaction between Viral Open Reading Frame 3 Protein and Host Tumor Susceptibility Gene 101.

Hepatitis E virus (HEV) generally causes self-limiting acute viral hepatitis in normal individuals. It causes a more severe disease in immunocompromised persons and pregnant women. Due to the lack of an efficient cell culture system or animal model, the life cycle of the virus is understudied, few antiviral targets are known, and very few antiviral candidates against HEV infection have been identified. Inhibition of virus release is one possible antiviral development strategy, which limits the spread of the virus. Previous studies have demonstrated the essential role of the interaction between the PSAP motif of the viral open reading frame 3 protein (ORF3-PSAP) and the UEV domain of the host tumor susceptibility gene 101 (TSG101) protein (UEV-TSG101) in mediating the release of genotype 3 HEV. Cyclic peptide (CP) inhibitors of the interaction between the human immunodeficiency virus (HIV) gag-PTAP motif and UEV-TSG101 are known to block the release of HIV. Using a molecular dynamic simulation, we observed that both gag-PTAP and ORF3-PSAP motifs bind to the same site in UEV-TSG101 by hydrogen bonding. HIV-released inhibitory CPs also displayed binding to the same site in UEV-TSG101, indicating that they may compete with ORF3-PSAP or gag-PTAP for binding to UEV-TSG101. Two independent assays confirmed the ability of a cyclic peptide (CP11) to inhibit the ORF3-TSG101 interaction. CP11 treatment also reduced the release of both genotype 1 and genotype 3 HEV by approximately 90%, with a 50% inhibitory concentration (IC50) of 2 µM. Thus, CP11 appears to be an attractive candidate for further validation of its anti-HEV properties.IMPORTANCE There is no specific therapy against hepatitis E virus (HEV)-induced hepatic and nonhepatic health problems. Prevention of the release of the progeny viruses from infected cells is an attractive strategy to limit the spread of the virus. Interactions between the viral open reading frame 3 and the host tumor susceptibility gene 101 proteins have been shown to be essential for the release of genotype 3 HEV from infected cells. In this study, we have identified a cyclic peptide inhibitor of the above-mentioned interaction and demonstrate the efficiency of the inhibitor in preventing virus release from infected cells. Thus, our findings uncover the possibility of developing a specific antiviral agent against HEV by blocking its release from infected cells.

CpG enhances the immunogenicity of heterologous DNA-prime/protein-boost vaccination with the heavy chain myosin of Brugia malayi in BALB/c mice.

The recombinant heavy chain myosin of Brugia malayi (Bm-Myo) has earlier been reported as a potent vaccine candidate in our lab. Subsequently, we further enhanced its efficacy employing heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo) immunization approach that produced superior immune-protection than protein or DNA vaccination. In the present study, we evaluated the efficacy of heterologous prime boost vaccination in combination with CpG, synthetic oligodeoxynucleotides (ODN) adjuvant in BALB/c mice. The results showed that CpG/Myo-pcD+Bm-Myo conferred 84.5 ± 0.62% protection against B. malayi infective larval challenge which was considerably higher than Myo-pcD+Bm-Myo (75.6 ± 1.10%) following immunization. Although, both the formulations of immunization elicited robust production of specific IgG antibody and their isotypes (IgG1, IgG2a, IgG2b, and IgG3); however, CpG/Myo-pcD+Bm-Myo predominantly enhanced the level of IgG2a suggesting Th1 biased immune response in presence of CpG. Furthermore, spleen isolated from mice that immunized with CpG/Myo-pcD+Bm-Myo had greater accumulation of CD4+, CD8+, and CD19+ B cells and there was an augmented expression of co-stimulatory molecules CD40, CD86 on host dendritic cells (DCs). In contrast to Myo-pcD+Bm-Myo group, the splenocytes of CpG/Myo-pcD+Bm-Myo immunized mice developed comparatively higher pro-inflammatory cytokines IL-2 and IFN-γ leaving anti-inflammatory cytokine levels unchanged. Moreover, CpG formulation also upregulated the RNA expression of IL-12 and TNF-α in spleenocytes. The current findings suggest that the use of CpG would be more advantageous as an adjuvant predominantly in DNA/protein prime boost vaccine against Bm-Myo and presumably also for filarial infection.

Computational Prediction and Experimental Realization of p-Type Carriers in the Wide-Band-Gap Oxide SrZn1- xLi xO2.

It is challenging to achieve p-type doping of zinc oxides (ZnO), which are of interest as transparent conductors in optoelectronics. A ZnO-related ternary compound, SrZnO2, was investigated as a potential host for p-type conductivity. First-principles investigations were used to select from a range of candidate dopants the substitution of Li+ for Zn2+ as a stable, potentially p-type, doping mechanism in SrZnO2. Subsequently, single-phase bulk samples of a new p-type-doped oxide, SrZn1- xLi xO2 (0 < x < 0.06), were prepared. The structural, compositional, and physical properties of both the parent SrZnO2 and SrZn1- xLi xO2 were experimentally verified. The band gap of SrZnO2 was calculated using HSE06 at 3.80 eV and experimentally measured at 4.27 eV, which confirmed the optical transparency of the material. Powder X-ray diffraction and inductively coupled plasma analysis were combined to show that single-phase ceramic samples can be accessed in the compositional range x < 0.06. A positive Seebeck coefficient of 353(4) µV K-1 for SrZn1- xLi xO2, where x = 0.021, confirmed that the compound is a p-type conductor, which is consistent with the pO2 dependence of the electrical conductivity observed in all SrZn1- xLi xO2 samples. The conductivity of SrZn1- xLi xO2 is up to 15 times greater than that of undoped SrZnO2 (for x = 0.028 σ = 2.53 µS cm-1 at 600 °C and 1 atm of O2).

Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure - U.S. Zika Pregnancy Registry, 2016.

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy.

Importance: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births. Objective: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Design, Setting, and Participants: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Exposures: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Main Outcomes and Measures: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Results: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. Conclusions and Relevance: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.