The number and popularity of electronic nicotine delivery systems (ENDS) and especially e-cigarettes (e-cigs) have been increasing in the last decade. Although ENDS owe their popularity to excluding ...the harmful chemicals that are present in tobacco smoke, there is a debate whether they are safe, regulated, and as harmless as they are assumed to be and have potential unknown long-term effects. Involvement of cigarette smoking to the progression of periodontal diseases, other adverse oral health outcomes, and its detrimental effects to oral health are well-described. ENDS producer companies claim that these products can improve oral health by providing alternatives to smoking. However, the effect of e-cigs on oral health is not fully understood and is still debated among many scientists and clinicians. The number of studies addressing the potential toxic effect of ENDS or e-cig aerosol on oral cells is limited along with the clinical studies which are still preliminary, and their sample size is limited. The long-term effects of inhaled aerosols and the potential synergistic effect of the e-cigs components are not known. It is essential and of utmost importance to determine whether exposure to ENDS aerosol contributes to the progression of periodontal diseases and how it affects periodontal ligament and gingival cells which are believed to be its first targets. This review briefly summarizes the available evidence about the effects of e-cigs on periodontal health including several pathophysiological events, such as oxidative stress, DNA damage, inflammation, cellular senescence, dysregulated repair, and periodontal diseases.
Many studies have reported the role of arthrocentesis to alleviate symptoms in patients with disc displacement without reduction (DDWoR). Nevertheless, the benefit of injectable platelet-rich fibrin ...(i-PRF) remains unclear. The aim of this study was to answer the following question: Among patients with DDWoR, do those treated with intra-articular injection of i-PRF after arthrocentesis, when compared to those treated with arthrocentesis only, have better clinical outcomes in terms of pain reduction and improvement of jaw movement?
This single-blind randomized, controlled study included patients with diagnosed DDWoR, in the Department of Oral and Maxillofacial Surgery at the School of Dentistry, Ege University, who had localized joint pain and limited range of motion. Patients were treated either with arthrocentesis (AC group) or arthrocentesis in combination with intra-articular i-PRF injection (AC + i-PRF group). The predictor variable was treatment (ie, arthrocentesis with or without i-PRF). The primary outcome variable was pain (visual analog scale). The secondary outcome variables were maximum mouth opening, lateral and protrusive movements. Outcome variables were recorded at pretreatment and at the postoperative 1st, 2nd, 3rd, 6th, and 12th months. Statistical analysis was performed using the Brunner-Langer model, with a significance level P < .05.
This study comprised 76 patients (34 females/4 males, mean age 47.2 ± 9.1 for the AC + i-PRF group; 35 females/3 males, mean age 46.8 ± 10.2 for the AC group). The treatment success rate was 73.7% for the AC group and 100% for the AC + i-PRF group (P = .012). Pain levels in the AC + i-PRF group were found to decrease more than the AC group over 12 months postoperatively (palpation: −6.9 ± 1.2 vs −5.3 ± 1.3; chewing: −6.9 ± 1.5 vs −5.1 ± 1.7; jaw movements: −6.9 ± 1.1 vs −5.1 ± 1.4). This difference was statistically significant (P < .001). The degree of jaw movement in the AC + i-PRF group was found to increase more than the AC group over 12 months postoperatively (maximum mouth opening: 8.0 ± 2.1 vs 4.9 ± 2.0; contralateral: 1.8 ± 0.8 vs 0.2 ± 1.0; ipsilateral: 2.9 ± 1.3 vs 0.8 ± 1.5; protrusive: 2.6 ± 1.1 vs 0.8 ± 1.3). This difference was statistically significant (P < .001).
Intra-articular injection of i-PRF after arthrocentesis produced greater improvements in pain reduction and jaw movement when compared to arthrocentesis only. These results indicate that i-PRF used in combination with arthrocentesis is an effective adjunctive treatment.
Steps in the right directionHIV-1 mutates rapidly, making it difficult to design a vaccine that will protect people against all of the virus' iterations. A potential successful vaccine design might ...protect by eliciting broadly neutralizing antibodies (bNAbs), which target specific regions on HIV-1's trimeric envelope glycoprotein (Env) (see the Perspective by Mascola). Jardine et al. used mice engineered to express germline-reverted heavy chains of a particular bNAb and immunized them with an Env-based immunogen designed to bind to precursors of that bNAb. Sanders et al. compared rabbits and monkeys immunized with Env trimers that adopt a nativelike conformation. In both cases, immunized animals produced antibodies that shared similarities with bNAbs. Boosting these animals with other immunogens may drive these antibodies to further mutate into the longsought bNAbs. Chen et al. report that retaining the cytoplasmic domain of Env proteins may be important to attract bNAbs. Removing the cytoplasmic domain may distract the immune response and instead generate antibodies that target epitopes on Env that would not lead to protection.Science, this issue p. 139, 10.1126/science.aac4223, p. 156; see also p. 191 A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.
Africa's Silk Road Broadman, Harry G; Isik, Gozde
2006, 11-02-2006, 2007
eBook, Book
Open access
China and India's new-found interest in trade and investment with Africa - home to 300 million of the globe's poorest people and the world's most formidable development challenge - presents a ...significant opportunity for growth and integration of the Sub-Saharan continent into the global economy. Africa's Silk Road finds that China and India's South-South commerce with Africa is about far more than natural resources, opening the way for Africa to become a processor of commodities and a competitive supplier of goods and services to these countries - a major departure from its long established relations with the North. A growing number of Chinese and Indian businesses active in Africa operate on a global scale, work with world-class technologies, produce products and services according to the most demanding standards, and foster the integration of African businesses into advanced markets. There are significant imbalances, however, in these emerging commercial relationships. These can be addressed through a series of reforms in all countries:"At-the-border" reforms, such as elimination of China and India's escalating tariffs on Africa's leading exports, and elimination of Africa's tariffs on certain inputs that make exports uncompetitive "Behind-the-border" reforms in Africa, to unleash competitive market forces and strengthen its basic market institutions "Between-the-border" improvements in trade facilitation mechanisms to decrease transactions costs Reforms that leverage linkages between investment and trade, to allow African businesses to participate in global production networks that investments by Chinese and Indian firms can generate.
Context: Bacterial vaginosis (BV) is related to the increased risk of miscarriage, preterm labor, and postpartum endometritis.
Aims: The aim of this study was to evaluate the association between BV ...and the history of spontaneous abortion and recurrent pregnancy losses. We also examined periods of gestation, including the first and second trimester miscarriages.
Materials and Methods: The study population consisted of 200 fertile women. Sixty one (30.5%) of 200 women had the history of a spontaneous abortion in the last six months (N = 30) and at least three recurrent pregnancy losses (N = 31). BV was diagnosed either by using Papanicolaou staining, Gram staining, or by culturing with BV-associated bacteria, Gardnerella vaginalis.
Results: The presence of BV was statistically associated with the history of a spontaneous abortion in the last 6 months (P < 0.05), whereas there was no significant relationship between BV and recurrent pregnancy losses (P > 0.05). These women were also evaluated in view of periods of gestation. Forty-seven (77%) of 61 women had first trimester miscarriage (≤12 weeks) and 14 (23%) of 61 women had second trimester miscarriage (>12 weeks). There was a statistically significant relationship between BV and second trimester miscarriage (P < 0.05). Positive BV findings were not associated with discharge, itching, and pain (P > 0.05).
Conclusion: BV may contribute to spontaneous abortion and second trimester miscarriage.
Many therapeutic proteins and protein subunit vaccines contain heterologous trimerization domains, such as the widely used GCN4-based isoleucine zipper (IZ) and the T4 bacteriophage fibritin foldon ...(Fd) trimerization domains. We found that these domains induced potent anti-IZ or anti-Fd antibody responses in animals when fused to an HIV-1 envelope glycoprotein (Env) immunogen. To dampen IZ-induced responses, we constructed an IZ domain containing four N-linked glycans (IZN4) to shield the underlying protein surface. When fused to two different vaccine antigens, HIV-1 Env and influenza hemagglutinin (HA), IZN4 strongly reduced the antibody responses against the IZ, but did not affect the antibody titers against Env or HA. Silencing of immunogenic multimerization domains with glycans might be relevant for therapeutic proteins and protein vaccines.
Background: Trimerization domains are commonly used to stabilize trimeric protein vaccines and therapeutics.
Results: The GCN4-based isoleucine zipper domain induces strong antibody responses in vivo but this can be overcome by introducing glycans.
Conclusion: Appropriately positioned glycans can effectively immunosilence the GCN4-based trimerization domain.
Significance: Immunosilencing trimerization domains could be important for the exploitation of trimerization domains in protein vaccines and therapeutics.
The HIV-1 envelope glycoprotein (Env) trimer is responsible for viral entry into target cells and is the sole target of neutralizing antibodies. The Env protein is therefore the focus of HIV-1 ...vaccine design. Env consists of two noncovalently linked subunits (gp120 and gp41) that form a trimer of heterodimers and this 6-subunit complex is metastable and conformationally flexible. Several approaches have been pursued to stabilize the Env trimer for vaccine purposes, which include structure-based design, high-throughput screening, and selection by mammalian cell display. Here, we employed directed virus evolution to improve Env trimer stability. Accordingly, we deliberately destabilized the Env gp120-gp41 interface by mutagenesis in the context of replicating HIV-1 LAI virus and virus evolution over time. We identified compensatory changes that pointed at convergent evolution, as they were largely restricted to specific Env regions, namely, the V1V2 domain of gp120 and the HR1 and HR2 domain of gp41. Specifically, S614G in V1V2 and Q567R in HR1 were frequently identified. Interestingly, the majority of the compensatory mutations were at distant locations from the original mutations and most likely strengthen intersubunit interactions. These results show how the virus can overcome Env instability and illuminate the regions that play a dominant role in Env stability.
A successful HIV-1 vaccine most likely requires an envelope glycoprotein (Env) component, as Env is the only viral protein on the surface of the virus and the target for neutralizing antibodies. However, HIV Env is metastable and flexible because of the weak interactions between the Env subunits, complicating the generation of recombinant mimics of native Env. Here, we used directed viral evolution to study Env stability. We deliberately destabilized the interface between Env subunits and explored the capacity of the virus to repair trimer instability by evolution. We identified compensatory mutations that converged in specific Env locations: the apex and the trimer interface. Selected mutations enhanced the stability of recombinant soluble Env trimer proteins. These results provided clues on understanding the structural mechanisms involved in Env trimer stability, which can guide future immunogen design.
A simple, fast, and efficient ionic liquid based dispersive liquid-liquid microextraction has been developed for the determination of trace amounts of zearalenone for the first time. Preconcentrated ...zearalenone was determined by high performance liquid chromatography with fluorescence detector. Two ionic liquids, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide and 1-methyl-3-octylimidazolium bis(trifluoromethanesulfonyl) imide were used as extraction solvents. Several analytical parameters affecting the extraction efficiency such as sample pH, type, and volume of dispersive solvent, volume of ionic liquid, time of extraction, and centrifugation were optimized. The 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide showed the better extraction efficiency. Thus, the method validation and the application of the method to real samples were carried out with 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide. Under the optimum conditions, the calibration curve for zearalenone determination was linear in the range of 1-750 µg L
−1
(R
2
= 0.9960) and the limit of detection was 0.25 µg L
−1
for zearalenone. The inter-day and intra-day precisions of the developed method were in the range of 1.36-3.02%. The method was successfully applied to beer and cereal (wheat and corn) samples. The recovery percentages of zearalenone for spiked samples were between were 80.0 and 100.0%.
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