Smile Analysis: Diagnosis and Treatment Planning.

Smile design is defined as the process of creating an esthetic smile based on scientific and artistic guidelines established through studies, perception, and cultural and racial standards that have been recognized over time. Smile design is a dynamic field with evolving trends that take into consideration: facial esthetics, lip dynamics, pink and white esthetics, and personality. Traditional smile design focused on the orodental complex. Modern smile designers must have a global understanding of the entire patient to design the perfect smile.

A retrospective analysis of dental implant survival in HIV patients.

AIM: This 5 years retrospective cohort survival study compared failure rates of dental implants placed in HIV (+) and HIV (-) patients relative to several risk factors. MATERIALS AND METHODS: Between 2006 and 2015, 484 implants placed in HIV (+) patients and 805 implants placed in HIV (-) patients were assessed for survival. The effects of HIV were estimated using propensity weighting. The effects of age, smoking status, diabetes, restoration status, gender, implant type, placement site, hepatitis C status, baseline CD4 count and CD4%, post-placement average CD4%, nadir CD4%, nadir CD4 count and antiviral therapy were analysed. RESULTS: Implants placed in HIV (+) patients and HIV (-) patients had similar failure rates (HR = 1.4, p = 0.34). Increased failure rates were observed in HIV (+) patients with baseline CD4% ≤20 (HR = 2.72, p = 0.04), post-placement CD4% average ≤20% (HR = 2.71, p = 0.04), protease inhibitor administration (HR = 2.74, p = 0.04), smoking (HR = 2.61, p = 0.05) and anterior maxillary placement (HR = 5.82, p < 0.01). Hepatitis C coinfection, viral titre, baseline CD4 count, gender, implant type and restoration type were non-contributory. CONCLUSION: Implants placed in HIV (+) patients had similar survival rates as HIV (-) patients. Failure rates increase significantly when confounding risk factors are present in HIV (+) patients.

Foreign service special care opportunity in SCDA.

A foreign service clinic in Guatemala caring for patients with special needs was initiated by joining SCDA efforts with the Open Wide Foundation. The trip included five SCDA members: two AEGD residents and three support staff. Open Wide participants included the Executive Director, the Clinical Director in Guatemala, as well as two dentists, dental support staff, and Guatemalan dental students. Two physician anesthesiologists provided general anesthesia. Care adjuncts included general anesthesia, oral sedation, and medical stabilization. LESSONS LEARNED: (1) Conducting a dental clinic for patients with special needs is possible and relatively easy to accomplish, given a partnership with a foundation that agrees with and facilitates this service; (2) advance planning is required to maximize the service provided; (3) committed and flexible team members can accomplish a significant amount of care in a short period of time; and (4) limited but invaluable training of in-country healthcare providers is possible. The Special Care Dentistry Association is long known for service and care delivery to patients with special needs by its members, and for its advocacy and organizational support for these activities. A foreign service opportunity in Guatemala, Central America, was sought out by members of the SCDA to further the outreach efforts of the organization, give members clinical experience in a foreign setting, and train in-country providers to deliver care to patients with special needs. This was the first effort by SCDA members to host a clinic to deliver care specifically to patients with special needs outside of North America.

TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.

Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1ß (IL-1ß) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1ß is synthesized as an immature pro-IL-1ß form. It is cleaved by activated caspase-1 to yield mature IL-1ß that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1ß release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1ß secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1ß production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1ß and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K(+)) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1ß release during RSV infection.

Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles.

Cholesterol and sphingolipid enriched lipid raft micro-domains in the plasma membrane play an important role in the life-cycle of numerous enveloped viruses. Although human respiratory syncytial virus (RSV) proteins associate with the raft domains of infected cells and rafts are incorporated in RSV virion particles, the functional role of raft during RSV infection was unknown. In the current study we have identified rafts as an essential component of host cell that is required for RSV infection. Treatment of human lung epithelial cells with raft disrupting agent methyl-beta-cyclodextrin (MBCD) led to drastic loss of RSV infectivity due to diminished release of infectious progeny RSV virion particles from raft disrupted cells. RSV infection of raft deficient Niemann-Pick syndrome type C human fibroblasts and normal human embryonic lung fibroblasts revealed that during productive RSV infection, raft is required for release of infectious RSV particles.

Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense.

BACKGROUND: Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. METHODS: The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors RESULTS: We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/ß)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further borne out by our finding that neutralizing IFN activity resulted in enhanced RSV infection in non-tumorigenic RWPE-1 prostate cells. CONCLUSIONS: We demonstrated that RSV is potentially a useful therapeutic tool in the treatment of androgen-sensitive and androgen-independent prostate cancer. Moreover, impaired IFN-mediated antiviral response is the likely cause of higher viral burden and resulting oncolysis of androgen-sensitive prostate cancer cells.

Retinoic acid inducible gene I activates innate antiviral response against human parainfluenza virus type 3.

Human parainfluenza virus type 3 (HPIV3) is a respiratory paramyxovirus that infects lung epithelial cells to cause high morbidity among infants and children. To date, no effective vaccine or antiviral therapy exists for HPIV3 and therefore, it is important to study innate immune antiviral response induced by this virus in infected cells. Type-I interferons (IFN, interferon-alpha/beta) and tumor necrosis factor-alpha (TNFalpha activated by NFkappaB) are potent antiviral cytokines that play an important role during innate immune antiviral response. A wide-spectrum of viruses utilizes pattern recognition receptors (PRRs) like toll-like receptors (TLRs) and RLH (RIG like helicases) receptors such as RIGI (retinoic acid inducible gene -I) and Mda5 to induce innate antiviral response. Previously it was shown that both TNFalpha and IFNbeta are produced from HPIV3 infected cells. However, the mechanism by which infected cells activated innate response following HPIV3 infection was not known. In the current study, we demonstrated that RIGI serves as a PRR in HPIV3 infected cells to induce innate antiviral response by expressing IFNbeta (via activation of interferon regulatory factor-3 or IRF3) and TNFalpha (via activation of NF-kappaB).

Activation of innate immune antiviral responses by Nod2.

Pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs) and RIG-like helicase (RLH) receptors, are involved in innate immune antiviral responses. Here we show that nucleotide-binding oligomerization domain 2 (Nod2) can also function as a cytoplasmic viral PRR by triggering activation of interferon-regulatory factor 3 (IRF3) and production of interferon-beta (IFN-beta). After recognition of a viral ssRNA genome, Nod2 used the adaptor protein MAVS to activate IRF3. Nod2-deficient mice failed to produce interferon efficiently and showed enhanced susceptibility to virus-induced pathogenesis. Thus, the function of Nod2 as a viral PRR highlights the important function of Nod2 in host antiviral defense mechanisms.

Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappaB-mediated innate antiviral response against human respiratory syncytial virus.

Human respiratory syncytial virus (RSV) constitutes a highly pathogenic virus that infects lung epithelial cells to cause a wide spectrum of respiratory diseases. Our recent studies have revealed the existence of an interferon-alpha/beta-independent, innate antiviral response against RSV that was dependent on activation of NF-kappaB. We demonstrated that NF-kappaB inducing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) confers potent antiviral function against RSV in an NF-kappaB-dependent fashion, independent of interferon-alpha/beta. During our efforts to study this pathway, we identified HBD2 (human beta-defensin-2), a soluble secreted cationic protein as an antiviral factor induced during NF-kappaB-dependent innate antiviral activity in human lung epithelial cells. Our results demonstrated that HBD2 is induced by TNF and RSV in an NF-kappaB-dependent manner. Induction of HBD2 in infected cells was mediated by the paracrine/autocrine action of TNF produced upon RSV infection. HBD2 plays a critical role during host defense, because purified HBD2 drastically inhibited RSV infection. We also show that the antiviral mechanism of HBD2 involves blocking of viral cellular entry possibly because of destabilization/disintegration of the viral envelope. The important role of HBD2 in the innate response was also evident from loss of antiviral activity of TNF upon HBD2 silencing by short interfering RNA. The in vivo physiological relevance of HBD2 in host defense was apparent from induction of murine beta-defensin-4 (murine counterpart of HBD2) in lung tissues of RSV-infected mice. Thus, HBD2 functions as an antiviral molecule during NF-kappaB-dependent innate antiviral immunity mediated by the autocrine/paracrine action of TNF.