Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges

Introduction: The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO₂ nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization.

Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity.

Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.     

Analysis of a Statewide Early Intervention Program for Young Children with ASD

Journal of Autism and Developmental Disorders - We evaluated the effectiveness of a statewide Medicaid program providing in-home Early Intensive Behavioral Intervention services to young children...     

Thirty-Day Readmission After Laparoscopic Sleeve Gastrectomy—a Predictable Event?

Background

Thirty-day readmission post-bariatric surgery is used as a metric for surgical quality and patient care. We sought to examine factors driving 30-day readmissions after laparoscopic sleeve gastrectomy (LSG).

Methods

We reviewed 1257 LSG performed between March 2012 and June 2014. Readmitted and nonreadmitted patients were compared in their demographics, medical histories, and index hospitalizations. Multivariable regression was used to identify risk factors for readmission.

Results

Forty-five (3.6 %) patients required 30-day readmissions. Forty-seven percent were readmitted with malaise (emesis, dehydration, abdominal pain) and 42 % with technical complications (leak, bleed, mesenteric vein thrombosis). Factors independently associated with 30-day readmission include index admission length of stay (LOS) ≥3 days (OR 2.54, CI?=?[1.19, 5.40]), intraoperative drain placement (OR 3.11, CI?=?[1.58, 6.13]), postoperative complications (OR 8.21, CI?=?[2.33, 28.97]), and pain at discharge (OR?8.49, CI?=?[2.37, 30.44]). Patients requiring 30-day readmissions were 72 times more likely to have additional readmissions by 6 months (OR?72.4, CI?=?[15.8, 330.5]).

Conclusions

The 30-day readmission rate after LSG is 3.6 %, with near equal contributions from malaise and technical complications. LOS, postoperative complications, drain placement, and pain score can aid in identifying patients at increased risk for 30-day readmissions. Patients should be educated on postoperative hydration and pain management, so readmissions can be limited to technical complications requiring acute inpatient management.

     

Synthesis, evaluation, and molecular docking studies of cycloalkyl/aryl-3,4,5-trimethylgallates as potent non-ulcerogenic and gastroprotective anti-inflammatory agents

In our effort to identify the effective gastric sparing and protective anti-inflammatory agents, a series of cycloalkyl/aryl-3,4,5-trimethylgallates were synthesized and characterized. The physicochemical properties were studied to assess the lipophilicity and chemical stability. Subsequently, the compounds were evaluated for their anti-inflammatory activity and effect on gastric mucosa by most active compounds. All the compounds exhibited promising anti-inflammatory activity. In particular, 4a, 4b, 4g, and 4h emerged as the most active compounds in the series. The results of gastric mucosal studies and biochemical estimations suggested that these compounds are non-ulcerogenic and gastroprotective. The molecular docking analysis was performed to understand the binding interactions of these compounds to cyclooxygenase isoenzyme (COX-1 and COX-2). The results from this investigation suggests cycloalkyl/aryl-3,4,5-trimethylgallates as potent safer gastrosparing and protective anti-inflammatory agents.     

Results of a phase I/II trial of recombinant human granulocyte- macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM- CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)