Comparative Study of Alveolar Bone Height and Implant Survival Rate Between Autogenous Bone Mixed with Platelet Rich Plasma Versus Venous Blood for Maxillary Sinus Lift Augmentation Procedure

Aim and Objectives

The aim of this study was to evaluate changes in alveolar bone height by means of radiographic examination and Straumann implant survival rate following maxillary sinus lift augmentation using autogenous bone in combination with platelet rich plasma (PRP) versus venous blood (VB).

Methods

Fifty patients requiring sinus lift augmentation procedure included in the study were divided into two groups (n = 25). During the procedure the sub antral sinus cavity was augmented using autogenous bone taken from mandibular ramus area and mixed with PRP in one group and autogenous bone mixed with VB in the other group. Orthopantomograms were taken preoperatively, immediate, at 6 months and 1 year postoperatively. Height of alveolar bone at the site of sinus augmentation was measured on the radiographs. One hundred and twenty-one Straumann dental implants were placed after healing period.

Results

Age of the patients in the study groups ranged from 36 to 69 years. Differences in mean values of bone height measurements recorded in the PRP series revealed significant differences among the three subgroups (P = 0.001). Significant differences were noted between immediate postop and 6 month (P < 0.01), immediate postop and year (P < 0.01). In the VB series also significant differences were revealed among the three subgroups (P = 0.0280). Significant differences were noted between immediate postop and 6 month (P < 0.05). Comparison of results of subgroups of the two series at the three intervals revealed significant differences at ‘immediate postop’ values (P = 0.0002) and ‘sixmon’ values (P = 0.0435). Differences between ‘year’ values were not significant. Two implants were lost in PRP group.

Conclusion

The results of this limited study reveals that both groups recorded a good increase in the alveolar bone height after sinus augmentation and showed no significant differences between these groups when compared to each other at 1 year postoperatively. When both sub groups compared with immediate postop to year, PRP group showed significant difference and blood group showed no significant difference.     

Kapetansky-Juri Technique to Correct the Whistlers Lip in the Multiple Operated Cleft Patient

Purpose

One of the common sequels of a cleft lip repair may be “whistling lip deformity” but other deformities are also seen particularly in failed or multiple resurgery cases. This retrospective study was carried out to evaluate the usefulness of “Kapetansky-Juri” advancement flap technique to correct such deformities.

Methods

Ten patients of bilateral cleft lip with history of minimum five failed cleft lip surgeries and having residual lip deformity were operated using “Kapetansky-Juri” advancement flap technique and were followed up to minimum 36 months.

Results

All patients showed good tissue fullness and complete correction of the deformity. There was no contracture of surrounding skin or vermilion during follow-up period. In eight patients minimal scar formation was seen while two showed midline scar formation.

Conclusion

No tissue loss due to vascular insufficiency was observed. The technique gives good tissue distribution and minimal surface scar formation.     

Venous thromboembolism in colorectal surgery: skip SCIP or comply?

Background

The Surgical Care Improvement Project (SCIP) includes recommendations for mechanical and pharmacologic venous thromboembolism (VTE) prophylaxis after colorectal surgery. Compliance with these recommendations is publicly reported and included in current pay for performance plans. Presently, there is limited evidence to support compliance with these recommendations.

Aim

To determine the incidence of venous thromboembolic events in colorectal surgery patients who did or did not receive the recommended pharmacologic prophylaxis.

Methods

We performed a retrospective analysis of prospectively accrued data from a single-center, tertiary care, colorectal surgery department. The main outcome measure was the occurrence of venous thromboembolic events and the need for blood transfusion after surgery.

Results

Of 674 patients, 613(91 %) received the recommended pharmacologic VTE prophylaxis and 61 (9 %) did not. Diagnosis, patient variables, and type of surgery performed were similar in each group while operative time was increased in the compliant group (251 vs. 194 min, p < 0.05). In the compliant and noncompliant groups, the incidence of extremity deep venous thrombosis was 2.8 and 8.2 % (p = 0.04), the incidence of pulmonary embolus 1.1 and 3.3 % (p = 0.19), the incidence of portomesenteric venous thrombosis 2.6 and 4.9 % (p = 0.38), and the incidence of any VTE 5.4 and 13.1 % (p = 0.02), respectively. The use of perioperative red blood cell transfusions in the two groups was 9.1 and 14.8 %, p = 0.17. In the subgroup analysis of open cases, there were no statistical differences in the occurrence of any type or combination of VTE.

Conclusions

Compliance with SCIP recommendations for pharmacologic VTE prophylaxis decreased the incidence of VTE after colorectal surgery with no increase in the use of perioperative transfusion. Colorectal surgeons who elect to skip these recommendations may jeopardize both the reputational score and financial reimbursement of their hospital and may put their patients at unnecessary risk for a preventable postoperative complication.     

Structural tuning enables piezochromic and photochemical properties in N-aryl-β-enaminones

An efficient synthesis of N-aryl-β-enaminones via Et₃N-mediated, one-pot three-component reaction of 4-hydroxycoumarin/dimedone, β-nitrostyrene/2-(2-nitrovinyl)thiophene, and arylamine in toluene under refluxed conditions is herein presented. Some prepared compounds were found to exhibit piezochromic properties. The XRD and SEM measurements of the piezochromic compound showed substantial crystal packing and morphology changes before and after grinding. Further, one prepared compound was found to be light-sensitive and can be converted to a furo[3,2-b]pyridin-2(4H)-one derivative upon UV irradiation. A plausible mechanism for this photochemical reaction was proposed.

N-Aryl-β-enaminones are synthesized via Et₃N-mediated, one-pot three-component reaction of 4-hydroxycoumarin/dimedone, β-nitrostyrene/2-(2-nitrovinyl)thiophene and arylamine, and their piezochromic behavior and photosensitivity explored.     

Retention of strong intramolecular hydrogen bonds in high polarity solvents in binaphthalene–benzamide derivatives: extensive NMR studies

Advanced multidimensional NMR techniques have been employed to investigate the intramolecular hydrogen bonds (HBs) in a series of N,N′-([1,1′-binaphthalene]-2,2′-diyl)bis(benzamide) derivatives, with the site-specific substitution of different functional groups. The existence of intramolecular HBs and the elimination of any molecular aggregation and possible intermolecular HBs are ascertained by various experimental NMR techniques, including solvent polarity dependent modifications of HB strengths. In the fluorine substituted derivative, direct evidence for the engagement of organic fluorine in HB is obtained by the detection of heteronuclear through-space correlation and the coupling between two NMR active nuclei where the transmission of spin polarization is mediated through HBs (^1hJ_FH). The extent of reduction in the strength of ^1hJ_FH on dilution with high polarity solvents directly provided the qualitative measure of HB strength. The HB, although becoming weakened, does not get nullified even in pure high polarity solvent, which is attributed to the structural constraints. The rate of exchange of a labile hydrogen atom with the deuterium of the solvent permitted the measurement of their half-lives, that are correlated to the relative strengths of HBs. The experimental NMR findings are further validated by XRD and DFT-based theoretical computations, such as, NCI and QTAIM.

NMR studies reveal very strong hydrogen bond unbreakable even in high polarity solvents.     

Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin

Background: The aim was to investigate cutaneous delivery and biodistribution of the hedgehog pathway inhibitor, vismodegib (VSD), indicated for basal cell carcinoma (BCC), from polymeric micelle formulations under infinite/finite dose conditions.

Methods: VSD-loaded micelles were characterized for drug content, particle size, and shape; a micelle gel was characterized for its rheological behavior. Cutaneous deposition and biodistribution of VSD were determined using porcine and human skin in vitro with quantification by UHPLC-MS/MS.

Results: The optimal micelle solution (Z_av 20–30 nm) increased the aqueous solubility of VSD by >8000-fold; drug content was stable after 4 weeks at 4°C. Application of micelle solution and micelle gel (0.086% w/v) to human skin for 12 h under infinite dose conditions resulted in statistically equivalent VSD deposition (0.62 ± 0.11 and 0.67 ± 0.14 μg/cm², respectively). Cutaneous biodistribution in human skin under infinite (micelle solution and gel) and finite (micelle gel) dose conditions showed that the VSD concentrations obtained in the basal epidermis, at depths of 120–200 μm, were ?3800- and ?2300-fold greater than the IC₅₀ reported for hedgehog signaling pathway inhibition in vitro.

Conclusion: Cutaneous delivery of VSD from micelle-based formulations might enable targeted, topical treatment of superficial BCC with minimal risk of systemic exposure.     

Addressing Cardiovascular Disease Burden in low and Middle Income Countries (LMICs)

The global epidemic of cardiovascular diseases (CVDs) is spiraling upwards primarily due to a sharp rise in the low and middle income countries (LMICs) which are experiencing rapid health transition driven by socioeconomic, technological and lifestyle changes. LMICs currently face a double burden of communicable and non-communicable diseases, leading to competing claims of health conditions that vie for policy makers’ attention as public health priorities in a setting of limited resources, substantially high out-of-pocket expenditure and weak systems of healthcare delivery. Evidence from high income countries suggests that most CVDs are largely preventable as the major CVD risk behaviours including tobacco use, physical inactivity, unhealthy diet, harmful use of alcohol, are avoidable and modifiable. Effective and sustainable behaviour change strategies for LMICs would require low cost, affordable and scalable interventions. There is limited evidence from LMICs on effective interventions to prevent, control and manage CVDs in LMICs. The global guidelines and framework for addressing CVD calls for an urgent need to identify and assess contextually relevant and resource sensitive health care interventions augmented by policy actions. A combination of population based and high risk individual based strategies which are evidence based, cost-effective, feasible as well as scalable would reduce CVD mortality and its devastating impact in LMICs.     

RIG-I–like receptor LGP2 protects tumor cells from ionizing radiation

An siRNA screen targeting 89 IFN stimulated genes in 14 different cancer cell lines pointed to the RIG-I (retinoic acid inducible gene I)–like receptor Laboratory of Genetics and Physiology 2 (LGP2) as playing a key role in conferring tumor cell survival following cytotoxic stress induced by ionizing radiation (IR). Studies on the role of LGP2 revealed the following: (i) Depletion of LGP2 in three cancer cell lines resulted in a significant increase in cell death following IR, (ii) ectopic expression of LGP2 in cells increased resistance to IR, and (iii) IR enhanced LGP2 expression in three cell lines tested. Studies designed to define the mechanism by which LGP2 acts point to its role in regulation of IFNβ. Specifically (i) suppression of LGP2 leads to enhanced IFNβ, (ii) cytotoxic effects following IR correlated with expression of IFNβ inasmuch as inhibition of IFNβ by neutralizing antibody conferred resistance to cell death, and (iii) mouse embryonic fibroblasts from IFN receptor 1 knockout mice are radioresistant compared with wild-type mouse embryonic fibroblasts. The role of LGP2 in cancer may be inferred from cumulative data showing elevated levels of LGP2 in cancer cells are associated with more adverse clinical outcomes. Our results indicate that cytotoxic stress exemplified by IR induces IFNβ and enhances the expression of LGP2. Enhanced expression of LGP2 suppresses the IFN stimulated genes associated with cytotoxic stress by turning off the expression of IFNβ.Several studies have shown that the response of tumor cells to ionizing radiation (IR) is associated with IFN-mediated signaling (1–6). IFN signaling leads to the induction of multiple IFN stimulated genes (ISGs) (7, 8) and activates growth arrest and cell death in exposed cell populations (9). The precise mechanism of IR-mediated induction of IFN signaling is unknown. Tumor cell clones that survive an initial cytotoxic insult are subsequently resistant to exposure to both IR and prodeath components of IFN signaling (10). These clones express IFN-dependent enhanced levels of constitutively expressed ISGs, which overlap in part with ISGs initially induced by cytotoxic stress. Many of these constitutively expressed ISGs have been characterized as antiviral genes (11). Recently, enhanced levels of constitutively expressed ISGs have been reported in advanced cancers and were often associated with a poor prognosis related to aggressive tumor growth, metastatic spread, resistance to IR/chemotherapy, or combinations of these factors (11–18). The studies presented in this report are based on the hypothesis that a specific set of constitutively expressed ISGs, whose enhanced expression is by cytotoxic stress, confers a selective advantage to individual tumor clones (5, 9, 10, 13, 19).To test this hypothesis, we designed a targeted siRNA screen against 89 ISGs selected from two sources. The first included ISGs identified in our earlier screen and designated the IFN-Related DNA Damage Signature (IRDS) (1, 13). The second set included related ISG signatures that have been reported in the literature (as described in Methods and Dataset S1). The 89 genes were individually targeted in 14 tumor cell lines derived from malignant gliomas, lung, breast, colon, head and neck, prostate, and bladder cancers.The most significant finding from this screen was that the RNA helicase Laboratory of Genetics and Physiology 2 (LGP2) encoded by DHX58 [DEXH (Asp-Glu-X-His) box polypeptide 58] confers survival and mediates the response to IR of multiple tumor cell lines. LGP2 acts as a suppressor of the RNA-activated cytoplasmic RIG-I RIG-I (retinoic acid inducible gene I)–like receptor’s pathway (20, 21). This pathway is a subtype of pattern recognition receptors responsible for primary recognition of pathogen and host-associated molecular patterns and the subsequent activation of type I IFN production that orchestrates an innate immune response (22–24). In addition to its role in inhibiting IFNβ expression, Suthar et al. recently demonstrated that LGP2 governs CD8+ T-cell fitness and survival by inhibiting death-receptor signaling (25). Here we demonstrate that suppression of LGP2 leads to an enhanced IFNβ expression and increased killing of tumor cells. Our results thereby provide a mechanistic connection between IR-induced cytotoxic response in tumor cells and the LGP2–IFNβ pathway.