Use of computer-aided three-dimensional prototyping to surgically assist in tooth autotransplantation.

Autotransplantation is a surgical technique in which a donor tooth belonging to the same individual is repositioned into a surgically prepared socket or site of previous tooth extraction. It is beneficial in patients with teeth affected by agenesis, trauma, significant caries, and in teeth in a non-restorable condition or prognostically poor due to other pathology. It is particularly useful in paediatric patients, as properly transplanted teeth have a vital periodontium that allows for continuous growth and functional adaptation leading to preservation of the alveolar ridge. Technological advances in rapid prototyping combined with three-dimensional (3D) computed tomography (CT) have the ability to revolutionise autotransplantation. Preoperative planning for atraumatic extraction of the donor tooth and precise preparation of the recipient site with a rapid prototyped surgical template of the donor tooth considerably reduces the extra-alveolar time, and also reduces manipulation of the root sheath and periodontal ligament, and related trauma. This case series demonstrates the efficient and successful autotransplantation of various types of teeth with the use of a rapid prototyped surgical template produced from 3D CT. The use of this technology is expected to refine the surgical technique and improve treatment outcomes.

Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.

Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012. Patients with inherited bleeding disorders such as haemophilia A, haemophilia B, and von Willebrand's disease were included. Retrospective chart review was conducted. The result showed 53 extraction events occurred in 45 patients over the 10-year period. Ten out of 53 extraction events (18.9%) had postoperative bleeding requiring further factor replacement or ddAVP. Postoperative bleeding in one patient with mild haemophilia A was complicated by the development of inhibitors. Type and severity of bleeding disorder, bone removal, and use of a local haemostatic agent did not have any significant effect on postoperative bleeding. Despite the use of perioperative factors and desmopressin, the postoperative bleeding rates remain high for patients with inherited bleeding disorders. More studies are required to assess the safety and effectiveness of using local haemostatic control to achieve haemostasis following extractions.

Loss of DAB2IP in RCC cells enhances their growth and resistance to mTOR-targeted therapies.

Targeted therapies using small-molecule inhibitors (SMIs) are commonly used in metastatic renal cell cancer (mRCC) patients; patients often develop drug resistance and eventually succumb to disease. Currently, understanding of mechanisms leading to SMIs resistance and any identifiable predictive marker(s) are still lacking. We discovered that DAB2IP, a novel Ras-GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. Loss of DAB2IP in RCC cells enhances their sensitivities to growth factor stimulation and resistances to SMI (such as mammalian target of rapamycin (mTOR) inhibitors). Mechanistically, loss of DAB2IP results in the activation of extracellular signal-regulated kinase/RSK1 and phosphoinositide-3 kinase/mTOR pathway, which synergizes the induction of hypoxia-inducible factor (HIF)-2α expression. Consequently, elevated HIF-2α suppresses p21/WAF1 expression that is associated with resistance to mTOR inhibitors. Thus combinatorial targeting both pathways resulted in a synergistic tumor inhibition. DAB2IP appears to be a new prognostic/predictive marker for mRCC patients, and its function provides a new insight into the molecular mechanisms of drug resistance to mTOR inhibitors, which also can be used to develop new strategies to overcome drug-resistant mRCC.

DAB2IP loss confers the resistance of prostate cancer to androgen deprivation therapy through activating STAT3 and inhibiting apoptosis.

Loss of DAB2IP, a novel tumor suppressor gene, is associated with the high risk of aggressive prostate cancer (PCa). Previously, we reported that DAB2IP modulated androgen receptor activation in the development of castration-resistant PCa; however, its direct action on the failure of androgen deprivation therapy (ADT) remains largely unknown. In this study, we showed that DAB2IP knockdown could significantly enhance in vitro growth and colony formation of PCa cells following ADT as well as tumorigenicity in pre-castrated nude mice. In addition, DAB2IP loss stabilized mitochondrial transmembrane potential, prevented release of cytochrome c, Omi/HtrA2 and Smac from the mitochondria to the cytoplasm and inhibited intrinsic apoptosis induced by ADT. Mechanistically, DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells. Moreover, the luminal epithelia in DAB2IP(-/-) mice with more activated STAT3 and survivin expression were resistant to castration-induced apoptosis. Consistently, DAB2IP expression inversely correlated with STAT3 phosphorylation and survivin expression in PCa patients. Together, our data indicate that DAB2IP loss reprograms intracellular signal transduction and anti-apoptotic gene expression, which potentiates PCa cell survival from ADT-induced cell death.

DAB2IP regulates cancer stem cell phenotypes through modulating stem cell factor receptor and ZEB1.

Cancer stem cell (CSC), the primary source of cancer-initiating population, is involved in cancer recurrence and drug-resistant phenotypes. This study demonstrates that the loss of DAB2IP, a novel Ras-GTPase activating protein frequently found in many cancer types, is associated with CSC properties. Mechanistically, DAB2IP is able to suppress stem cell factor receptor (c-kit or CD117) gene expression by interacting with a newly identified silencer in the c-kit gene. Moreover, DAB2IP is able to inhibit c-kit-PI3K-Akt-mTOR signaling pathway that increases c-myc protein to activate ZEB1 gene expression leading to the elevated CSC phenotypes. An inverse correlation between CD117 or ZEB1 and DAB2IP is also found in clinical specimens. Similarly, Elevated expression of ZEB1 and CD117 are found in the prostate basal cell population of DAB2IP knockout mice. Our study reveals that DAB2IP has a critical role in modulating CSC properties via CD117-mediated ZEB1 signaling pathway.

Knowledge translation and implementation in spinal cord injury: a systematic review.

OBJECTIVE: To conduct a systematic review examining the effectiveness of knowledge translation (KT) interventions in changing clinical practice and patient outcomes. METHODS: MEDLINE/PubMed, CINAHL, EMBASE and PsycINFO were searched for studies published from January 1980 to July 2012 that reported and evaluated an implemented KT intervention in spinal cord injury (SCI) care. We reviewed and summarized results from studies that documented the implemented KT intervention, its impact on changing clinician behavior and patient outcomes as well as the facilitators and barriers encountered during the implementation. RESULTS: A total of 13 articles featuring 10 studies were selected and abstracted from 4650 identified articles. KT interventions included developing and implementing patient care protocols, providing clinician education and incorporating outcome measures into clinical practice. The methods (or drivers) to facilitate the implementation included organizing training sessions for clinical staff, introducing computerized reminders and involving organizational leaders. The methodological quality of studies was mostly poor. Only 3 out of 10 studies evaluated the success of the implementation using statistical analyses, and all 3 reported significant behavior change. Out of the 10 studies, 6 evaluated the effect of the implementation on patient outcomes using statistical analyses, with 4 reporting significant improvements. The commonly cited facilitators and barriers were communication and resources, respectively. CONCLUSION: The field of KT in SCI is in its infancy with only a few relevant publications. However, there is some evidence that KT interventions may change clinician behavior and improve patient outcomes. Future studies should ensure rigorous study methods are used to evaluate KT interventions.

The role of DAB2IP in androgen receptor activation during prostate cancer progression.

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP(-/-) mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.

The role of sympathetic and parasympathetic nerve systems on the smooth muscle of rat seminal vesicles - experimental results and speculation for physiological implication on ejaculation.

Ejaculation is a process involving sympathetic and parasympathetic effects during different stages - emission and ejection. Some conditions of ejaculation dysfunction are associated with autonomic nerves. However, the exact effects of autonomic nerves on ejaculation are not well defined. Autonomic agonists induce different recorded trace patterns of seminal vesicular contraction. The different traces contain different components of phasic and tonic contraction, which may have physiological implications. In this study, we examined isolated rat seminal vesicle (SV) contraction by phenylephrine (PE), acetylcholine, and their respective antagonists and then speculated upon physiological roles of sympathetic and parasympathetic nerves on SV during ejaculation. We found that PE and Ach both achieved good contraction of rat SV. Compared to α1b for sympathetic and M1, M2 for parasympathetic receptors, α1a and M3 are the relatively dominant subtypes on rat SV. Adrenergic and cholinergic agonists cause different trace patterns of SV contraction. We speculated that the sympathetic effect is dominant during emission to squeeze seminal fluid out and that the parasympathetic effect is dominant during ejection to provide an anti-reflux effect on the ejaculatory duct.

Mitochondrial DNA depletion sensitizes cancer cells to PARP inhibitors by translational and post-translational repression of BRCA2.

Previous studies have shown that pharmacologic inhibition of poly (ADP-ribose) polymerase (PARP), a nuclear protein that is crucial in signaling single-strand DNA breaks, is synthetically lethal to cancer cells from patients with genetic deficiency in the DNA repair proteins BRCA1 and BRCA2. Herein, we demonstrate that depletion of the mitochondrial genome (mtDNA) in breast, prostate and thyroid transformed cells resulted in elevated steady-state cytosolic calcium concentration and activation of calcineurin/PI3-kinase/AKT signaling leading to upregulation of miR-1245 and the ubiquitin ligase Skp2, two potent negative regulators of the tumor suppressor protein BRCA2, thus resulting in BRCA2 protein depletion, severe reduction in homologous recombination (HR) and increased sensitivity to the PARP inhibitor rucaparib. Treatment of mtDNA-depleted cells with the PI3-kinase inhibitor LY294002, the calmodulin antagonist W-7, the calcineurin inhibitor FK506, the calcium chelator BAPTA-AM, or suppression of AKT activity by AKT small-interfering RNA (siRNA) enhanced BRCA2 protein levels as well as HR. Decreasing the intracellular calcium levels using BAPTA, or direct reconstitution of BRCA2 protein levels either by recombinant expression or by small molecule inhibition of both Skp2 and miR-1245 restored sensitivity to rucaparib to wild-type levels. Furthermore, by studying prostate tissue specimens from prostate carcinoma patients we found a direct correlation between the presence of mtDNA large deletions and loss of BRCA2 protein in vivo, suggesting that mtDNA status may serve as a marker to predict therapeutic efficacy to PARP inhibitors. In summary, our results uncover a novel mechanism by which mtDNA depletion restrains HR, and highlight the role of mtDNA in regulating sensitivity to PARP inhibitors in transformed cells.

Associations of endogenous testosterone and lipid profiles in middle-aged to older Taiwanese men.

The relationship between endogenous plasma testosterone and plasma lipids was assessed among 856 Taiwanese men ≧40 years old originally recruited for an epidemiological study of testosterone deficiency syndrome. Blood samples were drawn from fasting (n = 562) and non-fasting (n = 294) subjects between 0800 to 1100 hours. With adjustment of age, body mass index and sex hormone-binding globulin, the following results were shown: (i) triglyceride (TG) levels were negatively associated with quartile levels of testosterone, and the magnitudes of associations were greater for postprandial TGs than for fasting TGs; (ii) high-density lipoprotein cholesterol (HDL-C) levels were positively related to quartile levels of testosterone, but the associations became insignificant after further control of TGs; and (iii) the calculated low-density lipoprotein cholesterol (LDL-C) levels were positively associated with quartile levels of testosterone. Similar results were obtained in multivariate linear regression analyses with additional control of hypertension and diabetes. In these Taiwanese men, the favorable association of endogenous plasma testosterone with HDL-C counterbalances the unfavorable association of it with LDL-C, while the net influence of testosterone on plasma lipids for cardiovascular system was still in the beneficial direction due to its negative association with postprandial plasma TG levels.

Spasticity outcome measures in spinal cord injury: psychometric properties and clinical utility.

STUDY DESIGN: Comprehensive review and systematic analyses. OBJECTIVES: Assess published psychometric evidence for spinal cord injury (SCI) spasticity outcome measures. Considerations about the influence of spasticity on function have also been identified to understand treatment effects and guide service delivery. SETTING: London, Ontario and Vancouver, British Columbia, Canada. METHOD: Review of measures was based on availability of psychometric data, application in clinical settings and evaluated in SCI patients. RESULTS: Ashworth and Modified Ashworth Scales (AS, MAS), Penn Spasm Frequency Scale (PSFS), Spinal Cord Assessment Tool for Spasticity (SCATS), Visual Analogue Scale self-rated scale of spasticity (VAS) and the Wartenberg Pendulum Test (WPT) were included in this review. The most frequently used tools for SCI spasticity measurement include the AS, MAS, PSFS and VAS, of which the latter two are self-report spasticity measures. The SCATS has been partially validated for SCI, but is not widely used. The WPT has been minimally validated despite its use in a large-scale SCI spasticity randomized controlled trial. CONCLUSIONS: Since spasticity is multidimensional, focusing on one or two spasticity outcome measures can misrepresent the extent and influence of spasticity on SCI patients. Different scales measure different aspects of spasticity and individual tools correlate weakly with each other. Spasticity may be better measured with an appropriate battery of tests, including the AS or MAS, along with PSFS. These tools would benefit from further reliability and responsiveness testing. Tools that assess the influence of spasticity on patient activities, participation and quality of life are important, but lacking.

Prevalence of erectile dysfunction and impacts on sexual activity and self-reported intercourse satisfaction in men older than 40 years in Taiwan.

In order to assess the prevalence of erectile dysfunction (ED), and its association with chronic diseases and impact upon sexual activity and satisfaction during sexual intercourse, a reproductive survey was conducted among 1002 Taiwanese men aged over 40 y. The information collected comprised age, gender, level of education, history of chronic diseases, and self-reported data pertaining to erectile function, sexual activity, and sexual satisfaction during sexual intercourse. The prevalence of ED amongst study subjects was 17.7%, and the frequency increased with age. A history of chronic diseases were significantly associated with ED (P<0.05). A reduced incidence of sexual activity and a decreased level of satisfaction during sexual intercourse were observed among subjects suffering from ED as compared to those not suffering such a condition. In conclusion, based upon the results of a community-based survey the prevalence of ED among Taiwanese men aged 40 y or more was 17.7% and it increased with age. It was also found that ED was associated with various chronic diseases and that it exerted a negative impact upon sexual activity and the level of satisfaction associated with its conduct.

Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury.

Plasma concentration profiles of the K+ channel-blocking compound Fampridine were obtained from (1) control subjects (n = 6) following oral administration of doses of 10, 15, 20, and 25 mg and (2) patients with spinal cord injury (SCI) (n = 11) following a single oral dose of 10 mg of an immediate-release formulation. Plasma concentrations were determined using a reversed-phase ion-pair high-performance liquid chromatography (HPLC) assay with ultraviolet light detection employing liquid extraction. The drug was rapidly absorbed with a tmax approximately 1 hour for both groups; tmax was independent of dose. Cmax and AUC0-infinity were linearly related to dose, and t 1/2 was 3 to 4 hours for both groups. There were no obvious differences in the (10-mg) plasma concentration profiles between control subjects and SCI patients. The drug was well tolerated, with only mild and transient side effects of light-headedness, dysesthesias, and dizziness.

Retroperitoneoscopic nephropexy for symptomatic nephroptosis.

BACKGROUND: Open nephropexy for nephroptosis creates significant morbidity. We describe our technique for retroperitoneoscopic nephropexy and evaluate its efficacy. METHODS: Twenty-five renal units in 23 patients with symptomatic nephroptosis underwent retroperitoneoscopic nephropexy by suturing the posterior renal capsules and transfixing them to the back muscles. The diagnosis and postoperative assessment were made by typical symptoms (via patient questionnaire) and findings of intravenous urography (IVU) when the position was changed from supine to erect. RESULTS: Mean operative time was 188 min (range, 90-330). Mean narcotic use was 15.6 mg morphine. Complete resolution of symptoms occurred in 84% (21/25) renal units; 12% (three of 25) achieved partial improvement (>75% decrease of preoperative symptoms). Follow-up IVU showed that 88% of patients had a renal descent of <2 cm on standing; the others had a descent of 2-4 cm. All of the five renal units with hydronephrosis resolved completely after the operation. CONCLUSIONS: This modified technique of retroperitoneoscopic nephropexy is a minimally invasive, feasible, and highly successful option for treating patients with symptomatic nephroptosis.

The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction.

The coxsackievirus and adenovirus receptor (CAR) mediates viral attachment and infection, but its physiologic functions have not been described. In nonpolarized cells, CAR localized to homotypic intercellular contacts, mediated homotypic cell aggregation, and recruited the tight junction protein ZO-1 to sites of cell-cell contact. In polarized epithelial cells, CAR and ZO-1 colocalized to tight junctions and could be coprecipitated from cell lysates. CAR expression led to reduced passage of macromolecules and ions across cell monolayers, and soluble CAR inhibited the formation of functional tight junctions. Virus entry into polarized epithelium required disruption of tight junctions. These results indicate that CAR is a component of the tight junction and of the functional barrier to paracellular solute movement. Sequestration of CAR in tight junctions may limit virus infection across epithelial surfaces.

The relationship of penile rigidity and intracavernous vascular resistance in potent men during intracavernous pharmacological testing.

PURPOSE: We studied the relationship of penile rigidity and intracavernous vascular resistance in potent men during intracavernous pharmacological testing. MATERIALS AND METHODS: Enrolled in our study were 19 potent men undergoing intracavernous pharmacological testing for various reasons. Hemodynamic changes in response to the intracavernous injection of 20 microg. prostaglandin E1 were assessed by color Doppler sonography with simultaneous RigiScan (Dacomed Corp., Minneapolis, Minnesota) monitoring of penile rigidity. The relationship of penile rigidity and intracavernous vascular resistance was determined by correlating hemodynamic data with recorded penile rigidity values. RESULTS: Maximal mean rigidity plus or minus standard deviation of the penile tip and base after intracavernous injection of prostaglandin E1 was 76.8% +/- 8.5% and 97.3% +/- 4.7%, respectively. Penile tip and base rigidity correlated positively with the resistive index (r = 0.69 and 0.75, p <0.0001) and negatively with end diastolic velocity (r = -0.62 and -0.70, respectively, p <0.0001). The formula, rigidity = -128 + 195 x resistive index, was derived to describe the linear regression of penile base rigidity and the resistive index. The formula, rigidity = 59.8 - 3.3 x end diastolic velocity, was derived to describe the linear regression of penile base rigidity and end diastolic velocity. CONCLUSIONS: Penile rigidity correlated strongly with intracavernous vascular resistance in potent men during intracavernous pharmacological testing. The resistive index and end diastolic velocity of the cavernous arteries may each be used to estimate penile rigidity quantitatively.

The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of car protein structure.

The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity receptor for adenovirus type 5. We observed that invasive bladder cancer specimens had significantly reduced CAR mRNA levels compared with superficial bladder cancer specimens, which suggests that CAR may play a role in the progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR-negative cells) increased its sensitivity to adenovirus infection and significantly inhibited its in vitro growth, accompanied by p21 and hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro growth. To unveil the mechanism of action of CAR, we showed that the extracellular domain of CAR facilitated intercellular adhesion. Furthermore, interrupting intercellular adhesion of CAR by a specific antibody alleviates the growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane and intracellular domains of CAR were critical for its growth-inhibitory activity. These data indicate that the cell-cell contact initiated by membrane-bound CAR can elicit a negative signal cascade to modulate cell cycle regulators inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot only facilitate viral uptake of adenovirus but also inhibit cell growth. These results can be integrated to formulate a new strategy for bladder cancer therapy.

Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial.

4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown to reduce the latency and increase the amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) in patients with chronic spinal cord injury (SCI). These effects on MEPs are thought to reflect enhanced conduction in long tract axons brought about by overcoming conduction deficits due to focal demyelination and/or by enhancing neuroneuronal transmission at one or more sites of the neuraxis. The present study was designed to obtain further evidence of reduced central motor conduction time (CMCT) and to determine whether MEPs could be recorded from paretic muscles in which they were not normally elicited. MEPs were elicited with TMS being delivered to subjects (n = 25) pre- and post-administration of 4-AP (10 mg capsule) or placebo. The principal finding was that 4-AP lowered the stimulation threshold, increased the amplitude and reduced the latency of MEPs in all muscles tested, including those that were unimpaired, but did not alter measures of the peripheral nervous system (i.e., M-wave, H-reflex, F-wave). These 4-AP-induced changes in MEPs were significantly greater than those seen with placebo (p < 0.05). The primary implication of these results is that a low dose of 4-AP (immediate-release formulation) appears to improve the impaired central motor conduction of some patients with incomplete SCI. This is most likely attributable to overcoming conduction deficits at the site of injury but may also involve an increase in cortical excitability.

ASSESS-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan.

The efficacy and safety of sildenafil were evaluated in a randomised, double-blind, placebo-controlled, flexible-dose study in Taiwanese men aged 26 to 80 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months' duration. A total of 236 patients were randomised at six medical centres in Taiwan to receive either sildenafil (50 mg initially increased if necessary to 100 mg or decreased to 25 mg depending on efficacy and toleration) (n=119) or matching placebo (n=117) taken on an 'as needed' basis 1 h prior to anticipated sexual activity for a period of 12 weeks. At the end of 12 weeks, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the IIEF (International Index of Erectile Function) scale, (2) the percentage of successful intercourse attempts; and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P<0.0001). Treatment-related adverse events occurred in 43.7% of patients receiving sildenafil and 18.8% receiving placebo. The most common adverse events with sildenafil were flushing, dizziness and headache (25.2, 6.7 and 5.9% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in the population of Taiwanese men appears similar to that reported in other studies in western populations.

The prospect of gene therapy for prostate cancer: update on theory and status.

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.