Re-evaluating the Epistemic Authority of Systematic Reviews and Meta-analyses in Contemporary Clinical Discourse.

How to cite this article: Yadav S. Re-evaluating the Epistemic Authority of Systematic Reviews and Meta-analyses in Contemporary Clinical Discourse. J Contemp Dent Pract 2023;24(12):919-920. Keywords: Evidence-based medicine, Evidence-based science, Meta-analyses, Systematic reviews and meta-analyses.

Research on Antimicrobial Resistance in the Last 15 Years, India: A Bibliometric Analysis.

SUMMARY: Effective antimicrobials play an important element in modern medicine's success in treating infections, without which the patients would be put at risk. Along with the naturally occurring process of antibiotic resistance, the misuse/overuse of these antibiotics also leads to them losing their effectiveness. It limits the treatment options as the microbe that had previously been sensitive becomes resistant. This bibliometric study was performed by searching the Scopus database according to a specific search strategy. A total of 4200 articles were retrieved from the search, and after applying inclusion and exclusion criteria, 1355 articles were included in the study. All of the bibliometric variables examined in this study revealed significant growth in this research field, especially during COVID-19, in terms of increasing scientific output and research collaboration. The study findings indicate an adequate quality and amount of antimicrobial resistance (AMR) research on microbiology and pharmacodynamics in India, whereas more research needs to be conducted on measures to tackle AMR, its public health, and policy aspects.

Use of Dupilumab in Glucocorticoid-Dependent Asthma.

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting ß-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.

IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis.

Background: There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods: PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I 2 > 50% and fixed-effects model was used if I 2 < 50%. Results: We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I 2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I 2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I 2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I 2 75.40%). Conclusion: This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.

Cell-free hemoglobin is a marker of systemic inflammation in mouse models of sepsis: a Raman spectroscopic study.

Sepsis is a life-threatening condition caused by heightened host immune responses post infection. Despite intensive research, most of the existing diagnostic methods remain non-specific, labour-intensive, time-consuming or are not sensitive enough for rapid and timely diagnosis of the onset and progression of sepsis. The present work was undertaken to explore the potential of Raman spectroscopy to identify the biomarkers of sepsis in a label-free and minimally invasive manner using different mouse models of inflammation. The sera of BALB/c mice infected with Salmonella Typhimurium reveal extensive hemolysis, as indicated by the Raman bands that are characteristic of the porphyrin ring of hemoglobin (668, 743, 1050, 1253 and 1397 cm-1) which increase in a kinetic manner. These markers are also observed in a lipopolysaccharide-induced endotoxic shock model, but not in a thioglycollate-induced sterile peritonitis model. These data demonstrate that hemolysis is a signature of systemic, but not localised, inflammation. To further validate our observations, sepsis was induced in the nitric oxide synthase 2 (Nos2-/-) deficient strain which is more sensitive to infection. Interestingly, Nos2-/- mice exhibit a higher degree of hemolysis than C57BL/6 mice. Sepsis-induced hemolysis was also confirmed using resonance Raman spectroscopy with 442 nm excitation which demonstrated a pronounced increase in the resonant Raman bands at 670 and 1350 cm-1 in sera of the infected mice. This is the first study to identify inflammation-induced hemolysis in mouse models of sepsis using Raman spectral signatures for hemoglobin. The possible implications of this method in detecting hemolysis in different inflammatory pathologies, such as the ongoing COVID-19 pandemic, are discussed.

Pediatric Mucormycosis and COVID-19.

As of May 19, 2021, due to the increase in reported mucormycosis cases in COVID-19 patients, mucormycosis has been declared as a notifiable disease under Epidemic Disease Act 1897 by the Government of India with the prevalence being 140 per million population. The first case of mucormycosis in a pediatric COVID-19 positive child has been reported in Ahmedabad1 and we should prepare ourselves with the probability of more pediatric cases being reported in the near future.

Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice.

Toll-like receptors (TLRs) are a family of pattern-recognition receptors involved in innate immunity. Previous studies have shown that TLR2 inhibition protects the heart from acute stress, including myocardial infarction and doxorubicin-induced cardiotoxicity in animal models. However, the role of TLR2 in the development of aging-associated heart failure is not known. In this work, we studied aging-associated changes in structure and function of TLR2-deficient mice hearts. Whereas young TLR2-KO mice did not develop marked cardiac dysfunction, 8- and 12-month-old TLR2-KO mice exhibited spontaneous adverse cardiac remodeling and cardiac dysfunction in an age-dependent manner. The hearts of the 8-month-old TLR2-KO mice had increased fibrosis, cell death, and reactivation of fetal genes. Moreover, TLR2-KO hearts displayed reduced infiltration by macrophages, increased numbers of myofibroblasts and atrophic cardiomyocytes, and higher levels of the atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Mechanistically, TLR2 deficiency impaired the PI3K/Akt signaling pathway, leading to hyperactivation of the transcription factor Forkhead box protein O1 (FoxO1) and, in turn, to elevated expression of FoxO target genes involved in the regulation of muscle wasting and cell death. AS1842856-mediated chemical inhibition of FoxO1 reduced the expression of the atrophy-related ubiquitin ligases and significantly reversed the adverse cardiac remodeling while improving the contractile functions in the TLR2-KO mice. Interestingly, TLR2 levels decreased in hearts of older mice, and the activation of TLR1/2 signaling improved cardiac functions in these mice. These findings suggest that TLR2 signaling is essential for protecting the heart against aging-associated adverse remodeling and contractile dysfunction in mice.

Triple chamber: a clinical rarity after deep anterior lamellar keratoplasty and role of optical coherence tomography in management.

PURPOSE: To report a case demonstrating triple chamber following deep anterior lamellar keratoplasty (DALK) and its successful intra-operative optical coherence tomography-guided management. METHOD: Case report of a young male with macular corneal dystrophy, who underwent DALK in his left eye by Big-Bubble technique. The surgery was uneventful. On the first post-operative day, triple chamber was observed and followed-up with serial clinical photography and anterior segment optical coherence tomography. Due to decrease in graft clarity and increase in volume of the two extra chambers, interface drainage along with descemetopexy was undertaken 4 days later. RESULT: The compartments constituting the triple chamber were those in-between the donor tissue and host pre-Descemet layer (Dua's layer), the latter and host Descemet membrane and the true anterior chamber. Presence of viscoelastic in the interface was identified as the cause. Microscope integrated optical coherence tomography (MiOCT) guided drainage followed by intracameral air tamponade ensured near total disappearance of the two extra chambers at the end of surgery. Examination on the next day confirmed complete apposition of the graft and host. CONCLUSION: To the best of our knowledge, this is a unique demonstration of Dua's layer in vivo by slit lamp biomicroscopy and description of MiOCT guided management of triple chamber.

Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective.

Current regenerative medicine tactics focus on regenerating tissue structures pathologically modified by cell transplantation in combination with supporting scaffolds and biomolecules. Natural and synthetic polymers, bioresorbable inorganic and hybrid materials, and tissue decellularized were deemed biomaterials scaffolding because of their improved structural, mechanical, and biological abilities.Various biomaterials, existing treatment methodologies and emerging technologies in the field of Three-dimensional (3D) and hydrogel processing, and the unique fabric concerns for tissue engineering. A scaffold that acts as a transient matrix for cell proliferation and extracellular matrix deposition, with subsequent expansion, is needed to restore or regenerate the tissue. Diverse technologies are combined to produce porous tissue regenerative and tailored release of bioactive substances in applications of tissue engineering. Tissue engineering scaffolds are crucial ingredients. This paper discusses an overview of the various scaffold kinds and their material features and applications. Tabulation of the manufacturing technologies for fabric engineering and equipment, encompassing the latest fundamental and standard procedures.

A Landscape on Lymphatic Filariasis with its Effects and Recent Advanced Treatments.

Lymphatic filariasis is an infection caused by parasites that poses a significant health, social, and economic burden, affecting a vast population that exceeds 120 million individuals globally. The Etiology of the infection is attributed to three nematode parasites, namely Wuchereria bancrofti, B. timori, and Brugia malayi, as well as which are phylogenetically related. These parasites are transmitted to humans via mosquitoes belonging to the Anopheles, Aedes genera, and Culex. As per the estimation provided by the WHO, the current number of individuals infected with filariasis stands at approximately 120 million across 81 countries. Furthermore, it is estimated that around 1.34 billion individuals reside in regions that are endemic to filariasis, thereby putting them at risk of contracting the disease. Different synthetic drugs such as Ivermectin, Doxycycline, Albendazole, and Suramin are used in the treatment. Some natural plants are Azadirachta indica, Tinospora cordifolia, Zingiber officinal, as well as, some marine sources are also included for better treatment. We also touch briefly on a few additional filarial diseases. Although there are only a few medications available to treat filariasis, their frequent usage may result in drug resistance. Furthermore, there is no effective vaccination for the treatment of filariasis. Due to these restrictions, it has been crucial to create new anti-filarial medications, which motivates researchers to find novel pharmaceuticals with anti-filarial action. In this article, we examine the latest achievements in the anti-filarial area, including the many forms of filariasis and their historical contexts, elimination programmes, various therapeutic classes (both synthetic and natural), investigated product-derived targets as well as clinical investigations.

Revolutionizing Wound Healing: Unleashing Nanostructured Lipid Carriers Embodied with Herbal Medicinal Plant.

Wound healing is crucial for maintaining skin integrity and preventing complications from external threats. Various plants, such as Achillea millefolium, Aloe vera, Curcuma longa, Calendula officinalis, Camellia sinensis, Azadirachta indica, and Plantago, have demonstrated wound healing capabilities and have been used in herbal medicine for wound care. NLCs are second-generation lipid nanoparticles, blending solid and liquid lipids to improve medication loading and limit leakage. NLCs have been used in various applications, including cosmeceuticals, chemotherapy, gene therapy, and brain targeting. Wound healing is divided into four stages: hemostasis, inflammatory response, proliferation, and remodeling. Factors such as age, gender, chronic disorders, and local agents like infections can affect recovery. These plants' antiinflammatory, antioxidant, and antibacterial activities have demonstrated potential in wound healing. Combining herbal medicinal plants and nanostructured lipid carriers (NLCs) can revolutionise wound treatment and improve overall healthcare outcomes.

Theranostic and Combined Approaches Exploiting Multifunctional Gold Nanoclusters in Tumoral Ecosystems: A Paradigm Shift in Precision Oncology.

Malignant tumors pose a significant threat to human life and well-being because of their rising occurrence and size. The current treatment methods and diagnostic techniques employed in clinical practice are inadequate for effectively treating tumors. Fluorescence, photothermal effects, radiosensitization, and biocompatibility are only a few instances of the unique photonic and physicochemical properties exhibited. Gold nanoclusters (AuNCs) are nanomaterials that possess modest dimensions, typically measuring approximately 3 nm, and are composed of a limited number of particles. AuNCs have three primary functions in practical applications: serving as imaging agents, drug transporters, and therapeutic agents. This article discusses nanosystems. The text emphasizes the promise of AuNCs for tumor theranostic and combination treatment while also acknowledging any existing limitations. Lastly, it is anticipated that the information presented here will serve as a valuable tool for researchers in this sector, resulting in novel perspectives and, ultimately, a wider adoption of AuNCs in pharmaceuticals. This study focuses on the expansion of diagnostic applications in cancer therapy by utilizing AuNC-based devices, made possible by the use of dynamic or passive tumor targeting techniques. The utilization of AuNCs has been thoroughly investigated for their prospective applicability as light-activated and radiation agents. Furthermore, they have been investigated as nanocarriers for transporting anticancer drugs. The medications can either bind to the closure receptor or be linked to the AuNCs through various techniques, showcasing their extensive potential for therapeutic applications.

Potential Neuroprotective Strategies using Smart Drug Delivery Systems for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common neurological disorder, affecting more than 50 million individuals worldwide and causing gradual but progressive cognitive decline. The rising cost of medical treatment is mostly attributable to AD. There are now mainly a few slightly symptomatic therapeutic options accessible. Although this is not the primary reason, the failure to develop effective treatments for AD is often attributed to the disease's complicated pathophysiology and the wide range of underlying ideas. OBJECTIVE: Studies undertaken over the past decade have aimed to find novel methods of overcoming these barriers and effectively delivering drugs to the central nervous system. As a result, nanotechnology provides a promising alternative to the standard means of administering anti-amyloidosis drugs, enhancing expectations for a successful treatment of Alzheimer's disease. These therapeutic implications of using nanoparticle-based approaches for the treatment of Alzheimer's disease are discussed in this paper. METHODOLOGY: Published articles from PubMed, SciFinder, Google Scholar, ClinicalTrials.org, and the Alzheimer Association reports were carefully examined to compile information on the various strategies for combating AD. That has been studied to summarize the recent advancements and clinical studies for the treatment of Alzheimer's disease (AD). Statistics is the study and manipulation of data, including ways to gather, review, analyze, and draw conclusions from data. CONCLUSION: The biology of the BBB and its processes of penetration must be carefully taken into account while creating DDSs. If we have a better grasp of the disease's mechanism, we might be able to overcome the shortcomings of current treatments for AD. Different DDSs show interesting properties for delivering medication tailored to the brain. This review paper examines the recent applications of DDSs in diverse domains. By selecting the best targeting vectors and optimizing the combination of carriers, multifunctionalized DDS may be produced, and these DDS have a significant impact on AD therapy potential. To develop DDSs with the best therapeutic efficacy and manageable side effects, experts from a variety of fields may need to contribute their efforts. Currently, the therapeutic use of nanotechnology-based DDSs appears to be a promising prospect for AD therapy, and as the pathophysiology of AD is better understood, this strategy will develop over time.

Flavonoids as Potential Natural Compounds for the Prevention and Treatment of Eczema.

Eczema is a systemic autoimmune disease characterized by inflammation and skin manifestation with a range of comorbidities that include physical and psychological disorders. Despite recent advancements in understanding the mechanisms involved in atopic dermatitis, current marketed products have shown varying results with more side effects. The present ob-jective of the research studies is to develop new agents for eczema that cut down the cost of the novel drugs available and also improve the efficacy with the least adverse effects. Natural compounds and medicinal plants have been traditionally used since ancient civilizations. Now-adays, research in the herbal field is at its peak. One such natural compound, flavonoid, was found to be beneficial for the treatment of eczema. This review describes the use of certain flavonoid products to prepare preparations suitable for the treatment of prophylaxis or eczema. This is especially true for prophylaxis or atopic eczema treatment. These compounds exhibit anti-inflammatory, anti-inflammatory, anti-inflammatory, and anti-inflammatory properties and are, therefore, used in treatments to prevent allergies, inflammation, and irritation to the skin. We also dock the flavonoid derivatives used with the protein associated with the inhibi-tion of eczema for better lead optimization. These preparations appear to be used for cosmetic, dermatological, or herbal remedies as a local application.

RiTe conjugate mediated corneal collagen crosslinking, a novel therapeutic intervention for keratoconus - in vitro and in vivo study.

Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues. The present study has employed cell penetrating peptide (CPP), Tat2, to enhance the penetration of riboflavin molecule, and thereby improve currently followed CXL protocol. This study demonstrates approximately two-fold enhanced uptake of CPP riboflavin conjugate, Tat2riboflavin-5'Phosphate (RiTe conjugate), both in vitro and in vivo. Two different CXL protocols (Epi ON and Epi OFF) have been introduced and implemented in rabbit corneas using RiTe conjugate in the present study. The standard and RiTe conjugate mediated CXL procedures exhibited an equivalent extent of crosslinking in both the methods. Reduced keratocyte loss and no endothelial damage in RiTe conjugate mediated CXL further ascertains the safety of the proposed CXL protocols. Therefore, RiTe conjugate mediated CXL protocols present as potential alternatives to the standard keratoconus treatment in providing equally effective, less invasive and patient compliant treatment modality.

Endothelial Drp1 Couples VEGF-induced Redox Signaling with Glycolysis Through Cysteine Oxidation to Drive Angiogenesis.

Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H 2 O 2 signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys 644 , promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys 299 / 304 via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. In vivo , mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered "redox-dead" (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.

Advanced therapeutics avenues in hepatocellular carcinoma: a novel paradigm.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and it poses a significant risk to patients health and longevity due to its high morbidity and fatality rates. Surgical ablation, radiotherapy, chemotherapy, and, most recently, immunotherapy have all been investigated for HCC, but none have yielded the desired outcomes. Several unique nanocarrier drug delivery techniques have been studied for their potential therapeutic implications in the treatment of HCC. Nanoparticle-based imaging could be effective for more accurate HCC diagnosis. Since its inception, nanomedicine has significantly transformed the approach to both the treatment and diagnostics of liver cancer. Nanoparticles (NPs) are being studied as a potential treatment for liver cancer because of their ability to carry small substances, such as treatment with chemotherapy, microRNA, and therapeutic genes. The primary focus of this study is on the most current discoveries and practical uses of nanomedicine-based diagnostic and therapeutic techniques for liver cancer. In this section, we had gone over what we know about metabolic dysfunction in HCC and the treatment options that attempt to fix it by targeting metabolic pathways. Furthermore, we propose a multi-target metabolic strategy as a viable HCC treatment option. Based on the findings given here, the scientists believe that smart nanomaterials have great promise for improving cancer theranostics and opening up new avenues for tumor diagnosis and treatment.

Management of Oral Squamous Papilloma Using Annona squamosa (Custard Apple) Leaves: A Novel Case.

This report presents the case of a 36-year-old male who was diagnosed with oral squamous papilloma in the palatal region. Excision was planned. The patient in the meantime chewed upon custard apple leaves and reported that the lesion prolapsed over the next few days. On examination, the site showed no signs of scarring or contracture and presented with healthy palatal tissue. The patient was prevented from requiring surgery, which would have shown a longer healing period with heavy reliance on an expensive resource base. This novel observation highlights the benefits of custard apple (Annona squamosa) leaves and warrants that its hepatoprotective, anticancer, antidiabetic, antioxidant, antibacterial, anti-obesity, and lipid-lowering properties are studied in an astute scientific setup with a well-drawn-out research plan.

Advancement and application of novel cell-penetrating peptide in cancer management.

Cell-penetrating peptides (CPPs) are small amino acid sequences with the potential to enter cell membranes. Along with nucleic acids, large proteins, and other chemical compounds, they can deliver several bioactive cargos inside cells. Numerous CPPs have been extracted from natural or synthetic materials since the discovery of the first CPP. In the past few decades, a significant variety of studies have shown the potential of CPPs to cure different diseases. The low toxicity in peptide compared to other drug delivery carriers is a significant benefit of CPP-based therapy, in addition to the high efficacy brought about by swift and effective delivery. A significant tendency for intracellular DNA delivery may also be observed when nanoparticles and the cell penetration peptide are combined. CPPs are frequently used to increase intracellular absorption of nucleic acid, and other therapeutic agents inside the cell. Due to long-term side effects and possible toxicity, its implementation is restricted. The use of cell-permeating peptides is a commonly used technique to increase their intracellular absorption. Additionally, CPPs have lately been sought for application in vivo, following their success in cellular studies. This review will go through the numerous CPPs, the chemical modifications that improve their cellular uptake, the various means for getting them across cell membranes, and the biological activity they acquire after being conjugate with specific chemicals.

Nanotechnology-based Nose-to-brain Delivery in Epilepsy: A Novel Approach to Diagnosis and Treatment.

Epilepsy is a serious neurological disease, and scientists have a significant challenge in developing a noninvasive treatment for the treatment of epilepsy. The goal is to provide novel ideas for improving existing and future anti-epileptic medications. The injection of nano treatment via the nose to the brain is being considered as a possible seizure control method. Various nasal medicine nanoformulations have the potential to cure epilepsy. Investigations with a variety of nose-to-brain dosing methods for epilepsy treatment have yielded promising results. After examining global literature on nanotechnology and studies, the authors propose nasal administration with nanoformulations as a means to successfully treat epilepsy. The goal of this review is to look at the innovative applicatio of nanomedicine for epilepsy treatment via nose-to-brain transfer, with a focus on the use of nanoparticles for load medicines. When nanotechnology is combined with the nose to brain approach, treatment efficacy can be improved through site specific delivery. Furthermore, this technique of administration decreases adverse effects and patient noncompliance encountered with more traditional procedures.