Self-assembling peptides for managing white spot lesions: a systematic review and meta-analysis.

PURPOSE: The primary objective of the review was to assess the effectiveness of self-assembling P11-4 peptide (SAP) with or without any fluoride agents (FA) in remineralization of the White spot lesions (WSLs)/incipient carious lesions (ICLs) compared to other enamel remineralizing agents/non-intervention/placebo. METHODS: Human RCTs published during the period from 1st January 2000-30th June 2021 were searched in the electronic bibliographic databases and scanning reference lists of articles from PubMed, Google Scholar, and The Cochrane Central Register of Controlled Trials. The Risk-of-Bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) tool for all included studies. The statistical heterogeneity between studies was assessed by the Cochrane Q test and I2 test. A random-effects model was used considering the variations in true effects size between the included studies. The quality of the evidence for remineralizing effectiveness of SAP/SAP + FA was done using the GRADEpro GDT software which employs GRADE. RESULTS: Four out of eight included trials were assessed to have "high risk" of bias. Mean difference for Laser fluorescence outcome assessment method (SAP v/s FA) was - 4.89 (95% CI: - 17.35 to 7.57; p = 0. 44; I2 = 89%). The combined risk ratio observed through Nyvad criteria (SAP v/s FA) was 0.12 (95% CI: 0.01-1.59; p = 0.11; I2 = 71%). Mean difference for Laser fluorescence outcome assessment method (SAP + FA v/s FA) was - 11.52 (95% CI: - 14.43 to - 8.61; p = < 0.001;I2 = 0%). The combined risk ratio for ICDAS outcome assessment method (SAP + FA v/s FA) was 0.27 (95% CI: 0.03-2.84; p = 0.15; I2 = 53%). CONCLUSION: Considering the results observed from the included trials we are uncertain whether SAP/SAP + FA increases/decreases the remineralizing/regeneration of WSLs/ICLs.

En Plaque Meningiomas: A Narrative Review.

Background En plaque meningiomas are a rare subtype of meningiomas that are frequently encountered in the spheno-orbital region. Characterized by a hyperostotic and dural invasive architecture, these tumors present unique diagnostic and treatment considerations. Objective The authors conduct a narrative literature review of clinical reports of en plaque meningiomas to summarize the epidemiology, clinical presentation, diagnostic criteria, and treatment considerations in treating en plaque meningiomas. Additionally, the authors present a case from their own experience to illustrate its complexity and unique features. Methods A literature search was conducted using the MEDLINE database using the following terminology in various combinations: meningioma , meningeal neoplasms, en plaque , skull base , spheno-orbital, and sphenoid wing . Only literature published in English between 1938 and 2018 was reviewed. All case series were specifically reviewed for sufficient data on treatment outcomes, and all literature was analyzed for reports of misdiagnosed cases. Conclusion En plaque meningiomas may present with a variety of symptoms according to their location and degree of bone invasion, requiring a careful diagnostic and treatment approach. While early and aggressive surgical resection is generally accepted as the optimal goal of treatment, these lesions require an individualized approach, with further investigation needed regarding the role of new therapies.

Submucosal injection of dexamethasone and methylprednisolone for the control of postoperative sequelae after third molar surgery: randomized controlled trial.

Pain, swelling, and trismus are known sequelae of third molar surgery that can significantly affect the individual's quality of life (QOL). These should be minimized to improve QOL. The purpose of this study was to compare the effects of the preoperative submucosal administration of equivalent doses of two commonly used steroids on these postoperative sequelae. A randomized controlled clinical trial was conducted involving 60 subjects requiring the removal of impacted mandibular third molars. Extraction cases with a similar difficulty index were included. The participants were allocated randomly to three groups: the placebo group received normal saline injection (control), while the 8mg dexamethasone group and 40mg methylprednisolone group received submucosal injections of these steroids preoperatively. Each participant was assessed for postoperative pain, swelling, and trismus, along with a subjective assessment of QOL through a structured questionnaire. The participants administered dexamethasone showed significant reductions in pain and trismus compared to the control group (P<0.05). Submucosal injection of dexamethasone was found to be superior to methylprednisolone only in terms of the reduction in swelling. QOL was minimally affected in patients administered dexamethasone as compared to methylprednisolone and control subjects. The preoperative submucosal use of steroids can be considered an effective, safe, and simple therapeutic strategy to reduce swelling, pain, and trismus after the surgical removal of impacted mandibular third molars.

Pial Arteriovenous Fistula and Capillary Malformation-Arteriovenous Malformation Associated with RASA1 Mutation: 2 Pediatric Cases with Successful Surgical Management.

We present case reports of 2 pediatric patients who were both found to have pial arteriovenous fistulas (AVFs) with subsequent genetic analysis revealing mutations in the RASA1 gene. Considering their family history of distinct cutaneous lesions, these mutations were likely inherited as opposed to de novo mutations. Patient 1 had large capillary malformations on the left side of the face and neck, associated with macrocephaly, and presented at the age of 32 months with speech delay, right-sided weakness, and focal seizures involving the right side of the body. Patient 2 presented with proptosis at the age of 9 months, but was otherwise neurologically intact. Given the chance for definitive single-stage control of vascular shunt (obviating chances for radiation exposure with endovascular treatment) and surgically accessible location of these intracranial lesions, both patients were treated with surgery with excellent clinical and radiological outcome. In general, given the high mortality secondary to severe congestive heart failure when treated conservatively, the goal of treatment in cortical AVF in young children, even when asymptomatic, is rapid control of the shunt. This was achieved successfully in our cases - both patients experienced significant symptomatic improvement following surgery and remained neurologically stable in the subsequent follow-up visits.

Use of a surgical rehearsal platform and improvement in aneurysm clipping measures: results of a prospective, randomized trial.

OBJECTIVE The field of neurosurgery is constantly undergoing improvements and advances, both in technique and technology. Cerebrovascular neurosurgery is no exception, with endovascular treatments changing the treatment paradigm. Clipping of aneurysms is still necessary, however, and advances are still being made to improve patient outcomes within the microsurgical treatment of aneurysms. Surgical rehearsal platforms are surgical simulators that offer the opportunity to rehearse a procedure prior to entering the operative suite. This study is designed to determine whether use of a surgical rehearsal platform in aneurysm surgery is helpful in decreasing aneurysm dissection time and clip manipulation of the aneurysm. METHODS The authors conducted a blinded, prospective, randomized study comparing key effort and time variables in aneurysm clip ligation surgery with and without preoperative use of the SuRgical Planner (SRP) surgical rehearsal platform. Initially, 40 patients were randomly assigned to either of two groups: one in which surgery was performed after use of the SRP (SRP group) and one in which surgery was performed without use of the SRP (control group). All operations were videotaped. After exclusion of 6 patients from the SRP group and 9 from the control group, a total of 25 surgical cases were analyzed by a reviewer blinded to group assignment. The videos were analyzed for total microsurgical time, number of clips used, and number of clip placement attempts. Means and standard deviations (SDs) were calculated and compared between groups. RESULTS The mean (± SD) amount of operative time per clip used was 920 ± 770 seconds in the SRP group and 1294 ± 678 seconds in the control group (p = 0.05). In addition, the mean values for the number of clip attempts, total operative time, ratio of clip attempts to clips used, and time per clip attempt were all lower in the SRP group, although the between-group differences were not statistically significant. CONCLUSIONS Preoperative rehearsal with SRP increased efficiency and safety in aneurysm microsurgery as demonstrated by the statistically significant improvement in time per clip used. Although the rest of the outcomes did not demonstrate statistically significant between-group differences, the fact that the SRP group showed improvement in mean values for all measures studied suggests that preoperative rehearsal may increase the efficiency and safety of aneurysm microsurgery. Future studies aimed at improving patient outcome and safety during surgical clipping of aneurysms will be needed to keep pace with the quickly advancing endovascular field.

Predicting Postoperative C5 Palsy Using Preoperative Spinal Cord Rotation.

The development of C5 nerve palsy after cervical decompression surgery has been well documented. The goal of this study was to determine whether preoperative spinal cord rotation could be used as a predictor of C5 palsy in patients who underwent posterior cervical decompression at C4-C6. The authors reviewed the records of 72 patients who had posterior decompression and 77 patients who had anterior decompression. With the patients undergoing anterior decompression used as a control group, magnetic resonance imaging scans were analyzed for area of the spinal cord, anterior-posterior diameter, and cord rotation relative to the vertebral body. The rate of C5 palsy was 7.3%. Average degrees of rotation were 3.83°±2.47° and 3.45°±2.23° in the anterior and posterior groups, respectively. A statistically significant association was detected between degree of rotation and C5 palsy. Point-biserial correlations were 0.58 (P<.001) and 0.60 (P<.001) in the anterior and posterior groups, respectively. With a diagnostic cutoff of 6°, the sensitivity and specificity of identifying patients with C5 palsy in the posterior group were 0.67 (95% confidence interval, 0.24-0.94) and 0.95 (95% confidence interval, 0.86-0.98), respectively. The results suggested that preoperative spinal cord rotation may be a valid predictor of C5 nerve palsy after posterior cervical decompression. With mild rotation defined as less than 6°, moderate rotation as 6° to 10°, and severe rotation as greater than 10°, the prevalence of C5 palsy in the posterior group was 2 of 65 for mild rotation, 3 of 6 for moderate rotation, and 1 of 1 for severe rotation.

AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder.

BACKGROUND AND PURPOSE: AE9C90CB (N- [(1R, 5S, 6R)-3-azabicyclo [3.1.0] hex-6-ylmethyl]-2-hydroxy-N-methyl-2, 2-diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe the in vitro and in vivo profiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin). EXPERIMENTAL APPROACH: Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity. KEY RESULTS: In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M(3) muscarinic receptors with pKi of 9.90 +/- 0.11 and was 20-fold more selective for M(3) than for M(2) muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pK(B), 9.13 +/- 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin. CONCLUSIONS AND IMPLICATIONS: We have identified AE9C90CB, a compound exhibiting moderate selectivity for M(3) over M(2) receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs.

Neuromedin U: physiology, pharmacology and therapeutic potential.

Neuromedin U (NmU), a multifunctional neuropeptide, belongs to a family of neuropeptides, the neuromedins. It is ubiquitously distributed with highest levels found in the gastrointestinal tract and pituitary. The conservation of structural elements of NmU across species, the widespread distribution of NmU and its receptors throughout the body point to a fundamental role in key physiological processes. Two G protein coupled receptors for NmU have been cloned NmU R1 and NmU R2. NmU R1 is expressed pre-dominantly in the periphery especially the gastrointestinal tract whereas NmU R2 is expressed pre-dominantly in the central nervous system. Current evidence suggests a role of NmU in pain, in regulation of feeding and energy homeostasis, stress, cancer, immune mediated inflammatory diseases like asthma, inflammatory diseases, maintaining the biological clock, in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract, and in the control of blood flow and blood pressure. With the development of drugs selectively acting on receptors and knockout animal models, exact pathophysiological roles of NmU will become clearer.

Bone marrow-derived mesenchymal stems cells and cardiac repair.

UNLABELLED: Cardiovascular disease continues to be the most prevalent cause of morbidity and mortality worldwide. While pharmaceutical agents and interventional strategies have contributed greatly to therapy, new and superior treatment modalities are urgently needed given the overall disease burden. In this regard, therapy with adult stem cells has shown great promise toward inducing infarct repair and restoring cardiac function. Because of their inherent multipotent nature and the ability to secrete a multitude of growth factors and cytokines, adult bone marrow-derived mesenchymal stem cells (BMMSCs) have been utilized for cardiac repair with encouraging RESULTS: Numerous animal studies have established the feasibility and efficacy of this approach with further definition of molecular pathways underlying the reparative benefits. Early clinical trials have also confirmed the safety and efficacy of BMMSC therapy in patients with acute MI as well as ischemic heart failure. Following a brief historical perspective and description of the biological features of BMMSCs, this review will focus on the evidence from preclinical and clinical studies of cardiac repair with BMMSCs, the underlying mechanisms, and various cellular modification strategies aimed at enhancing the outcomes.

A novel recombinant multiepitope protein as a hepatitis C diagnostic intermediate of high sensitivity and specificity.

A novel recombinant multiepitope protein has been designed that consists of six linear, immunodominant, and phylogenetically conserved epitopes from hepatitis C virus. Five of these antigens (core, NS3, NS4I, NS4II, and NS5) are being used in many of the third-generation kits while sixth epitope (core3g) is an additional sequence from a newly identified Indian isolate. The genes for these epitopes have been joined together to code for a single multiepitope protein that has been evaluated for its diagnostic potential for the detection of anti-HCV antibodies in human plasma. Two separate synthetic genes have been designed, both encoding the same six epitopes in a single open reading frame along with spacers having additional amino acids to function as flexible (r-HCV-F-MEP) or rigid (r-HCV-R-MEP) linkers. High-level expression of hepatitis C multiepitope protein in Escherichia coli has been achieved. The protein has been purified using a single affinity step yielding >25 mg pure protein/liter culture and used as the coating antigen in anti-HCV EIA. The use of this multiepitope protein eliminates the requirement for multiple diagnostic intermediates for the development of anti-HCV diagnostic kit. The sensitivity and specificity of the HCV multiepitope protein was evaluated by Boston Biomedica Worldwide Performance Panels, HCV Seroconversion Panels and Viral Co-infection Panels, and was found to be comparable with commercially available anti-HCV EIA kits. This analysis indicated its unequivocal performance as capture antigen in anti-HCV EIA. The high epitope density, careful choice of epitopes and use of E. coli system for expression, coupled with simple purification protocol provides the potential for the development of an inexpensive diagnostic test with high degree of sensitivity and specificity.

Contemporary approach to ablation of paroxysmal atrial fibrillation.

Pulmonary veins have been shown to play an important role in the initiation and maintenance of paroxysmal atrial fibrillation. Seg-mental ostial isolation of the pulmonary veins results in cure in about 2/3 of the patients. This approach does not address non-pulmonary venous triggers of atrial fibrillation or the importance of the left atrium itself. Left atrial circumferential ablation has also been shown to be efficacious in patients with paroxysmal atrial fibrillation. This approach seems to address not only the various triggers of atrial fibrillation but also the left atrial substrate. Recently, a randomized study compared the 2 strategies and showed that left atrial ablation is superior to segmental ostial isolation. This review will highlight the anatomy and electrophysiology of the pulmonary veins, and the possible mechanisms by which they initiate and maintain paroxysms of atrial fibrillation. Segmental ostial isolation of the pulmonary veins and left atrial ablation will be compared as well.

Role of self-assembled gold nanodots in improving the electrical and optical characteristics of zinc oxide films.

We have studied the effect of embedding nanocrystalline Au particles on the electrical and optical characteristics of ZnO films. Au-embedded epitaxial ZnO films were deposited on (0001) sapphire substrates with a pulsed laser deposition technique. The crystalline quality of both the ZnO matrix and Au nanoparticles was investigated by X-ray diffraction and transmission electron microscopy. Composite films were characterized by photoluminescence, optical absorption, and low-temperature electrical resistivity measurements. Photoluminescence spectra of theses films showed a sharp excitonic peak at 3.22 +/- 0.05 eV without any signature of green band emission. Electrical resistivity measurements showed these films to be highly conducting, with a room-temperature resistivity of 3.4 +/- 0.2 m omega-cm.

Differential regulation of striatal G protein levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration in C57 BL/6 mice.

The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to produce a severe Parkinsonian state in both humans and animals. Unlike idiopathic Parkinson's disease, however, most MPTP models show some degree of behavioral recovery with time. Here we report that stimulatory G proteins are differentially regulated in the striatum of C57 BL/6 mice following systemic MPTP administration. As measured by Western blotting, the striatal stimulatory G proteins Gs and Golf were reduced by 20% and 25% at 10 days following cessation of MPTP treatment, despite a significant impairment in striatal dopamine levels (<90% reduction). Conversely, Gs and Golf levels were upregulated by 15% and 30% at 10 months following MPTP withdrawal. No change was observed in striatal inhibitory G proteins or any cortical G protein at any time post-treatment. These results suggest that G protein upregulation may play a role in mediating behavioral recovery following MPTP administration.

Cardiac risk assessment for noncardiac surgery: current concepts.

Strategies for perioperative risk assessment in patients undergoing noncardiac surgery vary among physicians and are aimed to estimate the risk and minimize complications. We propose simplistic guidelines for assessing and modifying risk for patients undergoing a wide variety of procedures.

Endothelin-receptor antagonists: current and future perspectives.

Despite much effort over recent years to design and develop endothelin-receptor antagonists, these compounds are far from becoming new drug entities. This article will review preclinical data on select endothelin-receptor antagonists as well as clinical data on bosentan, the only molecule currently in Phase III clinical trials. Though efficacious, bosentan is less potent than the angiotensin converting enzyme (ACE) inhibitor, enalapril, in patients with hypertension. We will therefore discuss the possible reason(s) for this low potency, the consequences thereof, and a few therapeutic areas where endothelin-receptor antagonists could find better use.

Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)

3(R)-[(2(S)-Pyrrolidinyl-carbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF-1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.

Development of neurogenic pulmonary edema at different grades of intracranial pressure in cats.

Development of neurogenic pulmonary edema (NPE) subsequent to increased intracranial pressure (ICP) was evaluated in an experimental model in cats. Experiments were conducted in chloralose anaesthetised animals, either on spontaneous respiration or on intermittent positive pressure ventilation. Hemodynamic parameters i.e., mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. Pulmonary artery/right ventricular systolic pressure was recorded in cats on spontaneous respiration. Increase in ICP for 180 minutes caused an increase in extravascular lung water (EVLW) content in both spontaneously breathing and artificially ventilated animals. In spontaneously breathing animals EVLW to blood free dry weight ratio (EVLW/BFDW) was 3.95 +/- 0.16 and 4.96 +/- 0.16 at ICP 40 and 80 mm Hg respectively while in animals on artificial ventilation, at 40, 60, 80 and 100 mm Hg ICP, it was 3.88 +/- 0.11, 4.09 +/- 0.10, 4.50 +/- 0.13 and 5.03 +/- 0.17 respectively. These values were significantly greater (P < 0.05) as compared to that in sham operated animals (3.43 +/- 0.10). This was accompanied by rise in MAP, HR and pulmonary artery pressure. The study establishes the graded development of NPE, the severity of which is proportional to the levels of ICP.