-
1.
Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics.
Zare, M, Pemmada, R, Madhavan, M, Shailaja, A, Ramakrishna, S, Kandiyil, SP, Donahue, JM, Thomas, V
Pharmaceutics. 2022;(8)
Abstract
Globally, cancer is amongst the most deadly diseases due to the low efficiency of the conventional and obsolete chemotherapeutic methodologies and their many downsides. The poor aqueous solubility of most anticancer medications and their low biocompatibility make them ineligible candidates for the design of delivery systems. A significant drawback associated with chemotherapy is that there are no advanced solutions to multidrug resistance, which poses a major obstacle in cancer management. Since RNA interference (RNAi) can repress the expression of genes, it is viewed as a novel tool for advanced drug delivery. this is being explored as a promising drug targeting strategy for the treatment of multiple diseases, including cancer. However, there are many obstructions that hinder the clinical uses of siRNA drugs due to their low permeation into cells, off-target impacts, and possible unwanted immune responses under physiological circumstances. Thus, in this article, we review the design measures for siRNA conveyance frameworks and potential siRNA and miRNA drug delivery systems for malignant growth treatment, including the use of liposomes, dendrimers, and micelle-based nanovectors and functional polymer-drug delivery systems. This article sums up the advancements and challenges in the use of nanocarriers for siRNA delivery and remarkably centers around the most critical modification strategies for nanocarriers to build multifunctional siRNA and miRNA delivery vectors. In short, we hope this review will throw light on the dark areas of RNA interference, which will further open novel research arenas in the development of RNAi drugs for cancer.
-
2.
Guidelines for Perioperative Care in Elective Abdominal and Pelvic Surgery at Primary and Secondary Hospitals in Low-Middle-Income Countries (LMIC's): Enhanced Recovery After Surgery (ERAS) Society Recommendation.
Oodit, R, Biccard, BM, Panieri, E, Alvarez, AO, Sioson, MRS, Maswime, S, Thomas, V, Kluyts, HL, Peden, CJ, de Boer, HD, et al
World journal of surgery. 2022;(8):1826-1843
-
-
Free full text
-
Abstract
BACKGROUND This is the first Enhanced Recovery After Surgery (ERAS®) Society guideline for primary and secondary hospitals in low-middle-income countries (LMIC's) for elective abdominal and gynecologic care. METHODS The ERAS LMIC Guidelines group was established by the ERAS® Society in collaboration with different representatives of perioperative care from LMIC's. The group consisted of seven members from the ERAS® Society and eight members from LMIC's. An updated systematic literature search and evaluation of evidence from previous ERAS® guidelines was performed by the leading authors of the Colorectal (2018) and Gynecologic (2019) surgery guidelines (Gustafsson et al in World J Surg 43:6592-695, Nelson et al in Int J Gynecol Cancer 29(4):651-668). Meta-analyses randomized controlled trials (RCTs), prospective and retrospective cohort studies from both HIC's and LMIC's were considered for each perioperative item. The members in the LMIC group then applied the current evidence and adapted the recommendations for each intervention as well as identifying possible new items relevant to LMIC's. The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE) methodology was used to determine the quality of the published evidence. The strength of the recommendations was based on importance of the problem, quality of evidence, balance between desirable and undesirable effects, acceptability to key stakeholders, cost of implementation and specifically the feasibility of implementing in LMIC's and determined through discussions and consensus. RESULTS In addition to previously described ERAS® Society interventions, the following items were included, revised or discussed: the Surgical Safety Checklist (SSC), preoperative routine human immunodeficiency virus (HIV) testing in countries with a high prevalence of HIV/AIDS (CD4 and viral load for those patients that are HIV positive), delirium screening and prevention, COVID 19 screening, VTE prophylaxis, immuno-nutrition, prehabilitation, minimally invasive surgery (MIS) and a standardized postoperative monitoring guideline. CONCLUSIONS These guidelines are seen as a starting point to address the urgent need to improve perioperative care and to effect data-driven, evidence-based care in LMIC's.
-
3.
Addressing Anxiety and Stress for Healthier Eating in Teens (ASSET): A Pilot Randomized Controlled Trial Protocol for Reducing Anxiety, Disinhibited Eating, Excess Weight Gain, and Cardiometabolic Risk in Adolescent Girls.
Repke, HE, Gulley, LD, Rice, AJ, Gallagher-Teske, JH, Markos, B, Sanchez, N, Bristol, M, Haynes, H, Lavender, JM, Higgins Neyland, MK, et al
Nutrients. 2022;(20)
Abstract
(1) Background: Standard-of-care lifestyle interventions show insufficient effectiveness for the prevention and treatment of excess weight and its associated cardiometabolic health concerns in adolescents, necessitating more targeted preventative approaches. Anxiety symptoms are common among adolescents, especially girls at risk for excess weight gain, and have been implicated in the onset and maintenance of disinhibited eating. Thus, decreasing elevated anxiety in this subset of adolescent girls may offer a targeted approach to mitigating disinhibited eating and excess weight gain to prevent future cardiometabolic health problems. (2) Methods: The current paper describes the protocol for a multisite pilot and feasibility randomized controlled trial of group cognitive behavioral therapy (CBT) and group interpersonal psychotherapy (IPT) in N = 40 adolescent girls (age 12-17 years) with elevated anxiety symptoms and body mass index (BMI; kg/m2) ≥ 75th percentile for age/sex. (3) Results: Primary outcomes are multisite feasibility of recruitment, protocol procedures, and data collection, intervention fidelity, retention at follow-ups, and acceptability of interventions and study participation. (4) Conclusions: Findings will inform the protocol for a future fully-powered multisite randomized controlled trial to compare CBT and IPT efficacy for reducing excess weight gain and preventing adverse cardiometabolic trajectories, as well as to evaluate theoretically-informed treatment moderators and mediators.
-
4.
Nanoscience and quantum science-led biocidal and antiviral strategies.
Zare, M, Thomas, V, Ramakrishna, S
Journal of materials chemistry. B. 2021;(36):7328-7346
Abstract
The severe acute respiratory syndrome coronavirus (SARS-CoV-2) caused the COVID-19 pandemic. According to the World Health Organization, this pandemic continues to be a serious threat to public health due to the worldwide spread of variants and their higher rate of transmissibility. A range of measures are necessary to slow the pandemic and save lives, which include constant evaluation and the careful adjustment of public-health responses augmented by medical treatments, vaccines and protective gear. It is hypothesized that nanostructured particulates underpinned by nanoscience and quantum science yield high-performing antiviral strategies, which can be applied in preventive, diagnostic, and therapeutic applications such as face masks, respirators, COVID test kits, vaccines, and drugs. This review is aimed at providing comprehensive and cohesive perspectives on various nanostructures that are suited to intensifying and amplifying the effectiveness of antiviral strategies. Growing scientific literature over the past eighteen months indicates that quantum dots, iron oxide, silicon oxide, polymeric and metallic nanoparticles have been employed in COVID-19 diagnostic assays, vaccines, and personal protective equipment (PPE). Quantum dots have displayed their suitability as more sensitive imaging probes in diagnostics and prognostics, and as controlled drug-release carriers that target the virus. Nanoscience and quantum science have assisted the design of advanced vaccine delivery since nanostructured materials are suited for antigen delivery, as mimics of viral structures and as adjuvants. Furthermore, the quantum science- and nanoscience-supported tailored functionalization of nanostructured materials offers insight and pathways to deal with future pandemics. This review seeks to illustrate several examples, and to explain the underpinning quantum science and nanoscience phenomena, which include wave functions, electrostatic interactions, van der Waals forces, thermal and electrodynamic fluctuations, dispersion forces, local field-enhancement effects, and the generation of reactive oxygen species (ROS). This review discusses how nanostructured materials are helpful in the detection, prevention, and treatment of the SARS-CoV-2 infection, other known viral infection diseases, and future pandemics.
-
5.
Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study.
Price, DB, Thomas, V, Richard Dekhuijzen, PN, Bosnic-Anticevich, S, Roche, N, Lavorini, F, Raju, P, Freeman, D, Nicholls, C, Small, IR, et al
BMC pulmonary medicine. 2018;(1):107
Abstract
BACKGROUND Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists. METHODS In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients. RESULTS Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05-6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80-1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09-0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25-3.54]). CONCLUSIONS In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler. TRIAL REGISTRATION EudraCT 2013-004630-14 (registration date 23 January 2014); NCT02570425 .
-
6.
The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study.
Jones, R, Martin, J, Thomas, V, Skinner, D, Marshall, J, Stagno d'Alcontres, M, Price, D
International journal of chronic obstructive pulmonary disease. 2017;:2445-2454
Abstract
Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 μg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 μg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 μg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.
-
7.
Temporal latency between pelvic floor trauma and presentation for prolapse surgery: a retrospective observational study.
Thomas, V, Shek, KL, Guzmán Rojas, R, Dietz, HP
International urogynecology journal. 2015;(8):1185-9
Abstract
INTRODUCTION AND HYPOTHESIS Levator avulsion is an etiological factor for female pelvic organ prolapse (POP) and generally occurs during a first vaginal birth. However, most women with POP present decades later. This study aimed to estimate latency between pelvic floor trauma and presentation for POP surgery. METHODS This was a retrospective observational study in a tertiary urogynecological unit to which 354 patients presented for evaluation prior to prolapse surgery between June 2011 and December 2012. All underwent an interview, clinical assessment [International Continence Society Pelvic Organ Prolapse Quantification score (ICS POPQ) and 4D translabial ultrasound (US). Postprocessing analysis of US volumes was blinded against clinical data. The main outcome measure was temporal latency between first vaginal birth and prolapse presentation in women with levator avulsion. RESULTS Three hundred and fifty-four patients presented with symptoms of prolapse, of whom 115 (32 %) were found to have an avulsion of the levator ani muscle. Of these, 30 patients were excluded due to previous prolapse surgery, leaving 85, all of whom showed significant prolapse on US and/or clinical staging. Mean latency between first vaginal delivery and presentation was 33.5 (3-66.3) years. There were no associations between latency and potential predictors, except for maternal age at first birth, which was associated with shorter latency (r = -0.45 , P < 0.001). There was a trend toward shorter latency after forceps delivery (P = 0.09). CONCLUSIONS Average latency between first birth and presentation for prolapse surgery in women with avulsion was 33.5 (3-66) years. Maternal age at first vaginal birth and possibly forceps delivery were associated with shorter time to presentation.
-
8.
DOCK 6: combining techniques to model RNA-small molecule complexes.
Lang, PT, Brozell, SR, Mukherjee, S, Pettersen, EF, Meng, EC, Thomas, V, Rizzo, RC, Case, DA, James, TL, Kuntz, ID
RNA (New York, N.Y.). 2009;(6):1219-30
Abstract
With an increasing interest in RNA therapeutics and for targeting RNA to treat disease, there is a need for the tools used in protein-based drug design, particularly DOCKing algorithms, to be extended or adapted for nucleic acids. Here, we have compiled a test set of RNA-ligand complexes to validate the ability of the DOCK suite of programs to successfully recreate experimentally determined binding poses. With the optimized parameters and a minimal scoring function, 70% of the test set with less than seven rotatable ligand bonds and 26% of the test set with less than 13 rotatable bonds can be successfully recreated within 2 A heavy-atom RMSD. When DOCKed conformations are rescored with the implicit solvent models AMBER generalized Born with solvent-accessible surface area (GB/SA) and Poisson-Boltzmann with solvent-accessible surface area (PB/SA) in combination with explicit water molecules and sodium counterions, the success rate increases to 80% with PB/SA for less than seven rotatable bonds and 58% with AMBER GB/SA and 47% with PB/SA for less than 13 rotatable bonds. These results indicate that DOCK can indeed be useful for structure-based drug design aimed at RNA. Our studies also suggest that RNA-directed ligands often differ from typical protein-ligand complexes in their electrostatic properties, but these differences can be accommodated through the choice of potential function. In addition, in the course of the study, we explore a variety of newly added DOCK functions, demonstrating the ease with which new functions can be added to address new scientific questions.
-
9.
Vitamin D receptor gene polymorphisms and breast cancer risk.
Guy, M, Lowe, LC, Bretherton-Watt, D, Mansi, JL, Peckitt, C, Bliss, J, Wilson, RG, Thomas, V, Colston, KW
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;(16):5472-81
Abstract
PURPOSE The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The actions of 1,25-dihydroxyvitamin D3 are mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a United Kingdom Caucasian population. EXPERIMENTAL DESIGN In a retrospective case-control study, female breast cancer patients (n = 398) and control women (n = 427) were recruited, and three VDR polymorphisms were determined. RESULTS The 3' VDR polymorphisms BsmI and variable-length poly(adenylate) sequence were both significantly associated with breast cancer risk; odds ratios (adjusted for age menopausal status and hormone replacement therapy usage) for bb genotype versus BB genotype = 1.92 (95% confidence interval, 1.20-3.10; P < 0.01) and for LL versus SS = 1.94 (95% confidence interval, 1.20-3.14; P < 0.01). A 5' VDR gene variant, FokI, was not associated with breast cancer risk when analyzed in isolation (P > 0.05). However, FokI did modulate the increased risk associated with the bb/LL genotype such that possession of one or more F alleles together with the bb/LL genotype augmented breast cancer risk. Furthermore, the highest proportion of bb and FFLL/FfLL genotypes occurred in women with metastatic breast cancer. CONCLUSIONS VDR polymorphisms are associated with breast cancer risk and may be associated with disease progression. Additional investigations into how different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments.
-
10.
The comprehensiveness care of sickle cell disease.
Okpala, I, Thomas, V, Westerdale, N, Jegede, T, Raj, K, Daley, S, Costello-Binger, H, Mullen, J, Rochester-Peart, C, Helps, S, et al
European journal of haematology. 2002;(3):157-62
Abstract
Millions of people across the world have sickle cell disease (SCD). Although the true prevalence of SCD in Europe is not certain, London (UK) alone had an estimated 9000 people with the disorder in 1997. People affected by SCD are best managed by a multidisciplinary team of professionals who deliver comprehensive care: a model of healthcare based on interaction of medical and non-medical services with the affected persons. The components of comprehensive care include patient/parent information, genetic counselling, social services, prevention of infections, dietary advice and supplementation, psychotherapy, renal and other specialist medical care, maternal and child health, orthopaedic and general surgery, pain control, physiotherapy, dental and eye care, drug dependency services and specialist sickle cell nursing. The traditional role of haematologists remains to co-ordinate overall management and liase with other specialities as necessary. Co-operation from the affected persons is indispensable to the delivery of comprehensive care. Working in partnership with the hospital or community health service administration and voluntary agencies enhances the success of the multidisciplinary team. Holistic care improves the quality of life of people affected by SCD, and reduces the number as well as length of hospital admissions. Disease-related morbidity is reduced by early detection and treatment of chronic complications. Comprehensive care promotes awareness of SCD among affected persons who are encouraged to take greater control of their own lives, and achieves better patient management than the solo efforts of any single group of professionals. This cost-effective model of care is an option for taking haemoglobinopathy services forward in the new millennium.