Exosome for mRNA delivery: strategies and therapeutic applications.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study.

OBJECTIVE: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. METHODS: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. RESULTS: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. CONCLUSION: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

Clinical outcomes of maitland mobilization in patients with Myofascial Chronic Neck Pain: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Myofascial neck pain is a common musculoskeletal problem caused by presence of trigger points and local and referred pain patterns. Chronic neck pain is responsible for the involvement of joints, ligaments, fascia and connective tissue as well. The objective of this study was to assess the effect of Maitland mobilization in patients with myofascial chronic neck pain. METHODS: In this randomized, placebo treatment-controlled trial, 30 patients consecutively aged 25-45 years meeting inclusion criteria were isolated into two groups. The study group was treated with Maitland mobilization consistently for eight weeks while the control group got placebo treatment for a similar timeframe. Visual analog Scale (VAS), Neck disability index (NDI) and cervical range of motion (ROM) questionnaire was filled by patients before, intermediate and after the intervention to evaluate the severity of pain, functional ability and range of motion. RESULTS: Following eight weeks of treatment, when compared the post treatment effects of both groups, the significance value for VAS was 0.008, for NDI p=0.030, for Flexion p=0.573, for extension p=0.001, for right rotation p<0.001, for left rotation p=0.002, for right and left side bending p<0.001. CONCLUSION: The study concluded that Maitland mobilization grades (I-IV) are effective in reducing pain and improving functional level of NDI scale and the ranges of cervical spine in patients with myofascial chronic neck pain.

Antioxidant and alpha amylase inhibitory activities of Fumaria officinalis and its antidiabetic potential against alloxan induced diabetes.

Fumaria officinalis belongs to family papaveraceae and is traditionally used to treat hypertension, hepatitis and diabetes. The current study was conducted to evaluate in vitro and in vivo antidiabetic activity of Fumaria officinalis. Aerial parts of the plant were sequentially extracted with n-hexane, chloroform, methanol and water. Phytochemical analysis was carried out on all extracts. Antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) inhibition method. In vitro alpha-amylase inhibitory activity was performed on all extracts by using dinitrosalicylic acid. Effect of aqueous and methanolic extracts of F. officinalis on blood glucose was evaluated in normo-glycaemic rats and alloxan induced diabetic rats. Glimepiride 0.2 mg/kg was used as standard therapy in diabetic rats. Results showed that methanolic extract exhibited the maximum percentage inhibition of DPPH (86.30%) and alpha-amylase inhibition (94.01%) at 500 µg/ml and 16 mg/ml concentration respectively. Administration in normo-glycaemic rats did not show any significant decrease in blood glucose level at 500 and 750 mg/kg dosage. Aqueous and methanolic extracts exhibited a significant hypoglycaemic effect (p˂0.05) at all doses. A significant increase in the body weight and an improvement in liver and kidney function tests of diabetic rats were observed. These extracts also reduced the damage to the cells of glomeruli, interstitial inflammation, necrosis of tubular cells and thrombosis in the kidney, the enlargement of sinusoids and steatosis in the liver of diabetic rats. This study concludes that F. officinalis may have antidiabetic potential possibly due to its antioxidant and alpha-amylase inhibitory activities.

DEVELOPMENT OF COMPRESSED COATED POLYPILL WITH MUCOADHESIVE CORE COMPRISING OF ATORVASTATIN/CLOPIDOGREL/ASPIRIN USING COMPRESSION COATING TECHNIQUE.

The study was conducted to formulate and assess a novel polypill comprising of atorvastatin calci- um (ATVC), clopidogrel bisulfate (CLB) and aspirin (ASP) which, after in vivo correlation, can be intended for use in hyperlipidemic chronic heart disease patients. Polypill was made by the compression coating technique (CCT) with multiple active ingredients along with different concentrations of mucoadhesive and sustained release polymers, i.e., Carbopol 934 (CAB), Methocel k15 (MTH) and sodium carboxymethyl cellulose (NaCMC). The effect of different concentration of polymers on physical properties, wash off time, mucoadhe- sion strength, swelling behavior, surface pH and drug release kinetics were investigated. In vitro drug release studies showed that combination of CAB-NaCMC (1 : 1) retarded drug release up to 96.7 ± 1.15%, while com- bination of CAB-MTH and MTH-NaCMC retarded drug release up to 81.9 ± 1.5% and 101.4 ± 1.3%, respec- tively, at the same polymer concentration. Core enteric coated tablet of ATVC (K 11) was compressed over with CLB and ASP granules with the help of CCT and produced the desired results with zero order release rate thus indicating successful formulation of proposed polypill.

EFFECT OF HYDROPHILIC AND HYDROPHOBIC POLYMER ON IN VITRO DISSOLUTION AND PERMEATION OF BISOPROLOL FUMARATE THROUGH TRANSDERMAL PATCH.

A matrix transdermal patch of bisoprolol fumarate was formulated with different concentrations of Eudragit RS 100 and Methocel E5 with PEG 400 as plasticizer by solvent evaporation technique. Tween 80 was added to the optimized patch to evaluate the effect of permeation enhancer at different concentration through the excised rabbit's skin. The patches were analyzed for weight variation, drug content, swelling index, erosion studies, moisture content, moisture uptake, water vapor transmission rate (WVTR) and water vapor permeability (WVP). In vitro dissolution test was carried out in USP dissolution apparatus V to select the optimized formulation. In vitr skin permeation studies were done in Franz diffusion cell using rabbit skin as a model membrane. The cumulative drug release and flux were determined to compare the result of test patches with a control patch. The greatest enhancement ratio (ER) was obtained in F03-PE with 30% Tween 80. F03-PE seemed to follow zero order kinetics with super case II mechanism of drug release. Statistical ANOVA suggested that there was a significant difference in formulations, steady flux and cumulative permeation rate at different Tween 80 concentrations.

ANTIOXIDANT ACTIVITY OF PISTACIA KHINJUK SUPPORTED BY PHYTOCHEMICAL INVESTIGATION.

Pistacia khinjuk is one of the fifteen known species of Pistacia belonging to Anacardiaceae family. Keeping in view the possible therapeutic utility of this genus and the lack of literature on this plant, this study involves phytochemical investigation of P. khinjuk and its antioxidant activity. The phytochemical investigation was conducted on crude methanolic extract and its fractions namely, n-hexane, chloroform, n-butanol, ethyl acetate and aqueous. Total phenolic contents and flavonoids were also determined by phosphomolybdenum and ferric thiocyanate method in crude extract and its fractions. The results of phytochemical investigation indicated the presence of alkaloids, tannins, flavonoids, saponins, triterpenoids, cardiac glycosides, carbohydrates, proteins and sterols in the crude extract of P. khinjuk. Crude extract and its fractions exhibited remarkable antioxidant activity. This study showed that the crude extract and its fractions have potent antioxidant activity, among all ethyl acetate showed 1.109 ± 0.029 the highest activity. This research concluded that crude extract of P. khinjuk and its fractions contained phenolic and flavonoid compounds that show significant antioxidant activity.

EVALUATION OF ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF AQUEOUS AND ETHANOLIC EXTRACTS OF SEEDS OF BUCHANANIA LANZAN SPRENG. IN ANIMAL MODELS.

The present study was designed to evaluate the anti-inflammatory, analgesic and antipyretic activities of the aqueous and ethanolic extracts of seeds of Buchanania lanzan Spreng. Albino mice were used as experimental animals to evaluate these activities. The study was performed in three phases; Phase-I for evaluation of anti-inflammatory activity, Phase-II for antipyretic and Phase-HI for analgesic activities were evaluated. Carrageenan induced paw edema, brewer yeast induced pyrexia and acetic acid induced writhing methods were used to evaluate anti-inflammatory, antipyretic and analgesic activities, respectively. Tests were performed by dividing the animals in five groups. First group was negative control, second group was positive control, third, fourth and fifth groups were treated with 125, 250 and 500 mg/kg of extracts. respectively. The data were statistically analyzed using ANOVA where p < 0.05 were considered significant. The results suggested that seeds of Buchanania lanzan Spreng. possess anti-inflammatory, analgesic and antipyretic activity.

Frequency of neck and shoulder pain and use of adjustable computer workstation among bankers.

BACKGROUND & OBJECTIVE: Neck and shoulder are the most susceptible areas for developing musculoskeletal symptoms among computer users. The modifiable risk factors for these work related musculoskeletal disorders include physical office environment and psychosocial work related factors. Computer workstation layout had been shown to be an important physical aspect of work environment that influences the upper quadrant symptoms. Our objective was to find the frequency of neck and shoulder pain and use of adjustable computer workstation among bankers of Islamabad/Rawalpindi/Multan. METHODS: A cross sectional study was conducted and 120 participants were questioned. Purposive sampling technique was used in this study. Maastricht Upper Extremity Questionnaire (MUEQ) was remodeled and important questions were extracted from its detailed version. The tool was then validated by taking expert opinion. Frequencies and percentages were calculated for categorical variables. RESULTS: Pain in the neck during working hours was experienced by 71.67% of the respondents and 48.33% of the participants had experienced shoulder pain during working hours. Adjustable keyboards were used by 16.67% of respondents. Back care material was used by 40% bankers. Adjustable chairs were used by 95.83% of the participants. Only 3% of the bankers did not have chairs with adjustable heights. Chairs with adjustable armrests were used by 25% bankers. CONCLUSION: Neck and shoulder pain are common occurrences among bankers. Most of the components of workstations of bankers were adjustable but some of them still need attention.

Prostate Segmentation in MRI Images using Transfer Learning based Mask RCNN.

INTRODUCTION: The second highest cause of death among males is Prostate Cancer (PCa) in America. Over the globe, it's the usual case in men, and the annual PCa ratio is very surprising. Identical to other prognosis and diagnostic medical systems, deep learning-based automated recognition and detection systems (i.e., Computer Aided Detection (CAD) systems) have gained enormous attention in PCA. METHODS: These paradigms have attained promising results with a high segmentation, detection, and classification accuracy ratio. Numerous researchers claimed efficient results from deep learning-based approaches compared to other ordinary systems that utilized pathological samples. RESULTS: This research is intended to perform prostate segmentation using transfer learning-based Mask R-CNN, which is consequently helpful in prostate cancer detection. CONCLUSION: Lastly, limitations in current work, research findings, and prospects have been discussed.

Development of a Novel Self-Dissolving Microneedle-Assisted Percutaneous Delivery System of Diacerein through Solid Dispersion Gel: Solubility Enhancement, Proof of Anti-inflammatory Activity and Safety.

BACKGROUND: Diacerein, an osteoarthiritis drug, experiences slow topical permeation due to limited solubility. Additionally, it shows a laxative effect due to acid/base hydrolysis of the drug in the colon. OBJECTIVE: Diacerein solubility was improved to increase percutaneous drug delivery. METHODS: To improve saturation solubility of the drug, Diacerein was pre-treated with Polysorbate 80 aqueous solution (1% v/v) to obtain lyophilized powder after wet milling or formulated as solid dispersion using PEG 4000 by fusion method. The lyophilized Diacerein in hydroxypropyl methylcellulose (HPMC 8% w/w) and polyvinyl pyrrolidone (PVP 30% w/w) matrix, with PEG 400 as co-solvent, provided an optimized array. The solid dispersion was loaded in the CMC based gel for subsequent administration on dissolving microneedle-treated skin. RESULTS: The addition of PEG 400 increased Diacerein loading in microneedles to 390.35±4.28 µg per array. The lyophilized drug displayed amorphous characteristics in the dissolving microneedles as per XRD analysis. SEM photographs showed uniformity in the surface topology of microneedles. The needles showed rapid polymer dissolution within 5 minutes, whereas methylene-blue distribution confirmed the formation of microcavities in excised rat skin. The drug-loaded arrays showed better permeation (74.39%) and skin deposition (15.75%) after 24 hours, however, ⁓12% of Diacerein remained in the baseplate. This led to the tailoring of CMC-based gel (3% w/v) containing 0.4% solid dispersion of Diacerein. When compared to untreated skin, the gel improved permeation rate by 2.43 folds through aqueous microchannels generated by dissolving microneedle pre-treatment and allowed 98% drug permeation. The quasi-Fickian diffusion mechanism was found to drive ex vivo release kinetics, with a shorter lag time (0.88 h) and higher flux (26.65 µg/sq.cm.h). Microneedle-assisted Diacerein gel showed a positive anti-inflammatory effect in the paw edema model and reduced diarrheal episodes in comparison to the marketed oral formulation. The gel showed desired characteristics at 5°C±2°C when tested under accelerated stability conditions. CONCLUSION: The present study reports for the first time the verification of efficacy and safety to advocate the suitability of Diacerein for percutaneous delivery through dissolving microneedle-treated skin.

Assessment of formulation variables of poor water soluble diacerein for its improved loading and anti-inflammatory activity.

Dissolving microneedles have become a popular method for percutaneous administrationof drugs. However, loading poorly soluble drugs into water-based dissolving microneedles remains a challenge. In view of this, we aimed to improve Diacerein (DCN) solubility formulating dissolving microneedles. DCN microsuspension was created by high-speed homogenization with organic solvents or wet milling with Tween 80 as a stabilizer (LD1). They were analyzed for particle size and saturation solubility. Subsequently, the organic solvent-based microneedles were prepared under vacuum, whereas LD1 was mixed with HPMC (8% w/w) and PVP (30% w/w) matrix to concentrate the drug in acral fraction through centrifugation. DCN microsuspension in DMSO had the highest drug solubility with an average particle size of 6 µm, whereas LD1 had a particle size of 3.28 µm showing improved solubility. TD-3 had the highest drug loading and the least amount of drug migration into the blank baseplate. Within 5 min, these microneedles dissolved completely in an agarose-gel block. LD1 was likewise put in the baseplate to generate TD3-B. Within 24 h, 74.39% of the medication was released from TD3-B, with only a small amount remaining in the baseplate. TLC examination indicated the conversion of DCN to Rhein in the skin, whereas DSC and TGA studies revealed amorphous features. DCN microneedles showed no sign of skin irritancy but showed anti-inflammatory response on carrageenan-induced paw edema model. Microneedles remained stable during accelerated stability testing. Wet milling in the presence of a stabilizer can be an effective approach for enhancing DCN solubility for improved drug loading in dissolving microneedles. Improvement in solubility of Diacerein for subsequent loading in Dissolving Microneedle for percutaneous delivery.

Biomaterial-assisted targeted and controlled delivery of CRISPR/Cas9 for precise gene editing.

RISPR-Cas9 has exhibited enormous potential in gene therapy. It can perform genome editing with single-nucleotide precision in various types of cell and tissue, providing a powerful breakthrough technology for genome editing in therapeutic development. But the limited delivery methods pose substantial challenges pertinent to safe and effective CRISPR/Cas9 delivery, thus hindering its application. These challenges should be tackled to develop next-generation genetic therapies. Biomaterial-based drug delivery systems can overcome these issues, for example using biomaterials as carriers for CRISPR/Cas9 targeted delivery, and conditional control of its function can improve precision, furnish on-demand and transient gene editing and reduce adverse consequences such as off-target events and immunogenicity, representing a promising direction for modern precision medicine. This review describes the application status and research progress of current CRISPR/Cas9 delivery approaches, including polymeric nanoparticles, liposomes, extracellular vesicles, inorganic nanoparticles and hydrogels. The unique properties of light-controlled and small-molecule drugs for spatially and temporally controlled genome editing are also illustrated. In addition, targetable delivery vehicles for the active delivery of CRISPR systems are also discussed. The perspectives to overcome the current limitations in the CRISPR/Cas9 delivery and their bench-to-bedside translation are also highlighted.

Targeting WNT signalling pathways as new therapeutic strategies for osteoarthritis.

Osteoarthritis (OA) is a highly prevalent chronic joint disease and the leading cause of disability. Currently, no drugs are available to control joint damage or ease the associated pain. The wingless-type (WNT) signalling pathway is vital in OA progression. Excessive activation of the WNT signalling pathway is pertinent to OA progression and severity. Therefore, agonists and antagonists of the WNT pathway are considered potential drug candidates for OA treatment. For example, SM04690, a novel small molecule inhibitor of WNT signalling, has demonstrated its potential in a recent phase III clinical trial as a disease-modifying osteoarthritis drug (DMOAD). Therefore, targeting the WNT signalling pathway may be a distinctive approach to developing particular agents helpful in treating OA. This review aims to update the most recent progress in OA drug development by targeting the WNT pathway. In this, we introduce WNT pathways and their crosstalk with other signalling pathways in OA development and highlight the role of the WNT signalling pathway as a key regulator in OA development. Several articles have reviewed the Wnt pathway from different aspects. This candid review provides an introduction to WNT pathways and their crosstalk with other signalling pathways in OA development, highlighting the role of the WNT signalling pathway as a key regulator in OA development with the latest research. Particularly, we emphasise the state-of-the-art in targeting the WNT pathway as a promising therapeutic approach for OA and challenges in their development and the nanocarrier-based delivery of WNT modulators for treating OA.

Flexible Topical Hydrogel Patch Loaded with Antimicrobial Drug for Accelerated Wound Healing.

A hydrogel topical patch of neomycin was developed by using sodium alginate (SA) and hydroxyethylcellulose (HEC) as polymers. Free radical polymerization in an aqueous medium was initiated by using acrylic acid (AA) and N,N'-methylenebisacrylamide (MBA). Prepared hydrogels were characterized for pH sensitivity and sol-gel analysis. In addition, the effect of reactant contents on the developed formulation was evaluated by swelling behavior. SEM assay showed the rough structure of the hydrogel-based polymeric matrix, which directly enhances the ability to uptake fluid. FTIR spectra revealed the formation of a new polymeric network between reactant contents. TGA and DSC verified that fabricated polymeric patches were more thermodynamically stable than pure components. Gel fractions increased with increases in polymer, monomer, and cross-linker contents. The swelling study showed the pH-dependent swelling behavior of patches at pH 5.5, 6.5, and 7.4. The release pattern of the drug followed zero-order kinetics, with diffusion-controlled drug release patterns according to the Korsmeyer-Peppas (KP) model. Ex vivo studies across excised rabbit skin verified the drug retention in the skin layers. The hydrogel patch effectively healed the wounds produced on the rabbit skin, whereas the formulation showed no sign of irritation on intact skin. Therefore, neomycin hydrogel patches can be a potential candidate for controlled delivery for efficient wound healing.

The impact of tinnitus on adult cochlear implant recipients: A mixed-method approach.

BACKGROUND: Tinnitus is a common problem in patients with a cochlear implant (CI). Between 4% and 25% of CI recipients experience a moderate to severe tinnitus handicap. However, apart from handicap scores, little is known about the real-life impact tinnitus has on those with CIs. We aimed to explore the impact of tinnitus on adult CI recipients, situations impacting tinnitus, tinnitus-related difficulties and their management strategies, using an exploratory sequential mixed-method approach. METHODS: A 2-week web-based forum was conducted using Cochlear Ltd.'s online platform, Cochlear Conversation. A thematic analysis was conducted on the data from the forum discussion to develop key themes and sub-themes. To quantify themes and sub-themes identified, a survey was developed in English with face validity using cognitive interviews, then translated into French, German and Dutch and disseminated on the Cochlear Conversation platform, in six countries (Australia, France, Germany, New Zealand, the Netherlands and United Kingdom). Participants were adult CI recipients experiencing tinnitus who received a Cochlear Ltd. CI after 18 years of age. RESULTS: Four key themes were identified using thematic analysis of the discussion forum: tinnitus experience, situations impacting tinnitus, difficulties associated with tinnitus and tinnitus management. Among the 414 participants of the survey, tinnitus burden on average was a moderate problem without their sound processor and not a problem with the sound processor on. Fatigue, stress, concentration, group conversation and hearing difficulties were the most frequently reported difficulties and was reported to intensify when not wearing the sound processor. For most CI recipients, tinnitus seemed to increase when performing a hearing test, during a CI programming session, or when tired, stressed, or sick. To manage their tinnitus, participants reported turning on their sound processor and avoiding noisy environments. CONCLUSION: The qualitative analysis showed that tinnitus can affect everyday life of CI recipients in various ways and highlighted the heterogeneity in their tinnitus experiences. The survey findings extended this to show that tinnitus impact, related difficulties, and management strategies often depend on sound processor use. This exploratory sequential mixed-method study provided a better understanding of the potential benefits of sound processor use, and thus of intracochlear electrical stimulation, on the impact of tinnitus.

Feasibility of Enhancing Skin Permeability of Acyclovir through Sterile Topical Lyophilized Wafer on Self-Dissolving Microneedle-Treated Skin.

Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10-26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer-drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7-11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours' study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.

The impact of chemotherapy-induced inner ear damage on quality of life in cancer survivors: a qualitative study.

PURPOSE: This study aimed to explore the burden of inner ear damage (ototoxicity) on adults living with and beyond cancer treated with chemotherapy and  the impact on their quality of life (QoL). Furthermore, this study aimed to explore patient awareness surrounding chemotherapy-induced inner ear damage, known as ototoxicity, and assess what support they had been offered. METHODS: Participants were adults who had undergone chemotherapy, recruited from cancer clinics, charities and social media. Using semi-structured interviews and fieldnotes, an inductive thematic analysis was used to develop key themes surrounding this topic. RESULTS: Twenty participants from the UK were interviewed. Two key themes were developed from the thematic analysis, cancer-related QoL and ototoxicity-related QoL, with each one including 5 subthemes. Subthemes consisted of impact of ototoxicity, hearing, tinnitus, clinical experience, audiological assessments, and impact of treatment, cancer and chemotherapy, other toxicities, information and patient reflections. CONCLUSIONS: Ototoxicity can have a negative impact on QoL, specifically on social life and the fear of hearing loss and/or tinnitus worsening. There are opportunities for increased awareness by patients and clinicians, including improved information sources, and hearing monitoring not only for those undergoing platinum-based chemotherapy but many others surviving after treatment for cancer. IMPLICATIONS FOR CANCER SURVIVORS: Better monitoring of hearing and information about ototoxicity during chemotherapy could potentially reduce the fear of the symptoms of ototoxicity worsening. Furthermore, hearing monitoring would facilitate the detection of hearing loss at early stages of survivorship, which would facilitate earlier access to clinical interventions and longer term counselling.

A comprehensive literature search to identify existing measures assessing "concentration" as a core outcome domain for sound-based interventions for chronic subjective tinnitus in adults.

The Core Outcome Measures in Tinnitus (COMiT) initiative has recommended a minimum standard of five outcomes when designing a clinical trial to assess the efficacy of sound-based interventions. These are: ability to ignore, concentration, quality of sleep, sense of control and tinnitus intrusiveness. The next stage is to consider what measurement instruments might be appropriate for assessing these constructs. The current study aimed to systematically gather existing instruments used to assess concentration. A total of 6240 potentially relevant records were identified. Duplicates and non-published works were removed, leaving a total of 3599 records. A procedure was developed to sample a subset of records, in order to identify relevant instruments without exhaustively reading all 3599 texts. Initially 559 records were identified by screening 1000 articles; 500 of which were randomly selected, and 500 were the most recent publications identified from the PubMed database. Using predefined criteria for data saturation, information about measures of concentration was extracted from the 559 full texts. However, data saturation was reached by 240. Thirteen candidate instruments were identified. The next step will be to assess content validity and feasibility of administration for all these candidate instruments. Findings will inform future recommendations for how to measure concentration in clinical trials to ensure results of trials can be easily compared, contrasted, and synthesized.

Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences.

Background: The Marie-Sklodowska-Curie Actions' (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD.