Nonclinical and Clinical Experiences with CPP-Based Self-Assembling Peptide Systems in Topical Drug Development

Ultrashort Self-Assembling Peptide Hydrogel for the Treatment of Fungal Infections

10.20944/preprints201805.0093.v1 ◽

2018 ◽

Author(s):

Alyaa Albadr ◽

Sophie M Coulter ◽

Raghu Raj Singh Thakur ◽

Garry Laverty

Keyword(s):

Drug Development ◽

Mammalian Cells ◽

Fungal Infections ◽

Drug Loading ◽

Fluorescent Microscopy ◽

Topical Formulation ◽

Fungal Cell ◽

Self Assembling ◽

Reduced Toxicity ◽

Highly Hydrophobic

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g. solubility, drug loading) issues associated with many current employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection.

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Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119430 ◽

1985 ◽

Vol 43 ◽

pp. 522-523

Author(s):

George C. Ruben ◽

Kenneth A. Marx

Keyword(s):

Tertiary Structure ◽

Dna Complexes ◽

Tertiary Structures ◽

Self Assembling ◽

Double Stranded Dna ◽

Calf Thymus ◽

Dna Organization ◽

Condensed Dna ◽

Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

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Developing an Early Intervention Preservice Specialization in Speech-Language Pathology

American Journal of Speech-Language Pathology ◽

10.1044/1058-0360.0402.31 ◽

1995 ◽

Vol 4 (2) ◽

pp. 31-36 ◽

Cited By ~ 4

Author(s):

Joanne E. Roberts ◽

Elizabeth Crais ◽

Thomas Layton ◽

Linda Watson ◽

Debbie Reinhartsen

Keyword(s):

Early Childhood ◽

Early Intervention ◽

Intervention Program ◽

Graduate Program ◽

Master's Level ◽

Clinical Experiences ◽

Speech Language Pathology ◽

Early Intervention Program ◽

Language Pathology ◽

Family Centered

This article describes an early intervention program designed for speech-language pathologists enrolled in a master's-level program. The program provided students with courses and clinical experiences that prepared them to work with birth to 5-year-old children and their families in a family-centered, interdisciplinary, and ecologically valid manner. The effectiveness of the program was documented by pre- and post-training measures and supported the feasibility of instituting an early childhood specialization within a traditional graduate program in speech-language pathology.

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Speech-Language Pathologists' Comfort Level With Use of Term “Stuttering” During Evaluations

American Journal of Speech-Language Pathology ◽

10.1044/2020_ajslp-19-00081 ◽

2020 ◽

Vol 29 (2) ◽

pp. 841-850 ◽

Cited By ~ 3

Author(s):

Courtney T. Byrd ◽

Danielle Werle ◽

Kenneth O. St. Louis

Keyword(s):

Communication Disorders ◽

Academic Experiences ◽

Comfort Level ◽

Future Research ◽

Clinical Experiences ◽

Speech Language Pathologists ◽

Comfort Levels ◽

Parents And Children ◽

Evaluation Feedback ◽

Study Participants

Purpose Speech-language pathologists (SLPs) anecdotally report concern that their interactions with a child who stutters, including even the use of the term “stuttering,” might contribute to negative affective, behavioral, and cognitive consequences. This study investigated SLPs' comfort in providing a diagnosis of “stuttering” to children's parents/caregivers, as compared to other commonly diagnosed developmental communication disorders. Method One hundred forty-one school-based SLPs participated in this study. Participants were randomly assigned to one of two vignettes detailing an evaluation feedback session. Then, participants rated their level of comfort disclosing diagnostic terms to parents/caregivers. Participants provided rationale for their ratings and answered various questions regarding academic and clinical experiences to identify factors that may have influenced ratings. Results SLPs were significantly less likely to feel comfortable using the term “stuttering” compared to other communication disorders. Thematic responses revealed increased experience with a specific speech-language population was related to higher comfort levels with using its diagnostic term. Additionally, knowing a person who stutters predicted greater comfort levels as compared to other clinical and academic experiences. Conclusions SLPs were significantly less comfortable relaying the diagnosis “stuttering” to families compared to other speech-language diagnoses. Given the potential deleterious effects of avoidance of this term for both parents and children who stutter, future research should explore whether increased exposure to persons who stutter of all ages systematically improves comfort level with the use of this term.

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A Response Evocation Program for /ɝ/

Journal of Speech and Hearing Disorders ◽

10.1044/jshd.4001.92 ◽

1975 ◽

Vol 40 (1) ◽

pp. 92-105 ◽

Cited By ~ 19

Author(s):

Lawrence D. Shriberg

Keyword(s):

Service Delivery ◽

Motor Skills ◽

Task Analysis ◽

Professional Issues ◽

Clinical Experiences ◽

Program Outcomes ◽

Program Step ◽

Skills Learning ◽

Learning Principles

A response evocation program, some principles underlying its development and administration, and a review of some clinical experiences with the program are presented. Sixty-five children with developmental articulation errors of the /ɝ/ phoneme were administered the program by one of 19 clinicians. Approximately 70% of program administrations resulted in a child emitting a good /ɝ/ within six minutes. Approximately 10% of children who were given additional training on program step failures emitted good /ɝ/'s in subsequent sessions. These preliminary observations are discussed in relation to the role of task analysis and motor skills learning principles in response evocation, clinician influences in program outcomes, and professional issues in service delivery to children with developmental articulation errors.

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Preservice Efforts To Promote School-Based SLPs' Roles in Written Language Development

Perspectives on School-Based Issues ◽

10.1044/sbi12.4.121 ◽

2011 ◽

Vol 12 (4) ◽

pp. 121-127 ◽

Cited By ~ 1

Author(s):

Elizabeth Lanter ◽

Claire Waldron

Keyword(s):

Public Schools ◽

Language Development ◽

Clinical Education ◽

Written Language ◽

School Age Children ◽

Leadership Roles ◽

Clinical Experiences ◽

School Based ◽

Language Pathology ◽

Written Language Development

Abstract The authors describe an innovative clinical education program that emphasizes the provision of written language services by preservice speech-language pathology graduate students at Radford University in Virginia. Clinicians combined academic coursework in language acquisition in school-age children and clinical experiences that target children's written language development to promote future literacy-based leadership roles and collaborative efforts among school-based speech-language pathologists (SLPs). These literacy-based experiences prepare SLPs to serve in the growing numbers of American public schools that are implementing Response to Intervention models.

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