Riboswitch-controlled IL-12 gene therapy reduces hepatocellular cancer in mice.

Hepatocellular carcinoma (HCC) and solid cancers with liver metastases are indications with high unmet medical need. Interleukin-12 (IL-12) is a proinflammatory cytokine with substantial anti-tumor properties, but its therapeutic potential has not been realized due to severe toxicity. Here, we show that orthotopic liver tumors in mice can be treated by targeting hepatocytes via systemic delivery of adeno-associated virus (AAV) vectors carrying the murine IL-12 gene.

What is Effective in Massage Therapy? Well, "It Depends…": a Qualitative Study of Experienced Orthopaedic Massage Therapists.

Background: Massage has been used as a treatment for musculoskeletal pain throughout history and across cultures, and yet most meta-analyses have only shown weak support for the efficacy of massage. There is a recognised need for more research in foundational questions including: how massage treatments are constructed; what therapists actually do within a treatment, including their clinical reasoning; and what role therapists play in determining the effectiveness of a massage treatment.

Purpose: The aim of this study was to explore what experienced orthopaedic massage therapists consider to be the aspects of their work that contribute to effectiveness.

[Retinal OCT biomarkers and neurodegenerative diseases of the central nervous system beyond Alzheimer's disease].

Background: Optical coherence tomography (OCT) biomarkers are increasingly used by neurologists, psychiatrists, and ophthalmologists for the diagnosis, prognosis, and follow-up of neurodegenerative diseases. Long-term data on OCT biomarkers of selected primary and secondary neurodegenerative diseases of the central nervous system (CNS), such as multiple sclerosis (MS) or Parkinson's disease, are already available in part. In addition, there are rare neurodegenerative diseases with early disease onset that may show OCT abnormalities.

The cumulative impacts of droughts and N deposition on Norway spruce (Picea abies) in Switzerland based on 37 years of forest monitoring.

Norway spruce is one of the most important tree species in Central Europe, however, it is facing major problems with recent droughts. In this study we present 37 years (1985-2022) of long-term forest observation data on 82 different forest sites across Switzerland including 134'348 tree observations. The sites consists of managed spruce or mixed forest stands with beech (Fagus sylvatica) and comprise large gradients in altitude (290-1870 m), precipitation (570-2448 mm a), temperature (3.

Intervention for residual speech errors in adolescents and adults: A systematised review.

When speech sound errors persist beyond childhood they are classified as residual speech errors (RSE) and may have detrimental impacts on an individual's social, educational and employment participation. Despite this, individuals who present with RSE are usually not prioritised on large caseloads. The aim of this literature review was to examine what intervention approaches are available in remediating RSE, and how effective are they for adolescents and adults? A systematised review was undertaken.

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo.

Targeted protein degradation offers an alternative modality to classical inhibition and holds the promise of addressing previously undruggable targets to provide novel therapeutic options for patients. Heterobifunctional molecules co-recruit a target protein and an E3 ligase, resulting in ubiquitylation and proteosome-dependent degradation of the target. In the clinic, the oral route of administration is the option of choice but has only been achieved so far by CRBN- recruiting bifunctional degrader molecules.

Attitudes toward the use of low-tech AAC in acute settings: a systematized review.

The purpose of this systematized review was to investigate how attitudes toward low-tech AAC might be impacting its use in acute care settings. A comprehensive and systematic search of databases identified 23 articles for inclusion. Thematic analysis using the World Health Organization International Classification of Functioning, Disability and Health (ICF) framework facilitated a narrative synthesis of findings.

Distribution of Pupil Size and Associated Factors: Results from the Population-Based Gutenberg Health Study.

Results: 18,335 eyes of 9,559 participants aged 40 to 80 years were included in the analysis. Median pupil diameter was 4.19 mm in right eyes and 4.

Family-centred practice in speech-language pathology practice with children and young people in out-of-home care in Australia: A scoping review.

: Communication difficulties are more common in children or young people (CYP) who have lived in out-of-home care (OOHC) compared to the general population. Principles of family-centred practice (FCP) are frequently utilised by speech-language pathologists (SLPs) when working with CYP with communication difficulties. The aim of this scoping review was to describe how the principles of FCP are applied in the literature to speech-language pathology practice with CYP aged 0-18 in OOHC in Australia.

Fijian school students' Fiji English speech sound acquisition.

The aim of this study was to investigate Fijian students' acquisition of Fiji English speech sounds. Participants were 72 multilingual students (5-10 years) living in Fiji who spoke the Fijian or Fiji Hindi dialects of Fiji English. The students' productions of single words from the Diagnostic Evaluation of Articulation and Phonology (DEAP) were analysed according to dialect using the Children's Independent and Relational Phonological Analysis (CHIRPA).

Five-Year Cumulative Incidence and Progression of Myopic Maculopathy in a German Population.

Purpose: To investigate the 5-year cumulative incidence and progression of myopic maculopathy in the general population in Germany and to analyze potential risk factors.

Design: The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants aged 35 to 74 years at baseline.

Participants: A total of 494 eyes of 323 participants (mean age, 50.

Impact of intraocular pressure fluctuations on progression of normal tension glaucoma.

Aim: To investigate short- and long-term intraocular pressure (IOP) fluctuations and further ocular and demographic parameters as predictors for normal tension glaucoma (NTG) progression.

Methods: This retrospective, longitudinal cohort study included 137 eyes of 75 patients with NTG, defined by glaucomatous optic disc or visual field defect with normal IOP (<21 mm Hg), independently from therapy regimen. IOP fluctuation, mean, and maximum were inspected with a mean follow-up of 38mo [standard deviation (SD) 18mo].

The Relationship between Ageism and Well-Being as Mediated through COVID-19-Related Experiences and Discourses.

Both COVID-19 and ageism can have a negative impact on the well-being of older people. Yet, our knowledge on the links between COVID-19, ageism and well-being is still emerging. The present study aimed to contribute to this knowledge by exploring the lived experiences of older adults during the COVID-19 pandemic.

Retinal thinning in phenylketonuria and Gaucher disease type 3.

Purpose: Retinal alterations in inherited metabolic diseases associated with neurodegeneration are poorly studied. The objective was to study retinal thickness, specifically the components of the ganglion cell complex (GCC)-nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL)-using spectral-domain optical coherence tomography (SD-OCT) in two different diseases with potential dopaminergic depletion, phenylketonuria (PKU) and Gaucher disease type 3 (GD3).

Methods: Retinal layers in 19 patients with PKU, 15 patients with GD3, and 93 healthy individuals were measured using peripapillary ring scan and macular SD-OCT.

Advancing Workplace Diversity Through the Culturally Responsive Teamwork Framework.

Purpose Diversification of the profession is an important element of combating racism, bias, and prejudice in the speech-language pathology workforce at national and systemic levels. However, national and systemic change needs to be combined with equipping individual speech-language pathologists to adapt to the challenges that they face to engaging in culturally responsive practice. This paper presents four interacting levels of practice within the Culturally Responsive Teamwork Framework (CRTF): (a) intrapersonal practices, (b) interpersonal practices, (c) intraprofessional practices, and (d) the interprofessional practices.

Vertical saccadic palsy and foveal retinal thinning in Niemann-Pick disease type C.

Introduction: Niemann-Pick type C (NPC) is a lysosomal storage disease that is progressive and life-limiting, with an estimated incidence of 1:120,000 live births. In addition to systemic manifestation with (hepato-)splenomegaly, there are a number of neurological manifestations (ataxia, dysarthria, dementia, cataplexy, epileptic seizures, and psychiatric disorders). Characteristic is vertical supranuclear gaze palsy, which is often overlooked.

Brimonidine-associated uveitis - a descriptive case series.

Background: Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon to avoid mis-diagnosis and over-treatment with topical steroids which in turn may increase intraocular pressure (IOP). This is the largest case series including the longest patient follow-up in the current literature.

Saccadic reaction time and ocular findings in phenylketonuria.

Background: Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Despite some obvious ocular changes, the disorder has been poorly recognized by ophthalmologists. Neurophysiologic tests imply prolonged reaction time correlating with increased phenylalanine blood concentrations.

The impact of intraocular pressure fluctuations and other factors on conversion of ocular hypertension to primary open-angle glaucoma.

Purpose: To evaluate the role of intraocular pressure (IOP) fluctuations and other factors on conversion of ocular hypertension to open-angle glaucoma (OAG) within a retrospective, longitudinal cohort study.

Patients And Methods: The study population included patients with ocular hypertension defined by IOP > 21 mmHg with normal appearing optic discs and no visual field defect. IOP fluctuation, mean and maximum were examined in 61 eyes over a follow-up period of 36 months (standard deviation (SD) 24).

Prevalence of myopic maculopathy in the German population: results from the Gutenberg health study.

Aims: To determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors.

Design: The Gutenberg Health Study is a population-based study, including 15 010 participants aged 35-74 years.

Methods: Myopic maculopathy was graded in phakic eyes with spherical equivalent ≤-6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM).

A comprehensive monocentric ophthalmic study with Gaucher disease type 3 patients: vitreoretinal lesions, retinal atrophy and characterization of abnormal saccades.

Background: The differentiation between Gaucher disease type 3 (GD3) and type 1 is challenging because pathognomonic neurologic symptoms may be subtle and develop at late stages. The ophthalmologist plays a crucial role in identifying the typical impairment of horizontal saccadic eye movements, followed by vertical ones. Little is known about further ocular involvement.