Longitudinal MRI and ¹H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction

by Jean-Baptiste Pérot, Anna Niewiadomska-Cimicka, Emmanuel Brouillet, Yvon Trottier, Julien Flament

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7^140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance. To characterize the temporal progression of brain degeneration of this model, we performed a longitudinal study spanning from early to late symptomatic stages using high-resolution magnetic resonance imaging (MRI) and in vivo ¹H-magnetic resonance spectroscopy (¹H-MRS). Compared to wild-type mouse littermates, MRI analysis of SCA7 mice shows progressive atrophy of defined brain structures, with the striatum, thalamus and cortex being the first and most severely affected. The volume loss of these structures coincided with increased motor impairments in SCA7 mice, suggesting an alteration of the sensory-motor network, as observed in SCA7 patients. MRI also reveals atrophy of the hippocampus and anterior commissure at mid-symptomatic stage and the midbrain and brain stem at late stage. ¹H-MRS of hippocampus, a brain region previously shown to be dysfunctional in patients, reveals early and progressive metabolic alterations in SCA7 mice. Interestingly, abnormal glutamine accumulation precedes the hippocampal atrophy and the reduction in myo-inositol and total N-acetyl-aspartate concentrations, two markers of glial and neuronal damage, respectively. Together, our results indicate that non-cerebellar alterations and glial and neuronal metabolic impairments may play a crucial role in the development of SCA7 mouse pathology, particularly at early stages of the disease. Degenerative features of forebrain structures in SCA7 mice correspond to current observations made in patients. Our study thus provides potential biomarkers that could be used for the evaluation of future therapeutic trials using the SCA7^140Q/5Q model.

The important factors nurses consider when choosing shift patterns: A cross‐sectional study

Abstract

Aim

To gain a deeper understanding of what is important to nurses when thinking about shift patterns and the organisation of working time.

Design

A cross-sectional survey of nursing staff working across the UK and Ireland collected quantitative and qualitative responses.

Methods

We recruited from two National Health Service Trusts and through an open call via trade union membership, online/print nursing profession magazines and social media. Worked versus preferred shift length/pattern, satisfaction and choice over shift patterns and nurses' views on aspects related to work and life (when working short, long, rotating shifts) were analysed with comparisons of proportions of agreement and crosstabulation. Qualitative responses on important factors related to shift preferences were analysed with inductive thematic analysis.

Results

Eight hundred and seventy-three survey responses were collected. When nurses worked long shifts and rotating shifts, lower proportions reported being satisfied with their shifts and working their preferred shift length and pattern. Limited advantages were realised when comparing different shift types; however, respondents more frequently associated ‘low travel costs’ and ‘better ability to do paid overtime’ with long shifts and ‘healthy diet/exercise’ with short shifts; aspects related to rotating shifts often had the lowest proportions of agreement. In the qualitative analysis, three themes were developed: ‘When I want to work’, ‘Impacts to my life outside work’ and ‘Improving my work environment’. Reasons for nurses' shift preferences were frequently related to nurses' priorities outside of work, highlighting the importance of organising schedules that support a good work-life balance.

Relevance to Clinical Practice

General scheduling practices like adhering to existing shift work guidelines, using consistent and predictable shift patterns and facilitating flexibility over working time were identified by nurses as enablers for their preferences and priorities. These practices warrant meaningful consideration when establishing safe and efficient nurse rosters.

Patient or Public Contribution

This survey was developed and tested with a diverse group of stakeholders, including nursing staff, patients, union leads and ward managers.

Reporting Method

The Strengthening the Reporting of Observational Studies (STROBE) checklist for cross-sectional studies was used to guide reporting.

Systematic review of end stage renal disease in Pakistan: Identifying implementation research outcomes

by Hamad AlRashed, Johanna Miele, Joshua Prasad, Deborah Adenikinju, Chukwuemeka Iloegbu, John Patena, Dorice Vieira, Joyce Gyamfi, Emmanuel Peprah

Aim and objectives

The aim of this study was to conduct a systematic review analysis to identify and evaluate the available literature on implementation science outcomes research in relation to End Stage Renal Disease (ESRD) in Pakistan.

Methods

A systematic database search of PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and Ovid was conducted through October 22^nd, 2022, without any restrictions on publication dates. A screening and data extraction tool, Covidence, was used to evaluate the literature against our inclusion and exclusion criteria. Furthermore, a Mixed Methods Appraisal Tool (MMAT) was used to evaluate the selected studies.

Results

We identified four studies that presented findings of implementation outcomes research which were related to appropriateness, feasibility, and acceptability. Appropriateness was examined using knowledge scores (p = 0.022) and medication adherence scores (p Conclusion

The preliminary results of this review indicate a gap in the availability of implementation research studies about ESRD in Pakistan. The burden of ESRD, and the implementation methods by which it is treated is notable in Pakistan and requires evidence-based measures to be implemented to support the critical healthcare delivery platforms that provide treatment.

Spatial confinement of <i>Trypanosoma brucei</i> in microfluidic traps provides a new tool to study free swimming parasites

by Mariana De Niz, Emmanuel Frachon, Samy Gobaa, Philippe Bastin

Trypanosoma brucei is the causative agent of African trypanosomiasis and is transmitted by the tsetse fly (Glossina spp.). All stages of this extracellular parasite possess a single flagellum that is attached to the cell body and confers a high degree of motility. While several stages are amenable to culture in vitro, longitudinal high-resolution imaging of free-swimming parasites has been challenging, mostly due to the rapid flagellar beating that constantly twists the cell body. Here, using microfabrication, we generated various microfluidic devices with traps of different geometrical properties. Investigation of trap topology allowed us to define the one most suitable for single T. brucei confinement within the field of view of an inverted microscope while allowing the parasite to remain motile. Chips populated with V-shaped traps allowed us to investigate various phenomena in cultured procyclic stage wild-type parasites, and to compare them with parasites whose motility was altered upon knockdown of a paraflagellar rod component. Among the properties that we investigated were trap invasion, parasite motility, and the visualization of organelles labelled with fluorescent dyes. We envisage that this tool we have named “Tryp-Chip” will be a useful tool for the scientific community, as it could allow high-throughput, high-temporal and high-spatial resolution imaging of free-swimming T. brucei parasites.

Contraceptive use by number of living children in Ghana: Evidence from the 2017 maternal health survey

by Sarah Compton, Emmanuel Nakua, Cheryl Moyer, Veronica Dzomeku, Emily Treleaven, Easmon Otupiri, Jody Lori

Background

There is a significant literature describing the link between parity and contraceptive use. However, there is limited knowledge about the disaggregation by parity of the type of contraceptives. In this study, we describe the use of contraceptives by parity among women of reproductive age in Ghana, focusing on use of highly effective methods (injection, pill, intrauterine device, implant, and sterilization).

Methods

Using the 2017 Ghana Maternal Health Survey, a nationally-representative cross-sectional household survey, we describe contraceptive method use by number of living children among sexually active women of reproductive age. We then estimated predictors of use of highly effective contraception in a multilevel logistic regression model.

Results

Most women in this survey are not using any method of contraception, although this varies by whether or not they have begun childbearing. Contraceptive method use varies by number of living children. Before having children, natural (periodic abstinence and withdrawal) and episodic (condoms) methods dominate. Once a woman has one living child, method preference changes to injectables and implants. Factors associated with using a highly effective method of contraception are: having >3 children, being in a relationship, having had an abortion, being younger than age 30, and having had sexual intercourse within days of answering the survey (p Conclusion

In this analysis, the number of living children a woman has, her age, and timing of last intercourse are the most significant predictors of using a highly effective method of contraception. However, the majority of participants in this study report not using any method of contraception to avoid unwanted pregnancies. Future research that attempts to unpack the disconnect between not wanting to become pregnant and not using contraception is warranted.

Seguridad de la terapia vasoactiva en adultos con choque séptico mediante un catéter venoso periférico

Objetivo principal: Evidenciar la seguridad del inicio de vasopresores mediante un catéter venoso periférico corto en pacientes adultos con diagnóstico de choque séptico, a través de la metodología Enfermería Basada en Evidencia. Metodología: Revisión sistemática. La búsqueda de evidencia se realizó en dos periodos, del 15 al 23 de septiembre del 2022 y del 3 al 20 de octubre del 2022, se utilizaron fuentes de búsqueda e información: base de datos PubMed y el buscador Google académico. Resultados principales: Se evaluaron 19679 pacientes, el tiempo de administración de la infusión fue de 101.05 horas, con una duración media de 22.63 horas, el evento adverso con más incidencia fue la extravasación con duración media de 7.5 horas, el vasopresor más utilizado fue la norepinefrina. Conclusión principal: Administrar vasopresores por vía periférica es seguro, considerando factores que reducirían significativamente el riesgo de complicaciones.