Proportion of paediatric admissions with any stage of noma at the Anka General Hospital, northwest Nigeria.

INTRODUCTION: Noma is a rapidly spreading infection of the oral cavity which mainly affects young children. Without early treatment, it can have a high mortality rate. Simple gingivitis is a warning sign for noma, and acute necrotizing gingivitis is the first stage of noma. The epidemiology of noma is not well understood. We aimed to understand the prevalence of all stages of noma in hospitalised children. METHODS: We conducted a prospective observational study from 1st June to 24th October 2021, enrolling patients aged 0 to 12 years who were admitted to the Anka General Hospital, Zamfara, northwest Nigeria. Consenting parents/ guardians of participants were interviewed at admission. Participants had anthropometric and oral examinations at admission and discharge. FINDINGS: Of the 2346 patients, 58 (2.5%) were diagnosed with simple gingivitis and six (n = 0.3%) with acute necrotizing gingivitis upon admission. Of those admitted to the Inpatient Therapeutic Feeding Centre (ITFC), 3.4% (n = 37, CI 2.5-4.7%) were diagnosed with simple gingivitis upon admission compared to 1.7% of those not admitted to the ITFC (n = 21, CI 1.1-2.6%) (p = 0.008). Risk factors identified for having simple gingivitis included being aged over two years (2 to 6 yrs old, odds ratio (OR) 3.4, CI 1.77-6.5; 7 to 12 yrs OR 5.0, CI 1.7-14.6; p = <0.001), being admitted to the ITFC (OR 2.1; CI 1.22-3.62) and having oral health issues in the three months prior to the assessment (OR 18.75; CI 10.65, 33.01). All (n = 4/4) those aged six months to five years acute necrotizing gingivitis had chronic malnutrition. CONCLUSION: Our study showed a small proportion of children admitted to the Anka General Hospital had simple or acute necrotizing gingivitis. Hospital admission with malnutrition was a risk factor for both simple and acute necrotizing gingivitis. The lack of access to and uptake of oral health care indicates a strong need for oral examinations to be included in routine health services. This provision could improve the oral status of the population and decrease the chance of patients developing noma.

[Students' perspective on generalized nursing education in Germany: Results of a nationwide online survey]. / Die generalistische Pflegeausbildung in Deutschland aus Sicht Auszubildender.

Students' perspective on generalized nursing education in Germany: Results of a nationwide online survey Abstract. Background: Generalized nursing education in Germany was introduced in 2020 as a reaction to changed care conditions. The reform's implementation is accompanied by a nationwide longitudinal survey with three surveys among students in generalized nursing education. Aims: We present results of the first survey round. The explorative approach provides data that allows insights into students' experiences and thus indicates adjustment opportunities. Method: The online survey used standardized questionnaires and was directed at students that had begun generalized nursing education in 2020. 1,267 students from 316 nursing schools in 15 German federal states participated in the first survey round. The survey recorded students' career choice motivations, learning experiences in nursing schools and practical placements, as well as contextual factors. Results: The students' career choice is mainly interest-driven (77.8%). The program is rated good to satisfactory (overall grade 2.45). Frequent and well-designed practical guidance and a transfer of information between nursing school and clinical placement appear important but insufficiently implemented. Data shows an increased need for support services. Conclusions: In addition to positive findings, the practical learning design and the dialogue between theory and practice appear challenging, while support services should be expanded.

[German nursing study programs from the students' perspective: First results of a nationwide longitudinal study]. / Primärqualifizierende Pflegestudiengänge aus Sicht Studierender.

German nursing study programs from the students' perspective: First results of a nationwide longitudinal study Abstract. Background: The Nursing Professions Act establishes a concrete framework for academic nursing education in Germany for the first time. The primary qualifying nursing courses started in 2020 and will be accompanied by a systematic reporting of students' experiences over a period of three years. Aims: The article presents the results of the initial survey period (2021) on the students' point of view. Challenges and the need for further regulation of the primary qualifying nursing studies are analyzed and approaches to solutions are developed. Methods: The online survey is designed as a longitudinal cohort study with three measurement periods (2021, 2022, 2023). A descriptive analysis considers data of N = 57 students in the initial survey period. Results: The primary qualifying nursing study program is rated good overall (overall grade 2.32). However, one third (35.85%) are more critical in their assessments. Every second student perceives a need for adjustment in the financing of students. Learning in clinical placement settings often does not meet students' expectations. 86% of respondents report that nursing practice sites are insufficiently informed about students' qualification. Conclusions: Students' financing, and in particular the payment of assignments in the nursing practice, represents a regulatory gap with need for short-term solutions. For learning in nursing practice, there is a need for an enhanced practical placement guidance that is better geared to academic nursing education. This is accompanied by the need for a more specific definition of later professional fields and job profiles.

[Examination in times of Corona: A cross-sectional study on the use of digital media and the implementation of examinations in nursing education]. / Prüfen in Zeiten von Corona.

Examination in times of Corona: A cross-sectional study on the use of digital media and the implementation of examinations in nursing education Abstract. Background: In the pandemic, performance assessments had to be carried out under new conditions during the school closures. The aim of vocational nursing education is to develop competence to act. So far, there are no empirical findings on learning assessments and final examinations under pandemic conditions. Aim: The study aims to record the mode of performance assessments under the changed conditions. Methods: Written online survey of teachers at nursing schools in Germany. The collected data were analysed descriptively and inferentially using Chi-Square tests, and subjected to an integrative content analysis. Results: 884 nursing schools were contacted, 430 questionnaires from 179 responding schools (school-related response rate: 20,2%) could be evaluated. PCs or laptops are mostly used to check learning levels (n = 222). 205 participants do not use digital media for this purpose. Digital media are also used for the oral (n = 108) and written (n = 116) parts of the final examination; various organisational and hygiene measures are taken for face-to-face examinations. The practical part is often conducted in new formats (OSCE, simulation). Conclusions: Based on the results, it remains unclear to what extent competence orientation of vocational nursing education is implemented with digital support in examinations. The practical examination in particular seems to pose a special challenge for all those involved.

[Tracking systems in people with dementia in long-term care - Update of an integrative review]. / Tracking-Systeme bei Menschen mit Demenz in der stationären Langzeitpflege.

Tracking systems in people with dementia in long-term care - Update of an integrative review Abstract. Background: This article is an update of the article by Hülsken-Giesler et al. (2019) and describes the latest findings on tracking systems in inpatient long-term care. RESEARCH QUESTION: The research question also follows on from the underlying article and again deals with the application of tracking systems and their consequences for residents and nursing staff. METHODS: A systematic literature search in the databases MEDLINE via PubMed and CINAHL as well as a hand search for the period starting in August 2017 was performed. The included literature was evaluated by two independent persons regarding content and methodology. RESULTS: In addition to deductive categories from the underlying work, further inductive categories could be formed and thus ethical and implementation aspects could be included. CONCLUSION: Since the first analysis, the focus in nursing science studies on the use of tracking systems in inpatient long-term care has shifted to ethical aspects. Also, the successful and long-term integration into care practice is now relevant.

Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation.

Chronic activation and dysregulation of the neuroendocrine stress response have severe physiological and psychological consequences, including the development of metabolic and stress-related psychiatric disorders. We provide the first unbiased, cell type-specific, molecular characterization of all three components of the hypothalamic-pituitary-adrenal axis, under baseline and chronic stress conditions. Among others, we identified a previously unreported subpopulation of Abcb1b+ cells involved in stress adaptation in the adrenal gland. We validated our findings in a mouse stress model, adrenal tissues from patients with Cushing's syndrome, adrenocortical cell lines, and peripheral cortisol and genotyping data from depressed patients. This extensive dataset provides a valuable resource for researchers and clinicians interested in the organism's nervous and endocrine responses to stress and the interplay between these tissues. Our findings raise the possibility that modulating ABCB1 function may be important in the development of treatment strategies for patients suffering from metabolic and stress-related psychiatric disorders.

Author Correction: Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Tracking systems in people with dementia in long-term care - an integrative review]. / Tracking-Systeme bei Menschen mit Demenz in der stationären Langzeitpflege.

Tracking systems in people with dementia in long-term care - an integrative review Abstract. Schlüsselwörter: Tracking-Systeme, Überwachungssysteme, Personenortung, Demenz, stationäre Langzeitpflege Tracking systems in people with dementia in long-term care - an integrative review Background: Tracking systems are used increasingly in long-term care settings. However, their use is controversial. AIM: This paper examines how tracking systems are used to monitor people with dementia in long-term care facilities and what the consequences are for both residents and staff. METHODS: A systematic literature review was conducted in the PubMed, CINAHL, Livivo, ScienceDirect data bases and a hand search also took place. Included were studies, reviews and research reports in German and English from 2013 onwards. RESULTS: A total of eight references were included in the analysis. The results point to an ambivalent use of tracking systems in nursing. Nursing professionals face challenges in the areas of trust and distrust as well as autonomy and security. For residents, this means new opportunities for mobility and self-determination, but also more pressure due to continuous monitoring. CONCLUSIONS: The results show that the current debate on the use of tracking systems for people with dementia in long-term care settings concentrates mostly on the economic aspects, whereas aspects of person-centered care, ethical conflicts or the experience of those affected are given less attention. A core finding is that the use of technology changes the work processes and roles of professional carers.

Technikbereitschaft in der ambulanten Pflege.

Technology commitment in outpatient care Abstract. Background: New technologies are becoming increasingly important in outpatient care. The willingness of professional carers to use new technologies is often considered to be low, especially where older and female carers are concerned who play a large role in outpatient care. However, reliable data on technology commitment in outpatient care are not yet available for German-speaking countries. AIM: This paper aims to provide insights into the state of technology commitment in outpatient care. METHODS: For data collection, the standardised assessment of technology commitment was used, which determines technology readiness via the facets "technology acceptance", "technology competence conviction" and "technology control conviction" (26-2Neyer et al., 2012). A first data collection (2013) concentrated on nursing services in the federal state of Lower Saxony (n = 263), a second data collection (2017) was carried out with a nationwide care service provider (n = 593). RESULTS: For the first time, the results of the present investigations provide differentiated insights into questions of technology commitment in outpatient care in Germany. In particular, there are indications of differences in the willingness to use technology in outpatient care depending on the age group of the interviewees. CONCLUSION: The introduction of new technologies into the everyday life of caregivers requires demographically sensitive concepts for preparing and supporting the users.

Plastin 3 influences bone homeostasis through regulation of osteoclast activity.

Over 200 million people suffer from osteoporosis worldwide, one third of which will develop osteoporotic bone fractures. Unfortunately, no effective cure exists. Mutations in plastin 3 (PLS3), an F-actin binding and bundling protein, cause X-linked primary osteoporosis in men and predisposition to osteoporosis in postmenopausal women. Moreover, the strongest association so far for osteoporosis in elderly women after menopause was connected to a rare SNP in PLS3, indicating a possible role of PLS3 in complex osteoporosis as well. Interestingly, 5% of the general population are overexpressing PLS3, with yet unknown consequences. Here, we studied ubiquitous Pls3 knockout and PLS3 overexpression in mice and demonstrate that both conditions influence bone remodeling and structure: while Pls3 knockout mice exhibit osteoporosis, PLS3 overexpressing mice show thickening of cortical bone and increased bone strength. We show that unbalanced PLS3 levels affect osteoclast development and function, by misregulating the NFκB pathway. We found upregulation of RELA (NFκB subunit p65) in PLS3 overexpressing mice-known to stimulate osteoclastogenesis-but strikingly reduced osteoclast resorption. We identify NFκB repressing factor (NKRF) as a novel PLS3 interactor, which increasingly translocates to the nucleus when PLS3 is overexpressed. We show that NKRF binds to the NFκB downstream target and master regulator of osteoclastogenesis nuclear factor of activated T cells 1 (Nfatc1), thereby reducing its transcription and suppressing osteoclast function. We found the opposite in Pls3 knockout osteoclasts, where decreased nuclear NKRF augmented Nfatc1 transcription, causing osteoporosis. Regulation of osteoclastogenesis and bone remodeling via the PLS3-NKRF-NFκB-NFATC1 axis unveils a novel possibility to counteract osteoporosis.

Evaluation of potential effects of Plastin 3 overexpression and low-dose SMN-antisense oligonucleotides on putative biomarkers in spinal muscular atrophy mice.

OBJECTIVES: Spinal muscular atrophy (SMA) is a devastating motor neuron disorder caused by homozygous loss of the survival motor neuron 1 (SMN1) gene and insufficient functional SMN protein produced by the SMN2 copy gene. Additional genetic protective modifiers such as Plastin 3 (PLS3) can counteract SMA pathology despite insufficient SMN protein. Recently, Spinraza, an SMN antisense oligonucleotide (ASO) that restores full-length SMN2 transcripts, has been FDA- and EMA-approved for SMA therapy. Hence, the availability of biomarkers allowing a reliable monitoring of disease and therapy progression would be of great importance. Our objectives were (i) to analyse the feasibility of SMN and of six SMA biomarkers identified by the BforSMA study in the Taiwanese SMA mouse model, (ii) to analyse the effect of PLS3 overexpression on these biomarkers, and (iii) to assess the impact of low-dose SMN-ASO therapy on the level of SMN and the six biomarkers. METHODS: At P10 and P21, the level of SMN and six putative biomarkers were compared among SMA, heterozygous and wild type mice, with or without PLS3 overexpression, and with or without presymptomatic low-dose SMN-ASO subcutaneous injection. SMN levels were measured in whole blood by ECL immunoassay and of six SMA putative biomarkers, namely Cartilage Oligomeric Matrix Protein (COMP), Dipeptidyl Peptidase 4 (DPP4), Tetranectin (C-type Lectin Family 3 Member B, CLEC3B), Osteopontin (Secreted Phosphoprotein 1, SPP1), Vitronectin (VTN) and Fetuin A (Alpha 2-HS Glycoprotein, AHSG) in plasma. RESULTS: SMN levels were significantly discernible between SMA, heterozygous and wild type mice. However, no significant differences were measured upon low-dose SMN-ASO treatment compared to untreated animals. Of the six biomarkers, only COMP and DPP4 showed high and SPP1 moderate correlation with the SMA phenotype. PLS3 overexpression neither influenced the SMN level nor the six biomarkers, supporting the hypothesis that PLS3 acts as an independent protective modifier.

Author Correction: Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA.

Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods in the motoneuron disease spinal muscular atrophy (SMA).

Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent. Moreover, we found that the PlexinD1 cleavage product binds to actin rods, pathological aggregate-like structures which had so far been described for age-related neurodegenerative diseases. Our data suggest a novel disease mechanism for SMA involving formation of actin rods as a molecular sink for a cleaved PlexinD1 fragment leading to dysregulation of receptor signaling.

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis.

Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca2+-dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies.

The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype.

Homozygous loss of SMN1 causes spinal muscular atrophy (SMA), the most common and devastating childhood genetic motor-neuron disease. The copy gene SMN2 produces only ∼10% functional SMN protein, insufficient to counteract development of SMA. In contrast, the human genetic modifier plastin 3 (PLS3), an actin-binding and -bundling protein, fully protects against SMA in SMN1-deleted individuals carrying 3-4 SMN2 copies. Here, we demonstrate that the combinatorial effect of suboptimal SMN antisense oligonucleotide treatment and PLS3 overexpression-a situation resembling the human condition in asymptomatic SMN1-deleted individuals-rescues survival (from 14 to >250 days) and motoric abilities in a severe SMA mouse model. Because PLS3 knockout in yeast impairs endocytosis, we hypothesized that disturbed endocytosis might be a key cellular mechanism underlying impaired neurotransmission and neuromuscular junction maintenance in SMA. Indeed, SMN deficit dramatically reduced endocytosis, which was restored to normal levels by PLS3 overexpression. Upon low-frequency electro-stimulation, endocytotic FM1-43 (SynaptoGreen) uptake in the presynaptic terminal of neuromuscular junctions was restored to control levels in SMA-PLS3 mice. Moreover, proteomics and biochemical analysis revealed CORO1C, another F-actin binding protein, whose direct binding to PLS3 is dependent on calcium. Similar to PLS3 overexpression, CORO1C overexpression restored fluid-phase endocytosis in SMN-knockdown cells by elevating F-actin amounts and rescued the axonal truncation and branching phenotype in Smn-depleted zebrafish. Our findings emphasize the power of genetic modifiers to unravel the cellular pathomechanisms underlying SMA and the power of combinatorial therapy based on splice correction of SMN2 and endocytosis improvement to efficiently treat SMA.

SMN regulates axonal local translation via miR-183/mTOR pathway.

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3' UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology.

Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality.

F-actin bundling plastin 3 (PLS3) is a fully protective modifier of the neuromuscular disease spinal muscular atrophy (SMA), the most common genetic cause of infant death. The generation of a conditional PLS3-over-expressing mouse and its breeding into an SMA background allowed us to decipher the exact biological mechanism underlying PLS3-mediated SMA protection. We show that PLS3 is a key regulator that restores main processes depending on actin dynamics in SMA motor neurons (MNs). MN soma size significantly increased and a higher number of afferent proprioceptive inputs were counted in SMAPLS3 compared with SMA mice. PLS3 increased presynaptic F-actin amount, rescued synaptic vesicle and active zones content, restored the organization of readily releasable pool of vesicles and increased the quantal content of the neuromuscular junctions (NMJs). Most remarkably, PLS3 over-expression led to a stabilization of axons which, in turn, resulted in a significant delay of axon pruning, counteracting poor axonal connectivity at SMA NMJs. These findings together with the observation of increased endplate and muscle fiber size upon MN-specific PLS3 over-expression suggest that PLS3 significantly improves neuromuscular transmission. Indeed, ubiquitous over-expression moderately improved survival and motor function in SMA mice. As PLS3 seems to act independently of Smn, PLS3 might be a potential therapeutic target not only in SMA but also in other MN diseases.