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Measles is a well-known childhood disease that is preventable through vaccination of children at 9 and 18 months of age. The first signs and symptoms are flu-like, soon followed by a fever and characteristic rash. Measles is a highly contagious disease that remains responsible for high numbers of deaths among children in spite of an effective vaccine. Treatment of the disease includes isolation, protection from sharp light, symptomatic support and close observation for possible complications. Measles is a notifiable disease and must be reported to the National Institute for Communicable Diseases (NICD). [ABSTRACT FROM AUTHOR]

This study of South African counterurbanisation demonstrates, in line with recent views, that substream counterurbanisation can be a meaningful subject of scientific interest even within contexts of mainstream concentration, as is the case in much of the developing world. This is due to its proportional impact on regional growth poles at the lower end of the settlement hierarchy. Both the South African results and evidence elsewhere indicate that counterurbanisation may be far more significant in the developing world than commonly assumed, and also far more varied. Apart from similar forms of counterurbanisation found in the developed world, the research also finds two other distinctive forms of developing world counterurbanisation: agrarian counterurbanisation occurring in countries with struggling urban economies and under-utilized agricultural capital, and industrial sector-led counterurbanisation, which, contrary to the developed world, may well be the dominant form of counterurbanisation in developing countries. While the study clearly admits that evidence for the developing world is limited at present, that which exists strongly argues for further research, particularly on the clear implications of developing world variations for migration and rural development policy differentiation. [ABSTRACT FROM AUTHOR]

Aim: The specific aims of this study were to propose a definition of the term informal settlement, validate the term informal settlement, and submit a term and definition for international utilization to the International Council of Nurses (ICN) for consideration for inclusion in the International Classification of Nursing Practice (ICNP®). Background: South Africa was one of four African countries (Botswana, South Africa, Swaziland and Zimbabwe) funded by the WK Kellogg Foundation to participate in the ICNP® project. South Africa had two research groups. One of the research groups identified the term informal settlement to define. Methods: This was a qualitative study where a philosophical perspective was used to explore, explain and describe nursing practice. The combined method proposed by the ICN was utilized to define and validate the term informal settlement. Findings: Validation and literature review provided sufficient support for the defined characteristics and the term was finally defined and submitted to ICN on 12 April 2001 as informal settlement is a type of residential development with the specific characteristics – temporary residential structures, erected with limited or no formal infrastructure, densely populated, no secure tenure for occupants, no property demarcations, often associated with overcrowding/limited or no privacy, and low standard of living, being situated in high risk areas with an increased risk for disease and disasters. Conclusion: The ICNP® Evaluation Committee recommended inclusion in the ICNP® with minor changes in February 2003. [ABSTRACT FROM AUTHOR]

PURPOSE: To present a model of health care delivery in South Africa that made health care services accessible and affordable to members of the community who do not have medical insurance. DATA SOURCES: Statutes and laws governing the practice of health care professionals in South Africa, published professional guidelines, local research data, and the author's experience of the model of health care delivery. CONCLUSIONS: The innovative and visionary approach of a few health care professionals has established a model of health care delivery specifically suited to their community's needs. This model of service delivery has provided an affordable and accessible health service to members of the local community, who have indicated their satisfaction with the service. IMPLICATIONS FOR PRACTICE: Economic and legal barriers to accessible and affordable health care services can be overcome to ensure that health care is available to the whole population. The nurse practitioner has an important role to play in making health care affordable and accessible to the community. [ABSTRACT FROM AUTHOR]

We report on the characterization of hexagonally ordered, vertically aligned silicon nanowires (SiNW) by means of analytical transmission electron microscopy. Combining colloidal lithography, plasma etching, and catalytic wet etching arrays of SiNW of a sub-50 nm diameter with an aspect ratio of up to 10 could be fabricated. Scanning transmission electron microscopy has been applied in order to investigate the morphology, the internal structure, and the composition of the catalytically etched SiNW. The analysis yielded a single-crystalline porous structure composed of crystalline silicon, amorphous silicon, and SiO x with x≤2. [ABSTRACT FROM AUTHOR]

Abstract It is reported in this article that Si nanowires can be employed as a positive template for the controllable electrochemical deposition of noble metal tube. The deposited tube exhibits good crystallinity. Scanning electron microscope and transmission electron microscope characterizations are conducted to reveal the growth process of metal tube, showing that the metal tube grows quasi-radially on the wall of Si nanowire. The quasi-radial growth of metal enables the fabrication of thickness-defined metal tube via changing deposition time. Inner-diameter-defined metal tube is achieved by choosing Si nanowires with desired diameter as a template. Metal tubes with inner diameters ranging from 1 μm to sub-50 nm are fabricated.

Background: Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca 2+ -overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca 2+ -release mechanism hypersensitive to certain ligands, including Ca 2+ , volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca 2+ -overload in PAC, we presumed that pancreata of MHS individuals are more prone to AP. Accordingly, a recent case study reported coincidence of MHS with recurrent AP, indicating a pathological link between the two diseases., Methods: We tested if MHS poses a risk for AP in mice carrying the Y522S MHS mutation. Fluorescent Ca 2+ imaging was performed in PACs. Conventional histopathological analysis and plazma amylase measurement was performed using a cerulein-induced pancreatitis mouse model., Results: The intracellular Ca 2+ -signals of PACs from MHS mice were slightly bigger then in wild type when stimulated with 0.2 and 2 μM carbachol (cch) or with 1 and 5 mM bile acid (taurocholic acid). Store-operated-Ca 2+ -entry was also higher in PACs from MHS mice. Nevertheless, histopathological analysis and plasma amylase levels did not indicate more severe AP in MHS., Conclusions: These results suggest that the Y522S RyR1 mutation alter the Ca 2+ -homeostasis in PACs, but not as much as to cause or aggravate AP., Competing Interests: Competing interests statement The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Nurse prescribing and dispensing are central to ensuring universal health access in South Africa., Objective: To describe the historical development of the legal enablements of nurse prescribing and dispensing in South Africa and highlight gaps in the current legislative framework., Method: This is a discussion article., Results: We emphasise significant deficiencies in the current legislative landscape that pose challenges to these vital nursing practices and call for urgent revisions of the legislative framework, particularly the revision of Section 56 of the Nursing Act (33 of 2005) and its related regulations, to formalise authorisation of specialist nurse prescribers in public and private practice. This will also entail an application to the South African Health Products Regulatory Authority (SAPHRA) for the scheduling of substances by authorised nurse prescribers in the defined professional nurse and specialist nurse categories by the Minister of Health., Conclusion: There is a necessity for prompt legislative revisions to address identified deficiencies., Contribution: The contribution of this article lies in its advocacy for changes to the regulatory framework to further enable nurses to deliver safe and comprehensive health care., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Cell competition is a mechanism for cellular quality control based on cell-cell comparisons of fitness. Recent studies have unveiled a central and complex role for cell competition in cancer. Early tumors exploit cell competition to replace neighboring normal epithelial cells. Intestinal adenomas, for example, use cell competition to outcompete wild-type epithelial cells. However, oncogenic mutations do not always confer an advantage: wild-type cells can identify mutant cells and enforce their extrusion through cell competition, a process termed "epithelial defense against cancer". A particularly interesting situation emerges in metastasis: supercompetitive tumor cells encounter heterotypic partners and engage in reciprocal competition with diverging outcomes. This article sheds light on the emerging complexity of cell competition by highlighting recent studies that unveil its context dependency. Finally, we propose that tissue histomorphology implies a crucial role for cell competition at tumor invasion fronts particularly in metastases, warranting increased attention in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The prevalence of nonalcoholic fatty liver disease (NASH) and cryptogenic cirrhosis (CC) is constantly increasing in adolescents and young adults (AYAs)., Methods: In a retrospective UNOS database evaluation, we analyzed postoperative outcomes of AYAs with nonalcoholic NASH/CC undergoing LT between January 1 st , 2003 and March 5 th , 2021. After exclusions, 85,970 LT recipients, 393 (47.1%) AYAs with NASH/CC and 441 (52.9%) AYAs with other metabolic conditions, were analyzed., Results: During the study period, the number of LTs performed for AYAs with NASH/CC increased from 4%-7% but decreased from 6.6%-5.3% compared to LTs performed for NASH/CC in all ages. In comparison to AYAs with other metabolic conditions, AYA LT recipients with NASH/CC had a higher prevalence of metabolic syndrome (MetS) components, including diabetes and increased body mass index (P < .0001 for both). Patient and graft survival in AYAs with NASH/CC were significantly lower in comparison to AYAs transplanted for other metabolic conditions (P < .0001) (Hazard Ratio = 1.93, P < .001). Patient survival in AYAs with NASH/CC was significantly better in comparison to older (40-65-year-old) patients with the same diagnosis (P = .01)., Conclusions: Our study found that the overall number of LTs in AYAs with NASH increased significantly, but to a lesser degree compared to the older population with the same diagnosis. Outcomes after LT in AYAs with NASH/CC were worse compared to LT for other metabolic conditions, but significantly better in comparison to older patients. The prevalence of LT for NASH/CC in AYAs is growing. MetS may contribute to worse outcomes in AYAs., Competing Interests: Declaration of Competing Interest This research was supported by a grant from the Department of Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K23DK131290 (Dr Sine). This grant was not used for the financial support of this study but has to be mentioned by all publication related to this author., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With the increasing use of fish as model species for research, cell cultures derived from caudal fin explants as well as pre-hatching stage embryos have provided powerful in vitro tools that can complement or serve as an ethically more acceptable alternative to live animal experiments. The widely-used protocols to establish these lines require, as a starting point, homogeneous pools of embryos or viable adult fish which are large enough for collecting sufficient fin tissue. This excludes the use of fish lines with adverse phenotypes or lines that exhibit mortality at early developmental stages and so can only be propagated as heterozygotes. Specifically, when no visually overt mutant phenotype is detectable for identifying homozygous mutants at early embryonic stages, it is then impossible to sort pools of embryos with the same genotypes to generate cell lines from the progeny of a heterozygote in-cross. Here, we describe a simple protocol to generate cell lines on a large scale starting from individual early embryos that can subsequently be genotyped by polymerase chain reaction. This protocol should help to establish fish cell culture models as a routine approach for the functional characterization of genetic changes in fish models such as the zebrafish. Furthermore, it should contribute to a reduction of experiments which are ethically discouraged to avoid pain and distress., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR high stroma at the liver edge to FAP high stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness., (© 2023. Springer Nature Limited.)

Background and Aims: Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. However, mechanisms underpinning the improvements in NAFLD seen with exercise are unclear. Exercise improved liver fat and serum biomarkers of liver fibrosis in the NASHFit trial. We investigated exercise's mechanism of benefit by conducting a post hoc analysis of these data to determine the relationship between serum fibroblast growth factor (FGF) 21, which is implicated in NAFLD development, and exercise., Methods: In the 20 wk NASHFit trial, patients with nonalcoholic steatohepatitis (NASH) were randomized to receive moderate-intensity aerobic exercise training or standard clinical care. Mediterranean-informed dietary counseling was provided to each group. Change in serum FGF21 was measured after an overnight fast., Results: There was a significant improvement in serum FGF21 with exercise training compared to standard clinical care ( p = 0.037) with serum FGF21 reducing by 22% (-243.4 +/-349 ng/mL) with exercise vs. a 34% increase (+88.4 ng/mL +/-350.3 ng/mL) with standard clinical care. There was a large inverse association between change in serum FGF21 and change in cardiorespiratory fitness (VO 2 peak) (r = -0.62, 95% CI -0.88 to -0.05, p = 0.031), and on multivariable analysis, change in VO 2 peak remained independently associated with change in FGF21 (β = -44.5, 95% CI -83.8 to -5.11, p = 0.031)., Conclusions: Serum FGF21 is markedly decreased in response to aerobic exercise training, offering a novel mechanism to explain the observed reduction in liver fat and improvement in serum biomarkers of liver fibrosis in patients with NASH who do exercise.

Background Aims: Lifestyle intervention remains the foundation of clinical care for patients with NASH; however, most patients are unsuccessful in enacting sustained behavioral change. There remains a clear unmet need to develop lifestyle intervention programs to support weight loss. Mobile health (mHealth) programs offer promise to address this need, yet their efficacy remains unexplored., Approach Results: We conducted a 16-week randomized controlled clinical trial involving adults with NASH. Patients were randomly assigned (1:1 ratio) to receive Noom Weight (NW), a mHealth lifestyle intervention program, or standard clinical care. The primary end point was a change in body weight. Secondary end points included feasibility (weekly app engagement), acceptability (>50% approached enrolled), and safety. Of 51 patients approached, 40 (78%) were randomly assigned (20 NW and 20 standard clinical care). NW significantly decreased body weight when compared to standard clinical care (-5.5 kg vs. -0.3 kg, p = 0.008; -5.4% vs. -0.4%, p = 0.004). More NW subjects achieved a clinically significant weight loss of ≥5% body weight (45% vs. 15%, p = 0.038). No adverse events occurred, and the majority (70%) of subjects in the NW arm met the feasibility criteria., Conclusions: This clinical trial demonstrated that NW is not only feasible, acceptable, and safe but also highly efficacious because this mHealth lifestyle intervention program led to significantly greater body weight loss than standard clinical care. Future large-scale studies are required to validate these findings with more representative samples and to determine if mHealth lifestyle intervention programs can lead to sustained, long-term weight loss in patients with NASH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Objectives: To determine if decreases in the Karnofsky Performance Score (KPS) while on the waitlist predict decreased survival after lung transplantation (LTx)., Design: A retrospective evaluation of the United Network for Organ Sharing database. The KPS was evaluated at the time of listing for transplant and at the time of transplantation. Group I consisted of patients having a decrease in KPS during the time on the waiting list (from the time of listing to the time of transplant), and Group II consisted of patients whose KPS stayed the same or increased during the same period. The authors used propensity-score weighting for comparisons of these groups., Setting: Retrospective observational database review., Participants: Adult patients undergoing lung transplantation., Interventions: None. Patients were stratified according to a change in their KPS., Measurements and Main Results: Patient and graft survival of patients with decreasing or not decreasing KPS were compared. Of the 27,558 subjects included in the analysis, 17,986 (65%) had worsening KPS, which was associated with worse graft (p = 0.0003) and patient (p = 0.0019) survival after LTx. Using multivariate regression, a decrease in KPS of ≥40 was associated with decreased survival, and an increase of ≥40 was associated with improved survival (HR = 1.245, 95% CI [1.181-1.312], p < 0.0001 and HR = 0.866, 95% CI [0.785, 0.955], respectively). Among patients with a KPS <40 at the time of transplant, those with a decrease in KPS of ≥40 had decreased graft and patient survival compared with those with a smaller decrease (p = 0.0002 and p = 0.0021, respectively)., Conclusions: Deterioration of KPS on the waiting list for LTx is associated with significantly greater postoperative mortality in patients after LTx. These results should be taken into consideration when allocating organs. Strategies to increase or to prevent a decrease in KPS before LTx should be evaluated., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The circadian clock, which drives a wide range of bodily rhythms in synchrony with the day-night cycle, is based on a molecular oscillator that ticks with a period of approximately 24 h. Timed proteasomal degradation of clock components is central to the fine-tuning of the oscillator's period. FBXL3 is a protein that functions as a substrate-recognition factor in the E3 ubiquitin ligase complex, and was originally shown in mice to mediate degradation of CRY proteins and thus contribute to the mammalian circadian clock mechanism. By exome sequencing, we have identified a FBXL3 mutation in patients with syndromic developmental delay accompanied by morphological abnormalities and intellectual disability, albeit with a normal sleep pattern. We have investigated the function of FBXL3 in the zebrafish, an excellent model to study both vertebrate development and circadian clock function and, like humans, a diurnal species. Loss of fbxl3a function in zebrafish led to disruption of circadian rhythms of promoter activity and mRNA expression as well as locomotor activity and sleep-wake cycles. However, unlike humans, no morphological effects were evident. These findings point to an evolutionary conserved role for FBXL3 in the circadian clock system across vertebrates and to the acquisition of developmental roles in humans.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche., Materials and Methods: We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background., Result: We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model., Discussion: Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of "intestinal mimicry" provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity., Competing Interests: Declaration of Competing Interest The authors declare that no conflicts of interest exist., (Copyright © 2021. Published by Elsevier Inc.)

The zebrafish represents a powerful model for exploring how light regulates the circadian clock due to the direct light sensitivity of its peripheral clocks, a property that is retained even in organ cultures as well as zebrafish-derived cell lines. Light-inducible expression of the per2 clock gene has been predicted to play a vital function in relaying light information to the core circadian clock mechanism in many organisms, including zebrafish. To directly test the contribution of per2 to circadian clock function in zebrafish, we have generated a loss-of-function per2 gene mutation. Our results reveal a tissue-specific role for the per2 gene in maintaining rhythmic expression of circadian clock genes, as well as clock-controlled genes, and an impact on the rhythmic behavior of intact zebrafish larvae. Furthermore, we demonstrate that disruption of the per2 gene impacts on the circadian regulation of the cell cycle in vivo . Based on these results, we hypothesize that in addition to serving as a central element of the light input pathway to the circadian clock, per2 acts as circadian regulator of tissue-specific physiological functions in zebrafish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruggiero, Ben-Moshe Livne, Wexler, Geyer, Vallone, Gothilf and Foulkes.)

Cellular identity in complex multicellular organisms is determined in part by the physical organization of cells. However, large-scale investigation of the cellular interactome remains technically challenging. Here we develop cell interaction by multiplet sequencing (CIM-seq), an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between cell types present in a tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution into constituent cell types. CIM-seq estimates parameters such as number of cells and cell types in each multiplet directly from sequencing data, making it compatible with high-throughput droplet-based methods. When applied to gut epithelium or whole dissociated lung and spleen, CIM-seq correctly identifies known interactions, including those between different cell lineages and immune cells. In the colon, CIM-seq identifies a previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is directly adjacent to colonic stem cells. Our results demonstrate that CIM-seq is broadly applicable to unsupervised profiling of cell-type interactions in different tissue types., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)