bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical factors associated with in-hospital mortality in elderly versus non-elderly pneumonia patients in the emergency department
Authors: Chongthanadon Brandon , Thirawattanasoot Netiporn , Ruangsomboon Onlak
Published: September 2023

Background

Pneumonia is a respiratory infection with an increasing incidence with age. However, limited evidence has identified factors associated with its outcome among different age groups, especially in the elderly and in the emergency department (ED) setting. We aimed to identify clinical factors associated with in-hospital mortality in elderly versus non-elderly pneumonia patients in the ED.

Methods

A retrospective observational study was conducted at the ED of Siriraj Hospital, Thailand. Patients aged at least 18 years old diagnosed with non-COVID pneumonia between June 1, 2021, and May 31, 2022, were included. They were categorized into the elderly (age ≥ 65 years) and non-elderly (age < 65 years) groups. The primary outcome was in-hospital mortality. We employed multivariate logistic regression models to identify independent factors associated with the outcome in each age group.

Results

We enrolled 735 patients, 515 elderly and 222 non-elderly. There was no difference in in-hospital mortality rate between the two groups (39.0% in the elderly and 32.9% in the non-elderly; p = 0.116). In the elderly cohort, independent factors associated with in-hospital mortality were do-not-resuscitate (DNR) status (adjusted odds ratio (aOR) 12.89; 95% confidence interval (CI) 7.19–23.1; p < 0.001), Glasgow Coma Scale (GCS) score (aOR 0.91; 95%CI 0.85–0.96; p = 0.002), hemoglobin level (aOR 0.9; 95%CI 0.82–0.98; p = 0.012) and the type of initial oxygen support (p = 0.05). Among non-elderly patients, independent factors were DNR status (aOR 6.81; 95%CI 3.18–14.59; p < 0.001), GCS score (aOR 0.89; 95%CI 0.8–0.99; p = 0.025), platelet level (aOR 1; 95%CI 1–1; p = 0.038), Charlson Comorbidity Index (CCI) (aOR 1.12; 95%CI 0.99–1.28; p = 0.078), and the type of initial oxygen support p = 0.079).

Conclusion

In pneumonia patients presenting to the ED, DNR status, lower GCS score, and more invasive initial oxygen supplementation were independently associated with in-hospital mortality in both elderly and non-elderly groups. However, lower hemoglobin level was only associated with in-hospital mortality in the elderly, while higher CCI and lower platelet count were independent factors only in the non-elderly. These findings emphasize the importance of age-specific considerations for the disease, and these factors are potential prognostic markers that may be used in clinical practice to improve patient outcomes.
Acute phase proteins and total antioxidant capacity in free-roaming cats infected by pathogenic leptospires
Authors: Murillo Andrea , Pastor Josep , Serrano Emmanuel , Tvarijonaviciute Asta , Cerón José , Goris Marga , Ahmed Ahmed , Cuenca Rafaela
Published: September 2023

Background

Leptospirosis is a neglected but widespread zoonotic disease throughout the world. Most mammals are hosts ofLeptospira spp.,including domestic cats, species in which no consensus has been reached on the clinical presentation or diagnosis of the disease. The study of acute-phase proteins (APPs) and biomarkers of oxidative status would contribute to knowledge about the disease in cats. This report evaluated four APPs: Serum amyloid A-SAA, Haptoglobin–Hp, albumin and Paraoxonase 1-PON1 and the antioxidant response through Total Antioxidant Capacity-TAC, in 32 free-roaming cats. Cats were classified as seroreactive for anti-leptospiral antibodies (group 1,n = 8), infected withLeptospira spp(group 2,n = 5) and leptospires-free cats (group 3,n = 19).

Results

SAA differences were observed between groups 1 and 2 (p-value = 0.01) and between groups 2 and 3 (p-value = 0.0001). Hp concentration differences were only detected between groups 2 and 3 (p-value = 0.001). Albumin concentrations only differed between groups 1 and 3 (p-value = 0.017) and 2 and 3 (p-value < 0.005). Cats in groups 1 (p-value < 0.005) and 2 (p-value < 0.005) had lower PON1 concentrations than group 3. No statistically significant differences between pairs of groups were detected for TAC concentrations. The principal component analysis (PCA) retained two principal components, (PC1 and PC2), explaining 60.1% of the observed variability of the inflammatory proteins and the antioxidant TAC.

Conclusions

Increases in Serum SAA, Hp, and decreases in PON1 activity may indicate an active inflammatory state in infected cats (currently or recently infected).
Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study
Authors: Robinson Andrew , Huff Ryan D. , Ryu Min Hyung , Carlsten Chris
Published: September 2023

Background

Environmental co-exposure to allergen and traffic-related air pollution is common globally and contributes to the exacerbation of respiratory diseases. Individual responses to environmental insults remain variable due to gene-environment interactions.

Objective

This study examined whether single nucleotide polymorphisms (SNPs) in lung cell surface receptor genes modifies lung function change and immune cell recruitment in allergen-sensitized individuals exposed to diesel exhaust (DE) and allergen.

Methods

In this randomized, double-blinded, four-arm, crossover study, 13 allergen-sensitized participants underwent allergen inhalation challenge following a 2-hour exposure to DE, particle-depleted diesel exhaust (PDDE) or filtered air (FA). Lung function tests and bronchoscopic sample collection were performed up to 48 h after exposures. Transient receptor potential channel (TRPA1 and TRPV1) and toll-like receptor (TLR2 and TLR4) risk alleles were used to construct an unweighted genetic risk score (GRS). Exposure-by-GRS interactions were tested using mixed-effects models.

Results

In participants with high GRS, allergen exposure was associated with an increase in airway hyperresponsiveness (AHR) when co-exposed to PDDE (p = 0.03) but not FA or DE. FA and PDDE also were associated with a relative increase in macrophages and decrease in lymphocytes in bronchoalveolar lavage.

Conclusions

TRPs and TLRs variants are associated with increased AHR and altered immune cellularity in allergen-exposed individuals. This effect is blunted by DE exposure, suggesting greater influence of unmeasured gene variants as primary meditators of a particulate-rich co-exposure.

Trial registration

The study was registered with ClinicalTrials.gov on December 20, 2013 (NCT02017431).
Association between gene methylation and experiences of historical trauma in Alaska Native peoples
Authors: Rogers-LaVanne Mary P. , Bader Alyssa C. , de Flamingh Alida , Saboowala Sana , Smythe Chuck , Atchison Bernadine , Moulton Nathan , Wilson Amelia , Wildman Derek E. , Boraas Alan , Uddin Monica , Worl Rosita , Malhi Ripan S.
Published: September 2023

Background

Historical trauma experienced by Indigenous peoples of North America is correlated with health disparities and is hypothesized to be associated with DNA methylation. Massive group traumas such as genocide, loss of land and foodways, and forced conversion to Western lifeways may be embodied and affect individuals, families, communities, cultures, and health. This study approaches research with Alaska Native people using a community-engaged approach designed to create mutually-beneficial partnerships, including intentional relationship development, capacity building, and sample and data care.

Methods

A total of 117 Alaska Native individuals from two regions of Alaska joined the research study. Participants completed surveys on cultural identification, historical trauma (historical loss scale and historical loss associated symptoms scale), and general wellbeing. Participants provided a blood sample which was used to assess DNA methylation with the Illumina Infinium MethylationEPIC array.

Results

We report an association between historical loss associated symptoms and DNA methylation at five CpG sites, evidencing the embodiment of historical trauma. We further report an association between cultural identification and general wellbeing, complementing evidence from oral narratives and additional studies that multiple aspects of cultural connection may buffer the effects of and/or aid in the healing process from historical trauma.

Conclusion

A community-engaged approach emphasizes balanced partnerships between communities and researchers. Here, this approach helps better understand embodiment of historical trauma in Alaska Native peoples. This analysis reveals links between the historical trauma response and DNA methylation. Indigenous communities have been stigmatized for public health issues instead caused by systemic inequalities, social disparities, and discrimination, and we argue that the social determinants of health model in Alaska Native peoples must include the vast impact of historical trauma and ongoing colonial violence.
Should I stay or should I go? Spatio-temporal control of cellular anchorage by hematopoietic factors orchestrates tumor metastatic cascade
Authors: Marabitti Veronica , Caruana Ignazio , Nazio Francesca
Published: September 2023

The term “metastatic cascade” defines a process whereby few tumor cells complete a sequence of steps to leave the primary tumor to reach one or more sites elsewhere in the body, usually through the bloodstream to develop one or several metastases. Due to the nature and plasticity of cancer, unfortunately no specific and functional anti-metastatic drugs are available. In this Commentary, we are highlighting how four essential factors are able to induce adhesion-to-suspension transition (herein referred to as AST) in human cancer cells and how this process may play a key role in tumor metastasis. We further underlined the potential role of hematopoietic transcriptional regulators in reprogramming anchorage dependency of cells, supporting the possible targeting of AST factors as promising therapeutic strategy to overcome metastasis in solid tumor cells.
“Dual sensitive supramolecular curcumin nanoparticles” in “advanced yeast particles” mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment
Authors: Han Xiaoqin , Luo Ruifeng , Qi Shanshan , Wang Yanli , Dai Linxin , Nie Wenbiao , Lin Meisi , He Haoqi , Ye Naijing , Fu Chaomei , You Yu , Fu Shu , Gao Fei
Published: September 2023

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for “supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects” in “advanced yeast particles”, but also provided strong theoretical support multi-effect therapy for UC.
Functional nanoparticle-enabled non-genetic neuromodulation
Authors: Zhang Zhimin , You Yanling , Ge Min , Lin Han , Shi Jianlin
Published: September 2023

Stimulating ion channels targeting in neuromodulation by external signals with the help of functionalized nanoparticles, which integrates the pioneering achievements in the fields of neurosciences and nanomaterials, has involved into a novel interdisciplinary field. The emerging technique developed in this field enable simple, remote, non-invasive, and spatiotemporally precise nerve regulations and disease therapeutics, beyond traditional treatment methods. In this paper, we define this emerging field as nano-neuromodulation and summarize the most recent developments of non-genetic nano-neuromodulation (non-genetic NNM) over the past decade based on the innovative design concepts of neuromodulation nanoparticle systems. These nanosystems, which feature diverse compositions, structures and synthesis approaches, could absorb certain exogenous stimuli like light, sound, electric or magnetic signals, and subsequently mediate mutual transformations between above signals, or chemical reactions, to regulate stimuli-sensitive ion channels and ion migrations which play vital roles in the nervous system. We will also discuss the obstacles and challenges in the future development of non-genetic NNM, and propose its future developments, to add the further progress of this promising field.

Graphical Abstract
ESRRG-PKM2 axis reprograms metabolism to suppress esophageal squamous carcinoma progression and enhance anti-PD-1 therapy efficacy
Authors: Wang Tianxiao , Zhu Yongjun , Chen Lu , Zhang WenXin , Qi Huijie , Shi Xiaojin , Zhong Mingkang , Chen Haifei , Li Qunyi
Published: September 2023

Background

Glycolysis under normoxic conditions, known as the Warburg effect, confers a selective advantage for the survival and proliferation of many tumors. In this study, we investigated the role of estrogen-related receptor gamma (ESRRG) in metabolic reprogramming in esophageal squamous cell carcinoma (ESCC).

Methods

Bioinformatics analysis indicated that ESRRG expression was decreased in ESCC tissue and associated with poor clinical outcomes. We also examined the effects of altered ESRRG expression on the proliferation and metabolic reprogramming of ESCC cells. We explored the impact of ESRRG on Pyruvate kinase M2 (PKM2) expression and malignant behavior in ESCC.

Results

Our study revealed the inhibitory effects of ESRRG on the growth, tumorigenesis, and glycolysis activity of ESCC cells, which were mediated by the downregulation of PKM2 expression. We further demonstrated that ESRRG directly interacts with the PKM2 promoter to inhibit its activity in ESCC. Notably, the ESRRG-specific agonist, DY131, inhibited ESCC cell proliferation and glycolysis activity by modulating genes in the glycolysis pathway. Moreover, we verified that DY131 exhibits enhanced activity as an immune checkpoint inhibitor, considering the significance of the ESRRG-PKM2 axis in the lactate regulation of ESCC cells.

Conclusion

Our findings provide novel insights into the role of ESRRG-PKM2 signaling in regulating ESCC cell metabolism and immune checkpoint regulation. Additionally, we suggest that DY131 holds promise as a promising therapeutic agent for ESCC treatment.
Cell-therapy for Parkinson’s disease: a systematic review and meta-analysis
Authors: Wang Fang , Sun Zhengwu , Peng Daoyong , Gianchandani Shikha , Le Weidong , Boltze Johannes , Li Shen
Published: September 2023

Background

Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson’s disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.

Methods

We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.

Results

The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the ‘off’ state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6–100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the ‘off’ state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.

Conclusions

This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia.

PROSPERO registration number: CRD42022369760
The interaction between muscle pathophysiology, body mass, walking speed and ankle foot orthosis stiffness on walking energy cost: a predictive simulation study
Authors: Waterval N. F. J. , van der Krogt M. M. , Veerkamp K. , Geijtenbeek T. , Harlaar J. , Nollet F. , Brehm M. A.
Published: September 2023

Background

The stiffness of a dorsal leaf AFO that minimizes walking energy cost in people with plantarflexor weakness varies between individuals. Using predictive simulations, we studied the effects of plantarflexor weakness, passive plantarflexor stiffness, body mass, and walking speed on the optimal AFO stiffness for energy cost reduction.

Methods

We employed a planar, nine degrees-of-freedom musculoskeletal model, in which for validation maximal strength of the plantar flexors was reduced by 80%. Walking simulations, driven by minimizing a comprehensive cost function of which energy cost was the main contributor, were generated using a reflex-based controller. Simulations of walking without and with an AFO with stiffnesses between 0.9 and 8.7 Nm/degree were generated. After validation against experimental data of 11 people with plantarflexor weakness using the Root-mean-square error (RMSE), we systematically changed plantarflexor weakness (range 40–90% weakness), passive plantarflexor stiffness (range: 20–200% of normal), body mass (+ 30%) and walking speed (range: 0.8–1.2 m/s) in our baseline model to evaluate their effect on the optimal AFO stiffness for energy cost minimization.

Results

Our simulations had a RMSE < 2 for all lower limb joint kinetics and kinematics except the knee and hip power for walking without AFO. When systematically varying model parameters, more severe plantarflexor weakness, lower passive plantarflexor stiffness, higher body mass and walking speed increased the optimal AFO stiffness for energy cost minimization, with the largest effects for severity of plantarflexor weakness.

Conclusions

Our forward simulations demonstrate that in individuals with bilateral plantarflexor the necessary AFO stiffness for walking energy cost minimization is largely affected by severity of plantarflexor weakness, while variation in walking speed, passive muscle stiffness and body mass influence the optimal stiffness to a lesser extent. That gait deviations without AFO are overestimated may have exaggerated the required support of the AFO to minimize walking energy cost. Future research should focus on improving predictive simulations in order to implement personalized predictions in usual care.

Trial Registration Nederlands Trial Register 5170. Registration date: May 7th 2015. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5170
Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis
Authors: Zhang Zhengwei , Ye Juan , Liu Xinyu , Zhao Wenjing , Zhao Bing , Gao Xuejiao , Lan Hongli , Wu Yuze , Yang Yang , Cao Peng
Published: September 2023

Background

Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.

Methods

In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora’s role in HGWD for chronic OIPN by pain scoring and related pathological analysis.

Results

HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.

Conclusions

HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.
Characterization of ginsenosides from Panax japonicus var. major (Zhu-Zi-Shen) based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry and desorption electrospray ionization-mass spectrometry imaging
Authors: Jiang Meiting , Li Xiaohang , Zhao Yuying , Zou Yadan , Bai Maoli , Yang Zhiming , Wang Wei , Xu Xiaoyan , Wang Hongda , Yang Wenzhi , Chen Qinhua , Guo Dean
Published: September 2023

Background

Panax japonicus var. major (PJM) belongs to the well-known ginseng species used in west China for hundreds of years, which has the effects of lung tonifying and yin nourishing, and exerts the analgesic, antitussive, and hemostatic activities. Compared with the other Panax species, the chemical composition and the spatial tissue distribution of the bioactive ginsenosides in PJM have seldom been investigated.

Methods

Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) were integrated for the systematic characterization and spatial tissue distribution studies of ginsenosides in the rhizome of PJM. Considering the great difficulty in exposing the minor saponins, apart from the conventional Auto MS/MS (M1), two different precursor ions list-including data-dependent acquisition (PIL-DDA) approaches, involving the direct input of an in-house library containing 579 known ginsenosides (M2) and the inclusion of the target precursors screened from the MS1 data by mass defect filtering (M3), were developed. The in situ spatial distribution of various ginsenosides in PJM was profiled based on DESI-MSI with a mass range of m/z 100–1500 in the negative ion mode, with the imaging data processed by the High Definition Imaging (HDI) software.

Results

Under the optimized condition, 272 ginsenosides were identified or tentatively characterized, and 138 thereof were possibly not ever reported from the Panax genus. They were composed by 75 oleanolic acid type, 22 protopanaxadiol type, 52 protopanaxatriol type, 16 octillol type, 19 malonylated, 35 C-17 side-chain varied, and 53 others. In addition, the DESI-MSI experiment unveiled the differentiated distribution of saponins, but the main location in the cork layer and phloem of the rhizome. The abundance of the oleanolic acid ginsenosides was high in the rhizome slice of PJM, which was consistent with the results obtained by UHPLC/QTOF-MS.

Conclusion

Comprehensive characterization of the ginsenosides in the rhizome of PJM was achieved, with a large amount of unknown structures unveiled primarily. We, for the first time, reported the spatial tissue distribution of different subtypes of ginsenosides in the rhizome slice of PJM. These results can benefit the quality control and further development of PJM and the other ginseng species.
The psychosocial impact of childhood dementia on children and their parents: a systematic review
Authors: Nevin Suzanne M. , McGill Brittany C. , Kelada Lauren , Hilton Gail , Maack Megan , Elvidge Kristina L. , Farrar Michelle A. , Baynam Gareth , Katz Naomi T. , Donovan Leigh , Grattan Sarah , Signorelli Christina , Bhattacharya Kaustuv , Nunn Kenneth , Wakefield Claire E.
Published: September 2023

Background

Childhood dementias are a group of rare and ultra-rare paediatric conditions clinically characterised by enduring global decline in central nervous system function, associated with a progressive loss of developmentally acquired skills, quality of life and shortened life expectancy. Traditional research, service development and advocacy efforts have been fragmented due to a focus on individual disorders, or groups classified by specific mechanisms or molecular pathogenesis. There are significant knowledge and clinician skill gaps regarding the shared psychosocial impacts of childhood dementia conditions. This systematic review integrates the existing international evidence of the collective psychosocial experiences of parents of children living with dementia.

Methods

We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched four databases to identify original, peer-reviewed research reporting on the psychosocial impacts of childhood dementia, from the parent perspective. We synthesised the data into three thematic categories: parents’ healthcare experiences, psychosocial impacts, and information and support needs.

Results

Nineteen articles met review criteria, representing 1856 parents. Parents highlighted extensive difficulties connecting with an engaged clinical team and navigating their child’s rare, life-limiting, and progressive condition. Psychosocial challenges were manifold and encompassed physical, economic, social, emotional and psychological implications. Access to coordinated healthcare and community-based psychosocial supports was associated with improved parent coping, psychological resilience and reduced psychological isolation. Analysis identified a critical need to prioritize access to integrated family-centred psychosocial supports throughout distinct stages of their child’s condition trajectory.

Conclusion

This review will encourage and guide the development of evidence-based and integrated psychosocial resources to optimise quality of life outcomes for of children with dementia and their families.
PHaLIR: prevent hernia after loop ileostomy reversal—a study protocol for a randomized controlled multicenter study
Authors: Eklöv Karolina , Bringman Sven , Löfgren Jenny , Nygren Jonas , Everhov Åsa H.
Published: September 2023

Background

Rectal cancer is a common cancer worldwide. Surgery for rectal cancer with low anterior resection often includes the formation of a temporary protective loop ileostomy. The temporary ostomy is later reversed in a separate operation.

One complication following stoma closure is the development of a hernia at the former stoma site, and this has been reported in 7–15% of patients. The best method to avoid hernia after stoma closure is unclear. The most common closure is by suturing only, but different forms of mesh have been tried. Biological mesh has in a randomized trial halved hernia incidence after stoma reversal. Biosynthetic mesh and retromuscular mesh are currently being evaluated in ongoing studies.

Methods

The present multicenter, double-blinded, randomized, controlled study will compare standard suture closure of the abdominal wall in loop ileostomy reversal with retromuscular synthetic mesh at the stoma site. The study has been approved by the Regional Ethical Review board in Stockholm.

Patients aged 18–90 years, operated on with low anterior resection and a protective loop ileostomy for rectal cancer and planned for ileostomy reversal, will be considered for inclusion in the study. Randomization will be 1:1 on the operation day with concealed envelopes. The estimated sample size is intended to evaluate the superiority of the experimental arm and to detect a reduction of hernia occurrence from 12 to 3%. The operation method is blinded to the patients and in the chart and for the observer at the 30-day follow-up. The main outcome is hernia occurrence at the stoma site within 3 years postoperatively, diagnosed through CT with strain. Secondary outcomes are operation time, length of hospital stay, pain, and 30-day complications.

Discussion

This double-blinded randomized controlled superiority study will compare retromuscular synthetic mesh during the closure of loop ileostomy to standard care. If this study can show a lower frequency of hernia with the use of prophylactic mesh, it may lead to new surgical guidelines during stoma closure.

Trial registration

ClinicalTrials.gov NCT03720262. Registered on October 25, 2018.
The triglyceride glucose index was U-shape associated with all-cause mortality in population with cardiovascular diseases
Authors: Li Haiyu , Jiang Yaohui , Su Xin , Meng Zhe
Published: September 2023

Background

The triglyceride and glucose (TyG) index has been considered a simple surrogate marker of insulin resistance, related to a high risk of mortality. However, few studies have investigated the specific relationship between the TyG index and all-cause mortality among population with cardiovascular diseases.

Methods

2,072 participants with cardiovascular diseases were enrolled from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. The TyG index was calculated as log [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. Outcomes were all-cause mortality and cardiovascular mortality. The baseline levels of TyG associated with the risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by a priori defined quantile categories with Cox regression models.

Results

After a follow-up of 16.8 years, 791 all-cause deaths and 184 cardiovascular deaths occurred. Restricted cubic splines showed that the association between levels of TyG index and the risk of all-cause mortality was non-linear (p < 0.001) and the TyG index associated with the lowest risk of all-cause mortality ranges 8.83 to 9.06 in individuals with cardiovascular diseases. Compared with the reference quartile of 8.84 ~ 9.29, the multivariate-adjusted hazards ratios and 95% confidence intervals were 1.40 (1.13–1.74; p = 0.002) in the lowest quartile and 1.08 (0.88, 1.32; p = 0.475) in the highest quartile for all-cause mortality. However, TyG was not associated with cardiovascular mortality.

Conclusions

TyG index was U-shape associated with the risk of all-cause mortality in participants with cardiovascular diseases and the level associated with the lowest risk ranged 8.83 to 9.06.
Retro-miRs: novel and functional miRNAs originating from mRNA retrotransposition
Authors: Mercuri Rafael L. V. , Conceição Helena B. , Guardia Gabriela D. A. , Goldstein Gabriel , Vibranovski Maria D. , Hinske Ludwig C. , Galante Pedro A. F.
Published: September 2023

Background

Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated.

Results

In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma.

Conclusions

Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer.
A hybrid RNA FISH immunofluorescence protocol on Drosophila polytene chromosomes
Authors: Gilbonio Hannah E. , Puckett Gwyn L. , Nguyen Erica , Rieder Leila E.
Published: September 2023

Objectives

Investigating protein-DNA interactions is imperative to understanding fundamental concepts such as cell growth, differentiation, and cell development in many systems. Sequencing techniques such as ChIP-seq can yield genome-wide DNA binding profiles of transcription factors; however this assay can be expensive, time-consuming, may not be informative for repetitive regions of the genome, and depend heavily upon antibody suitability. Combining DNA fluorescence in situ hybridization (FISH) with immunofluorescence (IF) is a quicker and inexpensive approach which has historically been used to investigate protein-DNA interactions in individual nuclei. However, these assays are sometimes incompatible due to the required denaturation step in DNA FISH that can alter protein epitopes, hindering primary antibody binding. Additionally, combining DNA FISH with IF may be challenging for less experienced trainees. Our goal was to develop an alternative technique to investigate protein-DNA interactions by combining RNA FISH with IF.

Results

We developed a hybrid RNA FISH-IF protocol for use on Drosophila melanogaster polytene chromosome spreads in order to visualize colocalization of proteins and DNA loci. We demonstrate that this assay is sensitive enough to determine if our protein of interest, Multi sex combs (Mxc), localizes to single-copy target transgenes carrying histone genes. Overall, this study provides an alternative, accessible method for investigating protein-DNA interactions at the single gene level in Drosophila melanogaster polytene chromosomes.
Septic shock due to Clostridium botulinum: a case report
Authors: Zomer P. M. L. , Kamps M. J. A.
Published: September 2023

Background

Clostridium botulinum is an anaerobic, Gram-positive, rod-shaped bacterium that forms spores and the neurotoxin botulinum. It is best known for its toxin-induced flaccid paralytic disease, which is deadly without correct treatment. In this report, we show a completely different clinical course with fatal outcome.

Case presentation

A 37-year-old African man born in Sierra Leone was admitted. After admission, his condition rapidly worsened due to severe septic shock and progressive multiorgan failure. No neurological signs were seen. Despite treatment with antibiotics, fluid resuscitation, and norepinephrine, the multiorgan failure deteriorated further and he died as a result. Blood and synovial fluid cultures showed Clostridium botulinum. No botulinum toxins were found.

Conclusion

This is a rare case of fatal septic shock due to Clostridium botulinum-induced septic arthritis without any sign of the classic clinical syndrome of botulism.
Prenatal transmission of severe acute respiratory syndrome coronavirus 2, resulting in neonatal severe acute pneumonia, from an asymptomatic mother: a case report
Authors: Elenga Narcisse , Aboubacar Ahidan Maman Rabiou , Buende Eyenga Régine , Houadjeto Dandjeffo
Published: September 2023

Background

We report a case of prenatal coronavirus disease 2019, which evolved 6 days after birth into severe pneumonia with signs of multiple organ failure, in a mother with asymptomatic coronavirus disease 2019.

Case presentation

At minute 11 of life, our patient from Afro-Caribbean had polypnea with mild signs of struggle; Silverman’s index was scored at three. Chest radiography showed bilateral opacities consistent with respiratory distress syndrome. On the 6th day of life, a thoracic computed tomography scan showed bilateral parenchymatous lesions (10–20%) in ground glass, compatible with coronavirus disease 2019-type infection. At the same time, the neonate showed signs of multiple organ failure (elevated liver and cardiac enzyme levels). She was treated with azithromycin (20 mg/kg/day) for 5 days. All the signs recovered fully by day 12. Real-time polymerase chain reaction results were positive in the first 30 min of life, suggesting prenatal transmission. Our patient has been followed until 2 years old and is developing well with no sequelae.

Conclusion

This case report demonstrates the incompatibility between maternal asymptomatic coronavirus disease 2019 and severe neonatal lung involvement. We emphasize the need for vigilance to avoid missing the most severe forms of neonatal coronavirus disease 2019.
Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3
Authors: Kobori Chie , Takagi Ryo , Yokomizo Ryo , Yoshihara Sakie , Mori Mai , Takahashi Hiroto , Javaregowda Palaksha Kanive , Akiyama Tomohiko , Ko Minoru S. H. , Kishi Kazuo , Umezawa Akihiro
Published: September 2023

Background

Melanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytes in vitro is too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps.

Method

We differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use.

Result

We successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice.

Conclusion

The robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.
RACK1 mediates NLRP3 inflammasome activation during Pasteurella multocida infection
Authors: Ran Jinrong , Yin Hang , Xu Yating , Wang Yu , Li Gang , Wu Xingping , Peng Lianci , Peng Yuanyi , Fang Rendong
Published: September 2023

Pasteurella multocida is a gram-negative bacterium that causes serious diseases in a wide range of animal species. Inflammasomes are intracellular multimolecular protein complexes that play a critical role in host defence against microbial infection. Our previous study showed that bovine P. multocida type A (PmCQ2) infection induces NLRP3 inflammasome activation. However, the exact mechanism underlying PmCQ2-induced NLRP3 inflammasome activation is not clear. Here, we show that NLRP3 inflammasome activation is positively regulated by a scaffold protein called receptor for activated C kinase 1 (RACK1). This study shows that RACK1 expression was downregulated by PmCQ2 infection in primary mouse peritoneal macrophages and mouse tissues, and overexpression of RACK1 prevented PmCQ2-induced cell death and reduced the numbers of adherent and invasive PmCQ2, indicating a modulatory role of RACK1 in the cell death that is induced by P. multocida infection. Next, RACK1 knockdown by siRNA significantly attenuated PmCQ2-induced NLRP3 inflammasome activation, which was accompanied by a reduction in the protein expression of interleukin (IL)-1β, pro-IL-1β, caspase-1 and NLRP3 as well as the formation of ASC specks, while RACK1 overexpression by pcDNA3.1-RACK1 plasmid transfection significantly promoted PmCQ2-induced NLRP3 inflammasome activation; these results showed that RACK1 is essential for NLRP3 inflammasome activation. Furthermore, RACK1 knockdown decreased PmCQ2-induced NF-κB activation, but RACK1 overexpression had the opposite effect. In addition, the immunofluorescence staining and immunoprecipitation results showed that RACK1 colocalized with NLRP3 and that NEK7 and interacted with these proteins. However, inhibition of potassium efflux significantly attenuated the RACK1-NLRP3-NEK7 interaction. Our study demonstrated that RACK1 plays an important role in promoting NLRP3 inflammasome activation by regulating NF-κB and promoting NLRP3 inflammasome assembly.
Environmental approaches to controlling Clostridioides difficile infection in healthcare settings
Authors: Carling Philip C. , Parry Michael F. , Olmstead Russell
Published: September 2023

As today’s most prevalent and costly healthcare-associated infection, hospital-onsetClostridioides difficileinfection (HO-CDI) represents a major threat to patient safety world-wide. This review will discuss how new insights into the epidemiology of CDI have quantified the prevalence ofC. difficile(CD) spore contamination of the patient-zone as well as the role of asymptomatically colonized patients who unavoidable contaminate their near and distant environments with resilient spores. Clarification of the epidemiology of CD in parallel with the development of a new generation of sporicidal agents which can be used on a daily basis without damaging surfaces, equipment, or the environment, led to the research discussed in this review. These advances underscore the potential for significantly mitigating HO-CDI when combined with ongoing programs for optimizing the thoroughness of cleaning as well as disinfection. The consequence of this paradigm-shift in environmental hygiene practice, particularly when combined with advances in hand hygiene practice, has the potential for significantly improving patient safety in hospitals globally by mitigating the acquisition of CD spores and, quite plausibly, other environmentally transmitted healthcare-associated pathogens.
Effects of bathing-induced changes in body temperature on sleep
Authors: Maeda Takafumi , Koga Hiroko , Nonaka Takashi , Higuchi Shigekazu
Published: September 2023

Background

Passive body heating before sleep is well known to lead to improved sleep. However, the effects of the degree of change in body temperature by bathing on sleep quality are unclear. The present study aimed to clarify the effects on sleep of bathing-induced changes in body temperature.

Methods

Twenty-three healthy males and females in their 20 s to 50 s bathed in their homes 1.5–2 h before bedtime under three bathing conditions: showering only; short bathing in a bathtub; and long bathing in a bathtub. Sublingual and skin temperatures and thermal sensation before and after bathing, sleep indices such as sleep onset latency, time in bed, sleep efficiency, and wake after sleep onset, all of which were evaluated using an actimeter, and subjective evaluations of sleep were compared among conditions.

Results

Sublingual temperature just after bathing was significantly higher with long bathing than with other conditions, and the fall in sublingual temperature from after bathing to before sleep was significantly larger with long bathing than with short bathing. Sleep onset latency by actimeter was significantly reduced with long bathing compared to showering. In addition, subjective evaluations of falling asleep and sleep quality were better with long bathing than with showering or short bathing.

Conclusions

In conclusion, bathing conditions that produce a 0.9 °C increase in sublingual temperature appear effective for falling asleep and sleep quality, because core temperature shows a greater drop to before sleep than those producing an increase of about 0.3 °C increase in sublingual temperature.
Microbiota-mediated competition between Drosophila species
Authors: Rombaut Antoine , Gallet Romain , Qitout Kenza , Samy Mukherjy , Guilhot Robin , Ghirardini Pauline , Lazzaro Brian P. , Becher Paul G. , Xuéreb Anne , Gibert Patricia , Fellous Simon
Published: September 2023

Background

The influence of microbiota in ecological interactions, and in particular competition, is poorly known. We studied competition between two insect species, the invasive pest Drosophila suzukii and the model Drosophila melanogaster, whose larval ecological niches overlap in ripe, but not rotten, fruit.

Results

We discovered D. suzukii females prevent costly interspecific larval competition by avoiding oviposition on substrates previously visited by D. melanogaster. More precisely, D. melanogaster association with gut bacteria of the genus Lactobacillus triggered D. suzukii avoidance. However, D. suzukii avoidance behavior is condition-dependent, and D. suzukii females that themselves carry D. melanogaster bacteria stop avoiding sites visited by D. melanogaster. The adaptive significance of avoiding cues from the competitor’s microbiota was revealed by experimentally reproducing in-fruit larval competition: reduced survival of D. suzukii larvae only occurred if the competitor had its normal microbiota.

Conclusions

This study establishes microbiotas as potent mediators of interspecific competition and reveals a central role for context-dependent behaviors under bacterial influence.