bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles
Authors: Polyak Andras , Harting Heidi , Angrisani Nina , Herrmann Timo , Ehlert Nina , Meißner Jessica , Willmann Michael , Al-Bazaz Silav , Ross Tobias L. , Bankstahl Jens P. , Reifenrath Janin
Published: August 2023

Background

Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model.

Methods

PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis.

Results

The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site.

Conclusion

Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.
Emerging non-viral vectors for gene delivery
Authors: Wang Chenfei , Pan Chaolan , Yong Haiyang , Wang Feifei , Bo Tao , Zhao Yitong , Ma Bin , He Wei , Li Ming
Published: August 2023

Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells or tissues to elicit manipulation of gene expression. However, the clinical implementation of gene therapy remains substantially impeded by the lack of safe and efficient gene delivery vehicles. This review comprehensively outlines the novel fastest-growing and efficient non-viral gene delivery vectors, which include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). Particularly, we discuss the research progress, potential development directions, and remaining challenges. Additionally, we provide a comprehensive overview of the currently approved non-viral gene therapeutics, as well as ongoing clinical trials. With advances in biomedicine, molecular biology, materials science, non-viral gene vectors play an ever-expanding and noteworthy role in clinical gene therapy.
Impact of compensation and willingness to keep same career path on burnout among long-term care workers in Japan
Authors: Kim Bum Jung , Choi Clara Jung Won
Published: August 2023

Background

This study examined the relationships between compensation, willingness to keep same career path, and burnout among long-term care workers in Japan.

Methods

Data were collected from 319 care workers at long-term care facilities in Japan. The study variables included data on demographics, compensation, willingness to keep same career path, and burnout.

Results

The study found that compensation and willingness to keep same career were significantly negatively associated with burnout levels among long-term care workers in Japan. Long-term care workers with high compensation levels were found to be more likely to have low burnout levels. In addition, care workers who expressed an intention to keep same career path were likely to have low burnout levels. In addition, compensation is associated with burnout as the mediating role of willingness to keep same career.

Conclusions

These results highlight the importance of implementing policies and measures that reduce the risk of burnout among care workers to improve the quality of care. Strategies for improving working conditions include increasing wages, increasing compensation for experienced care workers, and reorganizing benefits.
Consistency and quality in written accreditation protocols for pediatrician training programs: a mixed-methods analysis of a global sample, and directions for improvement
Authors: Coria Alexandra L. , Hassan Areej , Huang Jui-Yen , Genadry Katia C. , Kumar Rashmi K. , Sergios Ayten , Marshall Roseda E. , Russ Christiana M.
Published: August 2023

Background

The World Federation for Medical Education (WFME) defines accreditation as 'certification of the suitability of medical education programs, and of…competence…in the delivery of medical education.' Accreditation bodies function at national, regional and global levels. In 2015, WFME published quality standards for accreditation of postgraduate medical education (PGME). We compared accreditation of pediatric PGME programs to these standards to understand variability in accreditation and areas for improvement.

Methods

We examined 19 accreditation protocols representing all country income levels and world regions. For each, two raters assessed 36 WFME-defined accreditation sub-areas as present, partially present, or absent. When rating “partially present” or “absent”, raters noted the rationale for the rating. Using an inductive approach, authors qualitatively analyzed notes, generating themes in reasons for divergence from the benchmark.

Results

A median of 56% (IQR 43–77%) of WFME sub-areas were present in individual protocols; 22% (IQR 15–39%) were partially present; and 8.3% (IQR 5.5–21%) were absent. Inter-rater agreement was 74% (SD 11%). Sub-areas least addressed included number of trainees, educational expertise, and performance of qualified doctors. Qualitative themes of divergence included (1) variation in protocols related to heterogeneity in program structure; (2) limited engagement with stakeholders, especially regarding educational outcomes and community/health system needs; (3) a trainee-centered approach, including equity considerations, was not universal; and (4) less emphasis on quality of education, particularly faculty development in teaching.

Conclusions

Heterogeneity in accreditation can be appropriate, considering cultural or regulatory context. However, we identified broadly applicable areas for improvement: ensuring equitable access to training, taking a trainee-centered approach, emphasizing quality of teaching, and ensuring diverse stakeholder feedback.
Streptococcus pneumoniae disrupts the structure of the golgi apparatus and subsequent epithelial cytokine response in an H2O2-dependent manner
Authors: Klabunde Björn , Wesener André , Bertrams Wilhelm , Ringshandl Stephan , Halder Luke D. , Vollmeister Evelyn , Schmeck Bernd , Benedikter Birke J.
Published: August 2023

Background

Lung infections caused by Streptococcus pneumonia are a global leading cause of death. The reactive oxygen species H2O2 is one of the virulence factors of Streptococcus pneumoniae. The Golgi apparatus is essential for the inflammatory response of a eukaryotic cell. Golgi fragmentation was previously shown to be induced by bacterial pathogens and in response to H2O2 treatment. This led us to investigate whether the Golgi apparatus is actively involved and targeted in host–pathogen interactions during pneumococcal infections.

Methods

Following in vitro infection of BEAS-2B bronchial epithelial cells with Streptococcus pneumoniae for 16 h, the structure of the Golgi apparatus was assessed by fluorescence staining of the Golgi-associated protein, Golgin-97. To investigate the effect of H2O2 production on Golgi structure, BEAS-2B cells were treated with H2O2 or the H2O2 degrading enzyme Catalase, prior to Golgi staining. Artificial disruption of the Golgi apparatus was induced by treatment of cells with the GBF1 inhibitor, Golgicide A. A proinflammatory cellular response was induced by treatment of cells with the bacterial cell wall component and TLR4 ligand lipoteichoic acid.

Results

In vitro infection of bronchial epithelial cells with wild type Streptococcus pneumoniae led to a disruption of normal Golgi structure. Golgi fragmentation was not observed after deletion of the pneumococcal H2O2-producing gene, spxB, or neutralization of H2O2 by catalase treatment, but could be induced by H2O2 treatment. Streptococcus pneumoniae infection significantly reduced host cell protein glycosylation and artificial disruption of Golgi structure significantly reduced bacterial adherence, but increased bacterial counts in the supernatant. To understand if this effect depended on cell-contact or soluble factors, pneumococci were treated with cell-supernatant of cells treated with Golgicide A and/or lipoteichoic acid. This approach revealed that lipoteichoic acid conditioned medium inhibits bacterial replication in presence of host cells. In contrast, artificial Golgi fragmentation by Golgicide A treatment prior to lipoteichoic acid treatment rescued bacterial replication. This effect was associated with an increase of IL-6 and IL-8 in the supernatant of lipoteichoic acid treated cells. The increased cytokine release was abolished if cells were treated with Golgicide A prior to lipoteichoic acid treatment.

Conclusion

Streptococcus pneumoniae disrupts the Golgi apparatus in an H2O2-dependent manner, thereby inhibiting paracrine anti-infective mechanisms.
The tight junction protein claudin 6 is a potential target for patient-individualized treatment in esophageal and gastric adenocarcinoma and is associated with poor prognosis
Authors: Simon Adrian Georg , Lyu Su Ir , Laible Mark , Wöll Stefan , Türeci Özlem , Şahin Uğur , Alakus Hakan , Fahrig Luca , Zander Thomas , Buettner Reinhard , Bruns Christiane Josephine , Schroeder Wolfgang , Gebauer Florian , Quaas Alexander
Published: August 2023

Background

The prognosis of esophageal adenocarcinoma (EAC) and gastric adenocarcinoma (GAC) remains poor, and new therapeutic approaches are urgently needed. Claudin 6 (CLDN6) is an oncofetal antigen that is largely absent in healthy tissues and upregulated in several cancers, making it a promising therapeutical target. In this study, the expression of CLDN6 was assessed in an large Caucasian EAC and GAC cohort.

Methods

RNA-Seq data from 89 EACs and 371 GACs were obtained from The Cancer Genome Atlas project and EAC/GAC cases were stratified by CLDN6 mRNA expression based on a survival-associated cutoff. For groups with CLDN6 expression above or below this cutoff, differential gene expression analyses were performed using DESeq, and dysregulated biological pathways were identified using the Enrichr tool. Additionally, CLDN6 protein expression was assessed in more than 800 EACs and almost 600 GACs using a CLDN6-specific immunohistochemical antibody (clone 58-4B-2) that is currently used in Phase I/II trials to identify patients with CLDN6-positive tumors (NCT05262530; NCT04503278). The expression of CLDN6 was also correlated with histopathological parameters and overall survival (OS).

Results

EACs and GACs with high CLDN6 mRNA levels displayed an overexpression of pathways regulating the cell cycle, DNA replication, and receptor / extracellular matrix interactions. CLDN6 protein expression was associated with shorter OS in EAC and GAC, both in treatment-naïve subgroups and cohorts receiving neoadjuvant therapy. In multivariate analysis, CLDN6 protein expression was an independent adverse prognostic factor in EAC associated with a shorter OS (HR: 1.75; p = 0.01) and GAC (HR: 2.74; p = 0.028).

Conclusions

High expression of CLDN6 mRNA is associated with the dysregulation of distinct biological pathways regulating cell growth, proliferation, and cell–matrix interactions. Clinically, the expression of CLDN6 protein is a valuable adverse prognostic marker in EAC and GAC.
The health consequences of informal employment among female workers and their children: a systematic review
Authors: Aronsson Amanda Emma , Vidaurre-Teixidó Pilar , Jensen Magnus Rom , Solhaug Solvor , McNamara Courtney
Published: August 2023

Background

Informal employment is unprotected and unregistered and it is often characterized by precarious working arrangements. Although being a global phenomenon and the most common type of employment worldwide, scholarly attention to its health effects has only recently accelerated. While there is still some debate, informal employment is generally understood to be detrimental to workers’ health. However, because women are more vulnerable to informality than men, attention is required to the health consequences of female workers specifically. We conducted a systematic review with the objective to examine the global evidence on the consequences of informal employment, compared to formal employment, on the health of female workers and their children.

Methods

We searched peer-reviewed literature in Embase, Medline, PsychInfo, Scopus and Web of Science up until November 11, 2022. No restrictions were applied in terms of year, language or country. Individual-level quantitative studies that compared women of reproductive age in informal and formal employment, or their children (≤ 5 years), were eligible for inclusion. If studies reported outcomes per subgroup level, these were included. Study quality was assessed using the Joanna Briggs Institute checklist and a narrative synthesis of the results were conducted.

Results

13 articles were included in the review, looking at breastfeeding outcomes (n = 4), child nutritional status and low birthweight (n = 4), antenatal health (n = 3), and general health outcomes for women (n = 2). The overall evidence from the included studies was that compared to formal employment, there was an association between informal employment and worse health outcomes, especially on child nutritional status and antenatal health. The evidence for breastfeeding outcomes was mixed and showed that informal employment may be both protective and damaging to health.

Conclusion

This review showed that informal employment is a potential risk factor for health among female workers and their children. Further research on the pathways between informal employment and health is needed to strengthen the understanding of the health consequences of informal employment.
Changes in brain structure in subjects with resistance to thyroid hormone due to THRB mutations
Authors: Rogge Berenike , Heldmann Marcus , Chatterjee Krishna , Moran Carla , Göttlich Martin , Uter Jan , Wagner-Altendorf Tobias A. , Steinhardt Julia , Brabant Georg , Münte Thomas F. , Cirkel Anna
Published: August 2023

Background

Being critical for brain development and neurocognitive function thyroid hormones may have an effect on behaviour and brain structure. Our exploratory study aimed to delineate the influence of mutations in the thyroid hormone receptor (TR) ß gene on brain structure.

Methods

High-resolution 3D T1-weighted images were acquired in 21 patients with a resistance to thyroid hormone ß (RTHß) in comparison to 21 healthy matched-controls. Changes in grey and white matter, as well as cortical thickness were evaluated using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

Results

RTHß patients showed elevated circulating fT4 & fT3 with normal TSH concentrations, whereas controls showed normal thyroid hormone levels. RTHß patients revealed significantly higher scores in a self-rating questionnaire for attention deficit hyperactivity disorder (ADHD). Imaging revealed alterations of the corticospinal tract, increased cortical thickness in bilateral superior parietal cortex and decreased grey matter volume in bilateral inferior temporal cortex and thalamus.

Conclusion

RTHb patients exhibited structural changes in multiple brain areas. Whether these structural changes are causally linked to the abnormal behavioral profile of RTHß which is similar to ADHD, remains to be determined.
Radical antegrade modular pancreatosplenectomy (RAMPS) versus standard retrograde pancreatosplenectomy (SRPS) for resectable body and tail pancreatic adenocarcinoma: protocol of a multicenter, prospective, randomized phase III control trial (CSPAC-3)
Authors: Li Jialin , Shi Si , Liu Jiang , Liang Chen , Hua Jie , Meng Qingcai , Xu Hang , Wei Miaoyan , Zhang Bo , Xu Jin , Wang Wei , Yu Xianjun
Published: August 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Radical surgical resection offers the only potential cure. There is increasing agreement that radical antegrade modular pancreatosplenectomy (RAMPS) may benefit patients with tumors in the body and tail of the pancreas. To address this, the Chinese Study Group for Pancreatic Cancer (CSPAC)-3 trial is proposed to compare the effect of RAMPS and standard retrograde pancreatosplenectomy (SRPS) on patient survival and preoperative safety

Methods

The randomized controlled trial will be multicenter and two-armed with blinded outcomes and intention-to-treat analysis. Three hundred patients with resectable body and tail pancreatic adenocarcinoma will be enrolled and randomly assigned to RAMPS or SRPS. Adjuvant chemotherapy based on an initial regimen will be recommended 4–6 weeks after surgery if no serious complication occurs. The hypothesis that RAMPS improves survival outcomes compared with SRPS will be tested using a superiority trial. The primary outcome will be overall survival (OS). Secondary outcomes will include recurrence-free survival (RFS), R0 resection rate, the number of harvested lymph nodes, postoperative complications, and quality of life scores.

Discussion

The use of RAMPS has increased over the past decade. It is reported that RAMPS is superior to SRPS in improving both the rate of R0 resection and lymph node yield. Despite these advantages, however, there is little high-level documentation of the superiority of RAMPS in terms of survival and this needs to be investigated. To address this issue, CSPAC has instigated the first prospective, randomized phase III control trials, aiming to explore the optimal surgical strategy for improving the prognosis and OS of patients with left-sided pancreatic cancer

Trial registration

Chinese Clinical Trial Registry ChiCTR2100053844; pre-results. Registered on December 1, 2021.
Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial
Authors: Rees Chris A. , Brousseau David C. , Cohen Daniel M. , Villella Anthony , Dampier Carlton , Brown Kathleen , Campbell Andrew , Chumpitazi Corrie E. , Airewele Gladstone , Chang Todd , Denton Christopher , Ellison Angela , Thompson Alexis , Ahmad Fahd , Bakshi Nitya , Coleman Keli D. , Leibovich Sara , Leake Deborah , Hatabah Dunia , Wilkinson Hagar , Robinson Michelle , Casper T. Charles , Vichinsky Elliott , Morris Claudia R. ,   the SCD Arginine Study Group and PECARN
Published: August 2023

Background

Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

Methods

STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant’s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE.

Discussion

Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children.

Trial registration

The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).
The role of the communicated treatment rationale on treatment outcome: study protocol for a randomized controlled trial
Authors: Henrich Liv , Wilhelm Marcel , Lange Philipp , Rief Winfried
Published: August 2023

Background

Placebo effects are a well-established phenomenon in the treatment of depression. However, the mechanism underlying these effects are not fully understood. Treatment expectations are considered one explanation for why placebos work. Treatment expectations are likely to be affected by clinician-patient interactions. This study aims to investigate the role of the communicated treatment rationale in modulating treatment expectations and its effects on the treatment outcomes of a pharmacological and a psychological active placebo intervention for depression. In this study, treatment expectations are modulated by presenting illness models that are either congruent or incongruent with the treatment intervention that follows.

Methods

This 2 × 2 randomized controlled trial will involve patients with major depression. Participants will either receive a biological or a psychological illness model from a clinician. Following this, they are randomly assigned to receive either a pharmacological or a psychological active placebo intervention. The illness model and the treatment are either congruent or incongruent with each other, resulting in four groups. In addition, a natural course control group will be included.

Discussion

This study will provide insights into the mechanism of expectation modulation in active placebo treatments for major depression. The results may provide insights for clinicians to improve their communication with patients by focusing on treatment expectations. By identifying the factors that contribute to placebo effects, this study has the potential to improve the effectiveness of existing depression treatments and reduce the burden of this highly prevalent mental health condition.

Trial registration

This trial has been registered prospectively at ClinicalTrials.gov under the identifier: NCT04719663. Registered on January 22, 2021.
A member of the CAP protein superfamily, Hc-CAP-15, is important for the parasitic-stage development of Haemonchus contortus
Authors: Liu Hui , Tao Zhuolin , Wang Yifan , Liu Xin , Wang Chunqun , Liu Lu , Hu Min
Published: August 2023

Background

The CAP superfamily proteins are distributed widely in eukaryotes and play crucial roles in various biological processes. However, very little is known about their functions in parasitic nematodes, including Haemonchus contortus, a socioeconomically important parasitic nematode. We have therefore studied a member of the CAP protein family of H. contortus, named Hc-CAP-15, with the aim to explore its roles in regulating the parasitic developmental process.

Methods

The conservation and phylogenetic relationships, spatial expression and temporal transcription profiles of Hc-CAP/cap-15, as well its biological function during parasite development were investigated using bioinformatics, immunofluorescence, real-time PCR and RNA interference (RNAi).

Results

Hc-CAP-15 was found to be a single-domain CAP protein consisting of four conserved motifs that is localized in the cuticle, intestine and oocyte of adult worms. Hc-cap-15 was transcribed at all developmental stages of H. contortus, with the highest transcription level in parasitic fourth-stage larvae (L4s). Silencing of Hc-cap-15 resulted in a significant increase in the body length of L4s.

Conclusions

The results suggested that Hc-CAP-15 is important for the development of H. contortus. Our findings provide a basis for further study of the functions of the CAP family proteins in H. contortus and related parasitic nematodes.

Graphical Abstract
The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study
Authors: Lin Tsung-Kun , Lee Mei-Chun , Cheng Yu-Han , Ma Timothy , Chen Mei-Chun , Yang Tsung-Yuan , Jong Gwo-Ping
Published: August 2023

Background

Several observational cohorts and meta-analytical studies on humans have shown that users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a lower risk for new-onset acute coronary syndrome (ACS) than nonusers. However, some studies, including randomized clinical trials, reported the opposite results. This study aimed to investigate the impacts of a SGLT2i on new-onset ACS in a population.

Methods

We conducted a retrospective population-based cohort study involving 56,356 subjects who received SGLT2i therapy and 112,712 patients who did not receive SGLT2i therapy between May 1, 2016 and December 31, 2019. The outcome was the risk of new-onset ACS. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals for associations between SGLT2i use and ACS risk.

Results

A total of 670 and 1408 ACS events occurred in SGLT2i users and nonusers, respectively, during a follow-up of 3.7 years. SGLT2i use was associated with a nonsignificantly lower risk of ACS (adjusted HR 0.95, 95%confidence intervals (CI 0.87–1.04, P = 0.3218). We confirmed the robustness of these results through a propensity score 1:1 matching analysis. The results of the subgroup analysis of the subtype of the SGLT2i treatments were consistent with the main findings. An increased risk for the incidence of ACS in male and older (> 70 years) patients were also found.

Conclusions

In this population-based cohort study, we found that SGLT2i use is associated with a nonsignificantly decreased risk of ACS. No difference in the SGLT2i subtype was observed in subgroup analyses. However, the results of this study indicated an increased risk for the incidence of ACS in male and older (> 70 years) patients.
Draft genome sequence of two “Candidatus Intestinicoccus colisanans” strains isolated from faeces of healthy humans
Authors: Zhou Joyce , Boyd Joel A , Nyeverecz Bozica , Vivian Charlotte , Angel Nicola , Wood David L A , Hugenholtz Philip , Tyson Gene W , Krause Lutz , Ó Cuív Páraic
Published: August 2023

Objectives

In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, “Candidatus Intestinicoccus colisanans” gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome.

Data description

Here, we report the first draft genome sequences of “Candidatus Intestinicoccus colisanans” strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that “Candidatus Intestinicoccus colisanans” represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be > 98% completed and to range in size from 2.9 to 3.3 Mb with a G + C content of approximately 51%. The gene repertoire of “Candidatus Intestinicoccus colisanans” indicate it is likely a saccharolytic gut bacterium.
On the qualitative evaluation of the variable-order coupled boundary value problems with a fractional delay
Authors: Hammad Hasanen A. , Aydi Hassen , Zayed Mohra
Published: August 2023

The logical progression from the constant order differential equations is the field of variable-order differential equations. Such equations can frequently give a more succinct description of problems in the real world. In light of this, we therefore take into account a class of coupled boundary value problems under variable-order differentiation. By utilizing the fixed-point techniques of Banach and Schauder, we investigate the existence and uniqueness of solutions to the proposed problem. Also, sufficient results are documented for the necessary needs. Furthermore, some stability results based on the ideas of Ulam, Hyers, and Rassias are elaborated upon. Ultimately, appropriate examples and in-depth analysis are presented to support our results.
Prevalence of epilepsy in the onchocerciasis endemic middle belt of Ghana after 27 years of mass drug administration with ivermectin
Authors: Otabil Kenneth Bentum , Ankrah Blessing , Bart-Plange Emmanuel John , Donkoh Emmanuel Sam , Avarikame Fiona Amoabil , Ofori-Appiah Fredrick Obeng , Babae Theophilus Nti , Kudzordzi Prince-Charles , Darko Vera Achiaa , Ameyaw Joseph , Bamfo Joseph Gyekye , Sakibu Raji Abdul , Antwi-Berko Daniel , Fodjo Joseph Nelson Siewe , Basáñez María-Gloria , Schallig Henk D. F. H. , Colebunders Robert
Published: August 2023

Background

In onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission, a high prevalence of epilepsy has been reported. This study aimed to determine the prevalence and clinical characteristics of epilepsy in the Bono Region of Ghana following 27 years of implementation of ivermectin mass drug administration (MDA).

Methods

Between October 2020 and August 2021, cross-sectional surveys were conducted in nine communities in the Tain District and Wenchi Municipality of the Bono Region of Ghana. In the first stage, a random door-to-door approach was used to screen the population for epilepsy using a pre-tested questionnaire. Persons suspected of having epilepsy were invited for a second-stage neurological examination for case verification. Community O. volvulus microfilarial infection status and Ov16 seropositivity were also determined. Ninety-five confidence intervals (95% CI) for prevalence values were calculated using the Wilson Score Interval.

Results

Of the 971 participants, 500 (51.5%) were females, and the median age (interquartile range) was 26 (15‒43) years. Fourteen participants (1.4%, 95% CI: 1.0‒2.0) were diagnosed as having epilepsy with generalized seizures being the most frequent seizure type (85.7%, 12/14). The overall microfilarial prevalence of O. volvulus was 10.3% (November 2020) and 9.9% (August 2021); the Ov16 seroprevalence was 22.2% (June 2021). Only 63.2% took ivermectin in the last round of MDA distribution in March 2021.

Conclusions

The 1.4% prevalence of epilepsy in the Bono region is similar to the median epilepsy prevalence in sub-Saharan Africa. However, the persistent microfilarial prevalence and low ivermectin study coverage call for the Ghana Onchocerciasis Elimination Programme to step up its efforts to ensure that the gains achieved are consolidated and improved to achieve the elimination of onchocerciasis by 2030.

Graphical Abstract
Metamizole-induced agranulocytosis (MIA): a mini review
Authors: Tomidis Chatzimanouil Markos K. , Goppelt Ines , Zeissig Yvonne , Sachs Ulrich J. , Laass Martin W.
Published: August 2023

Metamizole is an analgesic, antipyretic, and spasmolytic drug in Germany only approved for the treatment of severe pain or high fever that does not respond to other measures. In recent years, an increased use has been described among both adults and children, often against the approved indication. The most important side effect of metamizole is the development of agranulocytosis (neutrophil count < 500/µL). Incidence of metamizole-induced agranulocytosis (MIA) ranges depending on the study from 0.96 cases per million per year to 1:1602 per patient and metamizole prescription. The risk of agranulocytosis in children remains unclear, but is probably lower than in adults. Female gender and older age are associated with higher incidence, reflecting prescription distribution. MIA is dose-independent and risk seems to increase with duration of intake. In patients with past exposure, re-exposure may lead to rapid onset. MIA is believed to be induced either through immunologic or toxic mechanisms. MIA presents with fever, sore throat, fatigue, and mucosal inflammation, up to ulceration. Even in the case of suspected MIA, treatment with metamizole should be immediately paused and an examination of the blood cell count is required. In case of local or systemic infections, empirical therapy with broad-spectrum antibiotics should be administered. G-CSF therapy should be limited to patients with poor prognostic factors. The patient should be monitored closely until the neutrophil count returns to normal. Re-exposure to metamizole must be avoided.
Distinct host-response signatures in circulatory shock: a narrative review
Authors: Soussi Sabri , dos Santos Claudia , Jentzer Jacob C. , Mebazaa Alexandre , Gayat Etienne , Pöss Janine , Schaubroeck Hannah , Billia Filio , Marshall John C. , Lawler Patrick R.
Published: August 2023

Circulatory shock is defined syndromically as hypotension associated with tissue hypoperfusion and often subcategorized according to hemodynamic profile (e.g., distributive, cardiogenic, hypovolemic) and etiology (e.g., infection, myocardial infarction, trauma, among others). These shock subgroups are generally considered homogeneous entities in research and clinical practice. This current definition fails to consider the complex pathophysiology of shock and the influence of patient heterogeneity. Recent translational evidence highlights previously under-appreciated heterogeneity regarding the underlying pathways with distinct host-response patterns in circulatory shock syndromes. This heterogeneity may confound the interpretation of trial results as a given treatment may preferentially impact distinct subgroups. Re-analyzing results of major ‘neutral’ treatment trials from the perspective of biological mechanisms (i.e., host-response signatures) may reveal treatment effects in subgroups of patients that share treatable traits (i.e., specific biological signatures that portend a predictable response to a given treatment). In this review, we discuss the emerging literature suggesting the existence of distinct biomarker-based host-response patterns of circulatory shock syndrome independent of etiology or hemodynamic profile. We further review responses to newly prescribed treatments in the intensive care unit designed to personalize treatments (biomarker-driven or endotype-driven patient selection in support of future clinical trials).
The relationship between the intake of fruits, vegetables, and dairy products with hypertension: findings from the STEPS study
Authors: Nouri Mehran , Shateri Zainab , Vali Mohebat , Faghih Shiva
Published: August 2023

Background

The current research aimed to evaluate the relationship between fruit, vegetable (FV), and dairy consumption with the odds of developing hypertension based on nationwide Stepwise approach to surveillance (STEPS) data in Iran.

Methods

This cross-sectional study was accomplished by the research center of non-communicable diseases (NCDs) in Tehran. In total, 29,378 individuals’ data were analyzed. Participants were classified into normal, elevated BP, stage I, and stage II hypertension according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) examinations. Based on the STEPS questionnaire, the consumption of FVs and dairy products was evaluated. Multinomial logistic regression was applied to assess the relationship between the consumption of FVs and dairy products with hypertension.

Results

The findings revealed that only fruit consumption (≥ 2 servings/day) was negatively related to stage I hypertension (odds ratio (OR) = 0.81; 95% confidence interval (CI): 0.69–0.95) in two servings per day and OR = 0.81; 95% CI: 0.68–0.96 in > two servings per day) in the adjusted model. There was no significant relationship between consuming vegetables and dairy products with elevated BP and hypertension.

Conclusion

Our study showed that increasing fruit consumption was related to reducing hypertension odds. Regarding the consumption of dairy products and vegetables, no significant relationship was found with the odds of hypertension. More studies, especially cohorts, are needed to evaluate the impacts of FV and dairy products on the risk of hypertension.
In-between duty and hope for recognition, the experience of physiotherapists working in a university hospital during the COVID-19 first wave in Switzerland: a qualitative study based on focus groups
Authors: Pichonnaz Claude , Foley Rose-Anna
Published: August 2023

Background

Learning more about the physiotherapists’ experience, perceived role and perception of events during the COVID-19 crisis, as well as their recovery and projection into the post-crisis future, may be useful to inform stakeholders about the impact of the crisis.

The objective of this study was to investigate the experience of physiotherapists working in a university hospital in Switzerland during the 1st wave of the COVID-19 crisis, more specifically their subjective experience, professional involvement, perception of management and perceived implications for the future.

Methods

This interpretative qualitative study investigated the subjective experience of a purposeful sample of 12 physiotherapists using two 2 h semi-directive focus group interviews conducted by a physiotherapist in June 2020. Data were recorded, transcribed, and analysed using a thematic analysis approach. The report was approved by participants and the study was audited by a health anthropologist.

Results

The most impressive points were the unprecedented nature of the crisis, the health threat, the hospital's capacity to reorganise on a large scale and the solidarity between colleagues. Participants expressed a high level of commitment to their role despite the potentially serious repercussions at an individual level. Pride and stress coexisted for those directly involved in the crisis, while those working in a reduced activity department felt anxious and idle. The need for immediacy in decision-making and action led to a flattening of hierarchies and an increase of uncertainties. Communication management was seen as the main area for improvement. Physiotherapists hoped that their involvement would improve recognition of the profession but feared that working conditions would deteriorate after the crisis.

Conclusions

The physiotherapists expressed high dedication to their profession and pride to be part of the “war effort” during the crisis. The stress level was partly tempered by the solidarity amongst health professionals and distraction by engaging in action. Despite the mental load, this situation was also seen as an opportunity to grow at a personal and professional level. The healthcare system capacity having not been exceeded in Switzerland, less distress related to death and powerlessness were expressed than in other studies investigating healthcare professionals’ experience of the COVID-19 crisis.
Stationary transport above the critical velocity in a one-dimensional superflow past an obstacle
Authors: Huynh J. , Hébert F. , Larré P.-É. , Albert M.
Published: August 2023

We consider in this work the different possible stationary flows of a one-dimensional quantum fluid in the mean-field regime. We focus on the supersonic regime where a transition from a time-dependent flow to a stationary diffractive flow occurs at a given critical velocity. We give nonperturbative results for this critical velocity in the presence of a localised obstacle of arbitrary size and strength. In addition, we discuss the existence of superfluid-like solution in the supersonic regime due to resonant transport and provide a complete map of the different regimes of stationary transport of a quantum fluid.
Non–REM Sleep Parasomnias
Authors: Spector Andrew R.
Published: August 2023

OBJECTIVE

Non–rapid eye movement (non-REM) parasomnias are common across the lifespan. This article describes the manifestations, diagnosis, and management of non-REM parasomnias in adults and discusses the social implications of these conditions.

LATEST DEVELOPMENTS

Non-REM parasomnias represent a hybrid state of wakefulness and sleep, often triggered by events that increase the frequency of arousals or make it more difficult to fully arouse from sleep. Sleep deprivation, certain medications, and untreated obstructive sleep apnea are known to provoke parasomnias, particularly in those who are genetically predisposed. Non-REM parasomnias include disorders of arousal (ie, sleepwalking, sleep terrors, and confusional arousals), sleep-related eating disorder, and exploding head syndrome. Clinical overlap exists between sleep-related eating disorder and disorders of arousal, suggesting that sleep-related eating disorder may be a fourth disorder of arousal or a manifestation of sleepwalking. Exploding head syndrome is a unique parasomnia of uncertain etiology.

ESSENTIAL POINTS

Non-REM parasomnias can range from minor nuisances to severe, life-altering events. While some patients with non-REM parasomnia experience significant consequences during sleep, wakefulness, or both, non-REM parasomnias do not pose a major risk to most patients. For all patients with non-REM parasomnias, safety should be explicitly discussed and addressed. Nonpharmacologic treatment should be prioritized, as increasing total sleep time, avoiding triggering substances, and treating comorbid sleep disorders is often sufficient for the management of non-REM parasomnias. If symptoms persist despite these interventions, treatment with clonazepam or other medications can be considered.
Obstructive Sleep Apnea
Authors: Johnson Karin G.
Published: August 2023

Objective

Obstructive sleep apnea (OSA) is the most common type of sleep-disordered breathing. This article describes advances in the diagnosis, testing, treatment, and monitoring of OSA.

Latest Developments

Home sleep apnea testing and in-laboratory polysomnography are the most commonly used diagnostic tools in the identification and monitoring of OSA, but new methods for diagnosis and at-home monitoring of treatment response are being developed and validated. While the apnea-hypopnea index is regularly used to define OSA severity, recognition is increasing of its inability to risk-stratify patients. Other sleep study data including arousal threshold, hypoxic burden, and pulse rate variability as well as clinical characteristics can help with risk stratification. The most effective treatment is continuous positive airway pressure (CPAP), which can be limited by adherence and tolerance in some patients. Newer masks and comfort features including heated tubing and expiratory pressure relief may improve tolerance to positive airway pressure (PAP) therapy. Additional treatment options include other PAP modalities, mandibular advancement devices, tongue stimulation therapy, negative inspiratory pressure, nasal expiratory pressure valves, nasal congestion treatments, upper airway surgeries including hypoglossal nerve stimulation, and medications.

Essential Points

OSA is a common disorder that causes sleep and daytime symptoms and increases the risk of neurologic and medical complications. Neurologists should be aware of atypical presentations and understand the diagnostic and treatment options.
Henry Hazlitt Unbound: Pamphlets, Markets, and Economic Education after World War II
Authors: Milazzo Paul Charles
Published: August 2023

Previous scholars have described the American business journalist Henry Hazlitt as “an intellectual middleman for orthodox economics.” This article examines Hazlitt's career during the immediate post–World War II era to flesh out how he performed this intermediary role in a specific historical context. A spotlight on unbound print media demonstrates how they enabled Hazlitt to transmit his ideas about the postwar political economy beyond traditional mainstream venues, extending and animating the reading public. Hazlitt's engagement with pamphlet literature likewise inspired a collaboration with Leonard Read that helped lay the groundwork for the Foundation for Economic Education (FEE), the first postwar libertarian think tank. Hazlitt and FEE embarked on a reciprocal relationship during the organization's early years: FEE raised Hazlitt's profile by publicizing and disseminating his influential books Economics in One Lesson (1946) and Will Dollars Save the World? (1947) in pamphlet form, while the organization sought to build its brand by linking itself to the journalist's mainstream credibility. Examining Hazlitt's pamphlet trail in this way reaffirms his popular reach; underscores his unique role as an intellectual, interpersonal, and institutional go-between; and makes a case for his inclusion alongside other key figures in the historiography of the twentieth-century American Right.
Economics as a “Story Engine”: John D. McDonald and Business as Game and Gamble
Authors: Mata Tiago
Published: August 2023

John D. McDonald was a writer and editor best known for his work at Fortune magazine in the 1950s and 1960s and as the ghostwriter of the memoirs of Alfred P. Sloan. McDonald was also the first person to popularize game theory. In this article I argue that game theory played a key role in McDonald's transition from documentary writer to business journalist. Game theory gave McDonald a journalistic device to discover business stories and to give those stories a driving tension; he called it a “story engine.” After decades writing with game theory, it began to serve a different purpose for McDonald. By coding business stories as games, McDonald gained insight into the characters, corporate executives who were often brief in explanations and shallow in self-understanding. McDonald's career gives us a glimpse at an extraordinary transformation of how a set of scholarly ideas can become a literary resource for vividness (of stories) and depth (of characters).