bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression in Torn Rotator Cuff Tendons Determined by RNA Sequencing
Authors: Tashjian Robert Z. , Lock Ian , Granger Erin K. , Wang Yangliang , Lee Younghee , Chalmers Peter N. , Jones Kevin B.
Published: June 2020

Background:

Although the cause of rotator cuff tearing is likely multifactorial and a genetic predisposition has been proposed, the biochemical basis remains unknown.

Purpose:

To determine gene expression profiles in torn rotator cuff tendon tissue through use of RNA sequencing.

Study Design:

Controlled laboratory study.

Methods:

The supraspinatus tendon edge was biopsied in 24 patients undergoing arthroscopic rotator cuff repair for full-thickness supraspinatus rotator cuff tears. The supraspinatus tendon was also biopsied in 9 patients undergoing open reduction and internal fixation for a proximal humeral fracture (controls). Total RNA was extracted and sequenced. Differential gene expression was analyzed between the tear and control groups, and a secondary analysis was conducted between groups defined by an unbiased clustering.

Results:

Tear and control transcriptomes demonstrated significant differential expression in more than 3000 genes. The identified differential genes were highlighted in pathways involved in inflammation in control patients and extracellular matrix generation in patients with tears. Secondary analysis using unsupervised and thus unbiased hierarchical clustering revealed 2 clusters (c2 and c3). Cluster c3 contained smaller ( P < .001) and less retracted ( P = .018) tears (ie, tears earlier in the progression of rotator cuff disease) with increased expression of hypoxia target genes. Cluster c2 contained larger, more retracted tears (ie, tears further in the progression of rotator cuff disease) with increased expression of endothelial cell markers and chronic inflammation target genes. Tears in c2 had significantly worse healing rates compared with tears in c3 (0% vs 89%; P = .007).

Conclusion:

Smaller, less retracted tears had increased expression of hypoxia target genes and improved healing, whereas larger, more retracted tears were associated with endothelial cell markers and worse healing. Thus, hypoxia may be the inciting event for tear development, whereas with tear enlargement, a chronic, inflammatory, angiogenic process may predominate.

Clinical Relevance:

Identification of differential gene expression in rotator cuff tears may be a reliable tool to predict repair healing in the future.
Painful Palpation of the Tibial Insertion of the Anterolateral Ligament Is Concordant With Acute Anterolateral Ligament Injury
Authors: Murgier Jérôme , Thomas Pierre , Reina Nicolas , Sylvie Rémi , Bérard Emilie , Cavaignac Etienne
Published: June 2020

Background:

The anterolateral ligament (ALL) has been shown to contribute to the rotational stability of the knee. However, no clinical sign specific to ALL injury has been described.

Purpose/Hypothesis:

The primary aim of this study was to determine the concordance between pain elicited upon ALL palpation and ALL injury diagnosed by ultrasonography (US). The secondary aim was to look for a relationship between ALL injury and high-grade pivot shift. We hypothesized that an ALL lesion can be diagnosed clinically in an acute knee injury by palpating its tibial insertion.

Study Design:

Cohort study (diagnosis); Level of evidence, 2.

Methods:

A total of 130 patients (89 men, 41 women; mean age, 27.2 ± 8.3 years) with an acute, isolated anterior cruciate ligament injury who were scheduled for ligament reconstruction were enrolled in this study. ALL palpation was carried out a mean 8.8 ± 3.2 days after injury. Preoperatively, ALL integrity was evaluated with US, and the pivot shift was determined under general anesthesia. The agreement between pain upon ALL palpation and ALL injury detected on US was determined by calculating the intraclass correlation coefficient (ICC), along with 95% CIs.

Results:

Distal palpation of the ALL tibial insertion elicited pain in 67 (51.5%) patients, and upon US the ALL was found to be damaged in 64 (49.2%) patients. The agreement between pain over the ALL tibial insertion and the ALL being damaged on US was excellent (ICC, 0.801; 95% CI, 0.730-0.855). Moreover, the clinical test had excellent sensitivity (92%; 95% CI, 88%-97%) and specificity (88%; 95% CI, 82%-93%). The agreement between pain at the ALL distal insertion and the pivot shift was good (ICC, 0.654; 95% CI, 0.543-0.742), and ALL palpation had excellent diagnostic accuracy for identifying rotational instability (sensitivity, 88% [95% CI, 82%-93%]; specificity, 97% [95% CI, 94%-100%]).

Conclusion:

Palpation of the ALL tibial insertion highly correlates with ultrasonographic evidence of an ALL injury in the context of an acute knee injury. This simple test should become part of our standard examination when evaluating patients with acute knee injuries.
These Are Still Good Days to Heal: Cancer Care and the Covid-19 Pandemic
Authors: Catedral Lance Isidore G
Published: June 2020

In this article, I narrate my experiences with telemedicine in cancer care as a medical oncology fellow-in-training during the period of enhanced community quarantine in Metro Manila due to the Covid-19 pandemic. Telemedicine has not only helped me communicate with and coordinate treatments for my patients but also offered me a way to offer encouragement and hope.
The Effect of Forearm Tattoos on Flap Choice in Transmasculine Phalloplasty Patients
Authors: Benson Travis A. , Boskey Elizabeth R. , Ganor Oren
Published: June 2020

Purpose. The radial forearm free flap (RFFF) is considered the gold standard for gender affirming phalloplasty. Ideally, a nondominant forearm flap is used to minimize the risk of functional morbidity. However, many transmasculine individuals have tattooed forearms, which can affect decision making. The purpose of this study was to understand the prevalence of forearm tattoos among transmasculine patients seeking phalloplasty and how and whether tattoos affected decision making about flap source. Methods. Participants were 50, consecutive, adult, transmasculine patients seeking phalloplasty. The presence and location of tattoos were assessed using consult notes in the electronic medical record. A one-tailed test of proportions was used to test whether forearm tattoos increased the likelihood of alternative flap choice. Results. More than half of patients (56%) had tattoos on either one or both forearms ( n = 28), 75% on their nondominant arm ( n = 21). Among the patients with forearm tattoos, the presence of tattoos affected the flap site decision for 46% of patients ( n = 13). For the patients that chose an alternative flap site, 46% chose a dominant forearm RFFF ( n = 6) and 54% an anterolateral thigh flap ( n = 7). The percentage of patients whose records indicated that they were planning on using an alternative flap due to a tattoo on their nondominant forearm was significantly higher than the percentage of patients without such tattoos, indicating the desire for an alternate flap ( P < 0.01). Conclusion. Many transmasculine patients seeking phalloplasty have tattoos on either one or both of their forearms. Because of this, a substantial fraction of patients may choose flap donor sites that are less ideal. Providers from all disciplines may wish to educate young transmasculine patients about how tattoo placement may affect surgical options earlier during transition.
Kingdom Come: The Eschatology of Missionary Maps
Authors: Onnekink David
Published: June 2020

Missionary maps were a ubiquitous feature of the missionary movement but have received little systematic attention. This article investigates the eschatological dimension of such maps through a review of nineteenth- and early twentieth-century Dutch missionary bulletins. It shows how missionary maps visualized the spatial march through history of the kingdom of God toward the fulfilling of time. Two eschatological spatial metaphors were used in connection with missionary maps: the (mission) field and the kingdom. The overall purpose of this article is to underscore the value of maps for missionary research.
Planning support science: Developments and challenges
Authors: Geertman Stan , Stillwell John
Published: June 2020

In this paper, we provide an update of recent developments and forthcoming challenges in the field of planning support systems, following earlier reviews in 2003 and 2009. The rationale for this update is the rapid development of information and communication technologies and their impact on planning support systems. After a brief retrospective assessment of past planning support system developments, the paper presents a synthesis of the experiences and views of a worldwide sample of invited planning support system experts, whose innovative contributions comprise a new Handbook of Planning Support Science. The developments documented by the experts together substantiate our impression that a fundamental transformation is taking place – a paradigm shift – wherein the field of planning support systems is maturing into a planning support science. From this perspective, it is expected that planning support systems will become indispensable instruments in the planning process in the not too distant future. The signs of this maturation are already visible in research, education and practice.
Socioeconomic Disadvantage, Chronic Stress, and Hippocampal Subfield Development in Children
Authors: Merz Emily C , He Xiaofu , Myers Brent , Noble Kimberly G
Published: June 2020

Recent findings indicate that hair cortisol concentrations significantly mediate associations between socioeconomic disadvantage and reduced hippocampal CA3 and dentate gyrus volumes in children. In this commentary, we discuss these results and highlight important future research directions, including focusing on hippocampal subfield structural development in relation to episodic memory and mental health; the mechanistic role of excitatory amino acids, such as glutamate; and how chronic stress and cognitive stimulation may make unique proximal contributions to socioeconomic differences in hippocampal subfield volume. Building on the findings in these ways will contribute to advances in strategies aimed at reducing socioeconomic disparities in academic achievement and mental health.
The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism
Authors: Bastian Thomas W , Rao Raghavendra , Tran Phu V , Georgieff Michael K
Published: June 2020

Iron deficiency (ID) is one of the most prevalent nutritional deficiencies in the world. Iron deficiency in the late fetal and newborn period causes abnormal cognitive performance and emotional regulation, which can persist into adulthood despite iron repletion. Potential mechanisms contributing to these impairments include deficits in brain energy metabolism, neurotransmission, and myelination. Here, we comprehensively review the existing data that demonstrate diminished brain energetic capacity as a mechanistic driver of impaired neurobehavioral development due to early-life (fetal-neonatal) ID. We further discuss a novel hypothesis that permanent metabolic reprogramming, which occurs during the period of ID, leads to chronically impaired neuronal energetics and mitochondrial capacity in adulthood, thus limiting adult neuroplasticity and neurobehavioral function. We conclude that early-life ID impairs energy metabolism in a brain region- and age-dependent manner, with particularly strong evidence for hippocampal neurons. Additional studies, focusing on other brain regions and cell types, are needed.
MYC-induced human acute myeloid leukemia requires a continuing IL-3/GM-CSF costimulus
Authors: Bulaeva Elizabeth , Pellacani Davide , Nakamichi Naoto , Hammond Colin A. , Beer Philip A. , Lorzadeh Alireza , Moksa Michelle , Carles Annaïck , Bilenky Misha , Lefort Sylvain , Shu Jeremy , Wilhelm Brian T. , Weng Andrew P. , Hirst Martin , Eaves Connie J.
Published: June 2020

Hematopoietic clones with leukemogenic mutations arise in healthy people as they age, but progression to acute myeloid leukemia (AML) is rare. Recent evidence suggests that the microenvironment may play an important role in modulating human AML population dynamics. To investigate this concept further, we examined the combined and separate effects of an oncogene (c-MYC) and exposure to interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and stem cell factor (SCF) on the experimental genesis of a human AML in xenografted immunodeficient mice. Initial experiments showed that normal human CD34+ blood cells transduced with a lentiviral MYC vector and then transplanted into immunodeficient mice produced a hierarchically organized, rapidly fatal, and serially transplantable blast population, phenotypically and transcriptionally similar to human AML cells, but only in mice producing IL-3, GM-CSF, and SCF transgenically or in regular mice in which the cells were exposed to IL-3 or GM-CSF delivered using a cotransduction strategy. In their absence, the MYC+ human cells produced a normal repertoire of lymphoid and myeloid progeny in transplanted mice for many months, but, on transfer to secondary mice producing the human cytokines, the MYC+ cells rapidly generated AML. Indistinguishable diseases were also obtained efficiently from both primitive (CD34+CD38−) and late granulocyte-macrophage progenitor (GMP) cells. These findings underscore the critical role that these cytokines can play in activating a malignant state in normally differentiating human hematopoietic cells in which MYC expression has been deregulated. They also introduce a robust experimental model of human leukemogenesis to further elucidate key mechanisms involved and test strategies to suppress them.
Pulmonary tularaemia: a differential diagnosis to lung cancer
Authors: Kravdal Astrid , Stubhaug Øystein Olav , Wågø Anne Grete , Steien Sætereng Magnus , Amundsen Dag , Piekuviene Ruta , Kristiansen Annette
Published: June 2020

Background

Pulmonary manifestations of tularaemia are reported to be infrequent in previous publications. During 2016, we noticed an increase in the number of hospitalised patients with pulmonary tularaemia in Eastern Norway. We aimed to investigate primary pulmonary tularaemia in Eastern Norway in terms of symptoms, radiological and microbiological findings, incidence and risk exposure.

Methods

A retrospective analysis of consecutive primary pulmonary tularaemia cases from 2016 until 2018 was conducted.

Results

From 1 September, 2016 until 31 December, 2018, 22 patients were diagnosed with primary pulmonary tularaemia at Innlandet Hospital Trust, representing 48% of all reported tularaemia cases in the region. A peak annual incidence of 3.4 in 100 000 was found in 2017.

All 22 patients lived in, or had recently visited, rural areas. Eighteen patients reported risk exposure for tularaemia, such as wood chopping, outdoor activities and farming prior to symptom onset. All patients experienced fever, and 19 patients had respiratory symptoms. Ten patients were in spontaneous recovery at diagnosis.

All patients had a chest computed tomography scan. Overall, 19 patients had pulmonary lesions and 18 had enlarged intrathoracic lymph nodes. The computed tomography images were described as suspicious of malignancy in 17 patients.

Conclusion

Pulmonary manifestations in tularaemia occurred more frequently in our region than expected from previous reports. Although all patients had symptoms consistent with infection, the majority were primarily investigated considering lung cancer due to the radiology report. In endemic areas, pulmonary tularaemia may be an important differential diagnosis to lung cancer.
Assessing paediatric exercise-induced bronchoconstriction using electromyography
Authors: Keijzer Pascal B. , van der Kamp Mattiènne R. , Thio Boony J. , de Jongh Frans H.C. , Driessen Jean M.M.
Published: June 2020

Background

Asthma is one of the most common chronic diseases in childhood, occurring in up to 10% of all children. Exercise-induced bronchoconstriction (EIB) is indicative of uncontrolled asthma and can be assessed using an exercise challenge test (ECT). However, this test requires children to undergo demanding repetitive forced breathing manoeuvres. We aimed to study the electrical activity of the diaphragm using surface electromyography (EMG) as an alternative measure to assess EIB.

Methods

Forty-two children suspected of EIB performed an ECT wearing a portable EMG amplifier. EIB was defined as a fall in FEV1of more than 13%. Children performed spirometry before exercise, and at 1, 3 and 6 min after exercise until the nadir FEV1was attained and after the use of a bronchodilator. EMG measurements were obtained between spirometry measurements.

Results

Twenty out of 42 children were diagnosed with EIB. EMG peak amplitudes measured at the diaphragm increased significantly more in children with EIB; 4.85 μV (1.82–7.84), compared to children without EIB; 0.20 μV (−0.10–0.54), (p<0.001) at the lowest FEV1post-exercise. Furthermore, the increase in EMG peak amplitude could accurately distinguish between EIB and non-EIB using a cut-off of 1.15 μV (sensitivity 95%, specificity 91%).

Conclusion

EMG measurements of the diaphragm are strongly related to the FEV1and can accurately identify EIB. EMG measurements are a less invasive, effort-independent measure to assess EIB and could be an alternative when spirometry is not feasible.
Large Spin-Dependent Thermoelectric Effects in NiFe-based Interconnected Nanowire Networks
Authors: Marchal Nicolas , da Câmara Santa Clara Gomes Tristan , Abreu Araujo Flavio , Piraux Luc
Published: June 2020

NiFe alloy and NiFe/Cu multilayered nanowire (NW) networks were grown using a template-assisted electrochemical synthesis method. The NiFe alloy NW networks exhibit large thermopower, which is largely preserved in the current perpendicular-to-plane geometry of the multilayered NW structure. Giant magneto-thermopower (MTP) effects have been demonstrated in multilayered NiFe/Cu NWs with a value of 25% at 300 K and reaching 60% around 100 K. A large spin-dependent Seebeck coefficient of –12.3 μV/K was obtained at room temperature. The large MTP effects demonstrate a magnetic approach to control thermoelectric properties of flexible devices based on NW networks.
Structural variation of the malaria-associated human glycophorin A-B-E region
Authors: Louzada Sandra , Algady Walid , Weyell Eleanor , Zuccherato Luciana W. , Brajer Paulina , Almalki Faisal , Scliar Marilia O. , Naslavsky Michel S. , Yamamoto Guilherme L. , Duarte Yeda A. O. , Passos-Bueno Maria Rita , Zatz Mayana , Yang Fengtang , Hollox Edward J.
Published: June 2020

Background

Approximately 5% of the human genome shows common structural variation, which is enriched for genes involved in the immune response and cell-cell interactions. A well-established region of extensive structural variation is the glycophorin gene cluster, comprising three tandemly-repeated regions about 120 kb in length and carrying the highly homologous genes GYPA, GYPB and GYPE. Glycophorin A (encoded by GYPA) and glycophorin B (encoded by GYPB) are glycoproteins present at high levels on the surface of erythrocytes, and they have been suggested to act as decoy receptors for viral pathogens. They are receptors for the invasion of the protist parasite Plasmodium falciparum, a causative agent of malaria. A particular complex structural variant, called DUP4, creates a GYPB-GYPA fusion gene known to confer resistance to malaria. Many other structural variants exist across the glycophorin gene cluster, and they remain poorly characterised.

Results

Here, we analyse sequences from 3234 diploid genomes from across the world for structural variation at the glycophorin locus, confirming 15 variants in the 1000 Genomes project cohort, discovering 9 new variants, and characterising a selection of these variants using fibre-FISH and breakpoint mapping at the sequence level. We identify variants predicted to create novel fusion genes and a common inversion duplication variant at appreciable frequencies in West Africans. We show that almost all variants can be explained by non-allelic homologous recombination and by comparing the structural variant breakpoints with recombination hotspot maps, confirm the importance of a particular meiotic recombination hotspot on structural variant formation in this region.

Conclusions

We identify and validate large structural variants in the human glycophorin A-B-E gene cluster which may be associated with different clinical aspects of malaria.
An efficient single-cell transcriptomics workflow for microbial eukaryotes benchmarked on Giardia intestinalis cells
Authors: Onsbring Henning , Tice Alexander K. , Barton Brandon T. , Brown Matthew W. , Ettema Thijs J. G.
Published: June 2020

Background

Most diversity in the eukaryotic tree of life is represented by microbial eukaryotes, which is a polyphyletic group also referred to as protists. Among the protists, currently sequenced genomes and transcriptomes give a biased view of the actual diversity. This biased view is partly caused by the scientific community, which has prioritized certain microbes of biomedical and agricultural importance. Additionally, some protists remain difficult to maintain in cultures, which further influences what has been studied. It is now possible to bypass the time-consuming process of cultivation and directly analyze the gene content of single protist cells. Single-cell genomics was used in the first experiments where individual protists cells were genomically explored. Unfortunately, single-cell genomics for protists is often associated with low genome recovery and the assembly process can be complicated because of repetitive intergenic regions. Sequencing repetitive sequences can be avoided if single-cell transcriptomics is used, which only targets the part of the genome that is transcribed.

Results

In this study we test different modifications of Smart-seq2, a single-cell RNA sequencing protocol originally developed for mammalian cells, to establish a robust and more cost-efficient workflow for protists. The diplomonad Giardia intestinalis was used in all experiments and the available genome for this species allowed us to benchmark our results. We could observe increased transcript recovery when freeze-thaw cycles were added as an extra step to the Smart-seq2 protocol. Further we reduced the reaction volume and purified the amplified cDNA with alternative beads to test different cost-reducing changes of Smart-seq2. Neither improved the procedure, and reducing the volumes by half led to significantly fewer genes detected. We also added a 5′ biotin modification to our primers and reduced the concentration of oligo-dT, to potentially reduce generation of artifacts. Except adding freeze-thaw cycles and reducing the volume, no other modifications lead to a significant change in gene detection. Therefore, we suggest adding freeze-thaw cycles to Smart-seq2 when working with protists and further consider our other modification described to improve cost and time-efficiency.

Conclusions

The presented single-cell RNA sequencing workflow represents an efficient method to explore the diversity and cell biology of individual protist cells.
Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts
Authors: Zhang Chenyang , Shao Haoqing , Li Dandan , Xiao Nenqun , Tan Zhoujin
Published: June 2020

Background

Although reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality.

Results

For the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. Seven of the 10 intestinal microbiota communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host.

Conclusions

Folium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.
Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China
Authors: Wang Qi , Zhang Feifei , Wang Zhanwei , Chen Hongbin , Wang Xiaojuan , Zhang Yawei , Li Shuguang , Wang Hui
Published: June 2020

Background

Ceftazidime-avibactam was approved in China in 2019 for treating complicated intra-abdominal infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and infections caused by Enterobacterales and Pseudomonas aeruginosa for which treatment options are limited. However, no currently available commercial systems have been approved for antimicrobial susceptibility testing of ceftazidime-avibactam in China. Here, we evaluated the Etest and disk diffusion method for detecting the activity of ceftazidime-avibactam against Enterobacterales and P. aeruginosa in China.

Results

In total, 194 Enterobacterales and 77 P. aeruginosa isolates, which were divided into a random selection group (140 Enterobacterales and 46 P. aeruginosa isolates) and stock group (54 Enterobacterales and 31 P. aeruginosa isolates), were assessed by the Etest, disk diffusion and broth microdilution methods. Minimum inhibitory concentrations and zone diameters were interpreted according to the CLSI supplement M100 30th edition. For all 271 tested isolates, no very major errors were found by using Etest, whereas the overall major error rate was 2.0% (4/203). The overall categorical agreement rates of Etest for Enterobacterales and P. aeruginosa were 99.5% (193/194) and 96.1% (74/77), respectively, and the essential agreement rates were 95.9% (186/194) and 94.8% (73/77), respectively. The disk diffusion method showed that the very major error and major error rates were 1.5% (3/204) and 2.5% (5/203), respectively. Overall categorical agreement rates values of the disk diffusion method for Enterobacterales and P. aeruginosa were 98.5% (191/194) and 93.5% (72/77) compared with broth microdilution, respectively.

Conclusions

For Enterobacterales and P. aeruginosa, both the Etest and disk diffusion method showed acceptable performance as alternatives to the standard broth microdilution method for clinical treatment interpretation. Application of the disk diffusion method in Enterobacterales was slightly better than that in P. aeruginosa.
Correction to: Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study
Authors: van der Mei Willem F. , Barbano Anna C. , Ratanatharathorn Andrew , Bryant Richard A. , Delahanty Douglas L. , deRoon-Cassini Terri A. , Lai Betty S. , Lowe Sarah R. , Matsuoka Yutaka J. , Olff Miranda , Qi Wei , Schnyder Ulrich , Seedat Soraya , Kessler Ronald C. , Koenen Karestan C. , Shalev Arieh Y. ,   International Consortium to Predict PTSD, Errera-Ankri Yael , Freedman Sarah , Frijling Jessie , Goslings J. Carel , Luitse Jan , McFarlane Alexander , Silove Derrick , Moergeli Hanspeter , Mouthaan Joanne , Nishi Daisuke , O’Donnell Meaghan , Rusch Mark , Sijbrandij Marit , Suliman Sharain , van Zuiden Mirjam
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
What matters to you when the nursing home is your home: a qualitative study on the views of residents with dementia living in nursing homes
Authors: Nygaard Agnete , Halvorsrud Liv , Grov Ellen Karine , Bergland Astrid
Published: June 2020

Background

Dementia is recognised as one of the greatest global public health challenges. A central tenet of national health and social care policy is to ensure that services support people in achieving their personal well-being and outcomes, defined as the things important to people in their lives, also people with dementia. The aim of this study is to explore what matters to nursing home residents with dementia based on their perceptions of nursing homes as home.

Methods

There were conducted 35 interviews with people with dementia in nursing homes. We conducted the in-depth unstructured qualitative interviews. Thematic analysis was applied to analyse the data.

Results

The analysis resulted in one over-arching theme “tension between the experiences of a nursing home being a home and an institution” and five themes; “myself and my relationships with fellow residents", “creation of individualised living spaces”, "single rooms with personal decor that enhances a sense of connectedness”, “transition between the old home and the new home” and “significant activities providing meaning”. The participants stated that the transition to the supported, structured living environment in nursing homes to be a clear need based on immediate, serious safety concerns. They went from being masters of their own lives to adhering to nursing home routines. Fellow residents could be both resources and burdens, creating feelings of security and insecurity. A home-like environment was created by allowing the participants to bring their important personal belongings into private spaces. The participants said they needed to be able to decorate their rooms to their own specifications. They wanted involvement in meaningful activities.

Conclusions

The findings showed that ‘home’ was an emotive word that awakened many associations. The participants reported mixed feelings and stated that they could thrive even if they missed their old homes. What mattered was that the participants felt safe, had single rooms where they could retire from the community, their own belongings and did activities. The participants wanted greater possibilities for meaningful relations. They appreciate that nursing home were similar to their previous homes. They desired opportunities to continue some activities they did in their former home.
Biofilm formation, antimicrobial susceptibility and virulence genes of Uropathogenic Escherichia coli isolated from clinical isolates in Uganda
Authors: Katongole Paul , Nalubega Fatuma , Florence Najjuka Christine , Asiimwe Benon , Andia Irene
Published: June 2020

Introduction

Uropathogenic E. coli is the leading cause of Urinary tract infections (UTIs), contributing to 80–90% of all community-acquired and 30–50% of all hospital-acquired UTIs. Biofilm forming Uropathogenic E. coli are associated with persistent and chronic inflammation leading to complicated and or recurrent UTIs. Biofilms provide an environment for poor antibiotic penetration and horizontal transfer of virulence genes which favors the development of Multidrug-resistant organisms (MDRO). Understanding biofilm formation and antimicrobial resistance determinants of Uropathogenic E. coli strains will provide insight into the development of treatment options for biofilm-associated UTIs. The aim of this study was to determine the biofilm forming capability, presence of virulence genes and antimicrobial susceptibility pattern of Uropathogenic E. coli isolates in Uganda.

Methods

This was a cross-sectional study carried in the Clinical Microbiology and Molecular biology laboratories at the Department of Medical Microbiology, Makerere University College of Health Sciences. We randomly selected 200 Uropathogenic E. coli clinical isolates among the stored isolates collected between January 2018 and December 2018 that had significant bacteriuria (> 105 CFU). All isolates were subjected to biofilm detection using the Congo Red Agar method and Antimicrobial susceptibility testing was performed using the Kirby disk diffusion method. The isolates were later subjected PCR for the detection of Urovirulence genes namely; Pap, Fim, Sfa, Afa, Hly and Cnf, using commercially designed primers.

Results

In this study, 62.5% (125/200) were positive biofilm formers and 78% (156/200) of these were multi-drug resistant (MDR). The isolates were most resistant to Trimethoprim sulphamethoxazole and Amoxicillin (93%) followed by gentamycin (87%) and the least was imipenem (0.5%). Fim was the most prevalent Urovirulence gene (53.5%) followed by Pap (21%), Sfa (13%), Afa (8%), Cnf (5.5%) and Hyl (0%).

Conclusions

We demonstrate a high prevalence of biofilm-forming Uropathogenic E. coli strains that are highly associated with the MDR phenotype. We recommend routine surveillance of antimicrobial resistance and biofilm formation to understand the antibiotics suitable in the management of biofilm-associated UTIs.
Adaptive-size dictionary learning using information theoretic criteria for image reconstruction from undersampled k-space data in low field magnetic resonance imaging
Authors: Ahishakiye Emmanuel , Van Gijzen Martin Bastiaan , Tumwiine Julius , Obungoloch Johnes
Published: June 2020

Background

Magnetic resonance imaging (MRI) is a safe non-invasive and nonionizing medical imaging modality that is used to visualize the structure of human anatomy. Conventional (high-field) MRI scanners are very expensive to purchase, operate and maintain, which limit their use in many developing countries. This study is part of a project that aims at addressing these challenges and is carried out by teams from Mbarara University of Science and Technology (MUST) in Uganda, Leiden University Medical Center (LUMC) in the Netherlands, Delft University of Technology (TU Delft) in the Netherlands and Pennsylvania State University (PSU) in the USA. These are working on developing affordable, portable and low-field MRI scanners to diagnose children in developing countries with hydrocephalus. The challenges faced by the teams are that the low-field MRI scanners currently under development are characterized by low Signal-to-Noise Ratio (SNR), and long scan times.

Methods

We propose an algorithm called adaptive-size dictionary learning algorithm (AS-DLMRI) that integrates information-theoretic criteria (ITC) and Dictionary learning approaches. The result of the integration is an adaptive-size dictionary that is optimal for any input signal. AS-DLMRI may help to reduce the scan time and improve the SNR of the generated images, thereby improving the image quality.

Results

We compared our proposed algorithm AS-DLMRI with adaptive patch-based algorithm known as DLMRI and non-adaptive CSMRI technique known as LDP. DLMRI and LDP have been used as the baseline algorithms in other related studies. The results of AS-DLMRI are consistently slightly better in terms of PSNR, SNR and HFEN than for DLMRI, and are significantly better than for LDP. Moreover, AS-DLMRI is faster than DLMRI.

Conclusion

Using a dictionary size that is appropriate to the input data could reduce the computational complexity, and also the construction quality since only dictionary atoms that are relevant to the task are included in the dictionary and are used during the reconstruction. However, AS-DLMRI did not completely remove noise during the experiments with the noisy phantom. Our next step in our research is to integrate our proposed algorithm with an image denoising function.
Prognostic imaging biomarkers for diabetic kidney disease (iBEAt): study protocol
Authors: Gooding Kim M. , Lienczewski Chrysta , Papale Massimo , Koivuviita Niina , Maziarz Marlena , Dutius Andersson Anna-Maria , Sharma Kanishka , Pontrelli Paola , Garcia Hernandez Alberto , Bailey Julie , Tobin Kay , Saunavaara Virva , Zetterqvist Anna , Shelley David , Teh Irvin , Ball Claire , Puppala Sapna , Ibberson Mark , Karihaloo Anil , Metsärinne Kaj , Banks Rosamonde E. , Gilmour Peter S. , Mansfield Michael , Gilchrist Mark , de Zeeuw Dick , Heerspink Hiddo J. L. , Nuutila Pirjo , Kretzler Matthias , Welberry Smith Matthew , Gesualdo Loreto , Andress Dennis , Grenier Nicolas , Shore Angela C. , Gomez Maria F. , Sourbron Steven ,   for the BEAt-DKD consortium
Published: June 2020

Background

Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim).

Methods

iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes.

Discussion

iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D.

Trial registration

Clinicaltrials.gov(NCT03716401).
Potential value of three-dimensional ultrasonography in diagnosis of diabetic nephropathy in Chinese diabetic population with kidney injury
Authors: Li Nan , Wang Yi-ru , Tian Xiao-qi , Lin Lin , Liang Shu-yuan , Li Qiu-yang , Fei Xiang , Tang Jie , Luo Yu-kun
Published: June 2020

Background

To explore the potential value of three-dimensional ultrasonography (3DUS) and contrast-enhanced ultrasound (CEUS) in the diagnosis of diabetic nephropathy (DN) in Chinese diabetic patients with kidney injury.

Methods

Patients with type 2 diabetes mellitus and kidney injury in our hospital were enrolled, and the clinical characteristics as well as the laboratory data of patients were collected; 3DUS and CEUS were used to evaluate the morphological structure and blood perfusion of kidneys. Eligible patients were categorized into two groups based on renal biopsy results: DN group and non-diabetic renal diseases (NDRD) group. Correlation analysis and logistic regression analysis were applied to identify the risk factors of DN development.

Results

A total of 115 patients aged from 24 to 78 years old were recruited in the experiment, of which 64 patients (55.65%) and 51 patients (44.35%) were in the DN group and NDRD group, respectively. After correction to CKD stage, BMI and right kidney volume index were retained to identify patients with DN. The ROC of the logistic regression model had an AUC of 0.703 (95% CI: 0.591–0.815) and it was higher than both indicators.

Conclusion

3DUS has potential value in the diagnosis of diabetic nephropathy in Chinese diabetic population with kidney injury and may act as an auxiliary diagnosis for DN. More prospective and well-designed studies with larger samples are needed to verify the result.
Integration of genomics, metagenomics, and metabolomics to identify interplay between susceptibility alleles and microbiota in adenoma initiation
Authors: Moskowitz Jacob E. , Doran Anthony G. , Lei Zhentian , Busi Susheel B. , Hart Marcia L. , Franklin Craig L. , Sumner Lloyd W. , Keane Thomas M. , Amos-Landgraf James M.
Published: June 2020

Background

Colorectal cancer (CRC) is a multifactorial disease resulting from both genetic predisposition and environmental factors including the gut microbiota (GM), but deciphering the influence of genetic variants, environmental variables, and interactions with the GM is exceedingly difficult. We previously observed significant differences in intestinal adenoma multiplicity between C57BL/6 J-ApcMin (B6-Min/J) from The Jackson Laboratory (JAX), and original founder strain C57BL/6JD-ApcMin (B6-Min/D) from the University of Wisconsin.

Methods

To resolve genetic and environmental interactions and determine their contributions we utilized two genetically inbred, independently isolated ApcMin mouse colonies that have been separated for over 20 generations. Whole genome sequencing was used to identify genetic variants unique to the two substrains. To determine the influence of genetic variants and the impact of differences in the GM on phenotypic variability, we used complex microbiota targeted rederivation to generate two Apc mutant mouse colonies harboring complex GMs from two different sources (GMJAX originally from JAX or GMHSD originally from Envigo), creating four ApcMin groups. Untargeted metabolomics were used to characterize shifts in the fecal metabolite profile based on genetic variation and differences in the GM.

Results

WGS revealed several thousand high quality variants unique to the two substrains. No homozygous variants were present in coding regions, with the vast majority of variants residing in noncoding regions. Host genetic divergence between Min/J and Min/D and the complex GM additively determined differential adenoma susceptibility. Untargeted metabolomics revealed that both genetic lineage and the GM collectively determined the fecal metabolite profile, and that each differentially regulates bile acid (BA) metabolism. Metabolomics pathway analysis facilitated identification of a functionally relevant private noncoding variant associated with the bile acid transporter Fatty acid binding protein 6 (Fabp6). Expression studies demonstrated differential expression of Fabp6 between Min/J and Min/D, and the variant correlates with adenoma multiplicity in backcrossed mice.

Conclusions

We found that both genetic variation and differences in microbiota influences the quantitiative adenoma phenotype in ApcMin mice. These findings demonstrate how the use of metabolomics datasets can aid as a functional genomic tool, and furthermore illustrate the power of a multi-omics approach to dissect complex disease susceptibility of noncoding variants.
Model of genetic and environmental factors associated with type 2 diabetes mellitus in a Chinese Han population
Authors: Li Zheng , Ye Cheng-yin , Zhao Tian-Yu , Yang Lei
Published: June 2020

Background

Type 2 diabetes mellitus (T2DM) is a metabolic disorder which accounts for high morbidity and mortality due to complications like renal failure, amputations, cardiovascular disease, and cerebrovascular events.

Methods

We collected medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype the SNPs, and a visit was conducted in August 2016 to obtain the incidence of Type 2 diabetes in the 2113 eligible people. To explore which genes and environmental factors are associated with type 2 diabetes mellitus in a Chinese Han population, we used elastic net to build a model, which is to explain which variables are strongly associated with T2DM, rather than predict the occurrence of T2DM.

Result

The genotype of the additive of rs964184, together with the history of hypertension, regular intake of meat and waist circumference, increased the risk of T2DM (adjusted OR = 2.38, p = 0.042; adjusted OR = 3.31, p < 0.001; adjusted OR = 1.05, p < 0.001). The TT genotype of the additive and recessive models of rs12654264, the CC genotype of the additive and dominant models of rs2065412, the TT genotype of the additive and dominant models of rs4149336, together with the degree of education, regular exercise, reduced the risk of T2DM (adjusted OR = 0.46, p = 0.017; adjusted OR = 0.53, p = 0.021; adjusted OR = 0.59, p = 0.021; adjusted OR = 0.57, p = 0.01; adjusted OR = 0.59, p = 0.021; adjusted OR = 0.57, p = 0.01; adjusted OR = 0.50, p = 0.007; adjusted OR = 0.80, p = 0.032) .

Conclusion

Eventually we identified a set of SNPs and environmental factors: rs5805 in the SLC12A3, rs12654264 in the HMGCR, rs2065412 and rs414936 in the ABCA1, rs96418 in the ZPR1 gene, waistline, degree of education, exercise frequency, hypertension, and the intake of meat. Although there was no interaction between these variables, people with two risk factors had a higher risk of T2DM than those only having one factor. These results provide the theoretical basis for gene and other risk factors screening to prevent T2DM.
Socioeconomic inequality in tobacco expenditure in Iran: a cross-sectional analysis at national and subnational levels
Authors: Rezaei Satar , Pulok Mohammad Habibullah , Ebrahimi Mohammad
Published: June 2020

Background

Tobacco expenditure has adverse impacts on expenditure on basic needs and resource allocation of the households. Using data from a nationally representative survey, we measured socioeconomic inequality in tobacco expenditure as the share of household budget (TEHB) and explained its main determinants among Iranian households at the national and sub-national levels.

Methods

This cross-sectional study used data from the Iranian Household Income and Expenditure Survey (IHIES), 2018. We included a total of 7649 households with tobacco expenditure more than zero in the analysis. Province-level data on the Human Development Index (HDI) was obtained from the Institute for Management Research at Radbound University. The concentration curve (CC) and the concentration index (C) were used to measure socioeconomic inequality in TEHB at national and sub-national levels. The C was decomposed to identify the factors explaining the observed socioeconomic inequality in TEHB.

Results

At the national level, households with at least one smoker spent more than 5% of their budget for tobacco consumption in the last month. Households from the urban areas allocated less of their budgets on tobacco products compared to rural households (4.6% vs. 5.8%). Overall, TEHB was more concentrated among the poorer households (C = 0.1423, 95% CI: − 0.1552 to − 0.1301). In other words, the distribution of TEHB was pro-poor in Iran. Pro-poor inequality in TEHB was also found in urban (C = − 0.1707, 95% CI: − 0.1998 to − 0.1516) and rural (C = − 0.1314, 95% CI: − 0.1474 to − 0.1152) areas. We also found that pro-poor inequalities were higher in Iranian provinces with low HDI. The decomposition results indicate that wealth and education were the main factors contributing to the concentration of TEHB among the poorer households.

Conclusion

This study found that TEHB was disproportionality concentrated among poorer households in Iran. The extent of inequality in TEHB was higher in urban areas and less developed provinces. Designing and implementing tobacco control interventions to decrease the smoking prevalence and increase smoking cessation could protect worse-off households against the financial burden of tobacco spending.