bluuebunny/crossref_metadata_2025 huggingface dataset:
A new murine model of Barth syndrome neutropenia links TAFAZZIN deficiency to increased ER stress-induced apoptosis
Authors: Sohn Jihee , Milosevic Jelena , Brouse Thomas , Aziz Najihah , Elkhoury Jenna , Wang Suya , Hauschild Alexander , van Gastel Nick , Cetinbas Murat , Tufa Sara F. , Keene Douglas R. , Sadreyev Ruslan I. , Pu William T. , Sykes David B.
Published: January 2022

Barth syndrome is an inherited X-linked disorder that leads to cardiomyopathy, skeletal myopathy, and neutropenia. These symptoms result from the loss of function of the enzyme TAFAZZIN, a transacylase located in the inner mitochondrial membrane that is responsible for the final steps of cardiolipin production. The link between defective cardiolipin maturation and neutropenia remains unclear. To address potential mechanisms of neutropenia, we examined myeloid progenitor development within the fetal liver of TAFAZZIN knockout (KO) animals as well as within the adult bone marrow of wild-type recipients transplanted with TAFAZZIN-KO hematopoietic stem cells. We also used the ER-Hoxb8 system (estrogen receptor fused to Hoxb8) of conditional immortalization to establish a new murine model system for the ex vivo study of TAFAZZIN-deficient neutrophils. The TAFAZZIN-KO cells demonstrated the expected dramatic differences in cardiolipin maturation that result from a lack of TAFAZZIN enzyme activity. Contrary to our hypothesis, we did not identify any significant differences in neutrophil development or neutrophil function across a variety of assays including phagocytosis and the production of cytokines or reactive oxygen species. However, transcriptomic analysis of the TAFAZZIN-deficient neutrophil progenitors demonstrated an upregulation of markers of endoplasmic reticulum stress and confirmatory testing demonstrated that the TAFAZZIN-deficient cells had increased sensitivity to certain ER stress-mediated and non-ER stress-mediated triggers of apoptosis. Although the link between increased sensitivity to apoptosis and the variably penetrant neutropenia phenotype seen in some patients with Barth syndrome remains to be clarified, our studies and new model system set a foundation for further investigation.
Compression enhances invasive phenotype and matrix degradation of breast cancer cells via Piezo1 activation
Authors: Luo Mingzhi , Cai Grace , Ho Kenneth K. Y. , Wen Kang , Tong Zhaowen , Deng Linhong , Liu Allen P.
Published: January 2022

Background

Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation.

Results

Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content.

Conclusions

Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.
Determine independent gut microbiota-diseases association by eliminating the effects of human lifestyle factors
Authors: Zhu Congmin , Wang Xin , Li Jianchu , Jiang Rui , Chen Hui , Chen Ting , Yang Yuqing
Published: January 2022

Lifestyle and physiological variables on human disease risk have been revealed to be mediated by gut microbiota. Low concordance between case-control studies for detecting disease-associated microbe existed due to limited sample size and population-wide bias in lifestyle and physiological variables. To infer gut microbiota-disease associations accurately, we propose to build machine learning models by including both human variables and gut microbiota. When the model’s performance with both gut microbiota and human variables is better than the model with just human variables, the independent gut microbiota -disease associations will be confirmed. By building models on the American Gut Project dataset, we found that gut microbiota showed distinct association strengths with different diseases. Adding gut microbiota into human variables enhanced the classification performance of IBD significantly; independent associations between occurrence information of gut microbiota and irritable bowel syndrome, C. difficile infection, and unhealthy status were found; adding gut microbiota showed no improvement on models’ performance for diabetes, small intestinal bacterial overgrowth, lactose intolerance, cardiovascular disease. Our results suggested that although gut microbiota was reported to be associated with many diseases, a considerable proportion of these associations may be very weak. We proposed a list of microbes as biomarkers to classify IBD and unhealthy status. Further functional investigations of these microbes will improve understanding of the molecular mechanism of human diseases.
An antimicrobial peptide specifically active against Listeria monocytogenes is secreted by Bacillus pumilus SF214
Authors: Saggese Anella , De Luca Ylenia , Baccigalupi Loredana , Ricca Ezio
Published: January 2022

Background

Members of the Bacillus genus produce a large variety of antimicrobial peptides including linear or cyclic lipopeptides and thiopeptides, that often have a broad spectrum of action against Gram-positive and Gram-negative bacteria. We have recently reported that SF214, a marine isolated strain of Bacillus pumilus, produces two different antimicrobials specifically active against either Staphylococcus aureus or Listeria monocytogenes. The anti-Staphylococcus molecule has been previously characterized as a pumilacidin, a nonribosomally synthesized lipopetide composed of a mixture of cyclic heptapeptides linked to fatty acids of variable length.

Results

Our analysis on the anti-Listeria molecule of B. pumilus SF214 indicated that it is a peptide slightly smaller than 10 kDa, produced during the exponential phase of growth, stable at a wide range of pH conditions and resistant to various chemical treatments. The peptide showed a lytic activity against growing but not resting cells of Listeria monocytogenes and appeared extremely specific being inactive also against L. innocua, a close relative of L. monocytogenes.

Conclusions

These findings indicate that the B. pumilus peptide is unusual with respect to other antimicrobials both for its time of synthesis and secretion and for its strict specificity against L. monocytogenes. Such specificity, together with its stability, propose this new antimicrobial as a tool for potential biotechnological applications in the fight against the dangerous food-borne pathogen L. monocytogenes.
MYB transcription factor family in sweet cherry (Prunus avium L.): genome-wide investigation, evolution, structure, characterization and expression patterns
Authors: Sabir Irfan Ali , Manzoor Muhammad Aamir , Shah Iftikhar Hussain , Liu Xunju , Zahid Muhmmad Salman , Jiu Songtao , Wang Jiyuan , Abdullah Muhammad , Zhang Caixi
Published: January 2022

Back ground

MYB Transcription factors (TFs) are most imperative and largest gene family in plants, which participate in development, metabolism, defense, differentiation and stress response. The MYB TFs has been studied in various plant species. However, comprehensive studies of MYB gene family in the sweet cherry (Prunus avium L.) are still unknown.

Results

In the current study, a total of 69 MYB genes were investigated from sweet cherry genome and classified into 28 subfamilies (C1-C28 based on phylogenetic and structural analysis). Microcollinearity analysis revealed that dispersed duplication (DSD) events might play an important role in the MYB genes family expansion. Chromosomal localization, the synonymous (Ks) and nonsynonymous (Ka) analysis, molecular characteristics (pI, weight and length of amino acids) and subcellular localization were accomplished using several bioinformatics tools. Furthermore, the members of distinct subfamilies have diverse cis-acting regions, conserved motifs, and intron-exon architectures, indicating functional heterogeneity in the MYB family. Moreover, the transcriptomic data exposed that MYB genes might play vital role in bud dormancy. The quantitative real-time qRT-PCR was carried out and the expression pattern indicated that MYB genes significantly expressed in floral bud as compared to flower and fruit.

Conclusion

Our comprehensive findings provide supportive insights into the evolutions, expansion complexity and functionality of PavMYB genes. These PavMYB genes should be further investigated as they seem to be brilliant candidates for dormancy manipulation in sweet cherry.
Novel insights into water-deficit-responsive mRNAs and lncRNAs during fiber development in Gossypium hirsutum
Authors: Wu Nan , Yang Jun , Wang Guoning , Ke Huifeng , Zhang Yan , Liu Zhengwen , Ma Zhiying , Wang Xingfen
Published: January 2022

Background

The fiber yield and quality of cotton are greatly and periodically affected by water deficit. However, the molecular mechanism of the water deficit response in cotton fiber cells has not been fully elucidated.

Results

In this study, water deficit caused a significant reduction in fiber length, strength, and elongation rate but a dramatic increase in micronaire value. To explore genome-wide transcriptional changes, fibers from cotton plants subjected to water deficit (WD) and normal irrigation (NI) during fiber development were analyzed by transcriptome sequencing. Analysis showed that 3427 mRNAs and 1021 long noncoding RNAs (lncRNAs) from fibers were differentially expressed between WD and NI plants. The maximum number of differentially expressed genes (DEGs) and lncRNAs (DERs) was identified in fibers at the secondary cell wall biosynthesis stage, suggesting that this is a critical period in response to water deficit. Twelve genes in cotton fiber were differentially and persistently expressed at ≥ five time points, suggesting that these genes are involved in both fiber development and the water-deficit response and could potentially be used in breeding to improve cotton resistance to drought stress. A total of 540 DEGs were predicted to be potentially regulated by DERs by analysis of coexpression and genomic colocation, accounting for approximately 15.76% of all DEGs. Four DERs, potentially acting as target mimics for microRNAs (miRNAs), indirectly regulated their corresponding DEGs in response to water deficit.

Conclusions

This work provides a comprehensive transcriptome analysis of fiber cells and a set of protein-coding genes and lncRNAs implicated in the cotton response to water deficit, significantly affecting fiber quality during the fiber development stage.
Identification of Pueraria spp. through DNA barcoding and comparative transcriptomics
Authors: Adolfo Laci M. , Rao Xiaolan , Dixon Richard A.
Published: January 2022

Background

Kudzu is a term used generically to describe members of the genus Pueraria. Kudzu roots have been used for centuries in traditional Chinese medicine in view of their high levels of beneficial isoflavones including the unique 8-C-glycoside of daidzein, puerarin. In the US, kudzu is seen as a noxious weed causing ecological and economic damage. However, not all kudzu species make puerarin or are equally invasive. Kudzu remains difficult to identify due to its diverse morphology and inconsistent nomenclature.

Results

We have generated sequences for the internal transcribed spacer 2 (ITS2) and maturase K (matK) regions of Pueraria montana lobata, P. montana montana, and P. phaseoloides, and identified two accessions previously used for differential analysis of puerarin biosynthesis as P. lobata and P. phaseoloides. Additionally, we have generated root transcriptomes for the puerarin-producing P. m. lobata and the non-puerarin producing P. phaseoloides. Within the transcriptomes, microsatellites were identified to aid in species identification as well as population diversity.

Conclusions

The barcode sequences generated will aid in fast and efficient identification of the three kudzu species. Additionally, the microsatellites identified from the transcriptomes will aid in genetic analysis. The root transcriptomes also provide a molecular toolkit for comparative gene expression analysis towards elucidation of the biosynthesis of kudzu phytochemicals.
Asynapsis and unreduced gamete formation in a Trifolium interspecific hybrid
Authors: Ansari Helal A. , Ellison Nicholas W. , Verry Isabelle M. , Williams Warren M.
Published: January 2022

Background

Unreduced gametes, a driving force in the widespread polyploidization and speciation of flowering plants, occur relatively frequently in interspecific or intergeneric hybrids. Studies of the mechanisms leading to 2ngamete formation, mainly in the wheat tribeTriticeaehave shown that unreductional meiosis is often associated with chromosome asynapsis during the first meiotic division. The present study explored the mechanisms of meiotic nonreduction leading to functional unreduced gametes in an interspecificTrifolium(clover) hybrid with three sub-genomes fromT. ambiguumand one sub-genome fromT. occidentale.

Results

Unreductional meiosis leading to 2ngametes occurred when there was a high frequency of asynapsis during the first meiotic division. In this hybrid, approximately 39% of chromosomes were unpaired at metaphase I. Within the same cell at anaphase I, sister chromatids of univalents underwent precocious separation and formed laggard chromatids whereas paired chromosomes segregated without separation of sister chromatids as in normal meiosis. This asynchrony was frequently accompanied by incomplete or no movement of chromosomes toward the poles and restitution leading to unreduced chromosome constitutions. Reductional meiosis was restored in progeny where asynapsis frequencies were low. Two progeny plants with approximately 5 and 7% of unpaired chromosomes at metaphase I showed full restoration of reductional meiosis.

Conclusions

The study revealed that formation of 2ngametes occurred when asynapsis (univalent) frequency at meiosis I was high, and that normal gamete production was restored in the next generation when asynapsis frequencies were low. Asynapsis-dependent 2ngamete formation, previously supported by evidence largely from wheat and its relatives and grasshopper, is also applicable to hybrids from the dicotyledonous plant genusTrifolium. The present results align well with those from these widely divergent organisms and strongly suggest common molecular mechanisms involved in unreduced gamete formation.
Slope analysis for the prediction of fluid responsiveness by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients
Authors: Vallier Sylvain , Bouchet Jean-Baptiste , Desebbe Olivier , Francou Camille , Raphael Darren , Tardy Bernard , Gergele Laurent , Morel Jérôme
Published: January 2022

Objective

Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients by analyzing the variations in central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device.

Design

Prospective observational cohort study.

Setting

Intensive Care Unit, Saint-Etienne University Central Hospital.

Patients

Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCO™), requiring volume expansion, with no right ventricular dysfunction.

Interventions.

None.

Measurements and main results

CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL fluid expansion to asses fluid responsiveness. 25 patients were screened and 18 patients analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamic parameters suggested the use of a linear regression model. Slopes for systolic arterial pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during the pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p = 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, prediction of fluid responsiveness can be achieved with 100% sensitivity and 100% specificity (AUC = 0.96; 95% CI, 0.90 to 1.00). One patient showed inconclusive values using the grey zone approach (5.5%).

Conclusions

In patients under mechanical ventilation with no right heart dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath LRM seems to offer a very promising method for prediction of fluid responsiveness without the use and associated cost of a cardiac output measurement device.

Trial registration

NCT04304521, IRBN902018/CHUSTE. Registered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP)
Outcomes of advance care directives after admission to a long-term care home: DNR the DNH?
Authors: Adekpedjou Rhéda , Heckman George A. , Hébert Paul C. , Costa Andrew P. , Hirdes John
Published: January 2022

Background

Residents of long-term care homes (LTCH) often experience unnecessary and non-beneficial hospitalizations and interventions near the end-of-life. Advance care directives aim to ensure that end-of-life care respects resident needs and wishes.

Methods

In this retrospective cohort study, we used multistate models to examine the health trajectories associated with Do-Not-Resuscitate (DNR) and Do-Not-Hospitalize (DNH) directives of residents admitted to LTCH in Ontario, Alberta, and British Columbia, Canada. We adjusted for baseline frailty-related health instability. We considered three possible end states: change in health, hospitalization, or death. For measurements, we used standardized RAI-MDS 2.0 LTCH assessments linked to hospital records from 2010 to 2015.

Results

We report on 123,003 LTCH residents. The prevalence of DNR and DNH directives was 71 and 26% respectively. Both directives were associated with increased odds of transitioning to a state of greater health instability and death, and decreased odds of hospitalization. The odds of hospitalization in the presence of a DNH directive were lowered, but not eliminated, with odds of 0.67 (95% confidence interval 0.65–0.69), 0.63 (0.61–0.65), and 0.47 (0.43–0.52) for residents with low, moderate and high health instability, respectively.

Conclusion

Even though both DNR and DNH orders are associated with serious health outcomes, DNH directives were not frequently used and often overturned. We suggest that policies recommending DNH directives be re-evaluated, with greater emphasis on advance care planning that better reflects resident values and wishes.
National trends in the proportion of in-hospital deaths by cause of death among older adults with long-term care: a nationwide observational study in Japan from 2007 to 2017
Authors: Taniguchi Yuta , Iwagami Masao , Jin Xueying , Sakata Nobuo , Sato Mikiya , Watanabe Taeko , Hanari Kyoko , Abe Kazuhiro , Noguchi Haruko , Tamiya Nanako
Published: January 2022

Background

Japan has promoted end-of-life care at home and in long-term care facilities, and the total proportion of in-hospital deaths has decreased recently. However, the difference in trends of in-hospital deaths by the cause of death remains unclear. We investigated the variation in trends of in-hospital deaths among older adults with long-term care from 2007 to 2017, by cause of death and place of care.

Methods

Using the national long-term care insurance registry, long-term care claims data, and national death records, we identified people aged 65 years or older who died between 2007 and 2017 and used long-term care services in the month before death. Using a joinpoint regression model, we evaluated time trends of the proportion of in-hospital deaths by cause of death (cancer, heart diseases, cerebrovascular diseases, pneumonia, and senility) and place of care (home, long-term care health facility, or long-term care welfare facility).

Results

Of the 3,261,839 participants, the mean age was 87.0 ± 8.0 years, and 59.2% were female. Overall, the proportion of in-hospital deaths decreased from 66.2% in 2007 to 55.3% in 2017. By cause of death, the proportion of in-hospital deaths remained the highest for pneumonia (81.6% in 2007 and 77.2% in 2017) and lowest for senility (25.5% in 2007 and 20.0% in 2017) in all types of places of care. The joinpoint regression analysis showed the steepest decline among those who died of senility, especially among long-term care health facility residents.

Conclusions

The findings of this nationwide study suggest that there was a decreasing trend of in-hospital deaths among older adults, although the speed of decline and absolute values varied widely depending on the cause of death and place of care.
Resident loneliness, social isolation and unplanned emergency department visits from supportive living facilities: a population-based study in Alberta, Canada
Authors: Chamberlain Stephanie A. , Bronskill Susan E. , Hsu Zoe , Youngson Erik , Gruneir Andrea
Published: January 2022

Background

Supportive living (SL) facilities are intended to provide a residential care setting in a less restrictive and more cost-effective way than nursing homes (NH). SL residents with poor social relationships may be at risk for increased health service use. We describe the demographic and health service use patterns of lonely and socially isolated SL residents and to quantify associations between loneliness and social isolation on unplanned emergency department (ED) visits.

Methods

We conducted a retrospective cohort study using population-based linked health administrative data from Alberta, Canada. All SL residents aged 18 to 105 years who had at least one Resident Assessment Instrument-Home Care (RAI-HC) assessment between April 1, 2013 and March 31, 2018 were observed. Loneliness and social isolation were measured as a resident indicating that he/she feels lonely and if the resident had neither a primary nor secondary caregiver, respectively. Health service use in the 1 year following assessment included unplanned ED visits, hospital admissions, admission to higher levels of SL, admission to NH and death. Multivariable Cox proportional hazard models examined the association between loneliness and social isolation on the time to first unplanned ED visit.

Results

We identified 18,191 individuals living in Alberta SL facilities. The prevalence of loneliness was 18% (n = 3238), social isolation was 4% (n = 713). Lonely residents had the greatest overall health service use. Risk of unplanned ED visit increased with loneliness (aHR = 1.10, 95% CI: 1.04–1.15) but did not increase with social isolation (aHR = 0.95, 95% CI: 0.84–1.06).

Conclusions

Lonely residents had a different demographic profile (older, female, cognitively impaired) from socially isolated residents and were more likely to experience an unplanned ED visit. Our findings suggest the need to develop interventions to assist SL care providers with how to identify and address social factors to reduce risk of unplanned ED visits.
Frailty-aware care: giving value to frailty assessment across different healthcare settings
Authors: Boreskie Kevin F. , Hay Jacqueline L. , Boreskie Patrick E. , Arora Rakesh C. , Duhamel Todd A.
Published: January 2022

Healthcare systems need to adapt to better serve an aging population with complex presentations. Frailty assessments are a potential means to address this heterogeneity in aging to identify individuals at increased risk for adverse health outcomes. Furthermore, frailty assessments offer an opportunity to optimize patient care in various healthcare settings. While the vast number of frailty assessment tools available can be a source of confusion for clinicians, each tool has features adaptable to the constraints and goals of different healthcare settings. This review discusses and compares barriers, facilitators, and the application of frailty assessments in primary care, the emergency department/intensive care unit and surgical care to cover a breadth of settings with different frailty assessment considerations. The implementation of frailty-aware care across healthcare settings potentiates better healthcare outcomes for older adults.
The relationship between social deprivation and a frailty index of cumulative deficits in French middle-aged caregivers
Authors: Giovannelli Jonathan , Pinon Anthony , Lenain Manon , Cleys Anne-Laure , Lefebvre Brigitte , Capon Nicolas , Spychala Simon , Boulanger Eric , Cassagnaud Pascaline , Barthoulot Mael
Published: January 2022

Background

The Institut Pasteur de Lille, in the north of France, has implemented a large, multidisciplinary health check, which aims to identify frailty in middle-aged caregivers. We aimed to construct an adapted frailty index of cumulative deficit (FI-CD) and study the associated factors, in particular socioeconomic factors.

Methods

The cross-sectional study included caregivers aged 45 to 65. A 34-item FI-CD including deficits adapted to a middle-aged population (related to cognition and autonomy, dietetics, physical activity, comorbidities, functional signs, lab values and paraclinical examinations) was constructed in accordance with standard procedures. It was calculated as a ratio of deficits present out of the total number of possible deficits, giving a continuous score between 0 and 1. Scores > 0.25 and >  0.4 were classified as frailty and severe frailty, respectively. Univariate and multivariate associations were studied using linear regressions.

Results

One hundred and seventeen caregivers were included; among them, 111 were analyzed due to missing values. The mean FI-CD was 0.22 ± 0.08. Forty (36%) individuals were classified as frailty and three (2.7%) as severe frailty. In multivariate analysis, FI-CD was significantly associated with age (beta [95% confidence interval] = 0.005 [0.002; 0.009] per 1-year increase, p = 0.005) and social deprivation (beta = 0.054 [0.007; 0.102], p = 0.025). A significant interaction was observed between and age and social deprivation (p = 0.036). The adjusted relationship between FI-CD and age was beta = 0.010 [0.002; 0.019], p = 0.017 in precarious caregivers, and beta = 0.003 [− 0.001; 0.007], p = 0.19 in non-precarious caregivers.

Conclusions

The study suggested that the 34-item FI-CD could have clinical utility in the management of middle-aged caregivers. Social deprivation appeared as an important factor associated with frailty, highlighting the importance of early care and social support for precarious caregivers.
Associations of a healthy lifestyle score from childhood to adulthood with subclinical kidney damage in midlife: a population-based cohort study
Authors: Liu Conghui , Tian Jing , Jose Matthew D. , He Ye , Dwyer Terence , Venn Alison J.
Published: January 2022

Background

The relationships of healthy lifestyle scores (HLS) of various kinds in adulthood with the risk of chronic kidney disease (CKD) have been reported, but little is known about the association of childhood lifestyle with later life CKD. This study examined the relationship of HLS from childhood to adulthood with subclinical kidney damage (SKD) in midlife, a surrogate measure for CKD.

Methods

Data were collected in an Australian population-based cohort study with 33 years follow-up. 750 participants with lifestyle information collected in childhood (ages 10–15 years) and midlife (ages 40–50 years), and measures of kidney function in midlife were included. The HLS was generated from the sum scores of five lifestyle factors (body mass index, smoking, alcohol consumption, physical activity, and diet). Each factor was scored as poor (0 point), intermediate (1 point), or ideal (2 points). Log-binomial regression was used to investigate the relationship of HLS in childhood and from childhood to adulthood with SKD defined as either 1) estimated glomerular filtration rate (eGFR) 30–60 mL/min/1.73m2 or 2) eGFR> 60 mL/min/1.73m2 with urine albumin-creatinine ratio ≥ 2.5 mg/mmol (males) or 3.5 mg/mmol (females), adjusting for socio-demographic factors and the duration of follow-up.

Results

The average HLS was 6.6 in childhood and 6.5 in midlife, and the prevalence of SKD was 4.9% (n = 36). Neither HLS in childhood nor HLS from childhood to adulthood were significantly associated with the risk of SKD in midlife.

Conclusions

A HLS from childhood to adulthood did not predict SKD in this middle-aged, population-based Australian cohort.
Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
Authors: Narikot Ambili , Pardeshi Varsha Chhotusing , Shubha A. M. , Iyengar Arpana , Vasudevan Anil
Published: January 2022

Background

Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5–20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT.

Methods

Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed.

Results

The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants.

Conclusions

The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT.
Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation
Authors: Divers Jasmin , Mohan Sumit , Brown W. Mark , Pastan Stephen O. , Israni Ajay K. , Gaston Robert S. , Bray Robert , Islam Shahidul , Sakhovskaya Natalia V. , Mena-Gutierrez Alejandra M. , Reeves-Daniel Amber M. , Julian Bruce A. , Freedman Barry I.
Published: January 2022

Background

African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics.

Methods

Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients.

Results

Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010.

Conclusion

Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.
Prevalence, correlates and in-hospital outcomes of kidney dysfunction in hospitalized patients with heart failure in Buea-Cameroon
Authors: Jingi Ahmadou Musa , Nkoke Clovis , Noubiap Jean Jacques , Teuwafeu Denis , Mambap Alex T. , Nkouonlack Cyrille , Gobina Ronald , Njume Debimeh , Dzudie Anastase , Ashuntantang Gloria
Published: January 2022

Background

Kidney dysfunction is common in patients with heart failure (HF) and has been associated with poor outcomes. This study aimed to determine the prevalence, correlates, and prognosis of kidney dysfunction in patients with HF in Cameroon, an understudied population.

Methods

We conducted a cross-sectional study in consecutive patients hospitalized with HF between June 2016 and November 2017 in the Buea Regional Hospital, Cameroon. Kidney dysfunction was defined as an estimated glomerular filtration rate < 60 ml/min/1.73m2. Prognostic outcomes included death and prolonged hospital stay (> 7 days). We also performed a sensitivity analysis excluding racial considerations.

Results

Seventy four patients (86.1% of those eligible) were included. Their median age was 60 (interquartile range: 44–72) years and 46.0% (n = 34) were males. Half of patients (n = 37) had kidney dysfunction. Correlates of kidney dysfunction included previous diagnosis of HF (adjusted odds ratio [aOR]4.3, 95% CI: 1.1–17.5) and left ventricular hypertrophy (aOR3.4, 95% CI: 1.1–9.9). Thirty-six (48.9%) had prolonged hospital stay, and seven (9.5%) patients died in hospital. Kidney dysfunction was not associated with in-hospital death (aOR 0.4, 95% CI: 0.1–2) nor prolonged hospital stay (aOR 2.04, 0.8–5.3). In sensitivity analysis (excluding racial consideration), factors associated with Kidney dysfunction in HF were; anemia (aOR: 3.0, 95% CI: 1.1–8.5), chronic heart failure (aOR: 4.7, 95% CI: 0.9–24.6), heart rate on admission < 90 bpm (aOR: 3.4, 95% CI: 1.1–9.1), left atrial dilation (aOR: 3.2, 95% CI: 1.04–10), and hypertensive heart disease (aOR: 3.1, 95% CI: 1.2–8.4). Kidney dysfunction in HF was associated with hospital stay > 7 days (OR: 2.6, 95% CI: 1–6.8).

Conclusion

Moderate-to-severe kidney dysfunction was seen in half of the patients hospitalized with HF in our setting, and this was associated with a previous diagnosis of HF and left ventricular hypertrophy. Kidney dysfunction might not be the main driver of poor HF outcomes in this population. In sensitivity analysis, this was associated with anemia, chronic heart failure, heart rate on admission less than 90 bpm, left atrial dilatation, and hypertensive heart disease. Kidney dysfunction was associated with hospital stay > 7 days.
DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats
Authors: Zhao Shanshan , Liu Fangxi , Shi Wei , Wang Jialu , Zhou Zhike , Zhang Xiaoqian
Published: January 2022

Background

A decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer’s disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE.

Methods

Nissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting.

Results

TLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity.

Conclusions

We provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.
Total magnetic resonance imaging of cerebral small vessel disease burden predicts dysphagia in patients with a single recent small subcortical infarct
Authors: Zhang Lulu , Tang Xiang , Li Yidan , Zhu Juehua , Ding Dongxue , Zhou Yun , Diao Shanshan , Kong Yan , Cai Xiuying , Yao Ye , Fang Qi
Published: January 2022

Background

This study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI).

Methods

We retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4.

Results

In total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level.

Conclusions

Dysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.
Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults: a population-based study
Authors: Liu Rui , Tang Shi , Wang Yongxiang , Dong Yi , Hou Tingting , Ren Yifei , Cong Lin , Liu Keke , Qin Yu , Sindi Shireen , Du Yifeng , Qiu Chengxuan
Published: January 2022

Background

Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear.

Methods

This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease (AD). Data were analysed using multiple logistic and general linear regression models.

Results

Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score.

Conclusions

Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers.

Trial registration

ChiCTR1800017758 (Aug 13, 2018).
Evaluation of the recurrence and fertility rate following salpingostomy in patients with tubal ectopic pregnancy
Authors: Poordast Tahereh , Naghmehsanj Zahra , Vahdani Razie , Moradi Alamdarloo Shaghayegh , Ashraf Mohammad Ali , Samsami Almtaj , Najib Fatemeh Sadat
Published: January 2022

Background

Ectopic pregnancy is one of the leading causes of pregnancy-related mortality; the treatment strategies associated with this condition entail complications, such as recurrence of ectopic pregnancy or infertility. The objective of this study was to evaluate the recurrence and fertility rate after salpingostomy in patients with tubal ectopic pregnancy.

Methods

This cross-sectional retrospective study was conducted at four referral centers of Obstetrics and Gynecology, under the supervision of Shiraz University of Medical Sciences (Iran). The medical records of 125 patients with tubal pregnancy were reviewed. These patients underwent laparoscopic salpingostomy from April 2009 to March 2016.Data on maternal age, BMI, history of previous EP, genital tract infection, IUD insertion, history of previous surgery, and infertility were further obtained. The patients were followed up for approximately 1 to 7 years. The recurrence of EP and subsequent pregnancy rate were assessed during the follow-up period.

Results

There was no statistically significant relationship between post-salpingostomy recurrence and maternal age, previous abdominopelvic surgery, and history of infertility(P = .425); however, the post-salpingostomy recurrence of EP was correlated with BMI (P = 0.001), previous history of EP (P = 0.001), genital tract infection (P = 0.001), and IUD insertion (P = 003). Among 95 women who had no contraception, pregnancy occurred in 51 cases (53.6%) and recurrence of EP was observed in 16 patients (12.8%).

Conclusions

Our results suggest that salpingostomy is a safe method with a low risk of recurrence and good fertility outcomes for women who consider future pregnancy.
Factors associated with maternal overall quality of life six months postpartum: a cross sectional study from The Norwegian Mother, Father and Child Cohort Study
Authors: Valla Lisbeth , Helseth Sølvi , Småstuen Milada Cvancarova , Misvær Nina , Andenæs Randi
Published: January 2022

Background

Having good Quality of Life (QoL) is essential, particularly for women after childbirth. However, little is known about the factors associated with maternal QoL after giving birth. We aimed to investigate the relationship between characteristics of the mother (socio-demographic variables), selected symptoms (depression and joy/anger), health perception (perception of birth) and possible characteristics of the environment (infant temperament, colic, sleep, parental relationship), with mothers’ overall quality of life when the child is 6 months of age.

Methods

This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa), conducted at the Norwegian Institute of Public Health from June 1999 to December 2008, which included a total of 86,724 children. Maternal QoL was assessed by the Satisfaction With Life Scale. Joy and anger were measured using the Differential Emotional Scale, mothers’ mental health was assessed using the Edinburgh Postnatal Depression Scale and satisfaction with relationship was measured using the Relationship Satisfaction Scale. Child temperament was measured using the Infant Characteristics Questionnaire and colic, sleep duration and feelings related to childbirth were assessed by mothers’ reports. The associations between life satisfaction and selected variables were analysed using stepwise multiple linear regression models, and the results are presented as effect sizes (ES).

Results

Maternal feelings of joy of having a baby (ES = 0.35), high relationship satisfaction (ES = 0.32), as well as having a baby with normal sleep (ES = 0.31), are factors associated with higher maternal overall QoL. Postnatal depression was negatively associated with mothers’ QoL, and infant colic or child’s temperament (fussiness) showed no such association with mothers’ QoL.

Conclusions

Health professionals and clinicians should focus on infants sleep but also on supporting joy of motherhood and strengthening relationships of the new parents when they develop health interventions or provide counselling to new mothers and their families.