bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation
Authors: Setty B. N. Yamaja , Kulkarni Surekha , Rao A. Koneti , Stuart Marie J.
Published: October 2019

In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children with SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thrombin generation. F cells correlated inversely with both microvesicles and PS positivity (P < .000001) in SS disease. Multiple regression analyses using various hematologic parameters as independent variables, and either microvesicles or PS positivity as the dependent variable, showed a strong relationship only with F cells. Additionally, plasma prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated with both PS positivity (P < .001) and F cells (P < .01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microvesicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers may provide valuable insights into the biology and consequences of in vivo sickling.
Granulocyte colony-stimulating factor regulates myeloid differentiation through CCAAT/enhancer-binding protein ε
Authors: Nakajima Hideaki , Ihle James N.
Published: October 2019

Granulocyte colony-stimulating factor (G-CSF) is a major cytokine that regulates proliferation and differentiation of myeloid cells, although the underlying mechanisms by which G-CSF controls myeloid differentiation are largely unknown. Differentiation of hematopoietic cells is regulated by lineage-specific transcription factors, and gene-targeting studies previously revealed the critical roles of CCAAT/enhancer-binding protein (C/EBP) α and C/EBPε, respectively, in the early and mid-late stages of granulocyte differentiation. The expression of C/EBPε in 32Dcl3 cells and FDCP1 cells expressing mutant G-CSF receptors was examined and it was found that G-CSF up-regulates C/EBPε. The signal for this expression required the region containing the first tyrosine residue of G-CSF receptor. Dominant-negative signal transducers and activators of transcription 3 blocked G-CSF–induced granulocytic differentiation in 32D cells but did not block induction of C/EBPε, indicating that these proteins work in different pathways. It was also found that overexpression of C/EBPε greatly facilitated granulocytic differentiation by G-CSF and, surprisingly, that expression of C/EBPε alone was sufficient to make cells differentiate into morphologically and functionally mature granulocytes. Overexpression of c-myc inhibits differentiation of hematopoietic cells, but the molecular mechanisms of this inhibition are not fully understood. In 32Dcl3 cells overexpressing c-myc that do not differentiate by means of G-CSF, induction of C/EBPε is completely abrogated. Ectopic expression of C/EBPε in these cells induced features of differentiation, including changes in nuclear morphologic characteristics and the appearance of granules. These data show that C/EBPε constitutes a rate-limiting step in G-CSF–regulated granulocyte differentiation and that c-myc antagonizes G-CSF–induced myeloid differentiation, at least partly by suppressing induction of C/EBPε.
Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI
Authors: Holm Teresa M. , Braun Anne , Trigatti Bernardo L. , Brugnara Carlo , Sakamoto Masa , Krieger Monty , Andrews Nancy C.
Published: October 2019

Mammalian erythrocytes undergo a unique maturation process in which they discard their nuclei and organelles and assume a flexible biconcave shape. We found that altered plasma lipoprotein metabolism can profoundly influence these events. Abnormal erythrocyte morphology was observed in hypercholesterolemic mice lacking the high-density lipoprotein receptor SR-BI. This was exacerbated by feeding mice a high-cholesterol diet or, more dramatically, by inactivating the apolipoprotein E gene. Erythrocytes fromSR-BI−/−/apolipoprotein E−/−mice and SR-BI−/−mice that were fed cholesterol had markedly increased membrane cholesterol. Their morphology appeared immature, with macrocytosis, irregular shape, and large autophagolysosomes. Autophagolysosomes fromSR-BI−/−/apolipoprotein E−/−erythrocytes were expelled when the erythrocytes were transfused into wild-type animals or incubated in vitro with normolipidemic serum or the cholesterol-sequestering agent methyl cyclodextrin. We propose that autophagocytosis and phagolysosome expulsion are essential steps in erythroid maturation and that expulsion is inhibited in the presence of markedly increased cellular cholesterol.
Heart disease in a mutant mouse model of spontaneous eosinophilic myocarditis maps to three loci
Authors: Zimmermann Nives , Gibbons William J. , Homan Shelli M. , Prows Daniel R.
Published: October 2019

Background

Heart disease (HD) is the major cause of morbidity and mortality in patients with hypereosinophilic diseases. Due to a lack of adequate animal models, our understanding of the pathophysiology of eosinophil-mediated diseases with heart complications is limited. We have discovered a mouse mutant, now maintained on an A/J inbred background, that spontaneously develops hypereosinophilia in multiple organs. Cellular infiltration into the heart causes an eosinophilic myocarditis, with affected mice of the mutant line (i.e.,A/JHD) demonstrating extensive myocardial damage and remodeling that leads to HD and premature death, usually by 15-weeks old.

Results

Maintaining the A/JHDline for many generations established that the HD trait was heritable and implied the mode of inheritance was not too complex. Backcross and intercross populations generated from mating A/JHDmales with females from four different inbred strains produced recombinant populations with highly variable rates of affected offspring, ranging from none in C57BL/6 J intercrosses, to a few mice with HD using 129S1/SvImJ intercrosses and C57BL/6 J backcrosses, but nearly 8% of intercrosses and > 17% of backcrosses from SJL/J related populations developed HD. Linkage analyses of these SJL/J derived recombinants identified three highly significant loci: a recessive locus mapping to distal chromosome 5 (LOD = 4.88; namedEmhd1for eosinophilic myocarditis to heart disease-1); and two dominant variants mapping to chromosome 17, one (Emhd2; LOD = 7.51) proximal to the major histocompatibility complex, and a second (Emhd3; LOD = 6.89) that includes the major histocompatibility region. Haplotype analysis identified the specific crossovers that defined theEmhd1(2.65 Mb),Emhd2(8.46 Mb) andEmhd3(14.59 Mb) intervals.

Conclusions

These results indicate the HD trait in this mutant mouse model of eosinophilic myocarditis is oligogenic with variable penetrance, due to multiple segregating variants and possibly additional genetic or nongenetic factors. The A/JHDmouse model represents a unique and valuable resource to understand the interplay of causal factors that underlie the pathology of this newly discovered eosinophil-associated disease with cardiac complications.
Comparative genomics of Leishmania (Mundinia)
Authors: Butenko Anzhelika , Kostygov Alexei Y. , Sádlová Jovana , Kleschenko Yuliya , Bečvář Tomáš , Podešvová Lucie , Macedo Diego H. , Žihala David , Lukeš Julius , Bates Paul A. , Volf Petr , Opperdoes Fred R. , Yurchenko Vyacheslav
Published: October 2019

Background

Trypanosomatids of the genus Leishmania are parasites of mammals or reptiles transmitted by bloodsucking dipterans. Many species of these flagellates cause important human diseases with clinical symptoms ranging from skin sores to life-threatening damage of visceral organs. The genus Leishmania contains four subgenera: Leishmania, Sauroleishmania, Viannia, and Mundinia. The last subgenus has been established recently and remains understudied, although Mundinia contains human-infecting species. In addition, it is interesting from the evolutionary viewpoint, representing the earliest branch within the genus and possibly with a different type of vector. Here we analyzed the genomes of L. (M.) martiniquensis, L. (M.) enriettii and L. (M.) macropodum to better understand the biology and evolution of these parasites.

Results

All three genomes analyzed were approximately of the same size (~ 30 Mb) and similar to that of L. (Sauroleishmania) tarentolae, but smaller than those of the members of subgenera Leishmania and Viannia, or the genus Endotrypanum (~ 32 Mb). This difference was explained by domination of gene losses over gains and contractions over expansions at the Mundinia node, although only a few of these genes could be identified. The analysis predicts significant changes in the Mundinia cell surface architecture, with the most important ones relating to losses of LPG-modifying side chain galactosyltransferases and arabinosyltransferases, as well as β-amastins. Among other important changes were gene family contractions for the oxygen-sensing adenylate cyclases and FYVE zinc finger-containing proteins.

Conclusions

We suggest that adaptation of Mundinia to different vectors and hosts has led to alternative host-parasite relationships and, thereby, made some proteins redundant. Thus, the evolution of genomes in the genus Leishmania and, in particular, in the subgenus Mundinia was mainly shaped by host (or vector) switches.
Mixed mating system and variable mating patterns in tropical woody bamboos
Authors: Xie Ning , Chen Ling-Na , Dong Yu-Ran , Yang Han-Qi
Published: October 2019

Background

So far, little is known in detail about mating systems of woody bamboos. Paternity analysis of offspring improved our understanding of these systems, and contributed to their germplasm conservation and genetic improvement.

Results

In this study, a paternity analysis of offspring from two consecutive mass or sporadically flowering events ofDendrocalamus membranaceusandD. sinicuswere conducted to determine their mating system and pollen dispersal using the program COLONY based on simple sequence repeat (SSR) markers. Two sporadically flowering populations ofD. sinicus(C1, C2) obtained relatively high paternity assignments rates (69.0–71.4%). Meanwhile, among three populations ofD. membranaceus, the sporadically flowering population A also had much higher paternity assignments rates (56.4%) than mass flowering populations B1(28.6%) and B2 (42.5%). BothD. membranaceusandD. sinicushad mixed mating systems while their mating patterns were variable depending on pollination conditions. The maximum pollen dispersal distances were 90 m and 4378 m forD. membranaceusandD. sinicuspopulations, respectively, and the mating distances of these two species focused on ranges of ca. 0–50 m and 0–1500 m, respectively.

Conclusions

These results revealed for the first time variable mating patterns in woody bamboos. This suggests half-sib seeds from the same bamboo clump may have different male parents and it is crucial to clarify genetic origin in woody bamboos’ breeding programs. The results also indicate the importance of pollinators in the mating systems of tropical woody bamboos.
Transcriptomic analysis of early fruit development in Chinese white pear (Pyrus bretschneideri Rehd.) and functional identification of PbCCR1 in lignin biosynthesis
Authors: Su Xueqiang , Zhao Yu , Wang Han , Li Guohui , Cheng Xi , Jin Qing , Cai Yongping
Published: October 2019

Background

The content of stone cells and lignin is one of the key factors affecting the quality of pear fruit. In a previous study, we determined the developmental regularity of stone cells and lignin in ‘Dangshan Su’ pear fruit 15-145 days after pollination (DAP). However, the development of fruit stone cells and lignin before 15 DAP has not been heavily researched.

Results

In this study, we found that primordial stone cells began to appear at 7 DAP and that the fruit had formed a large number of stone cells at 15 DAP. Subsequently, transcriptome sequencing was performed on fruits at 0, 7, and 15 DAP and identified 3834 (0 vs. 7 DAP), 4049 (7 vs. 15 DAP) and 5763 (0 vs. 15 DAP) DEGs. During the 7-15 DAP period, a large number of key enzyme genes essential for lignin biosynthesis are gradually up-regulated, and their expression pattern is consistent with the accumulation of lignin in this period. Further analysis found that the biosynthesis of S-type lignin in ‘Dangshan Su’ pear does not depend on the catalytic activity ofPbSADbut is primarily generated by the catalytic activity of caffeoyl-CoA through CCoAOMT, CCR, F5H, and CAD. We clonedPbCCR1,2and analysed their functions in Chinese white pear lignin biosynthesis.PbCCR1and2have a degree of functional redundancy; both demonstrate the ability to participate in lignin biosynthesis. However,PbCCR1may be the major gene for lignin biosynthesis, whilePbCCR2has little effect on lignin biosynthesis.

Conclusions

Our results revealed that ‘Dangshan Su’ pear began to form a large number of stone cells and produce lignin after 7 DAP and mainly accumulated materials from 0 to 7 DAP.PbCCR1is mainly involved in the biosynthesis of lignin in ‘Dangshan Su’ pear and plays a positive role in lignin biosynthesis.
Traffic police officers’ experience of post-crash care to road traffic injury victims: a qualitative study in Tanzania”
Authors: Lukumay Gift G. , Outwater Anne H. , Mkoka Dickson A. , Ndile Menti L. , Saveman Britt-Inger
Published: October 2019

Background

Recently, road traffic injuries (RTIs) have become a major health problem affecting health systems in many low- and middle-income countries. Regardless of whether an ambulance is available for evacuation, police officers have been shown to arrive at the crash scene first, becoming, in effect, the first responders to RTI victims. Therefore, the study aimed to explore the experiences of traffic police officers in regard to the provision of care to RTI victims in the prehospital environment, including the role of traffic police upon arriving at the crash scene, the challenges they face, and their opinions about how to improve care to RTI victims.

Method

The study used a qualitative approach in which data were obtained from 10 individual interviews and three focus group discussions. There were 41 participants, 27 of them were male and 14 were female. About half (48.7%) of the study participants were aged between 30 to 39 years. Qualitative content analysis was used to analyse all the materials.

Results

Three themes emerged from the analysis. The theme “Maintain safety while saving injured victims’ lives and facilitating access to a health facility” was comprised of safety, sorting, initial help, and assisting access to hospital care. “Overwhelmed working with limited resources and support” included limited care and transport resources, police fatigue, and little or no support. “Improving supportive system and empowering frontline personnel” included the need for an emergency care system, availability of resources and an emergency medical support system, and training for police and drivers regarding victims’ first-aid care, and road safety.

Conclusion

The study findings characterize an environment in which the police first responders have no knowledge or skills and no equipment and supplies to provide care to RTI victims at the scene before rushing them to definitive care. The results suggest a favorable climate for training and equipping officers so that they can deliver competent postcrash care at the scene while emergency medical services are yet to be established. However, more research will be needed to determine the efficacy of such training and its acceptability in the Tanzanian context.
Why do general practitioners not refer patients to behaviour-change programmes after preventive health checks? A mixed-method study
Authors: Kamstrup-Larsen Nina , Broholm-Jørgensen Marie , Dalton Susanne O. , Larsen Lars B. , Thomsen Janus L. , Tolstrup Janne S.
Published: October 2019

Background

This study was embedded in the Check-In randomised controlled trial that investigated the effectiveness of general practice-based preventive health checks on adverse health behaviour and early detection of non-communicable diseases offered to individuals with low socioeconomic positions. Despite successful recruitment of patients, the intervention had no effect. One reason for the lack of effectiveness could be low rates of referral to behaviour-change programmes in the municipality, resulting in a low dose of the intervention delivered. The aim of this study is to examine the referral pattern of the general practitioners and potential barriers to referring eligible patients to these behaviour-change programmes.

Methods

A mixed-method design was used, including patients’ questionnaires, recording sheet from the health checks and semi-structured qualitative interviews with general practitioners. All data used in the study were collected during the time of the intervention. Logistic regressions were used to estimate odds ratios for being eligible and for receiving referrals. The qualitative empirical material was analysed thematically. Emerging themes were grouped, discussed and the material was re-read. The themes were reviewed alongside the analysis of the quantitative material to refine and discuss the themes.

Results

Of the 364 patients, who attended the health check, 165 (45%) were marked as eligible for a referral to behaviour-change programme by their general practitioner and of these, 90 (55%) received referrals. Daily smoking (OR = 3.22; 95% CI:2.01–5.17), high-risk alcohol consumption (OR = 2.66; 95% CI:1.38–5.12), obesity (OR = 2.89; 95% CI:1.61–5.16) and poor lung function (OR = 2.05; 95% CI:1.14–3.70) were all significantly associated with being eligible, but not with receiving referral. Four themes emerged as the main barriers to referring patients to behaviour-change programmes: 1) general practitioners’ responsibility and ownership for their patients, 2) balancing information and accepting a rejection, 3) assessment of the right time for behavioural change and 4) general practitioners’ attitudes towards behaviour-change programmes in the municipality.

Conclusion

We identified important barriers among the general practitioners which influenced whether the patients received referrals to behaviour-change programmes in the municipality and thereby influenced the dose of intervention delivered in Check-In. The findings suggest that an effort is needed to assist the collaboration between general practices and the municipalities’ primary preventive services.

Trial registration

Clinical Trials NCT01979107; October 25, 2013.
A systematic literature review of the assessment of treatment burden experienced by patients and their caregivers
Authors: Sheehan Orla C. , Leff Bruce , Ritchie Christine S. , Garrigues Sarah K. , Li Lingsheng , Saliba Debra , Fathi Roya , Boyd Cynthia M.
Published: October 2019

Background

Many older adults with multiple chronic conditions, particularly those who are functionally impaired, spend considerable time juggling the competing demands of managing their conditions often assisted by caregivers. We examined methods of assessing the treatment burden experienced by this population as a first step to identifying strategies to reduce it.

Methods

Systematic searches were performed of the peer-reviewed and grey-literature (PubMed, Cochrane library, CINAHL, EMBASE, Web of Science, SCOPUS, New York Academy of Medicine Grey Literature Review, NLM catalog and ProQuest Digital Theses and Dissertations). After title and abstract screening, both qualitative and quantitative articles describing approaches to assessment of treatment burden were included.

Results

Forty-five articles from the peer reviewed and three items from the grey literature were identified. Most articles (34/48) discussed treatment burden associated with a specific condition. All but one examined the treatment burden experienced by patients and six addressed the treatment burden experienced by caregivers. Qualitative studies revealed many aspects of treatment burden including the burdens of understanding the condition, juggling, monitoring and adjusting treatments, efforts to engage with others for support as well as financial and time burdens. Many tools to assess treatment burden in different populations were identified through the qualitative data. The most commonly used instrument was the Treatment Burden Questionnaire.

Conclusions

Many instruments are available to assess treatment burden, but no one standardized assessment method was identified. Few articles examined approaches to measuring the treatment burden experienced by caregivers. As people live longer with more chronic conditions healthcare providers need to identify patients and caregivers burdened by treatment and engage in approaches to ameliorate treatment burden. A standard and validated assessment method to measure treatment burden in the clinical setting would help to enhance the care of people with multiple chronic conditions, allow comparison of different approaches to reducing treatment burden, and foster ongoing evaluation and monitoring of burden across conditions, patient populations, and time.
Impact and clinical profiles of Mycoplasma pneumoniae co-detection in childhood community-acquired pneumonia
Authors: Zhao Meng-chuan , Wang Le , Qiu Fang-zhou , Zhao Li , Guo Wei-wei , Yang Shuo , Feng Zhi-shan , Li Gui-xia
Published: October 2019

Background

Increasing number of hospitalized children with community acquired pneumonia (CAP) is co-detected withMycoplasma pneumoniae(Mp). The clinical characteristics and impact ofMpco-detected with other bacterial and/or viral pathogens remain poorly understood. The purpose of this study was to evaluate the demographic and clinical features of CAP children withMpmono-detection andMpco-detection.

Methods

A total of 4148 hospitalized children with CAP were recruited from January to December 2017 at the Children’s Hospital of Hebei Province, affiliated to Hebei Medical University. A variety of respiratory viruses, bacteria andMpwere detected using multiple modalities. The demographic and clinical features of CAP children withMpmono-detection andMpco-detection were recorded and analyzed.

Results

Among the 110 CAP children withMppositive, 42 (38.18%) of them were co-detected with at least one other pathogen. Co-detection was more common among children aged ≤3 years. No significant differences were found in most clinical symptoms, complications, underlying conditions and disease severity parameters among various etiological groups, with the following exceptions. First, prolonged duration of fever, lack of appetite and runny nose were more prevalent among CAP children withMp-virus co-detection. Second,Mp-virus (excludingHRV) co-detected patients were more likely to present with prolonged duration of fever. Third, patients co-detected withMp-bacteria were more likely to have abnormal blood gases. Additionally, CAP children withMp-HRVco-detection were significantly more likely to report severe runny nose compared to those withMpmono-detection.

Conclusion

Mpco-detection with viral and/or bacterial pathogens is common in clinical practice. However, there are no apparent differences betweenMpmono-detection andMpco-detections in terms of clinical features and disease severity.
The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research
Authors:   the EKiTE consortium, Lorent M. , Foucher Y. , Kerleau K. , Brouard S. , Baayen C. , Lebouter S. , Naesens M. , Bestard Matamoros O. , Åsberg A. , Giral M.
Published: October 2019

Background

Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies.

Main body

Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses.

Conclusion

EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.
Nightmare experience and family relationships in healthy volunteers and nightmare disorder patients
Authors: Wang Chu , Shao Xu , Jia Yanli , Shen Chanchan , Wang Wei
Published: October 2019

Background

Nightmares are associated with parental bonding styles and various psychiatric disorders, but the exact connections between different nightmare experience features and family relationships in healthy volunteers and nightmare disorder patients are still unclear.

Methods

We therefore invited 62 nightmare disorder patients and 135 healthy volunteers to undergo tests of the Nightmare Experience Questionnaire (NEQ), the Family Relationship Questionnaire (FRQ), and the Plutchik - van Praag Depression Inventory (PVP).

Results

Besides the higher nightmare frequency and the higher PVP and four NEQ scale scores, the nightmare disorder patients had higher scores of FRQ Paternal Abuse, and lower ones of General Attachment, Maternal Encouragement, Maternal Freedom Release, and Paternal Freedom Release. The PVP was correlated with some NEQ and FRQ scales in both healthy volunteers and patients, and it functioned as a mediator between Physical Effect and Maternal Dominance in patients. Regarding predicting NEQ by FRQ, Paternal Abuse predicted Physical Effect, Maternal Dominance predicted Physical Effect and Horrible Stimulation, General Attachment predicted Horrible Stimulation (−) in healthy volunteers; Maternal Dominance predicted Physical Effect, Meaning Interpretation, and Horrible Stimulation, Paternal Freedom Release predicted Physical Effect (−), and Paternal Dominance predicted Meaning Interpretation and nightmare frequency in patients.

Conclusions

Our study has demonstrated that the inappropriate family relationships were linked with different aspects of nightmare experience, especially in nightmare disorder patients.
Remarkable increase of musculoskeletal disorders among soldiers preparing for international missions – comparison between 2002 and 2012
Authors: Halvarsson Alexandra , Seth Monika , Tegern Matthias , Broman Lisbet , Larsson Helena
Published: October 2019

Background

Musculoskeletal disorders (MSD) are common among soldiers and constitute the most common reason for discontinuing military service within different military populations worldwide. The aims of this study were to investigate the prevalence of musculoskeletal disorders in two cohorts, 10 years apart, in the Swedish Armed Forces, to explore differences between these cohorts and to determine associated factors with MSD.

Method

Comparative cross-sectional study. Participants were recruited from the Swedish Armed Forces, i.e. soldiers preparing for international missions in 2002 and 2012. A total of 961 soldiers, 7% women, participated in the study.

Data were collected using the Musculoskeletal Screening Protocol (MSP), which includes questions regarding prevalence of MSD in ten anatomical locations (neck, upper back, low back, shoulders, elbow, hand, hip, knee, lower limb and foot). An additional five questions concern perceived self-rated health, i.e. how the respondent perceives their own physical body, mental health, social environment, physical environment and work ability.

Results

Over a ten-year period, both point prevalence and one-year prevalence of MSD in any body part increased significantly, with point prevalence increasing from 7.1 to 35.2% (p < 0.001) and one-year prevalence from 27.9 to 67.9% (p < 0.001). The knee was the most common anatomic location for MSD in both cohorts. Across each anatomical location (neck, upper back, low back, shoulders, elbow, hand, hip, knee, lower leg and foot), both point prevalence (p < 0.039) and one-year prevalence (p < 0.005) increased significantly from 2002 to 2012.

Most soldiers reported good to excellent perceived health, i.e. self-perception of their physical body, mental health, physical and social environments, and work ability.

The odds of reporting one-year prevalence of MSD in any body part was 5.28 times higher for soldiers in Cohort 2012, 1.91 times higher in age group 31–40 and 2.84 times higher in age group 41 and above.

Conclusions

The prevalence of MSD increased remarkably over a ten-year period among Swedish soldiers preparing for international missions. With increasing age as one risk factor, systematic monitoring of MSD throughout the soldiers’ careers and implementation of targeted primary-to-tertiary preventive programs are thus important.
Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer
Authors: Sun Jingbo , Huang Jingzhan , Lan Jin , Zhou Kun , Gao Yuan , Song Zhigao , Deng Yunyao , Liu Lixin , Dong Ying , Liu Xiaolong
Published: October 2019

Background

Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear.

Methods

Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis.

Results

The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1.

Conclusion

CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.
Why are olfactory ensheathing cell tumors so rare?
Authors: Murtaza Mariyam , Chacko Anu , Delbaz Ali , Reshamwala Ronak , Rayfield Andrew , McMonagle Brent , St John James A. , Ekberg Jenny A. K.
Published: October 2019

The glial cells of the primary olfactory nervous system, olfactory ensheathing cells (OECs), are unusual in that they rarely form tumors. Only 11 cases, all of which were benign, have been reported to date. In fact, the existence of OEC tumors has been debated as the tumors closely resemble schwannomas (Schwann cell tumors), and there is no definite method for distinguishing the two tumor types. OEC transplantation is a promising therapeutic approach for nervous system injuries, and the fact that OECs are not prone to tumorigenesis is therefore vital. However, why OECs are so resistant to neoplastic transformation remains unknown. The primary olfactory nervous system is a highly dynamic region which continuously undergoes regeneration and neurogenesis throughout life. OECs have key roles in this process, providing structural and neurotrophic support as well as phagocytosing the axonal debris resulting from turnover of neurons. The olfactory mucosa and underlying tissue is also frequently exposed to infectious agents, and OECs have key innate immune roles preventing microbes from invading the central nervous system. It is possible that the unique biological functions of OECs, as well as the dynamic nature of the primary olfactory nervous system, relate to the low incidence of OEC tumors. Here, we summarize the known case reports of OEC tumors, discuss the difficulties of correctly diagnosing them, and examine the possible reasons for their rare incidence. Understanding why OECs rarely form tumors may open avenues for new strategies to combat tumorigenesis in other regions of the nervous system.
An Arthrobacter citreus strain suitable for degrading ε-caprolactam in polyamide waste and accumulation of glutamic acid
Authors: Baxi Nandita N. , Patel Shweta , Hansoti Dipeksha
Published: October 2019

ε-Caprolactam-a toxic xenobiotic compound present in industrial polyamide waste was found to be degraded by caprolactam-degrading bacteria. Arthrobacter citreus was able to utilize up to 20 g ε-caprolactam/l as the sole source of carbon more efficiently as compared to the other Gram positive caprolactam-degrading bacteria Rhodococcus rhodochrous and Bacillus sphaericus. The cells of A. citreus remained viable in medium up to 40 g caprolactam/l. The degradation of 10 g caprolactam/l by A. citreus, when supplied as the sole source of carbon and nitrogen lead to the formation of 6-aminocaproic acid which was detected in broth and there was also an increase in the ammonium content. One of the other metabolites found to consistently accumulate in extracellular medium during the utilization of caprolactam by A. citreus was glutamic acid, though not reported in case of other caprolactam-degrading bacteria. A. citreus could metabolise caprolactam to form non toxic products such as 6-aminocaproic acid and glutamic acid which are amino acids of physiological and commercial importance. In the presence of 6-aminocaproic acid, the rate of caprolactam utilization by A. citreus was decreased but not inhibited and the viable count of cells was found to increase using both the substrates simultaneously. A. citreus was also suitable for degradation of caprolactam in presence of low phosphate as prevalent in soil, and in sterile soil without the supplementation of any other carbon or nitrogen, as well as in native non sterile soil where other microorganisms are present.
CTCF and cellular heterogeneity
Authors: Ren Gang , Zhao Keji
Published: October 2019

Cellular heterogeneity, which was initially defined for tumor cells, is a fundamental property of all cellular systems, ranging from genetic diversity to cell-to-cell variation driven by stochastic molecular interactions involved all cellular processes. Different cells display substantial variation in gene expression and in response to environmental signaling even in an apparently homogeneous population of cells. Recent studies started to reveal the underlying mechanisms for cellular heterogeneity, particularly related to the states of chromatin. Accumulating evidence suggests that CTCF, an important factor regulating chromatin organization, plays a key role in the control of gene expression variation by stabilizing enhancer–promoter interaction.
Cardio embolic stroke and blood biomarkers: diagnosis and predictors of short-term outcome
Authors: Mohamed Wafaa S. , Abd ElGawad Elhady A. , ElMotayam Amal SE. , Fathy Sabah E.
Published: October 2019

Background

The brain is a productive source of a variety of enzymes and any brain injury like a stroke to brain tissue could similarly result in an increase in these enzymes in cerebrospinal fluid and serum. Evaluation of these enzymes represents a simple method for the ischemic stroke subtype diagnosis and prognosis. Objective: This study aimed to determine the role of brain natriuretic peptide (BNP), d-dimer, creatine–kinase-MB (CK-MB), C-reactive protein (CRP) serum levels, and globulin/albumin ratio in the diagnosis of CES stroke and its ability to predict short-term outcome.

Methods

This study was conducted on 96 patients with acute ischemic stroke, subdivided into two groups: group Ι was 48 patients with cardio-embolic stroke and group ΙΙ was 48 patients with non-cardio-embolic. All patients were subjected to the assessment of serum BNP, d-dimer and CK-MB, and CRP and globulin/albumin ratio within the first 24 h of stroke. In the third week, they were assessed by mRS.

Results

The mean levels of BNP, d-dimer level, and CK-MB were significantly higher in patients with cardio-embolic stroke than in patients with non-cardio-embolic stroke (P < 0.001) and also were associated with poor short-term outcome.

Conclusion

Elevated plasma levels of BNP, d-dimer levels, and CK-MB can be used as surrogate biomarkers for the diagnosis of cardio-embolic stroke and prediction of poor short-term outcomes.
Alluvial sedimentation and tectono-stratigraphic evolution in a narrow extensional zigzag basin margin (northern Teruel Basin, Spain)
Authors: Ezquerro Lope , Luzón Aránzazu , Simón José L. , Liesa Carlos L.
Published: October 2019

The northern part of the eastern margin of the extensional Neogene Teruel Basin (central-eastern Spain) consists of a non-linear, zigzag fault zone made of alternating ca. 2 km long, NNW-SSE trending segments and shorter NNE-SSW ones. Good outcrop conditions made possible a comprehensive integrated stratigraphic and structural study, especially focused on coarse clastic sediments deposited along the basin margin. Well-exposed stratal relationships with boundary faults, allowed the analysis of tectonic influence on sedimentation. Synsedimentary deformation includes growth faulting, rollover anticlines, and monoclines and associated onlap stratal terminations, angular unconformities, and other complex growth strata geometries. One of them is the onlap-over-rollover bed arrangement described here for the first time, which reveals the competition between tectonic subsidence and sedimentary supply. Both, the structural inheritance (dense Mesozoic fracture grid) and the dominant, nearly ‘multidirectional’ (σ1 vertical, σ2 ≈ σ3), Pliocene extensional regime with σ3 close to E-W, are considered to have controlled the margin structure and evolution. Tectono-stratigraphic evolution includes: (i) reactivation of inherited NNW-SSE faults and development of W-SW-directed small alluvial fans (SAF) while NNE-SSW segments acted as gentle relay ramp zones; (ii) progressive activation of NNE-SSW faults and development of NW-directed very small alluvial fans (VSAF); during stages i and ii sediments were trapped close to the margin, avoiding widespread progradation; (iii) linking of NNW-SSE and NNE-SSW structural segments, overall basin sinking and widespread alluvial progradation; (iv) fault activity attenuation and alluvial retrogradation. The particular structure and kinematic evolution of this margin controlled alluvial system patterns. Size of alluvial fans, directly set up at the border faults, was conditioned by the narrowness of the margin, small catchment areas, and proximity between faults, which prevented the development of large alluvial fans. The size of the relay zones, only a few hundred meters wide, acted in the same way, avoiding them to act as large sediment transfer areas and large alluvial fans to be established. These features make the Teruel Basin margin different to widely described extensional margins models.
Coverage, Financial Burden, and the Patient Protection and Affordable Care Act for Patients With Cancer
Authors: Segel Joel E. , Jung Jeah
Published: October 2019

PURPOSE:

Evidence suggests coverage has improved significantly for patients with cancer, particularly in the lower-income population, after the implementation of the Affordable Care Act (ACA). Yet no study has examined changes in type of coverage or the resulting effect on spending and financial burden.

METHODS:

Using 2011 to 2015 Medical Expenditure Panel Survey data, we examine changes in type of coverage, spending, and financial burden among lower-income (< 400% of federal poverty level [FPL]) individuals diagnosed with cancer after the ACA. To better understand the changes, we compare this sample to the lower-income patients without cancer and patients with cancer with a higher income (≥ 400% of FPL). All analyses were conducted in 2018.

RESULTS:

In adjusted analyses, we found a decline in months uninsured (−0.78 months; P = .001) and an increase in months with Medicaid coverage (0.40 months; P = .059) among the lower-income patients with cancer. This change is similar to the lower-income patients without cancer. We found an increase in total expenditures ($3,020; P = .071) but a modest decline in the fraction of family income spent on health (−0.014; P = 0.099), although neither is statistically significant. For the higher income patients with cancer, we observed significant increases in both out-of-pocket premiums and medical financial burden.

CONCLUSION:

After the ACA, lower-income people diagnosed with cancer experienced significant gains in coverage largely through Medicaid at rates similar to lower-income patients without cancer, but patients with cancer with incomes 400% or greater of FPL faced a higher financial burden.
Brown Adipose Tissue Response to Cold Stimulation Is Reduced in Girls With Autoimmune Hypothyroidism
Authors: Law James M , Morris David E , Astle Valerie , Finn Ellie , Muros José Joaquín , Robinson Lindsay J , Randell Tabitha , Denvir Louise , Symonds Michael E , Budge Helen
Published: October 2019

Objective

The interaction between thyroid status and brown adipose tissue (BAT) activation is complex. We assessed the effect of autoimmune hypothyroidism (ATD) in female children on BAT activation, measured using infrared thermography.

Design

Twenty-six female participants (14 with ATD and 12 healthy controls) between 5 and 17 years of age attended a single study session. Thermal images were taken of the supraclavicular region before, and after, the introduction of a cool stimulus.

Results

Participants with ATD had lower resting (hypothyroid, 34.9 ± 0.7°C; control, 35.4 ± 0.5°C; P = 0.03) and stimulated (hypothyroid, 35.0 ± 0.6°C; control, 35.5 ± 0.5°C; P = 0.04) supraclavicular temperatures compared with controls, but there was no difference between groups in the temperature increase with stimulation. BAT activation, calculated as the relative temperature change comparing the supraclavicular temperature to a sternal reference region, was reduced in participants with ATD (hypothyroid, 0.1 ± 0.1°C; control, 0.2 ± 0.2°C; P = 0.04). Children with ATD were frequently biochemically euthyroid due to replacement therapy, but, despite this, increased relative supraclavicular temperature was closely associated with increased TSH (r = 0.7, P = 0.01) concentrations.

Conclusions

Girls with ATD had an attenuated thermogenic response to cold stimulation compared with healthy controls, but, contrary to expectation, those with suboptimal biochemical control (with higher TSH) showed increased BAT activation. This suggests that the underlying disease process may have a negative effect on BAT response, but high levels of TSH can mitigate, and even stimulate, BAT activity. In summary, thyroid status is a complex determinant of BAT activity in girls with ATD.
Perioperative Oxidative Stress: The Unseen Enemy
Authors: Stevens Jia L. , Feelisch Martin , Martin Daniel S.
Published: October 2019

Reactive oxygen species (ROS) are essential for cellular signaling and physiological function. An imbalance between ROS production and antioxidant protection results in a state of oxidative stress (OS), which is associated with perturbations in reduction/oxidation (redox) regulation, cellular dysfunction, organ failure, and disease. The pathophysiology of OS is closely interlinked with inflammation, mitochondrial dysfunction, and, in the case of surgery, ischemia/reperfusion injury (IRI). Perioperative OS is a complex response that involves patient, surgical, and anesthetic factors. The magnitude of tissue injury inflicted by the surgery affects the degree of OS, and both duration and nature of the anesthetic procedure applied can modify this. Moreover, the interindividual susceptibility to the impact of OS is likely to be highly variable and potentially linked to underlying comorbidities. The pathological link between OS and postoperative complications remains unclear, in part due to the complexities of measuring ROS- and OS-mediated damage. Exogenous antioxidant use and exercise have been shown to modulate OS and may have potential as countermeasures to improve postoperative recovery. A better understanding of the underlying mechanisms of OS, redox signaling, and regulation can provide an opportunity for patient-specific phenotyping and development of targeted interventions to reduce the disruption that surgery can cause to our physiology. Anesthesiologists are in a unique position to deliver countermeasures to OS and improve physiological resilience. To shy away from a process so fundamental to the welfare of these patients would be foolhardy and negligent, thus calling for an improved understanding of this complex facet of human biology.
Cognitive Impairment during High-Intensity Exercise: Influence of Cerebral Blood Flow
Authors: KOMIYAMA TAKAAKI , TANOUE YUKIYA , SUDO MIZUKI , COSTELLO JOSEPH T. , UEHARA YOSHINARI , HIGAKI YASUKI , ANDO SOICHI
Published: October 2019

Purpose

Cognitive performance appears to be impaired during high-intensity exercise, and this occurs concurrently with a reduction in cerebral blood flow (CBF). However, it is unclear whether cognitive impairment during high-intensity exercise is associated with reduced CBF. We tested the hypothesis that a reduction in CBF is responsible for impaired cognitive performance during high-intensity exercise.

Methods

Using a randomized crossover design 17 healthy males performed spatial delayed response and Go/No-Go tasks in three conditions (exercise [EX], exercise+CO2 [EX+CO2], and a nonexercising control [CON]). In the EX and EX+CO2, they performed cognitive tasks at rest and during 8 min of moderate and high-intensity exercise. Exercise intensity corresponded to ~50% (moderate) and ~80% (high) of peak oxygen uptake. In the EX+CO2, the participants inspired hypercapnic gas (2% CO2) during high-intensity exercise. In the CON, they performed the cognitive tasks without exercise.

Results

Middle cerebral artery mean velocity increased during high-intensity exercise in the EX+CO2 relative to the EX (69.4 [10.6] cm·s−1, vs 57.2 [7.7] cm·s−1, P < 0.001). Accuracy of the cognitive tasks was impaired during high-intensity exercise in the EX (84.1% [13.3%], P < 0.05) and the EX+ CO2 (85.7 [11.6%], P < 0.05) relative to rest (EX: 95.1% [5.3%], EX+CO2: 95.1 [5.3%]). However, no differences between the EX and the EX+CO2 were observed (P > 0.10). These results demonstrate that restored CBF did not prevent cognitive impairment during high-intensity exercise.

Conclusions

We conclude that a reduction in CBF is not responsible for impaired cognitive performance during high-intensity exercise.