bluuebunny/crossref_metadata_2025 huggingface dataset:
Parenteral cytotoxic drug wastage at a tertiary hospital in Kuala Lumpur: How much and why?
Authors: Ang Zen Yang , Cheah Kit Yee , Abdullah Nadiah B , Samsuri Safawati B , Lee Siao Hui , Yem Andrew WH , Sriraman Malathi AP
Published: December 2019

Purpose

To identify the cost and reasons of returned parenteral chemotherapy regimens at a tertiary hospital in Kuala Lumpur, Malaysia.

Methods

Data were retrospectively extracted from all the Chemotherapy Return Forms in 2016, which is a compulsory documentation accompanying each return of parenteral chemotherapy regimen. The following data were extracted: patient’s diagnosis, gender, location of treatment (i.e. ward/daycare clinic), start date of chemotherapy regimen, type of cytotoxic drug returned, dose of cytotoxic drug returned, number of cytotoxic drug preparations returned and reason for return as well as whether the returned cytotoxic drug preparations could be re-dispensed. The cost of wastage was calculated based on the cost per mg (or per unit) of the particular returned cytotoxic drug.

Results

One hundred and fifty-nine cases of returned chemotherapy regimen comprising of 231 parenteral cytotoxic drug preparations were analysed. The total cost of returned chemotherapy regimen for 2016 was €3632, with €756 (20.8%) worth of chemotherapy regimens returned due to preventable reasons and €2876 (79.2%) worth of chemotherapy regimens returned due to non-preventable reasons. Approximately 50% of cases returned chemotherapy regimen were due to deterioration of patient’s clinical condition and another 24.5% of cases of returned chemotherapy regimen were attributed to adverse drug reactions.

Conclusion

Wastage associated to non-preventable reasons such as adverse drug reactions and preventable causes like refusal of patients can be further reduced by using newer healthcare innovations and establishment of written institutional protocols or standard operating procedures as references for in-charge healthcare personnel when cytotoxic drug-related issues occur. Adoption of cost-saving strategies that have been proven by studies could further improve current cost containment strategies.
Numerical study of nonlinear stability boundaries for orifice-compensated hole-entry hybrid journal bearings
Authors: Li Jian , Chen Runchang , Cao Haiyin , Tian Zhuxin
Published: December 2019

A high-performance and finite-length bearing system requires that the shaft can be stabilized even under a strong perturbation. The linear stability theory neglects the effects of nonlinear forces and the initial point of the shaft. Therefore, the stability of the bearing system is largely determined by the rotating speed of the shaft. In the present numerical investigation, the nonlinear forces and initial point of the shaft are accounted for to obtain the nonlinear stability boundary. The objective of this study is extended to orifice-compensated and hole-entry hybrid journal bearings with finite length. The critical rotating speed and the shaft center trajectory are acquired by solving Reynolds equation using the finite element method. By identifying the states of the orbits (stable or unstable), the nonlinear stability boundaries can be obtained. Results show that for the hybrid bearing system under the nonlinear conditions, the critical speed is a determinant factor while the initial location is another key factor. The shaft can be unstable if the initial point is outside of the stability boundary, although the speed is lower than the critical speed. There exists an obvious transitional region between the stable and unstable condition when the speed approaches the critical speed.
Performing building vibration assessments by acoustic measurements
Authors: Isavand Javad , Peplow Andrew , Kasaei Afshar
Published: December 2019

This article presents an innovative application of the frequency domain decomposition method based on an acoustic and vibration response. Frequency domain decomposition method has been frequently used for operational modal analysis testing in the last decade to identify modal parameters for in-situ case studies. For these studies, the outputs of the vibration response through accelerometers have been employed in the analysis. In this article, the frequency domain decomposition method is employed, for the first time, to analyze both acoustic and vibration response of the building which is a novel application in building vibration response. As a case study, a cylindrical shaped seven-story building, which appears to be subjected to a vibration problem, was selected. In this research, both acoustic and vibration responses are captured to determine the source of this unknown excitation. The results show that using microphones, as an acoustic response, can be as reliable as accelerometers to identify forced vibration.
Electron impact ionization cross sections of hydrogen fluoride molecule
Authors: Kumar Rajeev , Sharma SP , Sharma Ravinder
Published: December 2019

Partial and total ionization cross sections of hydrogen fluoride molecule are determined from the ionization threshold to high energy (5 KeV) by using a modified Jain–Khare semiempirical approach. Partial single and double differential cross sections with their sums (total) through direct and dissociative ionization have been also evaluated at fixed primary electron energies 100 eV, 200 eV, and 500 eV. There is no other data for partial ionization cross sections and differential ionization cross sections for comparison. In this paper, the total ionization cross sections data have compared with available experimental data and/or with other theoretical data which are available from intermediate to high energy. It is found that the present result gives a better account for the ionization cross sections up to higher energies.
Public goods in Michael Oakeshott’s ‘world of pragmata’
Authors: de Jongh Maurits
Published: December 2019

Michael Oakeshott’s account of political economy is claimed to have found its ‘apotheosis under Thatcherism’. Against critics who align him with a preference for small government, this article points to Oakeshott’s stress on the indispensability of an infrastructure of government-provided public goods, in which individual agency and associative freedom can flourish. I argue that Oakeshott’s account of political economy invites a contestatory politics over three types of public goods, which epitomize the unresolvable tension he diagnosed between nomocratic and teleocratic conceptions of the modern state. These three types are the system of civil law, the by-products of the operation of civil law and public goods which result from policies. The article concludes that Oakeshott offers an important corrective to political theories which favour either market mediation or radical democratic governance of the commons as self-sustaining modes of providing and enjoying goods.
Clinical and laboratory parameters, risk factors predisposing to the development of priapism in sickle cell patients
Authors: Alkindi Salam , Almufargi Said S , Pathare Anil
Published: December 2019

Although sickle cell disease is very common in Oman, priapism is a relatively rare complication of this disease. This study was aimed to identify the clinical and laboratory risk factors that predispose sickle cell disease patients to priapism. In a retrospective, case-control study, data on 21 male sickle cell disease patients, with priapism, were compared to 20 age and sex-matched sickle cell disease patients without priapism from the hospital medical records. Specifically, the demographical, hematological, biochemical, and clinical parameters including complications attributable to priapism were studied. Means for continuous measures and independent t-test were used to evaluate the association between the parameter studied and the occurrence of priapism. Priapism occurrence was associated with low basal hemoglobin (Hb), along with an increase in other parameters such as white blood cell count (WBC) ( P = 0.010), platelet count ( P = 0.001), reticulocyte count ( P < 0.001), mean corpuscular volume (MCV) ( P < 0.001), and mean corpuscular hemoglobin (MCH) ( P < 0.001). Biochemical laboratory parameters revealed an association with an increased total bilirubin ( P < 0.001). Patients with priapism were more likely to have acute chest syndrome, stroke, pulmonary hypertension, asplenia ( P = 0.006), gallbladder stones, and consequently cholecystectomy. Blood exchange and Penile aspiration were the most frequent medical therapies ( P = 0.010 and P < 0.001 respectively). Patients with sickle cell disease who presented with priapism were young adults with low Hb, high WBC’s, platelets, reticulocytes, MCV, MCH, bilirubin, and LDH. These findings suggest an association of priapism with increased hemolysis.

Impact statement

Sickle cell disease is prevalent throughout the world with a 5.8% incidence of sickle cell trait among the Omani population, yet priapism was a relatively rare complication. Penile erection and detumescence are complex physiological processes, which require a delicate neurohormonal and cardiovascular response. In this cohort, young SCD patients developed priapism with a low incidence of complications. These patients had high WBCs, platelets, bilirubin, LDH, and reticulocytes with low hemoglobin as compared to controls, suggesting an increased hemolytic process. Favorable outcome was dependent on early intervention, with almost half of these patients needing surgical intervention.
Intersectoral oral health promotion interventions for schoolchildren living in remote rural Andean communities: a realist evaluation
Authors: Bergeron Dave A. , Talbot Lise R. , Gaboury Isabelle
Published: December 2019

Background:

Intersectoral oral health promotion entails the participation of local communities. IOHP interventions were introduced in Peru in primary schools in 2013 but oral health among schoolchildren living in rural Andean communities remains suboptimal.

Objectives:

To understand the contextual elements and the underlying mechanisms associated with intersectoral oral health promotion interventions’ current effects on schoolchildren living in remote rural Andean communities.

Method:

A realist evaluation was carried out in three rural Andean communities where intersectoral oral health promotion interventions aimed at schoolchildren have been implemented. Following an evaluation of the effects among schoolchildren, contextual elements and mechanisms were explored with various stakeholders involved in intersectoral oral health promotion through focus groups and semi-structured interviews. Subsequently, an iterative data analysis and a validation process resulted in the identification of context-mechanism configurations.

Results:

Previous positive experiences of collaboration, a focus on communication, feelings of being respected and considered, and development of leadership and trust among stakeholders involved in intersectoral oral health promotion were elements of configurations that positively influence intersectoral oral health promotion. On the other hand, unfavorable physical, social and political environments, previous negative health experiences, feelings of not being respected or considered, demotivation, development of mistrust and insufficient leadership were shown to negatively influence outcomes.

Conclusion:

This research highlights the complexity associated with the deployment of intersectoral oral health promotion interventions in rural communities. Local stakeholders should be further involved to build trust, to facilitate coordination processes among remote rural communities and oral health professionals, and to optimize deployment of intersectoral oral health promotion interventions.
How Biographies of Women in Science, Technology, and Medicine Influence Fifth Graders’ Attitudes Toward Gender Roles
Authors: Chen Ming-Hsiu Mia
Published: December 2019

This research focuses on elementary pupils’ attitudes toward gender roles and the learning results from using two types of teaching materials, multimedia animation and a role-play transcript, based on the biographies of women in science, technology, and medicine. We selected two fifth-grade classes for the experiment, which was conducted during the students’ science period. The findings revealed that using the two teaching materials positively benefited elementary pupils’ attitudes toward gender roles, particularly in terms of games and toys.
Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice
Authors: Wood Katherine C. , Durgin Brittany G. , Schmidt Heidi M. , Hahn Scott A. , Baust Jeffrey J. , Bachman Tim , Vitturi Dario A. , Ghosh Samit , Ofori-Acquah Solomon F. , Mora Ana L. , Gladwin Mark T. , Straub Adam C.
Published: December 2019

Key Points

Vascular SMC CYB5R3 delays development of SCD-associated PH in mice. PH in SCD can exist in mice by 5 weeks of age when SMC CYB5R3 protein is deficient.
Resolution of secondary hemophagocytic lymphohistiocytosis after treatment with the JAK1/2 inhibitor ruxolitinib
Authors: Goldsmith Scott R. , Saif Ur Rehman Sana , Shirai Cara L. , Vij Kiran , DiPersio John F.
Published: December 2019

Key Points

Ruxolitinib was an effective salvage therapy for relapsed/refractory secondary hemophagocytic lymphohistiocytosis. Prolonged maintenance with a ruxolitinib taper obviated the need for intensive chemotherapy or allogeneic transplant in secondary HLH.
Effects of resistance training on self-reported disability in older adults with functional limitations or disability – a systematic review and meta-analysis
Authors: Olsen Pia Øllgaard , Termannsen Anne-Ditte , Bramming Maja , Tully Mark A. , Caserotti Paolo
Published: December 2019

Background

Self-reported disability has a strong negative impact on older people’s quality of life and is often associated with the need for assistance and health care services. Resistance training (RT) has been repeatedly shown to improve muscle function (e.g. strength) and functional capacity (e.g. gait speed, chair-rise) in older adults with functional limitations. Nevertheless, it is unclear whether such objectively assessed improvements translate into a reduction in self-reported disability.

Objectives

To assess: i) whether and to what extent RT interventions have an effect on self-reported disability in older adults (≥65 years) with functional limitations or disability; and ii) whether the effects on self-reported disability are associated with changes in objective measures of muscle strength and functional capacity across studies.

Methods

PubMed, Embase, Web of Science, CINAHL and SPORTDiscus electronic databases were searched in June 2018. Randomized controlled trials reporting effects of RT on self-reported disability/function in ≥65 year-old adults with defined, functional limitations or self-reported disability were eligible. Data on self-reported disability/function were pooled by calculating adjusted standardized mean differences (SMD) using Hedges’g. Likewise, effect sizes for three secondary outcomes: knee extensor muscle strength; gait capacity; and lower body functional capacity were calculated and fit as covariates in separate meta-regressions with self-reported disability as the dependent factor.

Results

Fourteen RCTs were eligible for the primary meta-analysis on self-reported disability. The total number of participants was 651 (intervention n = 354; control n = 297). A significant moderate positive effect of RT was found (SMD: 0.59, 95% CI: 0.253 to 0.925, p = 0.001). Between-study heterogeneity was present (I2 statistic = 75,1%, p <  0.001). RT effects on objective measures of lower body functional capacity were significantly associated with effects on self-reported disability (Adj. R2 = 99%, p = 0.002, n = 12 studies), whereas no significant associations with gait capacity or knee extensor strength were found.

Conclusions

This review provides evidence that RT has a moderate positive effect on self-reported disability/function in old people with or at risk for disability. The effects are strongly associated with effects on objective measures of lower body functional capacity.
Prenatal tobacco exposure and ADHD symptoms at pre-school age: the Hokkaido Study on Environment and Children’s Health
Authors: Minatoya Machiko , Araki Atsuko , Itoh Sachiko , Yamazaki Keiko , Kobayashi Sumitaka , Miyashita Chihiro , Sasaki Seiko , Kishi Reiko
Published: December 2019

Background

There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated.

Methods

This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children’s Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n= 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22–0.51 ng/ml (low-passive smoker), 0.52–11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker).

Results

Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys.

Conclusion

Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.
Prostate cancer awareness and attitude toward early detection among male soldiers in Ghana: a cross-sectional study
Authors: Necku Juliana Gyasi , Anaba Emmanuel Anongeba , Abuosi Aaron Asibi
Published: December 2019

Background

Prostate cancer (PC) is the leading cause of cancer deaths among men in Ghana. This poses a public health threat, especially among the Ghana Armed Force (GAF) where the majority are males. This study aimed to assess male soldiers’ awareness, knowledge and attitudes toward early detection of prostate cancer.

Results

It was found that 58.3% of the soldiers were less aware of PC and 76.0% had low or neutral knowledge regarding risk factors and symptoms of PC. The soldiers had positive attitudes toward early detection but had low intentions of getting tested. Awareness was significantly associated with education, rank, haven received PC information from a health worker and being knowledgeable of signs of PC.

Conclusion

We recommend that management of the GAF should liaise with the Ministry of Health to sensitize and educate soldiers on prostate cancer, and if possible, organize periodic screening activities for the soldiers to aid in early detection and effective management of the disease. The findings of this study provide valuable information for health interventions in Ghana.
Comparative transcriptomics reveals PrrAB-mediated control of metabolic, respiration, energy-generating, and dormancy pathways in Mycobacterium smegmatis
Authors: Maarsingh Jason D. , Yang Shanshan , Park Jin G. , Haydel Shelley E.
Published: December 2019

Background

Mycobacterium smegmatisis a saprophytic bacterium frequently used as a genetic surrogate to study pathogenicMycobacterium tuberculosis. The PrrAB two-component genetic regulatory system is essential inM. tuberculosisand represents an attractive therapeutic target. In this study, transcriptomic analysis (RNA-seq) of anM. smegmatisΔprrABmutant was used to define the PrrAB regulon and provide insights into the essential nature of PrrAB inM. tuberculosis.

Results

RNA-seq differential expression analysis ofM. smegmatiswild-type (WT), ΔprrABmutant, and complementation strains revealed that during in vitro exponential growth, PrrAB regulates 167 genes (q < 0.05), 57% of which are induced in the WT background. Gene ontology and cluster of orthologous groups analyses showed that PrrAB regulates genes participating in ion homeostasis, redox balance, metabolism, and energy production. PrrAB induced transcription ofdosR(devR), a response regulator gene that promotes latent infection inM. tuberculosisand 21 of the 25 M. smegmatisDosRS regulon homologues. Compared to the WT and complementation strains, the ΔprrABmutant exhibited an exaggerated delayed growth phenotype upon exposure to potassium cyanide and respiratory inhibition. Gene expression profiling correlated with these growth deficiency results, revealing that PrrAB induces transcription of the high-affinity cytochromebdoxidase genes under both aerobic and hypoxic conditions. ATP synthesis was ~ 64% lower in the ΔprrABmutant relative to the WT strain, further demonstrating that PrrAB regulates energy production.

Conclusions

TheM. smegmatisPrrAB two-component system regulates respiratory and oxidative phosphorylation pathways, potentially to provide tolerance against the dynamic environmental conditions experienced in its natural ecological niche. PrrAB positively regulates ATP levels during exponential growth, presumably through transcriptional activation of both terminal respiratory branches (cytochrome cbc1-aa3and cytochromebdoxidases), despite transcriptional repression of ATP synthase genes. Additionally, PrrAB positively regulates expression of the dormancy-associateddosRresponse regulator genes in an oxygen-independent manner, which may serve to fine-tune sensory perception of environmental stimuli associated with metabolic repression.
Human gene expression variability and its dependence on methylation and aging
Authors: Bashkeel Nasser , Perkins Theodore J. , Kærn Mads , Lee Jonathan M.
Published: December 2019

Background

Phenotypic variability of human populations is partly the result of gene polymorphism and differential gene expression. As such, understanding the molecular basis for diversity requires identifying genes with both high and low population expression variance and identifying the mechanisms underlying their expression control. Key issues remain unanswered with respect to expression variability in human populations. The role of gene methylation as well as the contribution that age, sex and tissue-specific factors have on expression variability are not well understood.

Results

Here we used a novel method that accounts for sampling error to classify human genes based on their expression variability in normal human breast and brain tissues. We find that high expression variability is almost exclusively unimodal, indicating that variance is not the result of segregation into distinct expression states. Genes with high expression variability differ markedly between tissues and we find that genes with high population expression variability are likely to have age-, but not sex-dependent expression. Lastly, we find that methylation likely has a key role in controlling expression variability insofar as genes with low expression variability are likely to be non-methylated.

Conclusions

We conclude that gene expression variability in the human population is likely to be important in tissue development and identity, methylation, and in natural biological aging. The expression variability of a gene is an important functional characteristic of the gene itself and the classification of a gene as one with Hyper-Variability or Hypo-Variability in a human population or in a specific tissue should be useful in the identification of important genes that functionally regulate development or disease.
A mixed-methods study on toilet hygiene practices among Chinese in Hong Kong
Authors: Wu Dan , Lam Tai Pong , Chan Hoi Yan , Lam Kwok Fai , Zhou Xu Dong , Xu Jia Yao , Sun Kai Sing , Ho Pak Leung
Published: December 2019

Background

Public toilets are a common transmission vector of infectious diseases due to environmental contamination. Research on Chinese people’s hygiene practices in public lavatories are lacking. This study examined Chinese people’s hygiene practices in public lavatories in Hong Kong.

Methods

We conducted qualitative interviews and a self-administered questionnaire survey with local residents from June 2016 to April 2018. Four focus group discussions and three individual interviews informed the design of the questionnaire. We recruited interviewees and survey respondents via social service centers. The interviews and questionnaire focused on the public’s daily practices and hygiene behaviors in public toilets. Content analysis of qualitative data was conducted. Multivariable logistic regressions were used to examine the association between age and toilet hygiene behaviors.

Results

Our qualitative component revealed a range of handwashing practices, from not washing at all, washing without soap, to washing for a longer time than instructions. Other toilet use practices were identified, such as not covering toilet lid before flushing and stepping on toilet seats due to dirtiness, and spitting into toilet bowls or hand basin.

Totally, 300 respondents completed the questionnaire. Among them, 212 (70.9%) were female and 246 (86.1%) were aged 65 or below. More than two thirds always washed hands with soap (68.7%) and dried hands with paper towels (68.4%). Up to 16.2% reported stepping on toilet seats and 43.9% never covered the toilet lid before flushing. Over one fourth (26.4%) spit into squat toilets/ toilet bowl. Regression analyses showed that the elderly group were less likely to report stepping on toilet seats (adjusted odds ratio, AOR = 0.17, 95%CI 0.03–0.88), flushing with the toilet lid closed (AOR = 0.40, 0.16–0.96), but more likely to spit into squat toilets/ toilet bowl (AOR = 4.20, 1.50–11.74).

Conclusions

Hong Kong Chinese’s compliance to hygiene practices in public toilets is suboptimal. Stepping on toilet seat is a unique Chinese practice due to the dirtiness of toilet seats. Spitting practices may increase the risk of airborne infectious diseases and need improvement. Measures are needed to improve toilet hygiene behaviors, including public education campaigns and keeping toilet environment clean.
Serum oxidative stress influences neurological recovery after surgery to treat acutely worsening symptoms of compression myelopathy: a cross-sectional human study
Authors: Takahashi Hiroshi , Aoki Yasuchika , Saito Junya , Nakajima Arata , Sonobe Masato , Akatsu Yorikazu , Taniguchi Shinji , Yamada Manabu , Koyama Keita , Akiyama Yuki , Shiga Yasuhiro , Inage Kazuhide , Orita Sumihisa , Eguchi Yawara , Maki Satoshi , Furuya Takeo , Akazawa Tsutomu , Koda Masao , Yamazaki Masashi , Ohtori Seiji , Nakagawa Koichi
Published: December 2019

Background

Recent reports indicate that oxidative stress induced by reactive oxygen species is associated with the pathobiology of neurodegenerative disorders that involve neuronal cell apoptosis. Here we conducted a cross-sectional study to evaluate serum levels of oxidative stress in cervical compression myelopathy.

Methods

Thirty-six serum samples were collected preoperatively from patients treated for acutely worsening compression myelopathy (AM) and chronic compression myelopathy (CM). Serum levels of oxidative stress markers were evaluated by measuring derivatives of reactive oxygen metabolites (ROM), which reflect concentrations of hydroperoxides. ROM in healthy individuals range from 250 to 300 (U. CARR), whereas ROM >340–400 and > 400 define moderate and severe levels of oxidative stress, respectively. Difference of ROM by the cause of disorders whether cervical spondylotic myelopathy (CSM) or cervical ossification of longitudinal ligament (OPLL), correlations between ROM and patient age, body mass index (BMI), history of smoking, existence of diabetes were examined. Neurological evaluations according to Japanese Orthopaedic Association (JOA) scores were performed and correlated with ROM.

Results

ROM increased to 349.5 ± 54.8, representing a moderate oxidative stress, in CM samples. ROM increased to 409.2 ± 77.9 in AM samples, reflecting severe oxidative stress which were significantly higher than for CM samples (p < 0.05). There was no significant difference by the cause of disorders (CSM or OPLL). ROM were significantly increased in AM serum samples from female patients versus AM male and CM patients (p < 0.05). There were no correlations between ROM and age, BMI, history of smoking, and existence of diabetes. A negative correlation between ROM and recovery rate of JOA score (R2 = 0.454, p = 0.047) was observed in the AM group.

Conclusions

Although moderate oxidative stress was present in patients with CM, levels of oxidative stress increased in severity in patients with AM. These results suggest that postsurgical neurological recovery is influenced by severe oxidative stress in AM.
Health-related quality of life in early-onset-scoliosis patients treated with growth-friendly implants is influenced by etiology, complication rate and ambulatory ability
Authors: Hell Anna K. , Braunschweig Lena , Behrend Jennifer , Lorenz Heiko M. , Tsaknakis Konstantinos , von Deimling Urs , Mladenov Kiril
Published: December 2019

Background

Progressive Early-Onset Scoliosis (EOS) in children may lead to surgical interventions with growth-friendly implants, which require repeated lengthening procedures in order to allow adequate growth. Quality of life was studied using the validated German version of the EOS-Questionnaire (EOSQ-24-G) in surgically treated EOS children with different lengthening modalities.

Methods

EOSQ-24-G and the KINDLR questionnaire were given to families with EOS children who had been treated by either vertical expandable prosthetic titanium rib implants and repetitive lengthening surgeries every 6 months or children who had received a magnetically expansion controlled implant, which was externally lengthened every 3 months. Results were compared according to differences between the two tests, and with possible influencing factors such as surgical method, severity of scoliosis, relative improvement of curvature, etiology, weight, age, travelling distance, complications, ambulatory ability and others.

Results

56 children with an average curve angle of 69° corrected to 33° (52%; average age 5.6 yrs) answered the EOSQ-24-G and the KINDLR after an average follow-up of 3.9 years. Health-related quality of life (HRQoL) was not affected by the initial scoliosis correction, the number of surgeries or the implant type. However, there was a negative correlation with non-ambulatory status, complications during treatment and for children with a neuromuscular scoliosis.

Conclusion

Using the validated EOSQ-24-G, no statistically significant differences were found between the group of children receiving repetitive surgeries and children with external lengthening procedures without surgery. However, results were influenced by the etiology, complication rate or ambulatory ability.

Level of Evidence/Clinical relevance

Therapeutic Level IV
N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers: roles, mechanisms, and applications
Authors: Hu Bin-bin , Wang Xiao-yan , Gu Xu-Yu , Zou Chen , Gao Zhen-jun , Zhang Heng , Fan Yu
Published: December 2019

Analogous to DNA methylation and histone modification, RNA modification, as another epigenetic layer, plays an important role in many diseases, especially in tumours. As the most common form of RNA modification, m6A methylation has attracted increasing research interest in recent years. m6A is catalysed by RNA methyltransferases METTL3, METTL14 and WTAP (writers), m6A is removed by the demethylases FTO and ALKBH5 (erasers) and interacts with m6A-binding proteins, such as YT521-B homology (YTH) domain-containing proteins. This article reviews recent studies on methylation modification of m6A in gastrointestinal tract cancers.
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis
Authors: Magliozzi Roberta , Howell Owain William , Durrenberger Pascal , Aricò Eleonora , James Rachel , Cruciani Carolina , Reeves Cheryl , Roncaroli Federico , Nicholas Richard , Reynolds Richard
Published: December 2019

Background

Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases.

Methods

To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls.

Results

Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared with controls. Increased meningeal inflammation was found to be associated with a shift in the balance of TNF signalling away from TNFR1/TNFR2 and NFkB-mediated anti-apoptotic pathways towards TNFR1- and RIPK3-mediated pro-apoptotic/pro-necroptotic signalling in the grey matter, which was confirmed by RT-PCR analysis. TNFR1 was found expressed preferentially on neurons and oligodendrocytes in MS cortical grey matter, whereas TNFR2 was predominantly expressed by astrocytes and microglia.

Conclusions

We suggest that the inflammatory milieu generated in the subarachnoid space of the multiple sclerosis meninges by infiltrating immune cells leads to increased demyelinating and neurodegenerative pathology in the underlying grey matter due to changes in the balance of TNF signalling.
Potential treatment effect modifiers for manipulative therapy for children complaining of spinal pain.Secondary analyses of a randomised controlled trial
Authors: Dissing Kristina Boe , Vach Werner , Hartvigsen Jan , Wedderkopp Niels , Hestbæk Lise
Published: December 2019

Background

In children, spinal pain is transitory for most, but up to 20% experience recurrent and bothersome complaints. It is generally acknowledged that interventions may be more effective for subgroups of those affected with low back pain. In this secondary analysis of data from a randomized clinical trial, we tested whether five indicators of a potential increased need for treatment might act as effect modifiers for manipulative therapy in the treatment of spinal pain in children. We hypothesized that the most severely affected children would benefit more from manipulative therapy.

Method

This study was a secondary analysis of data from a randomised controlled trial comparing advice, exercises and soft tissue treatment with and without the addition of manipulative therapy in 238 Danish school children aged 9–15 years complaining of spinal pain. A text message system (SMS) and clinical examinations were used for data collection (February 2012 to April 2014).

Five pre-specified potential effect modifiers were explored: Number of weeks with spinal pain 6 months prior to inclusion, number of weeks with co-occurring musculoskeletal pain 6 months prior to inclusion, expectations of the clinical course, pain intensity, and quality of life.

Outcomes were number of recurrences of spinal pain, number of weeks with pain, length of episodes, global perceived effect, and change in pain intensity. To explore potential effect modification, various types of regression models were used depending on the type of outcome, including interaction tests.

Results

We found that children with long duration of spinal pain or co-occurring musculoskeletal pain prior to inclusion as well as low quality of life at baseline tended to benefit from manipulative therapy over non-manipulative therapy, whereas the opposite was seen for children reporting high intensity of pain. However, most results were statistically insignificant.

Conclusions

This secondary analysis indicates that children more effected by certain baseline characteristics, but not pain intensity, have a greater chance to benefit from treatment that include manipulative therapy. However, these analyses were both secondary and underpowered, and therefore merely exploratory. The results underline the need for a careful choice of inclusion criteria in future investigations of manipulative therapy in children.

Trial registration

NCT01504698; results
Socioeconomic factors and lifestyles influencing the incidence of calcaneal fractures, a national population-based survey in China
Authors: Zhu Yanbin , Li Jia , Liu Song , Chen Wei , Wang Lin , Zhang Xiaolin , Zhang Yingze
Published: December 2019

Background

We aimed to do a national survey on the population-based incidence of calcaneal fracture in China.

Methods

All the data on calcaneal fractures were available from the China National Fracture Survey (CNFS) between January and May in 2015. And in the CNFS, all eligible household members were sampled from 8 provinces, 24 urban cities and 24 rural counties in China, using stratified random sampling and the probability proportional to size method. Questionnaires were sent to every participant for data collection and quality control was accomplished by our research team members.

Results

A total of 512187 valid questionnaires were collected and relevant data were abstracted and analyzed. There were 59 patients with 62 calcaneal fractures occurring in 2014, indicating that the incidence was 11.5/100,000 person-years, 17.3/100,000 in males, and 5.5/100,000 in females. BMI ≥ 28.0 kg/m2, scarce meat consumption, smoking, alcohol consumption, average sleep time < 7 h/day, and previous history of fracture were identified as independent risk factors for calcaneal fracture.

Conclusions

Specific public health policies focusing on quitting smoking, decreasing alcohol consumption, and encouraging individuals to obtain sufficient sleep should be implemented. Reasonable meat consumption and maintaining a normal body weight should be emphasized in individuals, especially in those with previous fracture.
Associations of foot ulceration with quality of life and psychosocial determinants among patients with diabetes; a case‐control study
Authors: Alosaimi Fahad D. , Labani Reem , Almasoud Nouf , Alhelali Nora , Althawadi Lamya , AlJahani Dhaherah Mani
Published: December 2019

Background

Patients with diabetic foot ulcers may have a lower quality of life. The objective was to compare the quality of life and its psychosocial determinants among patients with and without diabetic foot ulcers.

Methods

A case‐control study was conducted in 2017 among patients with (cases) and without (controls) diabetic foot ulcers. The study tools included the World Health Organization's Quality of Life scale (WHOQOL‐BREF), the Hospital Anxiety and Depression (HAD) scale for anxiety and depression, the Patient Health Questionnaire Physical Symptoms (PHQ‐15) for the severity of somatic symptoms, and the Summary of Diabetes Self‐Care Activities (SDSCA) measure for self‐management.

Results

A total of 209 patients (45 cases and 164 controls) were included. The average age was 56.2 ± 11.7 years, and 55.5% were female. The average scores of WHOQOL‐BREF, PHQ‐15, and SDSCA were 74.4% ± 12.1% and 8.1 ± 6.1, and 30.4 ± 21.8, respectively. The prevalence of anxiety and depression were 19.6 and 24.9%, respectively. SDSCA was the only psychosocial determinants higher in cases than controls (mean difference = 15.0, 95% CI = ‐8.0–22.0). The correlation coefficients of WHOQOL‐BREF scores with anxiety, depression, and PHQ‐15 scores in all patients were − 0.559 (p < 0.001), − 0.582 (p < 0.001), and − 0.532 (p < 0.001), respectively, with similar numbers in both groups. In multivariate analysis, only the association between quality of life and depression was maintained.

Conclusion

Quality of life and psychosocial determinants with the exception of self‐management were not associated with diabetic foot ulcers. Depressive symptoms were independent determinant of poor quality of life, irrespective of the status of diabetic foot ulcers.
PET and CSF amyloid-β status are differently predicted by patient features: information from discordant cases
Authors: Reimand Juhan , de Wilde Arno , Teunissen Charlotte E. , Zwan Marissa , Windhorst Albert D. , Boellaard Ronald , Barkhof Frederik , van der Flier Wiesje M. , Scheltens Philip , van Berckel Bart N. M. , Ossenkoppele Rik , Bouwman Femke
Published: December 2019

Background

Amyloid-β PET and CSF Aβ42yield discordant results in 10–20% of memory clinic patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic, and imaging features for amyloid positivity has previously been investigated, it is unknown whether these features differentially predict amyloid-β status based on PET or CSF or whether this differs by disease stage.

Methods

We included 768 patients (subjective cognitive decline (SCD,n = 194), mild cognitive impairment (MCI,n = 127), dementia (AD and non-AD,n = 447) with amyloid-β PET and CSF Aβ42measurement within 1 year. Ninety-seven (13%) patients had discordant PET/CSF amyloid-β status. We performed parallel random forest models predicting separately PET and CSF status using 17 patient features (demographics, APOE4 positivity, CSF (p)tau, cognitive performance, and MRI visual ratings) in the total patient group and stratified by syndrome diagnosis. Thereafter, we selected features with the highest variable importance measure (VIM) as input for logistic regression models, where amyloid status on either PET or CSF was predicted by (i) the selected patient feature and (ii) the patient feature adjusted for the status of the other amyloid modality.

Results

APOE4, CSF tau, and p-tau had the highest VIM for PET and CSF in all groups. In the amyloid-adjusted logistic regression models, p-tau was a significant predictor for PET-amyloid in SCD (OR = 1.02 [1.01–1.04],pFDR = 0.03), MCI (OR = 1.05 [1.02–1.07],pFDR < 0.01), and dementia (OR = 1.04 [1.03–1.05],pFDR < 0.001), but not for CSF-amyloid. APOE4 (OR = 3.07 [1.33–7.07],punc < 0.01) was associated with CSF-amyloid in SCD, while it was only predictive for PET-amyloid in MCI (OR = 9.44 [2.93, 30.39],pFDR < 0.01). Worse MMSE scores (OR = 1.21 [1.03–1.41],punc = 0.02) were associated to CSF-amyloid status in SCD, whereas worse memory (OR = 1.17 [1.05–1.31],pFDR = 0.02) only predicted PET positivity in dementia.

Conclusion

Amyloid status based on either PET or CSF was predicted by different patient features, and this varied by disease stage, suggesting that PET-CSF discordance yields unique information. The stronger associations of both APOE4 carriership and worse memory z-scores with CSF-amyloid in SCD suggest that CSF-amyloid is more sensitive early in the disease course. The higher predictive value of CSF p-tau for a positive PET scan suggests that PET is more specific to AD pathology.
Scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia: a case report and review of the literature
Authors: Li Weijia , Huang Lei , Zhang Weixing
Published: December 2019

Background

Scrub typhus is an acute infectious zoonotic disease caused by Orientia tsutsugamushi. Multi-organ dysfunction secondary to scrub typhus is hard to diagnose and has a high mortality rate. Only one case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia has been reported thus far. In this study, we report a second case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia, and we summarize its diagnosis and treatment.

Case presentation

A 43-year-old Han Chinese woman, a sanitation worker, was admitted to our hospital after 7 days of a skin infection and 5 days of a sore throat with fever and dizziness. A physical examination revealed the presence of an eschar on the right side of her neck. She had a history of insect bites during her sanitation work. A diagnostic evaluation identified scrub typhus as the primary illness, which was associated with multi-organ dysfunction syndrome and immune thrombocytopenia. She recovered completely after 15 days of treatment and extensive symptomatic supportive care.

Conclusion

We report a second case of tsutsugamushi disease with multi-organ dysfunction syndrome and immune thrombocytopenia, which resolved after treatment and extensive care.
SUV variability in EARL-accredited conventional and digital PET
Authors: Koopman Daniëlle , Jager Pieter L. , Slump Cornelis H. , Knollema Siert , van Dalen Jorn A.
Published: December 2019

Background

A high SUV-reproducibility is crucial when different PET scanners are in use. We evaluated the SUV variability in whole-body FDG-PET scans of patients with suspected or proven cancer using an EARL-accredited conventional and digital PET scanner.

In a head-to-head comparison we studied images of 50 patients acquired on a conventional scanner (cPET, Ingenuity TF PET/CT, Philips) and compared them with images acquired on a digital scanner (dPET, Vereos PET/CT, Philips). The PET scanning order was randomised and EARL-compatible reconstructions were applied.

We measured SUVmean, SUVpeak, SUVmax and lesion diameter in up to 5 FDG-positive lesions per patient. The relative difference ΔSUV between cPET and dPET was calculated for each SUV-parameter. Furthermore, we calculated repeatability coefficients, reflecting the 95% confidence interval of ΔSUV.

Results

We included 128 lesions with an average size of 19 ± 14 mm. Average ΔSUVs were 6-8% with dPET values being higher for all three SUV-parameters (p < 0.001). ΔSUVmax was significantly higher than ΔSUVmean (8% vs. 6%, p = 0.002) and than ΔSUVpeak (8% vs. 7%, p = 0.03). Repeatability coefficients across individual lesions were 27% (ΔSUVmean and ΔSUVpeak) and 33% (ΔSUVmax) (p < 0.001).

Conclusions

With EARL-accredited conventional and digital PET, we found a limited SUV variability with average differences up to 8%. Furthermore, only a limited number of lesions showed a SUV difference of more than 30%. These findings indicate that EARL standardisation works.

Trial registration

This prospective study was registered on the 31th of October 2017 at ClinicalTrials.cov. URL: https://clinicaltrials.gov/ct2/show/NCT03457506?id=03457506&rank=1.