bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the genetic prediction of the eye and hair color for North Eurasian populations
Authors: Balanovska Elena , Lukianova Elena , Kagazezheva Janet , Maurer Andrey , Leybova Natalia , Agdzhoyan Anastasiya , Gorin Igor , Petrushenko Valeria , Zhabagin Maxat , Pylev Vladimir , Kostryukova Elena , Balanovsky Oleg
Published: September 2020

Background

Predicting the eye and hair color from genotype became an established and widely used tool in forensic genetics, as well as in studies of ancient human populations. However, the accuracy of this tool has been verified on the West and Central Europeans only, while populations from border regions between Europe and Asia (like Caucasus and Ural) also carry the light pigmentation phenotypes.

Results

We phenotyped 286 samples collected across North Eurasia, genotyped them by the standard HIrisPlex-S markers and found that predictive power in Caucasus/Ural/West Siberian populations is reasonable but lower than that in West Europeans. As these populations have genetic ancestries different from that of West Europeans, we hypothesized they may carry a somewhat different allele spectrum. Thus, for all samples we performed the exome sequencing additionally enriched with the 53 genes and intergenic regions known to be associated with the eye/hair color. Our association analysis replicated the importance of the key previously known SNPs but also identified five new markers whose eye color prediction power for the studied populations is compatible with the two major previously well-known SNPs. Four out of these five SNPs lie within the HERС2 gene and the fifth in the intergenic region. These SNPs are found at high frequencies in most studied populations. The released dataset of exomes from Russian populations can be further used for population genetic and medical genetic studies.

Conclusions

This study demonstrated that precision of the established systems for eye/hair color prediction from a genotype is slightly lower for the populations from the border regions between Europe and Asia that for the West Europeans. However, this precision can be improved if some newly revealed predictive SNPs are added into the panel. We discuss that the replication of these pigmentation-associated SNPs on the independent North Eurasian sample is needed in the future studies.
GLaMST: grow lineages along minimum spanning tree for b cell receptor sequencing data
Authors: Yang Xingyu , Tipton Christopher M. , Woodruff Matthew C. , Zhou Enlu , Lee F. Eun-Hyung , Sanz Inãki , Qiu Peng
Published: September 2020

Background

B cell affinity maturation enables B cells to generate high-affinity antibodies. This process involves somatic hypermutation of B cell immunoglobulin receptor (BCR) genes and selection by their ability to bind antigens. Lineage trees are used to describe this microevolution of B cell immunoglobulin genes. In a lineage tree, each node is one BCR sequence that mutated from the germinal center and each directed edge represents a single base mutation, insertion or deletion. In BCR sequencing data, the observed data only contains a subset of BCR sequences in this microevolution process. Therefore, reconstructing the lineage tree from experimental data requires algorithms to build the tree based on partially observed tree nodes.

Results

We developed a new algorithm named Grow Lineages along Minimum Spanning Tree (GLaMST), which efficiently reconstruct the lineage tree given observed BCR sequences that correspond to a subset of the tree nodes. Through comparison using simulated and real data, GLaMST outperforms existing algorithms in simulations with high rates of mutation, insertion and deletion, and generates lineage trees with smaller size and closer to ground truth according to tree features that highly correlated with selection pressure.

Conclusions

GLaMST outperforms state-of-art in reconstruction of the BCR lineage tree in both efficiency and accuracy. Integrating it into existing BCR sequencing analysis frameworks can significant improve lineage tree reconstruction aspect of the analysis.
Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species
Authors: Suntsova Maria V. , Buzdin Anton A.
Published: September 2020

Chimpanzees are the closest living relatives of humans. The divergence between human and chimpanzee ancestors dates to approximately 6,5–7,5 million years ago. Genetic features distinguishing us from chimpanzees and making us humans are still of a great interest. After divergence of their ancestor lineages, human and chimpanzee genomes underwent multiple changes including single nucleotide substitutions, deletions and duplications of DNA fragments of different size, insertion of transposable elements and chromosomal rearrangements. Human-specific single nucleotide alterations constituted 1.23% of human DNA, whereas more extended deletions and insertions cover ~ 3% of our genome. Moreover, much higher proportion is made by differential chromosomal inversions and translocations comprising several megabase-long regions or even whole chromosomes. However, despite of extensive knowledge of structural genomic changes accompanying human evolution we still cannot identify with certainty the causative genes of human identity. Most structural gene-influential changes happened at the level of expression regulation, which in turn provoked larger alterations of interactome gene regulation networks. In this review, we summarized the available information about genetic differences between humans and chimpanzees and their potential functional impacts on differential molecular, anatomical, physiological and cognitive peculiarities of these species.
Griseococcin (1) from Bovistella radicata (Mont.) Pat and antifungal activity
Authors: Ye Yong , Zeng Qinghua , Zeng Qingmei
Published: September 2020

Background

To evaluate the antimicrobial and microbicidel activity of B. radicata fermentation broth, the broth was purified by DEAE-cellulose and sephadex LC-20 column. The compounds were submitted to spectral analyses (HPLC, FT-IR, 1D and 2D NMR etc.).

Results

The purified compounds were identified as the Griseococcin(s) which were naphthoquinone derivatives, the Chemical formula and MW of Griseococcin (1) was determined as C37O10H43N and 661 Da. only Griseococcin (1) has good antimicrobial activity among the Griseococcin(s). The zone of inhibition (ZOI), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) of Griseococcin (1) were used to investigate the antimicrobial activity. Antifungal activity of Griseococcin (1) was significant, especially for main pathogenic fungus Trichophyton rubrum and Trichophyton mentagrophytes, MFC/MIC of Griseococcin (1) was 1, while MFC/MIC of postive control was greater than 4, the fungicidal effect of Griseococcin (1) was better than that of positive control.

Conclusions

In this paper, the secondary metabolite compound Griseococcin (1) from B. radicata was purified. The purified compound can restrain main pathogens (T. rubrum and T. mentagrophytes) leading to tinea pedis. The antifungal activity of Griseococcin (1) was similar to that of the positive control and the fungicidal effect of Griseococcin (1) was better than that of positive control, it might be suitable for pharmaceutical industries.
‘Motivational work’: a qualitative study of preventive health dialogues in general practice
Authors: Broholm-Jørgensen Marie , Langkilde Siff Monrad , Tjørnhøj-Thomsen Tine , Pedersen Pia Vivian
Published: September 2020

Background

The aim of this article is to explore preventive health dialogues in general practice in the context of a pilot study of a Danish primary preventive intervention ‘TOF’ (a Danish acronym for ‘Early Detection and Prevention’) carried out in 2016. The intervention consisted of 1) a stratification of patients into one of four groups, 2) a digital support system for both general practitioners and patients, 3) an individual digital health profile for each patient, and 4) targeted preventive services in either general practice or a municipal health center.

Methods

The empirical material in this study was obtained through 10 observations of preventive health dialogues conducted in general practices and 18 semi-structured interviews with patients and general practitioners. We used the concept of ‘motivational work’ as an analytical lens for understanding preventive health dialogues in general practice from the perspectives of both general practitioners and patients.

Results

While the health dialogues in TOF sought to reveal patients’ motivations, understandings, and priorities related to health behavior, we find that the dialogues were treatment-oriented and structured around biomedical facts, numeric standards, and risk factor guidance. Overall, we find that numeric standards and quantification of motivation lessens the dialogue and interaction between General Practitioner and patient and that contextual factors relating to the intervention framework, such as a digital support system, the general practitioners’ perceptions of their professional position as well as the patients’ understanding of prevention —in an interplay—diminished the motivational work carried out in the health dialogues.

Conclusion

The findings show that the influence of different kinds of context adds to the complexity of prevention in the clinical encounter which help to explain why motivational work is difficult in general practice.
Effectiveness of a health-social partnership program for discharged non-frail older adults: a pilot study
Authors: WONG Arkers Kwan Ching , WONG Frances Kam Yuet , NGAI Jenny Sau Chun , HUNG Shirley Yu Kan , LI Wah Chun
Published: September 2020

Background

Previous studies supporting discharged patients are hospital-based which admission criteria tend to include mainly those with complex needs and/or specific disease conditions. This study captured the service gap where these non-frail older patients might have no specific medical problem upon discharge but they might encounter residual health and social issues when returning home.

Methods

Discharged community-dwelling non-frail older adults from an emergency medical ward were recruited and randomized into either intervention (n = 37) or control (n = 38) group. The intervention group received a 12-week complex interventions that included structured assessment, health education, goal empowerment, and care coordination supported by a health-social team. The control group received usual discharge care and monthly social call. The primary outcome was health-related quality of life (HRQoL). Secondary outcomes included activities of daily living (ADL), the presence of depressive symptoms, and the use of health services. The outcomes were measured at pre-intervention (T1) and at three months post-intervention (T2). The independent t-test or the Mann-Whitney U test was used to analyze the group differences in HRQoL, ADL, and presence of depressive symptoms according to the normality of data.

Results

Analysis showed that the intervention group experienced a statistically significantly improvement in the mental component scale of quality of life (p = .036), activities of daily living (p = .005), and presence of depressive symptoms (p = .035) at T2 compared with at T1. No significant differences were found in the control group.

Conclusions

Supporting self-care is necessary to enable community-dwelling non-frail older adults to be independent to the fullest extent possible in the community. The promising results found in this pilot study suggested that the integration of the health-social partnership into transitional care practice is effective and can be sustained in the community. Future studies can draw on these findings and maximize the integrated care quality during the transition phase.

Trial registration

NCT04434742 (date: 17 June 2020, retrospectively registered).
Variation between nursing homes in drug use and in drug-related problems
Authors: Fog Amura Francesca , Mdala Ibrahimu , Engedal Knut , Straand Jørund
Published: September 2020

Background

Residents at nursing homes (NHs) are at particular risk for drug related harm. Regular medication reviews using explicit criteria for pharmacological inappropriateness and classification of drug related problems (DRPs) have recently been introduced as measures to improve the quality of medication use and for making the treatment more uniform across different institutions. Knowledge about variation in DRPs between NHs is scarce. To explore if increased attention towards more appropriate drug treatment in NHs have led to more uniform treatment, we have analyzed variations between different nursing homes’ drug use and DRPs.

Methods

Cross-sectional medication review study including 2465 long-term care residents at 41 NHs in Oslo, Norway. Regular drug use was retrieved from the patients’ medical records. DRPs were identified by using STOPP/START and NORGEP criteria and a drug-drug interactions database. NHs were grouped in quartiles based on average levels of drug use. The upper and lower quartiles were compared using independent samples t-test and associations between drug use and DRPs were tested by logistic regression.

Results

Patients’ mean age was 85.9 years, 74.2% were women.

Mean numbers of regular drugs per patient was 6.8 and varied between NHs from 4.8 to 9.3.

The proportion of patients within each NH using psychotropic and analgesic drugs varied largely: antipsychotics from three to 50%, benzodiazepines from 24 to 99%, antidepressants from nine to 75%, anti-dementia drugs from no use to 42%, opioids from no use to 65% and paracetamol from 16 to 74%.

Mean DRPs per patient was 2.0 and varied between NHs from 0.5 to 3.4.

The quartiles of NHs with highest and lowest mean drugs per patient (7.7 vs. 5.7, p < 0.001) had comparable mean number of DRPs per patient (2.2 vs. 1.8, p = 0.2). Using more drugs and the use of opioids, antipsychotics, benzodiazepines and antidepressants were associated with more DRPs.

Conclusions

The use of psychotropic and analgesic drugs was high and varied substantially between different NHs. Even if the use of more drugs, opioids and psychotropic drugs was associated with DRPs, no difference was found in DRPs between the NHs with highest vs. lowest drug use.
Adherence to World Health Organisation guidelines for treatment of early onset neonatal sepsis in low-income settings; a cohort study in Nepal
Authors: Ekman Beatrice , Paudel Prajwal , Basnet Omkar , KC Ashish , Wrammert Johan
Published: September 2020

Background

Neonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors.

Methods

This cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 h of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied.

Results

1564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines.

Conclusion

Adherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance.

Trial registration

ISRCTN, ISRCTN30829654, registered 17th of May, 2017.
Retrospective accuracy analysis of MRI based lesion size measurement in neuroblastic tumors: which sequence should we choose?
Authors: Gassenmaier Sebastian , Tsiflikas Ilias , Maennlin Simon , Urla Cristian , Warmann Steven W. , Schaefer Juergen F.
Published: September 2020

Background

MR imaging of neuroblastic tumors is widely used for assessing the effect of chemotherapy on tumor size. However, there are some concerns that MRI might falsely estimate lesion diameters due to calcification and fibrosis. Therefore, the aim of our study was to compare neuroblastic tumor size based on MRI measurements to histopathology measurements of the resected specimens as standard of reference.

Methods

Inclusion criteria were diagnosis of a neuroblastic tumor, MR imaging within 100 days to surgery and gross total resection without fragmentation of the tumor between 2008 and 2019. Lesion diameters were measured by two radiologists according to RECIST 1.1 in axial plane in T2w turbo spin echo (TSE), diffusion-weighted imaging (DWI), and in T1w pre- and postcontrast sequences. Furthermore, the largest lesion size in three-dimensions was noted. The largest diameter of histopathology measurements of each specimen was used for comparison with MRI.

Results

Thirty-seven patients (mean age: 5 ± 4 years) with 38 lesions (neuroblastoma: n = 17; ganglioneuroblastoma: n = 11; ganglioneuroma: n = 10) were included in this retrospective study. There was excellent intra-class correlation coefficient between both readers for all sequences (> 0.9) Tumor dimensions of reader 1 based on axial MRI measurements were significantly smaller with the following median differences (cm): T1w precontrast − 1.4 (interquartile range (IQR): 1.8), T1w postcontrast − 1.0 (IQR: 1.9), T2w TSE: -1.0 (IQR: 1.6), and DWI -1.3 (IQR: 2.2) (p < 0.001 for all sequences). However, the evaluation revealed no significant differences between the three-dimensional measurements and histopathology measurements of the resected specimens regardless of the applied MRI sequence.

Conclusions

Axial MRI based lesion size measurements are significantly smaller than histopathological measurements. However, there was no significant difference between three-dimensional measurements and histopathology measurements of the resected specimens. T2w TSE and T1w postcontrast images provided the lowest deviation and might consequently be preferred for measurements.
Diabetes prevalence and outcomes in hospitalized cardiorenal-syndrome patients with and without hyponatremia
Authors: Pliquett Rainer U. , Schlump Katrin , Wienke Andreas , Bartling Babett , Noutsias Michel , Tamm Alexander , Girndt Matthias
Published: September 2020

Background

Hyponatremia is known to be associated with a worse patient outcome in heart failure. In cardiorenal syndrome (CRS), the prognostic role of concomitant hyponatremia is unclear. We sought to evaluate potential risk factors for hyponatremia in patients with CRS presenting with or without hyponatremia on hospital admission.

Methods

In a retrospective study, we investigated 262 CRS patients without sepsis admitted to the University Hospital Halle over a course of 4 years. CRS diagnosis was derived from an electronic search of concomitant diagnoses of acute or chronic (NYHA 3–4) heart failure and acute kidney injury (AKIN 1–3) or chronic kidney disease (KDIGO G3-G5nonD). A verification of CRS diagnosis was done based on patient records. Depending on the presence (Na < 135 mmol/L) or absence (Na ≥ 135 mmol/L) of hyponatremia on admission, the CRS patients were analyzed for comorbidities such as diabetes, presence of hypovolemia on admission, need for renal replacement therapy and prognostic factors such as in-hospital and one-year mortality.

Results

Two hundred sixty-two CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na < 135 mmol/L). The diabetes prevalence among CRS patients was high (> 65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic patients had a lower serum osmolality, hypovolemia was more prevalent (41.1% versus 16.3%, p < 0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p = 0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p = 0.692).

Conclusions

All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood for temporary renal replacement therapy.
A case report of complement C4B deficiency in a patient with steroid and IVIG-refractory anti-NMDA receptor encephalitis
Authors: Chua Gilbert T. , Zhou Danlei , Ho Alvin Chi Chung , Chan Sophelia Hoi Shan , Yu Chack Yung , Lau Yu Lung
Published: September 2020

Background

Complement C4A or C4B deficiency has never been reported in autoantibody-associated encephalitides patient. Here we present a case of anti-N-methyl- D-aspartate (NMDA) receptor encephalitis associated with homozygous C4B deficiency, who did not respond to intravenous immunoglobulin and pulse methylprednisolone but plasmapheresis and rituximab.

Case presentation

A fourteen-year-old boy presented to our unit with subacute onset of behavioral changes and confusion, and was later confirmed to be anti-NMDA receptor encephalitis. He was initially managed with intravenous immunoglobulin (IVIG) and pulse methylprednisolone but did not achieve any clinical improvement. Seven sessions of plasmapheresis was commenced with remarkable improvement after the second session, and was followed by four doses of rituximab. His neurological and cognitive functioning gradually returned to baseline. Immunological investigations demonstrated persistently low C4 levels below 8 mg/dL. A more in-depth complement analysis of the patient and his family showed that he has homozygous C4B deficiency. Genetic analysis revealed that the index patient has homozygous deficiency in complement C4B and he carries one non-functioning mutant C4B gene inherited from his mother.

Conclusions

Low levels of serum C4 correlate with reduced functions of the classical and lectin pathways, leading to the impairment of immune-complexes removal. Plasmapheresis ameliorates complement deficiency and removes the offending immune-complexes leading to clinical improvement that was not achieved by IVIG and steroids. We postulate that serum C4 levels may serve as a biomarker for the need of plasmapheresis upfront rather than only after non-response to steroid and IVIG in treating anti-NMDA-receptor encephalitis.
The effect of midwifery led counseling based on Gamble’s approach on childbirth fear and self-efficacy in nulligravida women
Authors: Firouzan Laya , Kharaghani Roghieh , Zenoozian Saeedeh , Moloodi Reza , Jafari Elham
Published: September 2020

Background

Studies show that childbirth fear is a common problem among Iranian women. Therefore, most Iranian women prefer caesarean section for giving birth. This study investigated the effectiveness of a psychoeducational intervention by midwives (birth emotions - looking to improve expectant fear (BELIEF)) on decreasing childbirth fear and self-efficacy among first-time pregnant women who were afraid of giving birth.

Methods

A number of 80 pregnant women participated in the study. They had received a score of ≥66 on the Wijma delivery expectancy/experience questionnaire. They were randomly assigned into two groups: intervention (n = 40) and control groups (n = 40). The intervention group received two face-to-face counseling sessions based on the BELEF protocol in the 24th and 34th weeks of pregnancy. Between these two sessions, it also received eight telephone-counseling sessions once a week. The control group only received the prenatal routine care. The outcome measures were childbirth fear, childbirth self-efficacy, and childbirth preference.

Results

The intervention group showed significantly more reduction in childbirth fear and more increase in childbirth self-efficacy compared to the control group. In addition, more women in the intervention group reported that they preferred to give normal vaginal birth than women in the control group.

Conclusion

The BELIEF protocol could be an effective approach in reducing childbirth fear and increasing childbirth self-efficacy among first-time pregnant women who are afraid of giving birth.

Trial registration number

IRCT20101219005417N3, Date of Registration: 19-12-2018.
Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis
Authors: Jin Xiao , Dai Lu , Ma Yilan , Wang Jiayan , Yan Haihao , Jin Ye , Zhu Xiaojuan , Liu Zheng
Published: September 2020

Background

An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC.

Methods

A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively.

Results

Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored.

Conclusions

HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.
Antithrombin use and mortality in patients with stage IV solid tumor-associated disseminated intravascular coagulation: a nationwide observational study in Japan
Authors: Taniguchi Kohei , Ohbe Hiroyuki , Yamakawa Kazuma , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: September 2020

Background

Terminal-stage solid tumors are one of the main causes of disseminated intravascular coagulation (DIC); effective therapeutic strategies are therefore warranted. This study aimed to investigate the association between mortality and antithrombin therapy in patients with stage IV solid tumor-associated DIC using a large nationwide inpatient database.

Methods

From July 2010 to March 2018, patients with stage IV solid tumor-associated DIC in the general wards, intensive care unit, or high care unit were identified using the Japanese Diagnosis Procedure Combination Inpatient Database. Patients who received antithrombin within 3 days of admission were allocated to the antithrombin group, while the remaining patients were allocated to the control group. One-to-four propensity score matching analyses were applied to compare outcomes. The primary outcome was the 28-day in-hospital mortality.

Results

Of the 25,299 eligible patients, 919 patients had received antithrombin within 3 days of admission and were matched with 3676 patients in the control group. There were no significant differences in the 28-day mortality between the two groups (control vs. antithrombin: 28.9% vs. 30.3%; hazard ratio, 1.08; 95% confidence interval, 0.95–1.23). There were no significant differences in the organ failure score and the proportion of critical bleeding between the two groups. Subgroup analyses showed that the effects of antithrombin were not significantly different among different tumor types.

Conclusion

Using a nationwide Japanese inpatient database, this study showed that there is no association between antithrombin administration and 28-day mortality in patients with stage IV solid tumor-associated DIC. Therefore, establishing other therapeutic strategies for solid tumor-associated DIC is required.
Pre- and post-operative differences between genders in idiopathic macular holes
Authors: Wang Jing , Yu Yanping , Liang Xida , Wang Zengyi , Qi Biying , Liu Wu
Published: September 2020

Background

To compare idiopathic macular holes (IMHs) between male and female before and after surgery.

Methods

Patients with IMHs of stage 3 and stage 4 who underwent 23-gauge vitrectomy were retrospectively enrolled. Pre-operative clinical features like age of onset, and best-corrected visual acuity (BCVA) were reviewed. Optical coherence tomography parameters including minimum linear diameter (MLD), central macular thickness and some other indexes were measured and calculated. Main surgical outcomes included the primary closure rate, the highest BCVA during follow-up, and the recovery duration. All the metrics mentioned above were compared between genders with appropriate statistical methods.

Results

A total of 298 eyes from 280 patients (male: 51; female: 229) were enrolled. Compared with men, women demonstrated a significantly higher ratio of stage3/stage4 (P = 0.045), larger horizontal MLD (P = 0.009), but similar surgical outcomes except for a relatively longer recovery duration (P = 0.024). For stage 3 IMHs, women exhibited significantly younger age of onset (P = 0.023), larger MLD (P = 0.003), and smaller height of the hole (P = 0.029). However, for stage 4 IMHs, all the pre- and post-operative metrics showed no differences between genders.

Conclusions

Female IMHs seem to demonstrate an earlier age of onset and larger size of hole, especially in IMHs of stage 3. However, these differences, which may owe to normal gender-related variations, have limited influence on the surgical outcomes.
Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child
Authors: Freij Bishara J. , Gebara Bassam M. , Tariq Rabail , Wang Ay-Ming , Gibson John , El-Wiher Nidal , Krasan Graham , Patek Paul M. , Levasseur Kelly A. , Amin Mitual , Fullmer Joseph M.
Published: September 2020

Background

Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens.

Case presentation

A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child’s passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread.

Conclusion

The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.
Do children with left ventricular noncompaction and a noncompaction-to-compaction ratio < 2 have a better prognosis?
Authors: Gan Yi , Luo Li , Tian Jie , Liu Lingjuan , Lu Tiewei
Published: September 2020

Background

Ultrasonography is commonly used to diagnose left ventricular noncompaction (LVNC). A ratio of noncompacted to compacted myocardium (NC/C ratio) > >2 is often used to diagnose LVNC. However, a large proportion of patients with noncompact myocardium have NC/C < 2, and the prognosis of these patients have not been studied.

Methods

We included children diagnosed with LVNC between 0 and 15 years of age from January 2007 to December 2018. LVNC was diagnosed based on Stöllberger standard when over three trabeculae were found to be associated with the interventricular recesses. A maximal end systolic ratio of noncompacted to compacted layers was NC/C ratio. Outcomes for LVNC subjects with NC/C < 2 and NC/C > 2 were compared using Kaplan-Meier methods.

Results

There were 124 newly diagnosed LVNC cases, classified as isolated (i-LVNC, n = 47) or non-isolated (ni-LVNC, n = 77) LVNC and NC/C > 2 (n = 43) or < 2 (n = 81). The median (interquartile range) follow-up duration was 12 (3–30) months for all patients and 16 (6–36) months for survivors. Sixteen patients with i-LVNC died during follow-up. Patients with i-LVNC and NC/C > 2 had worse survival than those with NC/C < 2 (p = 0.022).

Conclusions

In conclusion, during a 12-month follow-up, patients with i-LVNC with NC/C < 2 had a benign prognosis and better outcomes than those with NC/C > 2, suggesting that the former could have a more active and routine lifestyle.
No differences in physical activity between children with overweight and children of normal-weight
Authors: van Leeuwen Janneke , Koes Bart W. , Paulis Winifred D. , Bindels Patrick J. E. , van Middelkoop Marienke
Published: September 2020

Background

The aim of this study was to investigate the differences in objectively measured physical activity and in self-reported physical activity between overweight and normal-weight children.

Methods

Data from a prospective cohort study including children, presenting at the participating general practices in the south-west of the Netherlands, were used. Children (aged 4–15 years) were categorized as normal-weight or overweight using age- and sex specific cut-off points. They wore an ActiGraph accelerometer for one week to register physical activity, and filled out a diary for one week about physical activity.

Results

A total of 57 children were included in this study. Overweight children spent significantly less percentage time per day in sedentary behavior (β − 1.68 (95%CI -3.129, − 0.07)). There were no significant differences in percentage time per day spent in moderate to vigorous physical activity (β 0.33 (− 0.11, 0.78)). No significant differences were found between children of normal-weight and overweight in self-reported measures of physical activity.

Conclusions

Overweight children are not less physically active than normal-weight children, which may be associated with the risen awareness towards overweight/obesity and with implemented interventions for children with overweight/obesity.
Parents’ multi-layered expectations when requesting an Autism Spectrum Disorder assessment of their young child: an in-depth interview study
Authors: Jacobs Delphine , Steyaert Jean , Dierickx Kris , Hens Kristien
Published: September 2020

Background

Parents are valued stakeholders in research, clinical practice and policy development concerning autism spectrum disorder (ASD). However, little is known about what drives and moves parents besides their obvious worries and help request when they ask for a diagnostic ASD assessment of their child.

Methods

Seventeen Flemish parents of 11 young children participated in a longitudinal study consisting of three in-depth interviews before and after their child’s diagnostic ASD assessment. Data were analysed in Nvivo 11 according to the procedures of Interpretative Phenomenological Analysis.

Results

In this paper we report the results of the first series of interviews which were conducted after parents had asked for an ASD assessment of their young child, and before this assessment started. The pre-assessment experiences of the parents were dominated by the anticipation of various implications of an ASD diagnosis, comprising both positive and negative expectations. The theme of positive expectations consisted of two equally prominent subthemes: treatment-related implications but also expectations pertaining to their psychological and relational experiences.

Conclusions

This study suggests important issues for clinicians to bear in mind during a consultation with parents who request an ASD assessment of their young child. We argue that attending to and communicating about parents’ expectations prior to their child’s ASD assessment may help clinicians to better understand parents’ requests for help, and to address their needs more effectively.
Long-term melatonin treatment for the sleep problems and aberrant behaviors of children with neurodevelopmental disorders
Authors: Yuge Kotaro , Nagamitsu Shinichiro , Ishikawa Yuko , Hamada Izumi , Takahashi Hiroyuki , Sugioka Hideyuki , Yotsuya Osamu , Mishima Kazuo , Hayashi Masaharu , Yamashita Yushiro
Published: September 2020

Background

Clinical evidence is required about the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions.

Methods

We conducted a 26-week, multicenter, collaborative, uncontrolled, open-label, phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems. The study consisted of the 2-week screening phase, the 26-week medication phases I and II, and the 2-week follow-up phase. Children received 1, 2, or 4 mg melatonin granules orally in the medication phases. Variables of sleep status including sleep onset latency (SOL), aberrant behaviors listed on the Aberrant Behavior Check List-Japanese version (ABC-J), and safety were examined. The primary endpoint was SOL in the medication phase I.

Results

Between June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan—74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximal dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly (mean ± standard deviation [SD], − 36.7 ± 46.1 min; 95% confidence interval [CI], − 45.9 to − 27.5;P <  0.0001) in the medication phase I from baseline, and the SOL-shortening effect of melatonin persisted in the medication phase II and the follow-up phase. Temper upon wakening and sleepiness after awakening improved significantly (P <  0.0001 each) in the medication phase I from baseline and persisted in the follow-up phase. The following subscales of the ABC-J improved significantly: stereotypic behavior (P = 0.0322) in the medication phase I; and irritability, hyperactivity, and inappropriate speech (P <  0.0001) in the medication phase II. Treatment-emergent adverse events did not occur subsequent to week 16 after medication onset, and NDDs did not deteriorate in the follow-up phase.

Conclusions

Long-term melatonin treatment in combination with adequate sleep hygiene interventions may afford clinical benefits to children with NDDs and potentially elevates their well-being.

Trial registration

ClinicalTrils.gov,NCT02757066. Registered April 27, 2016.
Changes in self-reported sleep duration with age - a 36-year longitudinal study of Finnish adults
Authors: Hublin Christer , Haasio Lassi , Kaprio Jaakko
Published: September 2020

Background

Sleep deprivation is often claimed to be increasingly common, but most studies show small changes in sleep duration over the last decades. Our aim was to analyze long-term patterns in self-reported sleep duration in a population-based cohort.

Methods

Members of the Older Finnish Twin Cohort have responded to questionnaires in 1975 (N = 30,915 individuals, response rate 89%, mean age 36 years), 1981 (24,535, 84%, 41 years), 1990 (12,450, 77%, 44 years), and 2011 (8334, 72%, 60 years). Weibull regression models were used to model the effects of follow-up time and age simultaneously.

Results

Sleep duration has decreased in all adult age groups and in both genders. The mean duration was in men 7.57 h in 1975 and 7.39 in 2011, and in women 7.69 and 7.37, respectively. The decrease was about 0.5 min in men and 0.9 in women per year of follow-up. In the age-group 18–34 years, mean sleep length was 7.69 h in 1975 and 7.53 in 1990. Among 35–54-year-old it was 7.57 h in 1975 and 7.34 in 2011, and in the age group of 55+ year olds 7.52 and 7.38, correspondingly. The change was largest in middle-aged group: about 23 min or about 0.6 min per year of follow-up.

Conclusions

There has been a slight decrease in mean sleep duration during the 36-year follow-up. Although the sleep duration was longer in 1970s and 1980s, the probable main cause for the change in this study population is the effect of aging.
Impact of quadrivalent influenza vaccines in Brazil: a cost-effectiveness analysis using an influenza transmission model
Authors: Crépey Pascal , Boiron Louis , Araujo Rafael Rodrigo , Lopez Juan Guillermo , Petitjean Audrey , de Albuquerque Luna Expedito José
Published: September 2020

Background

Influenza epidemics significantly weight on the Brazilian healthcare system and its society. Public health authorities have progressively expanded recommendations for vaccination against influenza, particularly to the pediatric population. However, the potential mismatch between the trivalent influenza vaccine (TIV) strains and those circulating during the season remains an issue. Quadrivalent vaccines improves vaccines effectiveness by preventing any potential mismatch on influenza B lineages.

Methods

We evaluate the public health and economic benefits of the switch from TIV to QIV for the pediatric influenza recommendation (6mo-5yo) by using a dynamic epidemiological model able to consider the indirect impact of vaccination. Results of the epidemiological model are then imputed in a health-economic model adapted to the Brazilian context. We perform deterministic and probabilistic sensitivity analysis to account for both epidemiological and economical sources of uncertainty.

Results

Our results show that switching from TIV to QIV in the Brazilian pediatric population would prevent 406,600 symptomatic cases, 11,300 hospitalizations and almost 400 deaths by influenza season. This strategy would save 3400 life-years yearly for an incremental direct cost of R$169 million per year, down to R$86 million from a societal perspective. Incremental cost-effectiveness ratios for the switch would be R$49,700 per life-year saved and R$26,800 per quality-adjusted life-year gained from a public payer perspective, and even more cost-effective from a societal perspective. Our results are qualitatively similar in our sensitivity analysis.

Conclusions

Our analysis shows that switching from TIV to QIV to protect children aged 6mo to 5yo in the Brazilian influenza epidemiological context could have a strong public health impact and represent a cost-effective strategy from a public payer perspective, and a highly cost-effective one from a societal perspective.
Considerations for the design of nutrition-sensitive production programmes in rural South Africa
Authors: Hendriks S. L. , Viljoen A. , Marais D. , Wenhold F. A. M. , McIntyre A. M. , Ngidi M. S. , Annandale J. G. , Kalaba M. , Stewart D.
Published: September 2020

Background

Very little has been researched about the efficacy, effectiveness, feasibility, sustainability and impact of food-based approaches on the diets and nutritional status of populations at risk of hunger and food insecurity. This study contributes knowledge about the impact of food-based approaches on the diets of populations at risk of hunger and food insecurity in four of the poorest rural communities in South Africa. The study investigated the consumption and production patterns of rural households (278 in summer and 280 in winter) in four sites in the poorest municipalities in South Africa.

Methods

A multistage stratified random sampling technique was applied to identify the communities and sample households for the quantitative survey and qualitative assessments. Qualitative and quantitative data were collected between 2013 and 2015 through focus group discussions (FGDs), key informant interviews and the two-round panel survey to cover both the summer and winter seasons at each site.

Results

Home gardening led to a significant positive increase in the consumption of white roots and tubers, dark green leafy vegetables, orange-coloured fruit and other fruit in the 24 h prior to the survey. Participation in a community garden led to significant increases in the consumption of dark green leafy vegetables and other vegetables. School gardening did not demonstrate any statistical relationships with the consumption of foods from the crop-related food groups. Crop production improved dietary diversity. Selling produce and irrigation showed a stronger improvement in dietary diversity. Seasonality affected the availability of fresh fruit and vegetables for home consumption in winter.

Conclusions

Producing beyond that solely for home consumption has greater benefits for dietary diversity and a consumption-smoothing effect during the post-harvest period. Politicians and the scientific community should recognise the role that household and small-scale crop production plays in supporting household consumption and the provision of essential micronutrients despite constraints and disincentives. Production and education programmes should focus on strengthening existing good consumption patterns and promoting the consumption of foods that can improve dietary diversity.