The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells.

Abstract: Prostate cancer (PC) is one of the most common cancers among men. Progression of prostate cancer is associated with an increase in cellular level of interleukin-6 (IL-6). Gallic acid (GA) is a polyhydroxy phenolic compound which can inhibit the growth of cancer cells. The aim of this study was to evaluate the effects of GA treatment on cell viability, proliferation, invasion, IL-6 gene expression, IL-6 secretion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins in human prostate cancer PC3 cells. PC3 cells viability after treatment with GA (0-120μM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of IL-6 was investigated using real-time polymerase chain reaction. Cellular concentration of pSTAT3, pERK1/2, and pAKT signaling proteins were determined by Western blotting technic. PC3 cells invasion was assessed by invasion assay test. Treatment with GA caused a significant decrease in cell viability, proliferation, invasion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins after 48h in a dose-dependent manner. The level of IL-6 and its gene expression decreased significantly in PC3 cells treated with GA. Our results show that IL-6 down-regulation and decreased IL-6 protein level in PC3 cells by GA resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins which lead to the reduction of the cell survival, proliferation, and invasion in PC3 cells. Therefore, it seems that GA can be considered an anticancer agent in the treatment of prostate cancer.

Heidarian|Esfandiar|E| Keloushadi|Mahnaz|M| Ghatreh-Samani|Keihan|K| Valipour|Parisa|P|

D015972:Gene Expression Regulation, Neoplastic

D019950:Mitogen-Activated Protein Kinase 1

D048052:Mitogen-Activated Protein Kinase 3

Gallic acid
PC3 cells
Interleukin-6
Antioxidant
Grape


Family physicians health-related absenteeism at the Al-Wazarat Healthcare Center.

Abstract:
Background
In general, physicians and family physicians more specifically tend to treat themselves in an informal matter. The evidence suggests that family physicians have a tendency not to consult other physicians while they are sick and tend to self-treat. Health-related absenteeism among family physicians in primary care settings is an issue that needs to be addressed.

Aim
The aim of this study is to identify the prevalence of health-related absenteeism among family physicians in Al-Wazarat Health Center and to investigate the medical causes associated with sickness absence.

Methods
The study used cross-sectional design to investigate the prevalence of health-related absenteeism among family physicians in a primary care setting.

Results
The study included 108 physicians from the Al-Wazarat Healthcare Center in Riyadh, KSA. On average, the physicians were absent for 2 days over the last year with 53.3% (64/108) have no health-related absence days. The most common recorded reasons for work absence are the severity of illness 75.0% (81/108) and workload 63.0% (68/108). Influenza was the most common health condition that causes absenteeism 60.2% (65/108). The attitude toward working while ill scored 2.3 ± 2.5, being responsible for affecting the patients if working while ill 8.0 ± 2.8, physicians with chronic diseases should stay away from work 3.7 ± 3.7, and the quality of healthcare service could be affected by the physician's illness 7.5 ± 2.5.

Conclusions
Further investigations are needed for more understanding of the physicians' tendencies and casual approach toward working with illness. Such understanding will help to formulate better guidelines for medical practices.

family physician
primary care
Absence
illness
sick-leave


Sex Differences in Cancer Immunotherapy Efficacy, Biomarkers, and Therapeutic Strategy.

Abstract: Sex differences in innate and adaptive immune responses are known, and women generally mount a stronger immune response than men. Cancer immunotherapy, represented by immune checkpoint inhibitors (ICIs), has revolutionized the treatment of cancer, and sex differences in cancer immunotherapy are just starting to be revealed. Here, we summarize recent research progress concerning sex differences in cancer immunotherapy efficacy. On their own, ICIs tend to be more effective in male cancer patients compared with female patients, while ICIs combined with chemotherapy tend to be more effective in female patients than male patients. Male tumors are usually more antigenic than female tumors, and this is reflected by their increased number of tumor mutations and cancer germline antigens. The biomarker tumor mutational burden (TMB), which reflects tumor antigenicity, is more effective at predicting immunotherapy response for female lung cancer patients than for male patients. In this review, we propose different therapeutic strategies for the different sexes: For male cancer patients, the immune environment should be enhanced, whereas for female cancer patients, tumor antigenicity should be enhanced.

sex differences
cancer immunotherapy
biomarker
immune checkpoint inhibitor
tumor mutational burden


Biohybrid Control of General Linear Systems Using the Adaptive Filter Model of Cerebellum.

Abstract: The adaptive filter model of the cerebellar microcircuit has been successfully applied to biological motor control problems, such as the vestibulo-ocular reflex (VOR), and to sensory processing problems, such as the adaptive cancelation of reafferent noise. It has also been successfully applied to problems in robotics, such as adaptive camera stabilization and sensor noise cancelation. In previous applications to inverse control problems, the algorithm was applied to the velocity control of a plant dominated by viscous and elastic elements. Naive application of the adaptive filter model to the displacement (as opposed to velocity) control of this plant results in unstable learning and control. To be more generally useful in engineering problems, it is essential to remove this restriction to enable the stable control of plants of any order. We address this problem here by developing a biohybrid model reference adaptive control (MRAC) scheme, which stabilizes the control algorithm for strictly proper plants. We evaluate the performance of this novel cerebellar-inspired algorithm with MRAC scheme in the experimental control of a dielectric electroactive polymer, a class of artificial muscle. The results show that the augmented cerebellar algorithm is able to accurately control the displacement response of the artificial muscle. The proposed solution not only greatly extends the practical applicability of the cerebellar-inspired algorithm, but may also shed light on cerebellar involvement in a wider range of biological control tasks.

Wilson|Emma D|ED|
Assaf|Tareq|T|
Pearson|Martin J|MJ|
Rossiter|Jonathan M|JM|
Dean|Paul|P|
Anderson|Sean R|SR|
Porrill|John|J|

adaptive filter
cerebellum
adaptive control
electroactive polymer
artificial muscles
soft robotics


Bone marrow haploidentical transplant with post-transplantation cyclophosphamide: does graft cell content have an impact on main clinical outcomes?

Abstract: We analyzed data relative to cell content in 88 consecutive patients receiving HLA haploidentical bone marrow (BM) transplants with post-transplantation cyclophosphamide (PT-CY). Median age was 54.5 (range, 17-72); diagnoses were acute leukemia (n = 46), lymphoproliferative disorders (n = 24), myelofibrosis (n = 11) and myelodysplastic syndromes (n = 5). Total nucleated cell (TNC) and CD34+, CD3+, CD4+ and CD8+ cell doses were stratified as higher than first, second and third quartile and the dose effect on various clinical outcomes was assessed. Median time to engraftment was 17 days for neutrophils and 24 days for platelets. To receive a dose of TNC ≥3.2 x 106/kg or CD34+ cells ≥2.7 x 106/kg significantly shortened the time to neutrophil and platelet engraftment and reduced the blood product requirements in the 30-day period after transplantation. Overall, TNC and CD34+ cell doses had no effect on acute graft-versus-host disease (GVHD) incidence, whereas patients receiving higher CD3+ and CD8+ cell doses seemed to have less chronic GVHD. No effect on non-relapse mortality, progression-free survival and overall survival was observed at different cell dose thresholds. These data suggest that in HLA haploidentical BM transplant with PT-CY, appropriate cell doses are relevant to the engraftment. The association between low CD3+/CD8+ cells and chronic GVHD deserves further investigation.

Teofili|Luciana|L|
Chiusolo|Patrizia|P|
Valentini|Caterina Giovanna|CG|
Metafuni|Elisabetta|E|
Bellesi|Silvia|S|
Orlando|Nicoletta|N|
Bianchi|Maria|M|
Giammarco|Sabrina|S|
Sica|Simona|S|
Bacigalupo|Andrea|A|

bone marrow
haploidentical transplant
cyclophosphamide
engraftment
graft-versus-host disease


Evaluation of QT Dispersion in Children with Breath Holding Spells.

Abstract:
OBJECTIVE
Breath holding spells (BHS) are common involuntary reflexes in infancy and early childhood. Differential diagnosis should embrace Long QT Syndrome (LQTS) and paroxysmal abnormalities of rhythm. The aim of this study was to compare QT dispersion (QTd) in children with breath holding spells and normal controls.

MATERIALS & METHODS
QT dispersion and Corrected QT(QTc) dispersion were measured in 12 lead surface electrocardiograms in 56 patients with BHS and compared with healthy children of the same age referred to the clinic for regular checkup visits.

RESULTS
The most common type of BHS was cyanotic (83.9%). Seven patients (12.5%) had pallid and two patients (3.5%) had mixed spells. There was a history of breath holding spells in 33.9% of the children. QT dispersion was 61.6± 22.5 and 47.1±18.8 ms in patient and control groups, respectively. QTc dispersion (QTcd) was 104 ± 29.6 and 71.9 ±18.2 ms, respectively. There was a significant difference between patient and control groups in terms of QTd and QTcd (P<0.001).

CONCLUSION
QTd and QTcd were increased in children with BHS. Therefore, the evaluation of EKG for early diagnosis of rhythm abnormalities seems reasonable in these children.

Movahedian|Amir Hosein|AH|
Heidarzadeh Arani|Marzieh|M|
Motaharizad|Davood|D|
Mousavi|Gholam Abbas|GA|
Mosayebi|Ziba|Z|

QT dispersion
Dispersion
Breath holding spell
QTc dispersion
QT interval


Molecular characterization of human lung and liver cystic echinococcosis isolates in Van Province, Turkey.

Abstract: Cystic echinococcosis (CE) is a zoonotic infection and could lead to significant public health problems. The genetic diversity of CE includes five species: E. granulosus sensu stricto (s.s.) (G1-G3), Echinococcus equinus (G4), Echinococcus ortleppi (G5), Echinococcus canadensis genotypic cluster (G6, G7, G8 and G10, with the doubtful G9) and the Echinococcus felidis (lion strain). The species are important in epidemiology, pathology, control, prevention measures and vaccine/drug designs. The aim of the present study was to determine the E. granulosus genotypes in humans in the Van province in east of Turkey. In total, 102 echinococcal cysts were collected from operated patients. Genomic analyses were conducted with PCR-RFLP of the rDNA internal transcribed spacer 1 (ITS1) fragment and partial PCR sequencing of the cytochrome c oxidase subunit 1 (cox1) mitochondrial DNA gene region. In total, DNAs of 96 isolates could be extracted, unfortunately six extractions failed. The PCR-RFLP analysis findings were identical in all isolates. Two bands were observed at approximately 300 bp and 600 bp. All profiles corresponded to the G1-G3 strain. Also, 446 bp amplified gene regions were observed for cox1. Out of 20 samples, alignment of 16 sequences exhibited a total identification (100%) of granulosus sensu stricto (G1/G3). Of 16 samples, 8 were obtained in the lung and 12 were obtained in the liver; 8 belonged to male and 12 belonged to female patients. Other four samples exhibited one nucleotide substitution at different positions. Four samples had one nucleotide substitution at different positions. We detected single nucleotide variations in TRH1, TRH67, TRH85 and TRH89 isolates at the positions C240T; G330T; G211A and T157C, respectively. In conclusion, the present study was the first comprehensive molecular investigation on genetic characterization of human CE isolates in Van region. The findings demonstrated that E. granulosus s.s. was the dominant species, which indicated that the sheep-dog cycle was the source in human infections. And, probably, it would be possible to describe these mutations as "Turkey" or "lung" variants. In addition to contributing molecular epidemiological data, the present results should be considered when designing and implementing E. granulosus control programs.

Beyhan|Yunus Emre|YE|
Çobanoğlu|Ufuk|U|
Çelik|Sebahattin|S|
Yılmaz|Hasan|H|
Halidi|Ahmed Galip|AG|

Molecular
Human
Cystic echinococcosis
Turkey
Mutation


A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.

Abstract:
BACKGROUND
Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy.

METHODS
MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched.

RESULTS
Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%; sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%) than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting.

CONCLUSION
Dulaglutide is effective in the treatment of patients with type 2 diabetes but we need long follow-up data for safety concerns.

Gurung|Tara|T|
Shyangdan|Deepson S|DS|
O'Hare|Joseph Paul|JP|
Waugh|Norman|N|

dulaglutide
glucagon-like peptide analogue
type 2 diabetes
effectiveness
glycemic control


The abundance of large, piscivorous Ferox Trout (Salmo trutta) in Loch Rannoch, Scotland.

Abstract:
BACKGROUND
Ferox Trout are large, long-lived piscivorous Brown Trout (Salmo trutta). Due to their exceptionally large size, Ferox Trout are highly sought after by anglers while their life-history strategy, which includes delayed maturation, multiphasic growth and extended longevity, is of interest to ecological and evolutionary modelers. However, despite their recreational and theoretical importance, little is known about the typical abundance of Ferox Trout.

METHODS
To rectify this situation a 16 year angling-based mark-recapture study was conducted on Loch Rannoch, which at 19 km2 is one of the largest lakes in the United Kingdom.

RESULTS
A hierarchical Bayesian Jolly-Seber analysis of the data suggest that if individual differences in catchability are negligible the population of Ferox Trout in Loch Rannoch in 2009 was approximately 71 fish. The results also suggest that a single, often unaccompanied, highly-experienced angler was able to catch roughly 8% of the available fish on an annual basis.

DISCUSSION
It is recommended that anglers adopt a precautionary approach and release all trout with a fork length ≥400 mm caught by trolling in Loch Rannoch. There is an urgent need to assess the status of Ferox Trout in other lakes.

Thorne|Alastair|A|
MacDonald|Alisdair I|AI|
Thorley|Joseph L|JL|

Abundance
Piscivorous
Ferox Trout
Brown Trout
Hierarchical
Bayesian
Jolly-Seber
Exploitation
Survival


Treatment of hyperlipidemic acute pancreatitis with modified Dachengqi decoction combining with conventional therapy based on "six-hollow-organs to be unblocked" theory.

Abstract:
BACKGROUND
The increase of triglyceride (TG) can induce coronary heart disease, atherosclerosis, pancreatitis and other diseases and is the most common inducing factor of acute pancreatitis (AP) second only to biliary tract disease and drinking. The pathogenesis of hyperlipidemic acute pancreatitis (HLAP) is not exactly clear, but it may be related to the toxic effect of the increase of free fatty acids produced by TG decomposition on the pancreas itself, microcirculation disorder of the pancreas, and calcium overload. At present, non-surgical therapy is the main treatment for HLAP. The key to preventing recurrence is to reduce blood lipids, change the diet structure, and reduce weight. This study aimed to treat HLAP with modified Dachengqi decoction combined with conventional therapy, based on the "six-hollow-organs to be unblocked" theory.

METHODS
Forty patients with HLAP who received treatment in the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine and Puding County Hospital of Traditional Chinese Medicine from September 2016 to August 2019 were selected and divided into a control group and an intervention group, each with 20 cases, following a random number table. The control group was treated with conventional therapy while the intervention group was treated with modified Dachengqi decoction combined with conventional therapy.

RESULTS
After treatment, the cure rate and the total effective rate were 60% and 95% respectively in the intervention group, and 25% and 75% respectively in the control group (P<0.05). The TG, serum amylase, leukocyte count, and neutrophil ratio of the two groups decreased significantly after treatment, and there was a greater decrease in the intervention group than that in the control group, with this being significantly different between the two groups. The gastrointestinal function score, total score of the acute physiology and chronic health evaluation II (APACHE II), and the pain score of the visual analog scale (VAS) decreased markedly in the two groups after the treatment, with scores in the intervention group being significantly lower than those in the control group (P<0.05).

CONCLUSIONS
Modified Dachengqi decoction combined with conventional therapy has a better therapeutic effect on HLAP than conventional therapy.

Liu|Guoxiong|G| Liu|Fang|F| Xiao|Long|L| Kuang|Qiaogui|Q| He|Xingfeng|X| Wang|Yu|Y| Yu|Yang|Y|

Hyperlipidemic acute pancreatitis (HLAP)

“six-hollow organs to be unblocked” theory


Paraneoplastic neuromyelitis optica and ovarian teratoma: A case series.

Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease of the central nervous system, characterized by the presence of auto-antibodies directed against aquaporin-4 (AQP4) expressed on astrocyte end-feet. Despite NMOSD does not primarily belong to the spectrum of paraneoplastic neurological syndromes, rare cases of association with neoplasia have been outlined. Here, we report the association of NMOSD with ovarian teratoma in 3 cases. Pathological analysis of teratomas revealed glial component strongly expressing AQP4 and closely localized to immune infiltrates. Our series highlight the rare association of teratoma with NMOSD and the possible paraneoplastic mechanism.

Bernard-Valnet|Raphaël|R| Cobo-Calvo|Alvaro|A| Siegfried|Aurore|A| Marasescu|Raluca|R| Bonnan|Mickael|M| Ballan|Guillaume|G| Ellie|Emmanuel|E| Bauer|Jan|J| Uro-Coste|Emmanuelle|E| Marignier|Romain|R| Brassat|David|D|

Neuromyelitis optica
Ovarian teratoma
Autoimmune diseases
Demyelinating diseases
Paraneoplastic syndromes


Coating M-CSF on plastic surface results in the generation of increased numbers of macrophages in vitro.

Abstract: Macrophages are one of the important cell types in the innate immune system that are present in various anatomical regions of the body and promote early control of pathogens. The relative proportion of macrophages in various lymphoid and non-lymphoid regions is small, and as such it is tedious to purify these cells to homogeneity. Culture of bone marrow precursors with macrophage colony-stimulating factor (M-CSF) results in their differentiation to macrophages, however this procedure results in low numbers of differentiated macrophages. Herein we reveal a new approach of generating increased numbers of differentiated macrophages from bone marrow precursors. We show that M-CSF delivered in a plate-bound form results in the differentiation of significantly more macrophages in comparison to soluble M-CSF. Furthermore, the macrophages differentiated with plate-bound M-CSF display increased metabolic activity and cell death following infection with pathogens.

Sadh|Sanathan|S|
Hajjar|Stephanie|S|
Ariana|Ardeshir|A|
Phuong|Melissa Sen|MS|
Cai|David|D|
Thakker|Parva|P|
Sad|Subash|S|


Language and language disorders: neuroscience to clinical practice.

Abstract: Language disorders are common in neurological practice but their accurate recognition and description can be challenging. In this review, we summarise the major landmarks in the understanding of language disorders and the organisation of language in the brain. We describe approaches to assessing language disorders at the bedside or in the clinic as well as the treatment and rehabilitation of aphasia. Finally, we describe how the field of neuroscience is providing new computational and neuroscientific approaches to study the mechanisms of recovery and rehabilitation of aphasia.

rehabilitation
aphasia
articulation
speech therapy


The orientation and attitudes of intermediate vocational trained nursing students (MBO-V) towards their future profession: A pre-post survey.

Abstract: Students' perceptions of nursing influence recruitment and retention in nursing education. Nursing education in the Netherlands differentiates two levels: Bachelor's (HBO-V) and intermediate vocational (MBO-V) level training, with MBO-V students accounting the majority. To avoid the expected nursing shortages, these students' perceptions of nursing need to be explored. We aimed to examine the orientation and attitudes of MBO-V students towards their future profession and their relation to demographic characteristics. A descriptive survey with a pretest-posttest design was conducted. Newly enrolled MBO-V students completed a questionnaire at the beginning and after five months of education, consisting of the Nursing Orientation Tool, the Nursing Attitude Questionnaire and demographic characteristics. The Wilcoxon signed-rank test, Mann-Whitney U test and regression analysis were used for data analyses. At the first time point, students agreed most with statements related to caring, nursing expertise, advocacy, empathy, and knowledge. After five months, students were more life-oriented, while caring, nursing expertise, advocacy, and empathy decreased. Selecting nursing as a first-choice programme and aiming for a nursing career influenced students' orientation and attitudes towards nursing positively. Being aware of students' orientation and attitudes towards nursing can help nursing educators in recruitment and retention strategies.

van den Boogaard|T C|TC|
Roodbol|P F|PF|
Poslawsky|I E|IE|
Ten Hoeve|Y|Y|

Orientation
Attitude
Nursing students
Survey


Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease.

Abstract: Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves. Using luciferase reporter systems, we found direct binding of miR-143 to the 3'UTR region of the matrix gla protein (MGP), which in turn is a key factor to sustain homeostasis in aortic valves. In subsequent experiments, we demonstrated a therapeutic potential of miRNA regulation during calcification in cardiac valvular interstitial cells. Collectively, our data provide evidence that deregulated miR expression contributes to the development of stenotic valve disease and thus form novel therapeutic opportunities of this severe cardiovascular disease.

Fiedler|Jan|J|0000-0002-8855-2883
Park|Da-Hee|DH|
Hobuß|Lisa|L|
Anaraki|Parnian Kalbasi|PK|
Pfanne|Angelika|A|
Just|Annette|A|
Mitzka|Saskia|S|
Dumler|Inna|I|
Weidemann|Frank|F|
Hilfiker|Andres|A|
Thum|Thomas|T|

microRNA
Calcium deposition dependent on miR-143
Human aortic stenosis
miR signature in aortic stenosis


Association between early echocardiography, therapy for patent ductus arteriosus, and outcomes in very low birth weight infants.

Abstract:
BACKGROUND
In very low birth weight infants, persistence of a patent ductus arteriosus results in morbidity and mortality. Therapies to close the ductus are effective, but clinical outcomes may depend on the accuracy of diagnosis and the timing of administration. The objective of the present study was to characterise the association between early echocardiography, therapy for patent ductus arteriosus, and outcomes in very low birth weight infants.

METHODS
This retrospective cohort study used electronic health record data on inborn infants of gestational age ⩽28 weeks and birth weight <1500 g who were discharged after day of life 7 from 362 neonatal ICU from 1997 to 2013. The primary outcome was death between day of life 7 and discharge. Secondary outcomes included bronchopulmonary dysplasia, necrotising enterocolitis, and grade 3 or 4 intraventricular haemorrhage.

RESULTS
This study included a total of 48,551 infants with a median gestational age of 27 weeks (interquartile range 25, 28) and birth weight 870 g (706, 1050). Early echocardiography - that is, performed during days of life 2 to 6 - was performed in 15,971/48,551 (33%) infants, and patent ductus arteriosus was diagnosed in 31,712/48,551 (65%). The diagnosis was more common in infants who had undergone early echocardiography (14,549/15,971 [91%] versus 17,163/32,580 [53%], p<0.001). In multivariable analysis, early echocardiography was not associated with reduced mortality (odds ratio 0.97, 95% CI 0.89-1.05). Results were similar in the subset of infants who received therapy for patent ductus arteriosus (odds ratio 1.01, 95% CI 0.90-1.15).

CONCLUSIONS
Early echocardiography was associated with an increased diagnosis of patent ductus arteriosus, but not with decreased mortality.

Lee|Jan Hau|JH|
Greenberg|Rachel G|RG|
Quek|Bin H|BH|
Clark|Reese H|RH|
Laughon|Matthew M|MM|
Smith|P Brian|PB|
Hornik|Christoph P|CP|

echocardiography
patent ductus arteriosus
mortality
neonate
Cardiology


miR-18a downregulates DICER1 and promotes proliferation and metastasis of nasopharyngeal carcinoma.

Abstract: Nasopharyngeal carcinoma, common in Southeast Asia and the southern provinces of China, often has metastasized by the time of diagnosis; thus there exists the need for improved diagnosis and treatment. Accumulating evidence indicates that microRNAs (miRNAs), which post-transcriptionally regulate protein expression, contribute to the processes of tumorigenesis, including metastasis and cellular invasion. Here, we studied the effect of one miRNA, miR-18a-which is believed to target the miRNA-processing enzyme DICERl-on nasopharyngeal carcinoma. In situ hybridization revealed that miR-18a was more highly expressed in nasopharyngeal carcinoma tissues than in control tissues (P < 0.05), and the overexpression correlated with clinical stage and lymph node metastasis (P < 0.05), but not with age and gender (P > 0.05). In vitro analysis of HK1 nasopharyngeal carcinoma cells transfected with miR-18a exhibited significantly decreased expression of DICER1 mRNA and protein but significantly increased proliferation and invasion properties compared to control cells (P < 0.05). Finally, nude mice injected with miR-18a transfected-HK1 cells displayed significantly increased tumor growth and lung metastasis in vivo (P < 0.05). These findings suggest that miR-18a expression can promote proliferation and metastasis of nasopharyngeal carcinoma cells and that these activities may occur through its regulation of DICER1.

Chen|Xi|X| Wang|Juan|J| Cheng|Lei|L| Lu|Mei-Ping|MP|

Dicer1
proliferation
metastasis
Nasopharyngeal carcinoma
HK1 cells
microRNA-18a


The role of community protection institution in disaster management at West Java, Indonesia.

Abstract: This research aimed to establish a mechanism of evolution of community protection, identify the support of facilities and infrastructure needed in facilitating the implementation of the tasks and functions of Linmas, especially in disaster management and formulate community protection institutions that are appropriate to the needs and capacities of the regions. The research method is carried out by a qualitative approach that is using focus group discussion (FGD) based on experience and perceptions of the benefits and impacts of the community protection unit's guidance in West Java province. The results show that the community protection institutions are needed in improving the independence of the community in tackling any disaster that is faced by an organization in which at least have the ability and skills in the field: early prevention, peace and orderly of safety fibre, health and psychologist and public and social work. The practical implication of this research is that the local government should empower the community protection unit through the regional work unit or related stakeholders in conducting training and facilitation of training and improving skills so that they can carry out their duties better.

community protection
disaster management
Linmas
Protection Unit
self-security


Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families.

Abstract:
BACKGROUND
Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB and DNAJB11, cause autosomal dominant PKD (ADPKD). Early onset and severe PKD can occur with PKD1 and PKD2 pathogenic variants and such phenotypes may be modified by second alleles inherited in trans. Homozygous or compound heterozygous hypomorphic PKD1 variants may also cause a moderate to severe disease PKD phenotype.

METHODS
Targeted renal gene panel followed by Sanger sequencing of PKD1 gene were employed to investigate molecular causes in early onset PKD patients.

RESULTS
In this study, we report four consanguineous Saudi Arabian families with early onset PKD which were associated with biallelic variants in PKD1 gene.

CONCLUSIONS
Our findings confirm that PKD1 alleles may combine to produce severe paediatric onset PKD mimicking the more severe autosomal recessive ciliopathy syndromes associated with PKD. Screening of parents of such children may also reveal subclinical PKD phenotypes.

D016891:Polycystic Kidney, Autosomal Dominant

PKD1
ADPKD
Consanguinity
Biallelic mutations
Molecular genetics


Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia.

Abstract: Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation and the ratio of Bax to Bcl-2 in the ischemic brain. CAG also inhibited NF-κB p65 nuclear translocation. As a result, CAG suppressed the mRNA expression of pro-inflammatory cytokines, including TNF-α and IL-1β, and inhibited the activation of microglia and astrocytes in the ischemic brain. Our findings suggest that CAG is neuroprotective against ischemic brain injury in mice and that its beneficial effect may involve SIRT1 upregulation and the inhibition of apoptosis and neuroinflammation in the ischemic brain.

Li|Man|M| Li|Shi-Chun|SC| Dou|Bao-Kai|BK| Zou|Ying-Xiang|YX| Han|Hao-Zhen|HZ| Liu|Dong-Xiang|DX| Ke|Zun-Ji|ZJ| Wang|Zhi-Fei|ZF|

D020244:Infarction, Middle Cerebral Artery

cycloastragenol
SIRT1
apoptosis
neuroinflammation
cerebral ischemia


Development and validation of a method using supported liquid extraction for aldosterone determination in human plasma by LC-MS/MS.

Abstract:
BACKGROUND
Accurate quantitation of aldosterone is essential for screening, diagnosis and subtype classification in primary aldosteronism. A simple, sensitive method for aldosterone in human plasma using supported liquid extraction (SLE) in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and validated.

METHODS
Plasma samples were diluted with water containing d7-aldosterone as internal standard. The samples were extracted with methyl-tert-butyl-ether (MTBE) on SLE cartridges. Separation was carried out on a Luna C18 (2) column using a methanol-water gradient. Detection was performed in the negative electrospray multiple reaction monitoring (MRM) quantitation. The use of water-based calibrators was evaluated against calibrators prepared in steroid-free serum.

RESULTS
The assay was linear up to 3265pmol/L with an LOQ of approximately 40pmol/L. Within-run and between-run precision for plasma aldosterone were less than 10% except at low level near LOQ but were still less than 14.7% (Westgard's desirable specification). The mean recovery of the analyte added to plasma was greater than 97.7% and matrix effects were less than 4%. Comparison with another LC-MS/MS method was performed on a more sensitive instrument (ABSciex TQ 5500) and gave the equation API 3000=0.957×TQ 5500+12.6, linear regression r(2)=0.974 (n=43). An estimation of the reference interval for adults was established on a group of healthy volunteers (n=53). Calibration with water-based calibrators was validated and can be used for measurement of aldosterone by LC-MS/MS.

CONCLUSIONS
This method is reliable, easy to perform on plasma specimens in a clinical environment and is attractive because of its simplicity.

Meunier|Cécile|C|
Blondelle|Dominique|D|
Faure|Patrice|P|
Baguet|Jean-Philippe|JP|
Le Goff|Caroline|C|
Chabre|Olivier|O|
Ducros|Véronique|V|


Digital Acrometastasis as Initial Presentation in Carcinoma of Lung A Case Report and Review of Literature.

Abstract: Bony metastases develop in 30% of all the cancers, but out of which only 1% to 3% occurs in the hand. Lung is the most common site for acrometastasis, followed by breast and renal cell cancer. Metastases to the digits are with non-specific presentation. We reported a case of 79-year-old male patient with initial presentation of swelling over left index finger, which was found to be squamous cell carcinoma of finger on histopathological examination. He was subsequently diagnosed as a case of squamous cell carcinoma of lung with acrometastasis.

Sahoo|Tapan Kumar|TK|
Das|Saroj Kumar|SK|
Majumdar|Saroj Kumar Das|SK|
Senapati|Surendra Nath|SN|
Parida|Dillip Kumar|DK|


Understanding the effect of miliary tuberculosis through the experience of one young person.

Abstract: In the UK, tuberculosis (TB) is on the increase. Miliary TB affects the lungs and can leave lasting damage, and affect a person's quality of life adversely. Healthcare professionals need to co-ordinate services efficiently, to ensure a smooth transition from hospital to home, and ensure there is appropriate support in the community for as long as necessary. In this article, a boy describes his journey through the illness: the associated bewilderment, deterioration, pain, fear and isolation; the emergencies; the prolonged but effective treatment; the care he received; and the support of his family. On discharge, he was still breathless and found it difficult to adapt to home life but, with thorough planning of his support with healthcare professionals, parents and relevant agencies, he was able to get back to school and continue his education.

miliary tuberculosis
tuberculosis
TB
Contact tracing
infection control
notifiable disease
psychological support
respiratory disease


Vector field statistical analysis of kinematic and force trajectories.

Abstract: When investigating the dynamics of three-dimensional multi-body biomechanical systems it is often difficult to derive spatiotemporally directed predictions regarding experimentally induced effects. A paradigm of 'non-directed' hypothesis testing has emerged in the literature as a result. Non-directed analyses typically consist of ad hoc scalar extraction, an approach which substantially simplifies the original, highly multivariate datasets (many time points, many vector components). This paper describes a commensurately multivariate method as an alternative to scalar extraction. The method, called 'statistical parametric mapping' (SPM), uses random field theory to objectively identify field regions which co-vary significantly with the experimental design. We compared SPM to scalar extraction by re-analyzing three publicly available datasets: 3D knee kinematics, a ten-muscle force system, and 3D ground reaction forces. Scalar extraction was found to bias the analyses of all three datasets by failing to consider sufficient portions of the dataset, and/or by failing to consider covariance amongst vector components. SPM overcame both problems by conducting hypothesis testing at the (massively multivariate) vector trajectory level, with random field corrections simultaneously accounting for temporal correlation and vector covariance. While SPM has been widely demonstrated to be effective for analyzing 3D scalar fields, the current results are the first to demonstrate its effectiveness for 1D vector field analysis. It was concluded that SPM offers a generalized, statistically comprehensive solution to scalar extraction's over-simplification of vector trajectories, thereby making it useful for objectively guiding analyses of complex biomechanical systems.

Pataky|Todd C|TC|
Robinson|Mark A|MA|
Vanrenterghem|Jos|J|

Biomechanics
Statistical parametric mapping
Random field theory
Multivariate statistics


Response of male reproductive function to environmental heavy metal pollution in a free-living passerine bird, Passer montanus.

Abstract: Heavy metals affect male reproductive function by impairing reproductive organs, disturbing reproductive hormone levels or directly affecting sperm quality. However, little attention has been given to the effect of environmental heavy metals on reproductive function in wild male birds. The present study investigated the alterations of reproductive function in male tree sparrows (Passer montanus) exposed to environments contaminated by heavy metals in terms of testis parameters, reproductive hormone levels and sperm movement characteristics. Two plots, Baiyin (BY, mainly polluted by copper, zinc, lead and cadmium) and Liujiaxia (LJX, a relatively unpolluted area) were selected as sampling sites. The results showed that tree sparrows from BY (1) accumulated higher levels of cadmium in the testes, (2) showed lower superoxide dismutase (SOD) activity and malondialdehyde level, with higher total antioxidant capacity and apoptosis level in the testes, (3) showed higher plasma levels of estrogen, follicle stimulating hormone and luteinizing hormone (LH), and (4) had better sperm movement performance. Additionally, we found that testis size, SOD activity in testes and LH levels were decisive factors in sperm movement performance in tree sparrows. Heavy metal concentrations in testes negatively correlated with testis size, SOD activity in testes, and estrogen levels in tree sparrows. The present study indicates that heavy metals accumulating in testes of tree sparrows adversely affected some key indicators of male reproductive function. However, testicular function, reproductive hormone levels and sperm quality showed adaptive responses that tended to partially compensate for the negative effects in the heavy metal polluted area. This study further indicated that the regulation of testicular function and reproductive hormone levels was the main factor for better sperm quality in tree sparrows exposed to environments contaminated by heavy metals.

Yang|Ying|Y| Zhang|Wenya|W| Wang|Shengnan|S| Zhang|Huijie|H| Zhang|Yingmei|Y|

Environmental heavy metals
Reproductive hormone
Sperm quality
Male tree sparrow
Testis parameters


Heterotopic Ossification following Suprapatellar Intramedullary Nailing.

Abstract:
Introduction
Tibial shaft fractures are common fractures seen in trauma and orthopedic practice today. The majority of these fractures are treated with intramedullary nailing (IMN) which is rapidly becoming a gold standard. The procedure itself is performed by either a suprapatellar approach or infrapatellar approach. Suprapatellar approach is gaining popularity due to relative ease of insertion, decreased associated risk of anterior knee pain, and more accurate reduction. We report a case of heterotopic ossification noted in the knee following IMN of tibia performed using a suprapatellar approach.

Case Report
A 27-year-old male, having sustained a left, Gustilo IIIB tibial shaft fracture following a motor vehicle accident, underwent a reamed intramedullary nail fixation performed through a suprapatellar approach. Two months later, he presented with intra-articular heterotopic ossification which was limiting his knee movement. He then underwent arthroscopic removal of the bony fragments which resolved his symptoms.

Conclusion
An extensive search of literature did not yield any reported incidence of heterotopic ossification associated with IMN performed through a suprapatellar approach. We present this case report to raise awareness that although IMN through a suprapatellar approach is a safe approach, it does have associated risk of heterotopic ossification which needs to be included in the consent process.

Rehman|Nasiur|N| Trompeter|Alex|A| Guthrie|Hugo|H| Goddard|Martin|M|

Heterotopic ossification
Intramedullary nailing
Tibial shaft fracture
Suprapatellar approach


A Novel Health Indicator Based on Cointegration for Rolling Bearings' Run-To-Failure Process.

Abstract: The extraction of rolling bearings' degradation features has been developed for decades. However, the degradation features always present different trends of different run-to-failure data. To find a consistent indicator of different data will be helpful to establish a general model and explore the nature of bearings' degradation. In this study, we have found there is a trend of similarity between the energy and complexity features. By using the cointegration test, we found the two kinds of features exhibit a certain degree of cointegration relationship. Fused by the cointegration method, we have obtained a novel health indicator which can depict different run-to-failure data in a unified way. The difference between the energy features and complexity features can be explained by the novel health indicator. The indicator has "two-stage" characters. The first stage is the zero-line stage and the second stage is the quickly raise stage, which presents like an exponential function. It is easy to think about using an exponential degradation model to model this indicator. Next, we have compared the indicator to root mean square (RMS) by using the exponential degradation model. It shows that the indicator is more suitable for the exponential degradation model. In this paper, we used eleven run-to-failure data to verify the generality and "two-stage" characters of the proposed indicator. The result shows that the novel indicator is general and effective and that it will promote the development of bearings' prognostics.

rolling bearings
generalization
degradation model
vibration signal


What is the proper way to apply the multiple comparison test?

Abstract: Multiple comparisons tests (MCTs) are performed several times on the mean of experimental conditions. When the null hypothesis is rejected in a validation, MCTs are performed when certain experimental conditions have a statistically significant mean difference or there is a specific aspect between the group means. A problem occurs if the error rate increases while multiple hypothesis tests are performed simultaneously. Consequently, in an MCT, it is necessary to control the error rate to an appropriate level. In this paper, we discuss how to test multiple hypotheses simultaneously while limiting type I error rate, which is caused by α inflation. To choose the appropriate test, we must maintain the balance between statistical power and type I error rate. If the test is too conservative, a type I error is not likely to occur. However, concurrently, the test may have insufficient power resulted in increased probability of type II error occurrence. Most researchers may hope to find the best way of adjusting the type I error rate to discriminate the real differences between observed data without wasting too much statistical power. It is expected that this paper will help researchers understand the differences between MCTs and apply them appropriately.

Multiple comparison
Statistics
Alpha inflation
Analysis of variance
Bonferroni
Dunnett
Scheffé


Prenatal vitamin D levels and child wheeze and asthma.

Abstract: Background: Maternal vitamin D status during pregnancy may influence lung development and risk of childhood wheeze and asthma. We investigated the relationship between prenatal vitamin D and child asthma in a racially diverse cohort with a high burden of vitamin D insufficiency and child asthma.Materials and methods: We included mother-child dyads in the prenatal Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort (2006-2011, Shelby County, Tennessee). Maternal plasma vitamin D [25(OH)D] was measured from second trimester (n = 1091) and delivery specimens (n = 907). At age 4-6 years, we obtained parent report of current child wheeze (symptoms within the past 12 months) and asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used multivariable logistic regression to assess associations of 25(OH)D and child wheeze/asthma, including an interaction term for maternal race.Results: Median second trimester 25(OH)D levels were 25.1 and 19.1 ng/ml in White (n = 366) and Black women (N = 725), respectively. We detected significant interactions by maternal race for second-trimester plasma 25(OH)D and child current wheeze (p = .014) and asthma (p = .011). Odds of current wheeze and asthma decreased with increasing 25(OH)D in dyads with White mothers and increased in dyads with Black mothers, e.g. adjusted odds ratio (95% confidence interval) for asthma: 0.63 (0.36-1.09) and 1.41 (1.01-1.97) per interquartile range (15-27 ng/ml 25[OH]D) increase, respectively. At delivery, protective associations in White dyads were attenuated.Conclusion: We detected effect modification by maternal race in associations between prenatal 25(OH)D and child wheeze/asthma. Further research in racially diverse populations is needed.

Adams|Sarah N|SN|
Adgent|Margaret A|MA|
Gebretsadik|Tebeb|T|
Hartman|Terryl J|TJ|
Vereen|Shanda|S|
Ortiz|Christina|C|
Tylavsky|Frances A|FA|
Carroll|Kecia N|KN|

D011297:Prenatal Exposure Delayed Effects

vitamin D
wheezing
asthma
25(OH)D
race
prenatal programing


Infiltrating immune cells in the kidney in salt-sensitive hypertension and renal injury.

Abstract: The importance of the immune system in hypertension, vascular disease, and renal disease has been appreciated for over 50 years. Recent experimental advances have led to a greater appreciation of the mechanisms whereby inflammation and immunity participate in cardiovascular disease. In addition to the experimental data, multiple studies in patients have demonstrated a strong correlation between the observations made in animals and humans. Of great interest is the development of salt-sensitive hypertension in humans with the concurrent increase in albumin excretion rate. Experiments in our laboratory have demonstrated that feeding a high-NaCl diet to Dahl salt-sensitive (SS) rats results in a significant infiltration of T lymphocytes into the kidney that is accompanied by the development of hypertension and renal disease. The development of disease in the Dahl SS closely resembles observations made in patients; studies were therefore performed to investigate the pathological role of infiltrating immune cells in the kidney in hypertension and renal disease. Pharmacological and genetic studies indicate that immune cell infiltration into the kidney amplifies the disease process. Further experiments demonstrated that infiltrating T cells may accentuate the Dahl SS phenotype by increasing intrarenal ANG II and oxidative stress. From these and other data, we hypothesize that infiltrating immune cells, which surround the blood vessels and tubules, can serve as a local source of bioactive molecules which mediate vascular constriction, increase tubular sodium reabsorption, and mediate the retention of sodium and water to amplify sodium-sensitive hypertension. Multiple experiments remain to be performed to refine and clarify this hypothesis.


Turning the page on 2021: an eventful year for the British Journal of Anaesthesia.

Abstract: The British Journal of Anaesthesia (BJA) had an eventful 2021, following what was a cataclysmic 2020 for the whole world. Despite the tragic challenges of multiple waves of the COVID-19 pandemic and the unparalleled burdens this created for everyone working in anaesthesia and critical care, the BJA underwent a major transformation during 2021. The BJA strongly supported research and education relevant to the pandemic, and to the broader missions of anaesthesia, critical, and pain medicine. Innovations to the BJA in 2021 included a special section on COVID-19 and the Anaesthetist; a new open access journal in the BJA stable; creation of a new social media editor position; new webinar and author interview series; transition to a new manuscript management system; and a move away from paper to electronic publication.

anaesthesia
COVID-19
open access
social media
medical journal
sustainability


Patterns of disease control and survival in patients with melanoma brain metastases undergoing immune-checkpoint blockade.

Abstract:
OBJECTIVES
Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival.

METHODS
A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included. Patient records were searched for the development of brain metastases. Demographic and clinical data of all patients were collected retrospectively.

RESULTS
We identified 177 patients with MBM who received ICBs (ipilimumab, nivolumab, pembrolizumab). Patients with and without brain metastases received similar ICB regimens. Prognosis was inferior in patients with brain metastases; patients with >1 brain metastasis showed even poorer survival. For extracranial (ec) metastases, disease control was associated with improved survival. However, when comparing patients with intracranial (ic) disease control during immunotherapy to patients with ic disease progression, no difference in OS could be observed.

CONCLUSIONS
In our study, ec disease control was the dominant predictive factor for OS in both patients with or without melanoma brain metastases. These data indicate that clinical trials in melanoma patients with brain metastases should address end-points such as symptom control, quality of life or OS in addition to ic response rates.

Milsch|Laura|L| Gesierich|Anja|A| Kreft|Sophia|S| Livingstone|Elisabeth|E| Zimmer|Lisa|L| Goebeler|Matthias|M| Schadendorf|Dirk|D| Schilling|Bastian|B|

D061025:Costimulatory and Inhibitory T-Cell Receptors

Melanoma
Brain metastases
Immune-checkpoint blockade


Pain and other symptoms in cancer survivors.

Abstract: Pain is common in cancer survivors. Long-term pain, often of neuropathic origin, is common after operations, radiotherapy, and chemotherapy. Pain and other concomitant symptoms and side effects should be assessed with validated and reliable scales and questionnaires. Cancer survivors with severe pain should be seen by a pain specialist. Multidisciplinary rehabilitation and individualized pain management may improve quality of life in cancer survivors. Four case reports are presented to illustrate this.

pain
cancer
survivors
neuropathic
concomitant symptoms


Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

Abstract: This review discusses completed phase II randomized clinical trials with high-quality published results for compounds that demonstrate effects on nonalcoholic steatohepatitis histology (obeticholic acid, elafibranor, and liraglutide). The authors also review the available preliminary data on cenicriviroc and selonsertib, with or without simtuzumab's phase II studies. Finally, the authors briefly discuss compounds that have been tested but did not achieve the primary end point of histologic improvement and appeared in high-quality published articles (cysteamine bitartrate and long-chain polyunsaturated fatty acids).

D017322:Clinical Trials, Phase II as Topic

D065626:Non-alcoholic Fatty Liver Disease

D016032:Randomized Controlled Trials as Topic

Obeticholic acid
Elafibranor
Liraglutide
Cenicriviroc
Selonsertib
NAFLD
NASH


The effect of HDL cholesterol on blood and plasma viscosity in healthy subjects.

Abstract:
OBJECTIVE
The influence of lipids on blood and plasma viscosity has not been fully elucidated. In this study we evaluated the contribution of HDL cholesterol to blood and plasma viscosity, in healthy subjects.

METHODS
One hundred and forty-four (80 males and 64 females) subjects were enrolled among free-living participants to a cardiovascular disease screening. Exclusion criteria were: diabetes, elevated triglycerides, elevated LDL cholesterol, smoking and drug use. Blood lipids were measured by routine methods. Blood and plasma viscosity were measured by a cone-plate viscometer (Wells-Brookfield DV-III, Stoughton, U.S.A.). Subjects were divided in two groups: at low (<50 mg/dl) and high HDL cholesterol (>50 mg/dl).

RESULTS
Blood and plasma viscosity were similar in subjects at low and high HDL cholesterol. In univariate analysis none of the lipid variables was significantly correlated with blood and/or plasma viscosity. In multivariate analysis only LDL cholesterol was marginally associated with blood viscosity.

CONCLUSION
HDL cholesterol does not influence blood and plasma viscosity in healthy normolipidemic subjects. LDL cholesterol is marginally associated with blood viscosity.

Carallo|Claudio|C|
Irace|Concetta|C|
De Franceschi|Maria S|MS|
Esposito|Teresa|T|
Tripolino|Cesare|C|
Scavelli|Faustina|F|
Merante|Valentina|V|
Gnasso|Agostino|A|

HDL
plasma viscosity
LDL
Blood viscosity
hyperlipidemia


The role of beaded activated carbon's surface oxygen groups on irreversible adsorption of organic vapors.

Abstract: The objective of this study is to determine the contribution of surface oxygen groups to irreversible adsorption (aka heel formation) during cyclic adsorption/regeneration of organic vapors commonly found in industrial systems, including vehicle-painting operations. For this purpose, three chemically modified activated carbon samples, including two oxygen-deficient (hydrogen-treated and heat-treated) and one oxygen-rich sample (nitric acid-treated) were prepared. The samples were tested for 5 adsorption/regeneration cycles using a mixture of nine organic compounds. For the different samples, mass balance cumulative heel was 14 and 20% higher for oxygen functionalized and hydrogen-treated samples, respectively, relative to heat-treated sample. Thermal analysis results showed heel formation due to physisorption for the oxygen-deficient samples, and weakened physisorption combined with chemisorption for the oxygen-rich sample. Chemisorption was attributed to consumption of surface oxygen groups by adsorbed species, resulting in formation of high boiling point oxidation byproducts or bonding between the adsorbates and the surface groups. Pore size distributions indicated that different pore sizes contributed to heel formation - narrow micropores (<7Å) in the oxygen-deficient samples and midsize micropores (7-12Å) in the oxygen-rich sample. The results from this study help explain the heel formation mechanism and how it relates to chemically tailored adsorbent materials.

Jahandar Lashaki|Masoud|M|
Atkinson|John D|JD|
Hashisho|Zaher|Z|
Phillips|John H|JH|
Anderson|James E|JE|
Nichols|Mark|M|

Activated carbon
Surface oxygen group
Irreversible adsorption
Cyclic adsorption/regeneration
Volatile organic compound


Injectable methylcellulose hydrogel containing silver oxide nanoparticles for burn wound healing.

Abstract: A thermo-sensitive methylcellulose (MC) hydrogel containing silver oxide nanoparticles (NPs) was prepared via one-pot synthesis in which a silver acetate precursor salt (CH3COOAg) induces a salt-out effect in the MC solution. The silver oxide NPs were synthesized in situ from Ag+ ions during the MC hydrogelation, and the residual CH3COO- ions decreased the gelation temperature of the MC solution through the salt-out effect. The gelation behavior of the MC solution varied according to the CH3COOAg content and was monitored. Also, the formation and structure of the silver oxide NPs in the MC hydrogel was confirmed. From the results, silver oxide NPs was successfully incorporated in MC hydrogels, simultaneously, acetate ion which was counter ion of Ag was affected gelation behavior of Ag. Finally, the antimicrobial activity and wound healing effect was examined using the shaking flask method and burn wound test, respectively. The MC hydrogel with silver oxide NPs showed excellent antimicrobial activity and burn wound healing. Therefore, this thermo-responsive MC hydrogel has great potential as an injectable hydrogel for wound regeneration.

Kim|Min Hee|MH|
Park|Hanna|H|
Nam|Hyung Chan|HC|
Park|Se Ra|SR|
Jung|Ju-Young|JY|
Park|Won Ho|WH|

Methylcellulose
Silver oxide nanoparticles
Wound healing
In situ formation
Thermo-sensitive hydrogel


To the fast calculation of the solvation free energy. Combining expanded ensembles with L2MC.

Abstract: A more efficient version of the Expanded Ensembles method for calculation of free energy in molecular-mechanical simulations is proposed. The method is based on the Horowitz L2MC approach to accelerate movement along the "alchemical" coordinate. It is possible to achieve the same efficiency of the algorithm both with the optimal number of "windows" and with a larger number of them compared to the original algorithm. Since the optimal number of windows is unknown a priory, the proposed algorithm is more robust than the traditional one. We can choose the number of windows in excess and do not worry about the loss of efficiency. We illustrate the method's efficiency with the computation of the hydration free energies of pyridine and water.

free energy
expanded ensembles
algorithm
Monte Carlo
molecular dynamics


Effect of vitamin A supplementation on iron status in humans: A systematic review and meta-analysis.

Abstract: Anemia is a worldwide public health problem that can be related to many causes, including vitamin A deficiency. The aim of this study was to assess and estimate the effect of vitamin A supplementation (VAS) on iron status biomarkers and anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed, Scopus and Web of Science, were searched for clinical trials and cohort studies that investigated the effect of vitamin A supplementation alone on iron status and anemia, without time-restriction. The search yielded 23 eligible studies, 21 clinical trials and 2 cohort studies, with children, teenagers, pregnant or lactating women. The meta-analysis of the clinical trials showed that VAS reduces the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated group, independent of the life stage. VAS did not alter the prevalence of iron deficiency among the clinical trials conducted with children and teenagers (RR 0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum ferritin levels was observed in trials conducted with pregnant and lactating women (WMD 6.61 μg/L; 95% CI 6.00 to 7.21 μg/L; p < 0.001). Therefore, vitamin A supplementation alone may reduce the risk of anemia, by improving hemoglobin and ferritin levels in individuals with low serum retinol levels.

da Cunha|Marcela de Sá Barreto|MSB|http://orcid.org/0000-0002-1388-033X

vitamin A supplementation
supplementation
iron status
Review
anemia
iron deficiency


Observer roles that optimise learning in healthcare simulation education: a systematic review.

Abstract:
Background
Simulation is widely used in health professional education. The convention that learners are actively involved may limit access to this educational method. The aim of this paper is to review the evidence for learning methods that employ directed observation as an alternative to hands-on participation in scenario-based simulation training. We sought studies that included either direct comparison of the learning outcomes of observers with those of active participants or identified factors important for the engagement of observers in simulation. We systematically searched health and education databases and reviewed journals and bibliographies for studies investigating or referring to observer roles in simulation using mannequins, simulated patients or role play simulations. A quality framework was used to rate the studies.

Methods
We sought studies that included either direct comparison of the learning outcomes of observers with those of active participants or identified factors important for the engagement of observers in simulation. We systematically searched health and education databases and reviewed journals and bibliographies for studies investigating or referring to observer roles in simulation using mannequins, simulated patients or role play simulations. A quality framework was used to rate the studies.

Results
Nine studies met the inclusion criteria. Five studies suggest learning outcomes in observer roles are as good or better than hands-on roles in simulation. Four studies document learner satisfaction in observer roles. Five studies used a tool to guide observers. Eight studies involved observers in the debrief. Learning and satisfaction in observer roles is closely associated with observer tools, learner engagement, role clarity and contribution to the debrief. Learners that valued observer roles described them as affording an overarching view, examination of details from a distance, and meaningful feedback during the debrief. Learners who did not value observer roles described them as passive, or boring when compared to hands-on engagement in the simulation encounter.

Conclusions
Learning outcomes and role satisfaction for observers is improved through learner engagement and the use of observer tools. The value that students attach to observer roles appear contingent on role clarity, use of observer tools, and inclusion of observers' perspectives in the debrief.

O'Regan|Stephanie|S| Molloy|Elizabeth|E| Watterson|Leonie|L| Nestel|Debra|D|

Observer
Observer role
Simulation
Directed observer
Vicarious learning


Factors associated with secondary traumatic stress and burnout in neonatal care staff: A cross-sectional survey study.

Abstract:
INTRODUCTION
High rates of secondary traumatic stress and burnout have been found across nursing populations. However, few studies have focused on neonatal staff.

OBJECTIVE
The objectives of this article are to explore the prevalence and severity of secondary traumatic stress (STS) and burnout in neonatal staff, and identify risk factors and protective factors for STS and burnout within this population with the aim of informing future staff support.

METHODS
A quantitative, cross-sectional study using a survey design was conducted; 246 neonatal staff reported measures of STS, burnout, self-compassion and satisfaction with ward climate.

RESULTS
Neonatal staff reported high rates of moderate-severe STS and burnout. STS and burnout were negatively associated with self-compassion and satisfaction with ward climate, suggesting them to be protective factors against STS and burnout. STS was found to be a risk factor for burnout and vice versa.

CONCLUSION
Interventions that increase understanding of STS and burnout, nurture self-compassion, provide support and enhance stress management could help mitigate the impact of STS and burnout amongst neonatal staff.

D002055:Burnout, Professional
D000068376:Compassion Fatigue
D003430:Cross-Sectional Studies
D004645:Empathy
D006801:Humans
D007231:Infant, Newborn
D011795:Surveys and Questionnaires

الإنهاك، أخصائي الرعاية الصحية، حديث الولادة، إجهاد الصدمة الثانوي

二次的心的外傷性ストレス

P P P P U P U U U U U U M M U U U U U U U U U


Perspective on the clone library method for infectious diseases.

Abstract: Recently, culture-independent molecular methods, such as DNA sequencing techniques targeting the 16S-ribosomal RNA (rRNA) gene and/or other housekeeping genes with Sanger method-based technologies, next generation sequencing (NGS), and metagenomic analysis, have been developed for detecting microorganisms in the human body; these can provide information on microbiomes of samples from individuals with or without infectious diseases. Determining the bacterial species is crucial in identifying causative bacteria of upper and lower respiratory tract infections, especially for Streptococcus species, but NGS analysis is often not precise enough to identify bacteria at the species level. This review briefly introduces previous observations of the microbiome of samples from various respiratory and other infections assessed using the clone library method with Sanger sequencing of the 16S-rRNA gene. On analysis of 16S-rRNA gene-sequence data of bronchoalveolar lavage fluid obtained from pneumonia lesions in patients with bacterial pneumonia and lung abscess, anaerobes are often detected in non-elderly patients with pneumonia, and the detection rate of Staphylococcus aureus in patients with hospital-acquired pneumonia is lower than that previously reported. Analysis of pleural effusion samples from patients with pleurisy indicated a more important role of anaerobes than previous believed. The other topics reviewed include microbiomes of nontuberculous mycobacteriosis and lower respiratory tract infections in children with permanent tracheostomy due to neuromuscular disorders, in nasal discharge, in bacterial vaginosis, in the intracystic fluid of postoperative maxillary cyst, and in bacterial conjunctivitis; urine microbiota in urethritis; fecal microbiota; and newly detected infectious organisms in the human respiratory tract.

Clone library method
Microbiome
16S ribosomal RNA
Respiratory infection


A Compound Heterozygous Mutation of Lipase Maturation Factor 1 is Responsible for Hypertriglyceridemia of a Patient.

Abstract:
AIM
Dyslipidemia is the most common lipid metabolism disorder in humans, and its etiology remains elusive. Hypertriglyceridemia (HTG) is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. Previous studies have demonstrated that mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1(LMF1), and glycerol-3 phosphate dehydrogenase 1 (GPD1) are responsible for HTG by using genomic microarrays and next-generation sequencing. The aim of this study was to identify genetic lesions in patients with HTG.

METHOD
Our study included a family of seven members from Jiangsu province across three generations. The proband was diagnosed with severe HTG, with a plasma triglyceride level of 38.70 mmol/L. Polymerase chain reaction (PCR) and Sanger sequencing were performed to explore the possible causative gene mutations for this patient. Furthermore, we measured the post-heparin LPL and hepatic lipase (HL) activities using an antiserum inhibition method.

RESULTS
A compound heterozygous mutation in the LMF1 gene (c.257C＞T/p.P86L and c.1184C＞T/p.T395I) was identified and co-segregated with the affected patient in this family. Both mutations were predicted to be deleterious by three bioinformatics programs (Polymorphism Phenotyping-2, Sorting Intolerant From Tolerant, and MutationTaster). The levels of the plasma post-heparin LPL and HL activities in the proband (57 and 177 mU/mL) were reduced to 24% and 75%, respectively, compared with those assayed in the control subject with normal plasma triglycerides.

CONCLUSION
A compound heterozygous mutation of LMF1 was identified in the presenting patient with severe HTG. These findings expand on the spectrum of LMF1 mutations and contribute to the genetic diagnosis and counseling of families with HTG.

Liu|Yihui|Y| Xu|Jiang|J| Tao|Wanyun|W| Yu|Rong|R| Zhang|Xinjiang|X|

Hypertriglyceridemia
HTG
LMF1
Compound mutation


Curing neurophobia in medical schools: evidence-based strategies.

Abstract: Medical students often perceive neurology as the most difficult medical specialty. This perception is described as 'neurophobia' in the medical literature. Several studies have cited poor teaching, complex examination, and separation of basic and clinical sciences as major factors in the development of neurophobia. These negative perceptions can have serious implications, such as decreasing the students' desire to consider neurology as a future career and increasing referrals from other specialists to avoid dealing with neurological conditions. Faced with increasing demands of healthcare systems and the global burden of neurological conditions, there is a rising need for further research and innovative strategies to improve students' perceptions of clinical neurology. This review discusses evidence-based recommendations and educational interventions to cure neurophobia in medical education.

Abushouk|Abdelrahman Ibrahim|AI|
Duc|Nguyen Minh|NM|

neurophobia
medical students
neurology
education
solutions


Spatial function of the oxidative DNA damage response in radiation induced bystander effects in intra- and inter-system of Caenorhabditis elegans.

Abstract: Though the signaling events involved in radiation induced bystander effects (RIBE) have been investigated both in vitro and in vivo, the spatial function of these communications, especially the related signaling pathways, is not fully elucidated. In the current study, significant increases of DNA damage were clearly observed in C. elegans germline upon irradiation to both intra-system of posterior pharynx and inter-system of vulva, in which more severe damage, even to F1 generation worms, was shown for vulva irradiation. Spatial function assay indicated the DDR key components of mrt-2/hus-1/cep-1/ced-4 were indispensable in germ cells for both sites irradiation, while those components in somatic cells were either not (cep-1/ced-4) or partially (mrt-2/hus-1) required to promote apoptosis. Moreover, production of reactive oxygen species (ROS) indicated by the superoxide dismutase expression and the unfolded protein response of the mitochondria was found systemically involved in the initiation of these processes for both two site irradiation. These results will give a better understanding of the RIBE mechanisms in vivo, and invaluable to assess the clinical relevance to radiotherapy.

Li|Qingqing|Q| Shi|Jue|J| Chen|Lianyun|L| Zhan|Furu|F| Yuan|Hang|H| Wang|Jun|J| Xu|An|A| Wu|Lijun|L|

RIBE
C. elegans
DDR
ROS
tissue specific RNAi


Comparison of enzyme-linked immunosorbent assay systems using rift valley fever virus nucleocapsid protein and inactivated virus as antigens.

Abstract:
BACKGROUND
Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis. To detect RVF virus (RVFV) infection, indirect immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme linked immunosorbent assays (ELISAs) which utilize recombinant RVFV nucleocapsid (RVFV-N) protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection.

METHODS
RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006-2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems.

RESULTS
rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established. Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%.

CONCLUSIONS
Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis. Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries.

Yu|Fuxun|F|0000-0001-8804-2755
Adungo|Ferdinard|F|
Konongoi|Samson Limbaso|SL|
Inoue|Shingo|S|
Sang|Rosemary|R|
Ashur|Salame|S|
Kwallah|Allan Ole|AO|
Uchida|Leo|L|
Buerano|Corazon C|CC|
Mwau|Matilu|M|
Zha|Yan|Y|
Nie|Yingjie|Y|
Morita|Kouichi|K|

Nucleocapsid protein
RVFV
Expression
IgG sandwich ELISA
IgM capture ELISA


Utility of Radial Probe Endobronchial Ultrasound-Guided Transbronchial Lung Biopsy in Diffuse Lung Lesions.

Abstract:
BACKGROUND
Radial probe endobronchial ultrasound (R-EBUS) is widely used for diagnosing peripheral pulmonary lesions. However, the utility of R-EBUS-guided transbronchial lung biopsy (TBLB) for diffuse lung lesions (DLLs) remains unknown. We designed this study to evaluate the utility of R-EBUS-guided TBLB in DLLs.

METHODS
This retrospective study enrolled patients admitted from January 2016 to November 2017 who underwent TBLB for DLLs. The R-EBUS-guided TBLB and blind TBLB groups were compared. DLL was defined as any lung disorder that involved more than one segment of the lung. In both the groups, fluoroscopy and guided sheath were not used during TBLB.

RESULTS
A total of 127 patients underwent TBLB for DLLs (67 patients in the R-EBUS-guided TBLB group and 60 in the blind TBLB group). There were no differences in age, sex, and comorbid illnesses between the two groups. Furthermore, there was no difference in the TBLB diagnostic yield of the two groups (p=0.660) although more samples were collected from the R-EBUS-guided TBLB group (p=0.003). Procedure time was significantly longer in the R-EBUS-guided TBLB group than in the blind TBLB group (p<0.001). Thus, incidence of pneumothorax was significantly lower in the R-EBUS-guided TBLB group than in the blind TBLB group (p=0.032).

CONCLUSION
Diagnostic yield in DLLs did not differ between the R-EBUS-guided TBLB and blind TBLB groups. Findings show that R-EBUS-guided TBLB in DLLs may reduce risk of pneumothorax.

Biopsy Pneumothorax Bronchoscopy Ultrasonography


Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry.

Abstract:
BACKGROUND
A shift from a standard to a personalized prophylaxis has been increasingly adopted in patients with severe haemophilia A (SHA). This approach has raised the likelihood of a significant variability in the prophylactic approaches and the relative Factor VIII (FVIII) consumptions. The aim of our study was to assess the treatment variability of SHA patients without inhibitors and on prophylaxis regimen in Italy.

MATERIAL AND METHODS
Data reported in the National Registry of Congenital Coagulopathies (NRCC) were analysed to assess treatment distribution within SHA patients without inhibitors, focussing on FVIII consumption in 2017, associated with prophylaxis regimen. The analysis was stratified based on age groups and Italian regions to describe the variability of FVIII consumption in Italy.

RESULTS
In 2017, the Registry reported the therapeutic plans of 1068 SHA patients without inhibitors on prophylaxis. The mean (95% CI) individual consumption ranges from 123 127 IU (99 736-146 518) in the age group 0-6 years to 345 000 IU (336 000-354 000) in the age group >20 years. A significant FVIII consumption variability was identified within the adult population. Regions with less than 50 patients reported the higher variability in mean FVIII consumption per patient-year within the different age groups. Similar difference in FVIII consumption variability was reported also in the age groups comparing "low," "middle" and "high" patient volume regions.

DISCUSSION
A reliable estimation of FVIII consumption for patients' treatment is necessary to manage and plan the appropriate budget and keep treatment's costs affordable. However, without the implementation of a methodology aiming to assess the overall value produced by these FVIII consumptions, the scenario will keep driven by FVIII consumptions, its costs and the budget available. An effort by haemophilic community, haemophilia treatment centres and institutions is required to develop and share this cultural shift in improving haemophilia management and assessment.

Haemophilia A
Prophylaxis
FVIII consumption
Personalized medicine


The treatment of veterinary antibiotics in swine wastewater by biodegradation and Fenton-like oxidation.

Abstract: Elevated concentrations and potential toxicities of antibiotics in swine wastewater prompt the exploration of effective treatment methods to minimize the amount of antibiotics released to the environment. This study examined the technical and economic feasibility of using combined biodegradation and advanced oxidation processes for swine wastewater treatment. The up-flow anaerobic sludge blanket (UASB) reactor was mainly responsible for conventional organic pollutant removal (i.e., a COD removal rate of 75%). The subsequent sequencing batch reactor (SBR) under a short sludge retention time (SRT) of 3 days removed the biodegradable antibiotics by >95%, and hindered the nitrification process which retained NH4+-N and reduced operational cost (since the treated wastewater was intended to be used as a farm fertilizer). The subsequent Fenton-like oxidation (with the aid of citric acid) achieved an average antibiotic removal efficiency of 74% under optimal reaction conditions: H2O2 dosage of 2.9 mM, [Fe2+]: [H2O2] = 1:3, [CA]: [Fe2+] = 1:1, pH 6.0, reaction time of 120 min. The superior treatment efficiency of Fenton-like compared to the conventional Fenton (74% vs 5%) under nearly neutral conditions was attributed to the chelating role of citric acid with Fe2+/Fe3+, leading to the enhanced Fe2+/Fe3+ solubility and therefore the promotion of ∙OH formation. This hybrid process of anaerobic and aerobic biodegradation and Fenton-like oxidation should be suitable and cost-effective for the treatment of wastewater with abundant conventional pollutants and persistent emerging trace contaminants.

Qian|Mengcheng|M| Yang|Linyan|L| Chen|Xingkui|X| Li|Kai|K| Xue|Weibo|W| Li|Yejin|Y| Zhao|Huihui|H| Cao|Guomin|G| Guan|Xiaohong|X| Shen|Genxiang|G|

D000818:Animals
D000900:Anti-Bacterial Agents
D001673:Biodegradation, Environmental
D006861:Hydrogen Peroxide
D010084:Oxidation-Reduction
D013552:Swine
D014865:Waste Disposal, Fluid
D062065:Waste Water
D014874:Water Pollutants, Chemical

Antibiotics
Swine wastewater
Biodegradation
Fenton-like
Citric acid
Short SRT


The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: A randomized placebo-controlled study.

Abstract:
BACKGROUND
Low dietary calcium is associated with the hypertensive disorders of pregnancy, and evidence suggests that the risks associated with pre-eclampsia are reduced by calcium supplementation. In the general (non-pregnant) population, low dietary calcium intake is associated with hypertension with inconsistent evidence that calcium supplementation may reduce blood pressure. Women with pre-eclampsia are also at risk of hypertension later in life. An exploratory sub-study among early participants enrolled in the WHO long-term calcium supplementation in women at high risk of pre-eclampsia (CAP) study reported a trend to more blood pressure reduction with calcium in non-pregnant women with previous severe as opposed to non-severe pre-eclampsia. The current study reports the effects of low-dose calcium supplementation in non-pregnant women in the complete trial cohort.

METHODS
The CAP Study was a multi-country randomized, double-blind placebo-controlled clinical trial to test the hypothesis that calcium deficiency may play a role in the genesis of pre-eclampsia in early pregnancy. From 2011 to 2016, non-pregnant women who had pre-eclampsia or eclampsia in their most recent pregnancy were randomized to receive either 500 mg/day elemental calcium or placebo. In this sub-study we compared the change in blood pressure from baseline to the 12-week visit between participants receiving calcium versus placebo for those not pregnant at the 12-week visit.

RESULTS
Of 1355 women randomized, 810 attended a 12-week visit without being pregnant, of whom 791 had blood pressure measurements available for both baseline and 12-week visits. There was a greater reduction in blood pressure in the calcium group compared with the placebo group for systolic pressure (difference 3.1 mmHg, 95% CI 0.8 to 5.4) and mean arterial pressure (MAP) (difference 2.0 mmHg, 95% CI 0.1 to 3.8). The difference in diastolic blood pressure reduction (1.4 mmHg, 95% CI -0.5 to 3.3) was not statistically significant (p = 0.140). For women with previous pre-eclampsia with severe features (n = 447), there was significantly greater reduction in blood pressure in the calcium than the placebo group (difference for systolic 4.0, 95% CI 0.7 to 7.3; diastolic 3.0, 95% CI 0.5 to 5.5 and mean arterial pressure 3.3, 95% CI 0.8 to 5.9 mmHg). For women with previous pre-eclampsia without severe features (n = 344), there were no significant differences between calcium and placebo groups. ANOVA analysis found no statistically significant interaction between previous pre-eclampsia severity and treatment, for systolic (p = 0.372), diastolic (p = 0.063) or mean blood pressure (p = 0.103).

CONCLUSIONS
Low-dose calcium supplementation significantly reduced systolic and mean arterial pressure in non-pregnant women with previous pre-eclampsia. We did not confirm a greater calcium effect in women with previous pre-eclampsia with severe versus non-severe features. The effect of low-dose calcium is of importance since even modest blood pressure reductions at a population level may have important benefits in terms of reduced major complications of hypertension. This study adds to the mounting evidence of health benefits which could be achieved for populations with low dietary calcium through strategies to increase calcium intake, particularly among women at high risk due to previous pre-eclampsia.

CLINICAL TRIAL REGISTRATION
The trial was registered with the Pan-African Clinical Trials Registry, registration number PACTR201105000267371 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=267).

Hofmeyr|G Justus|GJ|
Seuc|Armando|A|
Betrán|Ana Pilar|AP|
Cormick|Gabriela|G|
Singata|Mandisa|M|
Fawcus|Sue|S|
Mose|Simpiwe|S|
Frank|Karlyn|K|
Hall|David|D|
Belizán|José|J|
Roberts|James M|JM|
Magee|Laura A|LA|
von Dadelszen|Peter|P|
|||

Calcium
Supplementation
Blood pressure
Hypertension
Preeclampsia


Relationship with children and the psychological well-being of the elderly in Indonesia.

Abstract:
Objective
Many older adults in Indonesia live with their children. This study examined the relationship between the quality of the relationship that elderly parents may have with their children living with them and any effects on psychological well-being.

Methods
Relationship quality encompasses positive and negative aspects. This study employed convenience sampling and to reach 102 elderly participants. A measure of positive and negative social exchanges was used to measure the relationship between elderly parents and their children. Ryff's Scale of Psychological Well-Being was utilized to measure the psychological well-being of the subjects. We used descriptive statistics, Pearson correlation coefficient, an independent t-test, and one-way analysis of variance (ANOVA) to assess the statistics produced.

Results
The primary results showed no correlation between the positive qualities of the relationship and psychological well-being (r = 0.092, p > 0.01). However, the negative qualities of the relationship were negatively correlated with psychological well-being (r = -0.335, p < 0.01).

Conclusion
Thus, negative qualities of relationships with their children were found to be more impactful on psychological well-being than positive qualities in elderly parents who maintain coresidence with their children. This means that the greater the lack of sympathy, intrusion, failure to provide needed help, and rejection/neglect from the child, the worse the psychological well-being of the elderly parent.

psychological well-being
Coresidence
parent–child relationship


Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms' Tumor 1 in Patients with Advanced Colorectal Cancer.

Abstract: Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms' tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1-2 × 10⁷ DCs with 1-2 KE of OK-432 (streptococcal preparation) in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assays. WT1 expression with human leukocyte antigen (HLA)-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

Shimodaira|Shigetaka|S| Sano|Kenji|K| Hirabayashi|Koichi|K| Koya|Terutsugu|T| Higuchi|Yumiko|Y| Mizuno|Yumiko|Y| Yamaoka|Naoko|N| Yuzawa|Miki|M| Kobayashi|Takashi|T| Ito|Kenichi|K| Koizumi|Tomonobu|T|

colorectal cancer
immunohistochemistry
tetramer analysis
Wilms’ tumor 1
dendritic cell vaccines
enzyme-linked immunosorbent spot assay


Phylogenetic identification of marine bacteria isolated from deep-sea sediments of the eastern South Atlantic Ocean.

Abstract: The deep-sea environments of the South Atlantic Ocean are less studied in comparison to the North Atlantic and Pacific Oceans. With the aim of identifying the deep-sea bacteria in this less known ocean, 70 strains were isolated from eight sediment samples (depth range between 1905 to 5560 m) collected in the eastern part of the South Atlantic, from the equatorial region to the Cape Abyssal Plain, using three different culture media. The strains were classified into three phylogenetic groups, Gammaproteobacteria, Firmicutes and Actinobacteria, by the analysis of 16s rRNA gene sequences. Gammaproteobacteria and Firmicutes were the most frequently identified groups, with Halomonas the most frequent genus among the strains. Microorganisms belonging to Firmicutes were the only ones observed in all samples. Sixteen of the 41 identified operational taxonomic units probably represent new species. The presence of potentially new species reinforces the need for new studies in the deep-sea environments of the South Atlantic.

da Silva|Marcus Adonai Castro|MA|
Cavalett|Angélica|A|
Spinner|Ananda|A|
Rosa|Daniele Cristina|DC|
Jasper|Regina Beltrame|RB|
Quecine|Maria Carolina|MC|
Bonatelli|Maria Letícia|ML|
Pizzirani-Kleiner|Aline|A|
Corção|Gertrudes|G|
Lima|André Oliveira de Souza|AO|

Phylogenetic identification
Deep-sea sediments
South Atlantic Ocean
Halomonas
Cultivable bacteria


One-Dimensional Moiré Superlattices and Flat Bands in Collapsed Chiral Carbon Nanotubes.

Abstract: We demonstrate that one-dimensional moiré patterns, analogous to those found in twisted bilayer graphene, can arise in collapsed chiral carbon nanotubes. Resorting to a combination of approaches, namely, molecular dynamics to obtain the relaxed geometries and tight-binding calculations validated against ab initio modeling, we find that magic angle physics occur in collapsed carbon nanotubes. Velocity reduction, flat bands, and localization in AA regions with diminishing moiré angle are revealed, showing a magic angle close to 1°. From the spatial extension of the AA regions and the width of the flat bands, we estimate that many-body interactions in these systems are stronger than in twisted bilayer graphene. Chiral collapsed carbon nanotubes stand out as promising candidates to explore many-body effects and superconductivity in low dimensions, emerging as the one-dimensional analogues of twisted bilayer graphene.

moiré superlattices
flat bands
chiral carbon nanotubes
twisted bilayer graphene


Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation.

Abstract: We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers. The diagnosis of 5-α-reductase-2 deficiency syndrome was first hypothesized on clinical grounds and then confirmed by molecular analysis. Direct sequencing analysis of the SRD5A2 gene revealed in five patients a novel homozygous frame-shift mutation (c.453delC) and in two related patients a previous reported missense mutation. The presence of the same mutation in unrelated patients of the same population suggests a possible founder effect. This report brings the 5-α-reductase-2 deficiency syndrome to the attention of clinical geneticists and child surgeons and discusses the appropriate clinical and surgical strategies for treating these patients.

Di Marco|Chiara|C|
Bulotta|Anna Lavinia|AL|
Varetti|Concetta|C|
Dosa|Laura|L|
Michelucci|Angela|A|
Baldinotti|Fulvia|F|
Meucci|Daniela|D|
Castagnini|Cinzia|C|
Lo Rizzo|Caterina|C|
Di Maggio|Giovanni|G|
Simi|Paolo|P|
Mari|Francesca|F|
Bertelloni|Silvano|S|
Renieri|Alessandra|A|
Messina|Mario|M|

SRD5A2
SRD5A2 gene
Founder effect
46,XY DSD
5-α-reductase type 2
AR
DHT
DSD
MRI
Phenotypic variability
SRD
Steroid 5-α-reductase-2 deficiency
T
androgen receptor
dihydrotestosterone
hCG
human chorionic gonadotropin
magnetic resonance imaging
sex development disorder
steroid 5-α-reductase deficiency
testosterone

P P P M M U U U U U U M U U U U U U U M U


Diagnostic efficacy of PET and PET/CT for recurrent lung cancer: a meta-analysis.

Abstract:
BACKGROUND
Lung cancer is one of the most common malignant tumors in the world, and is the leading cause of cancer-related mortality. Although there are no conclusive data to support the survival benefits of early detection or early treatment for recurrence, an early and accurate diagnosis of recurrence is critical to optimize therapy.

PURPOSE
To compare the diagnostic value of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) using fluorine-18 deoxyglucose (18FDG) with conventional imaging techniques (CITs) for the detection of lung cancer recurrence.

MATERIAL AND METHODS
A meta-analysis was performed, with systematic searches conducted using PubMed and EMBASE databases (up to 31 December 2011). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) values were calculated for 1035 patients reported in 13 articles. Summary receiver-operating characteristic curves (SROC) were also generated.

RESULTS
The pooled sensitivity (95% CI) for PET, PET/CT, and CITs were 0.94 (0.91-0.97), 0.90 (0.84-0.95), and 0.78 (0.71-0.84), respectively. The pooled specificity (95% CI) for PET, PET/CT, and CITs were 0.84 (0.77-0.89), 0.90 (0.87-0.93), and 0.80 (0.75-0.84), respectively. Regarding sensitivity, lower values were associated with CITs than PET (P = 0.000) and PET/CT (P = 0.005), and there was no significant difference between PET/CT and PET (P = 0.102). Regarding specificity, values for PET/CT and PET were significantly higher than for CITs (both P = 0.000), and there was no significant difference between PET/CT and PET (P = 0.273). In the SROC curves, a better diagnostic accuracy was associated with PET/CT than PET and CITs.

CONCLUSION
PET/CT and PET were found to be superior modalities for the detection of recurrent lung cancer, and PET/CT was superior to PET.

He|Yan-Qi|YQ| Gong|Han-Lin|HL| Deng|Yi-Fu|YF| Li|Wei-Min|WM|

D003287:Contrast Media
D006801:Humans
D008175:Lung Neoplasms
D064847:Multimodal Imaging
D009364:Neoplasm Recurrence, Local
D049268:Positron-Emission Tomography
D019275:Radiopharmaceuticals
D012680:Sensitivity and Specificity
D014057:Tomography, X-Ray Computed

PET
recurrence
lung cancer
meta-analysis
diagnosis
integrated PET/CT


Electrical Signaling, Photosynthesis and Systemic Acquired Acclimation.

Abstract: Electrical signaling in higher plants is required for the appropriate intracellular and intercellular communication, stress responses, growth and development. In this review, we have focus on recent findings regarding the electrical signaling, as a major regulator of the systemic acquired acclimation (SAA) and the systemic acquired resistance (SAR). The electric signaling on its own cannot confer the required specificity of information to trigger SAA and SAR, therefore, we have also discussed a number of other mechanisms and signaling systems that can operate in combination with electric signaling. We have emphasized the interrelation between ionic mechanism of electrical activity and regulation of photosynthesis, which is intrinsic to a proper induction of SAA and SAR. In a special way, we have summarized the role of non-photochemical quenching and its regulator PsbS. Further, redox status of the cell, calcium and hydraulic waves, hormonal circuits and stomatal aperture regulation have been considered as components of the signaling. Finally, a model of light-dependent mechanisms of electrical signaling propagation has been presented together with the systemic regulation of light-responsive genes encoding both, ion channels and proteins involved in regulation of their activity. Due to space limitations, we have not addressed many other important aspects of hormonal and ROS signaling, which were presented in a number of recent excellent reviews.

electrical signal
photosynthesis
PsbS overexpression and npq-4
ion channel activity
plasma membrane