bluuebunny/crossref_metadata_2025 huggingface dataset:
Cow’s milk allergy prevention and treatment by heat‐treated whey—A study in Brown Norway rats
Authors: Graversen Katrine B. , Ballegaard Anne‐Sofie R. , Kræmer Louise H. , Hornslet Sofie E. , Sørensen Laila V. , Christoffersen Heidi F. , Jacobsen Lotte N. , Untersmayr Eva , Smit Joost J. , Bøgh Katrine L.
Published: February 2020

Background

Food processing, including heat‐treatment, can affect protein structure and stability, and consequently affect protein immunogenicity and allergenicity. A few studies have shown that structural changes induced by heat‐treatment impact the intestinal protein uptake and suggest this as a contributing factor for altered allergenicity.

Objective

To investigate the impact of heat‐treatment of a whey‐based protein product on allergenicity and tolerogenicity as well as on intestinal uptake in various animal models.

Methods

Immunogenicity and sensitizing capacity of the heat‐treated whey product were compared to that of the unmodified product by intraperitoneal and oral exposure studies, while tolerogenic properties were assessed by oral primary prevention and desensitization studies in high‐IgE responder Brown Norway rats.

Results

Heat‐treatment of whey induced partial protein denaturation and aggregation, which reduced the intraperitoneal sensitizing capacity but not immunogenicity. In contrast, heat‐treatment did not influence the oral sensitizing capacity, but the heat‐treated whey showed a significantly reduced eliciting capacity compared to unmodified whey upon oral challenge. Heat‐treatment did not reduce the tolerogenic properties of whey, as both products were equally good at preventing sensitization in naïve rats as well as desensitizing already sensitized rats. Results from inhibitory ELISA and immunoblots with sera from sensitized rats demonstrated that heat‐treatment caused an altered protein and epitope reactivity. Protein uptake studies showed that heat‐treatment changed the route of uptake with less whey being absorbed through the epithelium but more into the Peyer's patches.

Conclusion and Clinical Relevance

These results support the notion that the physicochemical features of proteins affect their route of uptake and that the route of uptake may affect the protein allergenicity. Furthermore, the study highlights the potential for heat‐treatment in the production of efficient and safe cow's milk protein‐based products for prevention and treatment of cow's milk allergy.
Attachment security differs by later autism spectrum disorder: A prospective study
Authors: Martin Katherine B. , Haltigan John D. , Ekas Naomi , Prince Emily B. , Messinger Daniel S.
Published: February 2020

Although difficulties with social relationships are key to autism spectrum disorder (ASD), no previous study has examined infant attachment security prior to ASD diagnosis. We prospectively assessed attachment security at 15 months in high‐risk infants with later ASD (high‐risk/ASD, n = 16), high‐risk infants without later ASD (high‐risk/no‐ASD, n = 40), and low‐risk infants without later ASD (low‐risk/no‐ASD, n = 39) using the Strange Situation Procedure. High‐risk/ASD infants were disproportionately more likely to be classified as insecure (versus secure) and more likely to be classified as insecure‐resistant (versus secure or avoidant) than high‐risk/no‐ASD and low‐risk/no‐ASD infants. High‐risk infants with insecure‐resistant attachments were over nine times more likely to receive an ASD diagnosis than high‐risk infants with secure attachments. Insecure‐resistant attachment in high‐risk infants suggests a propensity toward negative affect with the parent in conditions of stress. Insecure‐resistant attachment may prove useful as a potential early index of propensity toward ASD diagnosis in high‐risk siblings, while insecure‐resistant attachment in the context of emergent autism may contribute to difficulties experienced by children with ASD and their families.
Global work index correlates with established prognostic parameters of heart failure
Authors: Hedwig Felix , Soltani Sajjad , Stein Julia , Schoenrath Felix , Potapov Evgenij , Knosalla Christoph , Falk Volkmar , Knebel Fabian , Knierim Jan
Published: February 2020

Aim

Identification of patients with heart failure and a poor prognosis is paramount to ensure timely and adequate treatment. We investigated the relationship between the new measures of noninvasive pressure‐strain analysis, such as the global work index (GWI), and established prognostic parameters of echocardiography, cardiopulmonary exercise test (CPX), and N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP).

Methods and Results

We retrospectively analyzed data of 51 patients with heart failure. Echocardiography and CPX were performed, and NT‐pro‐BNP was determined. Patients with a GWI < 500 mm Hg% had a mean LVEDV of 286.1 ± 100.8 mL, an LVEF of 21.3 ± 5.7%, and a stroke volume (SV) of 45.9 ± 11.6 mL, and patients with a GWI > 1000 mm Hg% had an LVEDV of 147.9 ± 39.6 mL, an LVEF of 42.6 ± 4.8%, and a SV of 70.9 ± 14.3 mL. The GWI also showed a significant correlation with peak oxygen consumption (peak VO2) (r = .521; P < .001) and with NT‐pro‐BNP (r = .635; P < .001). Patients with a GWI of <500 mm Hg% had a significantly higher NT‐pro‐BNP (median 2415 pg/mL [IQR 1071, 5933]) and a lower peak VO2 (9.5 mL/min/kg ± 2.6) compared to patients with a GWI of >1000 mm Hg% (NT‐pro‐BNP median 253 pg/mL [IQR 150, 549]; peak VO2 15.6 ± 4.2 mL/min/kg).

Conclusion

GWI correlates with known prognostic markers of heart failure. A GWI of <500 mm Hg% was a predictor of severely impaired ejection fraction, very low exercise capacity, and strongly elevated NT‐pro‐BNP, indicating a poor prognosis.
Bicuspid aortic valve area in normal heart
Authors: Katz Moshe , Mazin Israel , Kuperstein Rafael , Beigel Roy , Vaturi Ori , Feinberg Micha S , Raanani Ehud , Ben Zekry Sagit
Published: February 2020

Introduction

Bicuspid aortic valve (BAV) is a common congenital valve abnormality. There are no data in the literature regarding the range of aortic valve area (AVA) in normal functioning BAV. We aimed to evaluate the normal range of BAV area and to compare it to subjects with tricuspid aortic valve (TAV).

Methods

Bicuspid aortic valve subjects were identified from Sheba medical center echocardiographic database and were compared with TAV subjects. Inclusion criteria were normal tissue leaflets appearance and normal functioning valve in the presence of normal echocardiogram. Echocardiographic data, patients hemodynamics, and size were collected. AVA was measured with both planimetry and the continuity equation.

Results

Fifty BAV and 50 control subjects were studied (37 men, age 40 ± 13 years). All studies were performed with normal hemodynamics. Fusion between the coronary leaflets was the most common morphology (82%), followed by fusion between the right coronary leaflet with the noncoronary leaflet (18%). The left ventricular outflow tract (LVOT) diameter in BAV group was significantly larger (2.3 ± 0.3 cm vs 2.1 ± 0.2; P < .001). The BAV group presented with a larger AVA planimetry (3.8 ± 0.9 vs 3.3 ± 0.6; P < .001). However, measuring AVA using continuity equation has shown no differences between groups. If using the principles of coefficient of contraction, it seems that measuring AVA by planimetry overestimates the real anatomic AVA.

Conclusion

This data provide normal values for echocardiographically determined AVA in BAV subjects. This population was characterized by large LVOT diameter and large AVA. The larger AVA measured with the planimetry emphasizes the limitation of this method in BAV population.
Effect of temperature on the walking behaviour of an egg parasitoid: disentangling kinetic response from integrated response
Authors: Augustin Julie , Boivin Guy , Brodeur Jacques , Bourgeois Gaétan
Published: February 2020

1. This study investigated the effect of temperatures ranging from 10.8 to 34.2 °C on seven walking parameters of an egg parasitoid, Anaphes listronoti. Those responses were compared with a theoretical kinetic model in order to disentangle the kinetic response of the insect from its integrated response.

2. Walking speed increased continuously with temperature, but walking distance and duration were maximised between 25 and 30 °C, and decreased at higher and lower temperatures. At the lowest temperature, females unexpectedly walked a greater distance and for a longer duration in comparison with intermediate temperatures.

3. The number of walking bouts followed the same polynomial trend as walking distance and duration, with a maximum between 30 and 35 °C. The duration of walking bouts was maximised at 20 °C and decreased at lower and higher temperatures, whereas the duration of resting bouts linearly decreased with increasing temperature. There was no effect of temperature on the turning rate of females.

4. For A. listronoti, walking speed and duration of resting bouts followed the kinetic response, but the other behavioural components did not, especially at the lowest and highest temperatures. Walking distance and duration were higher than expected under the kinetic response at 10.8 °C and lower than expected at 34.2 °C. This pattern suggests an integrated response combining behavioural escape from adverse temperature and energy saving.

5. This detailed analysis of the walking behaviour of A. listronoti illustrates the complexity of insect behavioural responses to temperature and the difficulty involved in assessing underlying mechanisms.
Development of a model to predict electroencephalographic seizures in critically ill children
Authors: Fung France W. , Jacobwitz Marin , Parikh Darshana S. , Vala Lisa , Donnelly Maureen , Fan Jiaxin , Xiao Rui , Topjian Alexis A. , Abend Nicholas S.
Published: February 2020

Objective

Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but ES identification with continuous electroencephalography (EEG) monitoring (CEEG) is resource‐intense. We aimed to develop an ES prediction model that would enable clinicians to stratify patients by ES risk and optimally target limited CEEG resources. We aimed to determine whether incorporating data from a screening EEG yielded better performance characteristics than models using clinical variables alone.

Methods

We performed a prospective observational study of 719 consecutive critically ill children with acute encephalopathy undergoing CEEG in the pediatric intensive care unit of a quaternary care institution between April 2017 and February 2019. We identified clinical and EEG risk factors for ES. We evaluated model performance with area under the receiver‐operating characteristic (ROC) curve (AUC), validated the optimal model with the highest AUC using a fivefold cross‐validation, and calculated test characteristics emphasizing high sensitivity. We applied the optimal operating slope strategy to identify the optimal cutoff to define whether a patient should undergo CEEG.

Results

The incidence of ES was 26%. Variables associated with increased ES risk included age, acute encephalopathy category, clinical seizures prior to CEEG initiation, EEG background, and epileptiform discharges. Combining clinical and EEG variables yielded better model performance (AUC 0.80) than clinical variables alone (AUC 0.69; P < .01). At a 0.10 cutoff selected to emphasize sensitivity, the optimal model had a sensitivity of 92%, specificity of 37%, positive predictive value of 34%, and negative predictive value of 93%. If applied, the model would limit 29% of patients from undergoing CEEG while failing to identify 8% of patients with ES.

Significance

A model employing readily available clinical and EEG variables could target limited CEEG resources to critically ill children at highest risk for ES, making CEEG‐guided management a more viable neuroprotective strategy.
Measuring the impact of age, gender and dementia on communication‐robot interventions in residential care homes
Authors: Obayashi Kazuko , Kodate Naonori , Masuyama Shigeru
Published: February 2020

Aim

The primary aim of this study was to examine the impact of age, gender and the stage of dementia on the results of an assistive technology intervention that make use of communication robots (com‐robots). The intervention was designed to improve the social participation and interactions of nursing home residents. While our previous study showed that the overall effects of com‐robot intervention were positive, it was unknown what impact age, gender and the stage of dementia of participants had on such an intervention.

Methods

This was a non‐randomized, multicenter quasi‐experimental intervention study conducted in residential care homes in Japan. Two types of com‐robots were introduced for 8 weeks after baseline evaluation. The World Health Organization's ICF was used for evaluating any changes present after the 8‐week intervention. In total, 78 residents (68 women, 10 men, 86.5 ± 7.7 years old) participated in the study. The Degree of Daily Life Independence Score for People with Dementia (DDLIS‐PD) was employed for measuring the stage of dementia.

Results

The results showed that the older participants aged ≥80 benefited more from the intervention than the younger cohort did (P < 0.05). A greater improvement was shown among those with a more advanced stage of dementia than those at a less advanced stage (P < 0.05), when using DDLIS‐PD.

Conclusions

The overall findings support the use of com‐robots within the context of a care team for older people with moderate dementia, and those who are aged ≥80 years. Geriatr Gerontol Int 2020; 20: 373–378.
Maternal stress suppresses cell proliferation in the forebrain of zebrafish larvae
Authors: Higuchi Maiko
Published: February 2020

Exposure to early life stress (ELS) can increase vulnerability to various psychiatric disorders. Although ELS has been shown to alter structure and functions of the hippocampus, amygdala and prefrontal cortex in the adult mammalian brain, it remains largely unclear whether ELS also affects embryonic or early‐stage brain development. In this study, I investigated the effects of a maternal stress (maternal starvation for 4 days) of adult zebrafish on offspring's larval brain development. Although maternal starvation did not largely affect proliferation rate in the midbrain and hindbrain, it significantly decreased that in the forebrain of larvae at 5 days post‐fertilization (dpf). I also found that embryos at 10 hr post‐fertilization (hpf) born from a starved mother showed elevated cortisol levels compared to those born from a control mother. Furthermore, cortisol treatment was sufficient to decrease proliferating cells in the forebrain of 5 dpf larvae. Our findings thus demonstrate for the first time that maternal starvation induces neurodevelopmental changes in the forebrain of zebrafish larvae and points to a possible role of maternal cortisol in mediating this effect of maternal stress to offsprings.
Paediatric obesity treatment during 14 years in Sweden: Lessons from the Swedish Childhood Obesity Treatment Register—BORIS
Authors: Hagman Emilia , Danielsson Pernilla , Lindberg Louise , Marcus Claude ,   the BORIS Steering Committee
Published: February 2020

Background

Treatment of paediatric obesity has been offered customarily and free of charge for more than 15 years in Sweden. The Swedish Childhood Obesity Treatment Register (BORIS) is a prospective register of children and adolescents undergoing obesity treatment.

Objectives

To investigate how patient characteristics and treatment efficacy has changed over 14 years on a national scale.

Methods

All subjects in BORIS with data from 2004 until 2017 were included, n = 21 499. Outcomes were age and BMI SDS at treatment initiation, dropout rates and treatment outcome up to 3 years after treatment initiation.

Results

Age and BMI SDS at treatment initiation have decreased during the years (both P < .0001). Of the patients who started treatment before 2009, more than 80% had at least 1‐year follow‐up. This number has decreased to about 60% in 2017. Since 2004, no trend in improvement of treatment results was observed when evaluating change in either BMI SDS or proportion of obesity remission. There was no difference between the sexes.

Conclusion

Although children in Sweden receive treatment at an earlier age, which is a major determinant of treatment success, and at a lower degree of obesity at treatment initiation, the effect of childhood obesity treatment on standard anthropometric measures has not improved over the investigated years.
Clinical guidelines for the diagnosis and treatment of lower urinary tract dysfunction in patients with spinal cord injury
Authors: Sekido Noritoshi , Igawa Yasuhiko , Kakizaki Hidehiro , Kitta Takeya , Sengoku Atsushi , Takahashi Satoru , Takahashi Ryosuke , Tanaka Katsuyuki , Namima Takashige , Honda Masashi , Mitsui Takahiko , Yamanishi Tomonori , Watanabe Toyohiko
Published: February 2020

The present article is an abridged English translation of the Japanese clinical guidelines for the diagnosis and treatment of lower urinary tract dysfunction in patients with spinal cord injury updated as of July 2019. The patients are adult spinal cord injured patients with lower urinary tract dysfunction; special consideration of pediatric and elderly populations is presented separately. The target audience is healthcare providers who are engaged in the medical care of patients with spinal cord injury. The mandatory assessment includes medical history, physical examination, frequency‐volume chart, urinalysis, blood chemistry, transabdominal ultrasonography, measurement of post‐void residual urine, uroflowmetry and video‐urodynamic study. Optional assessments include questionnaires on the quality of life, renal scintigraphy and cystourethroscopy. The presence or absence of risk factors for renal damage and symptomatic urinary tract infection affects urinary management, as well as pharmacological treatments. Further treatment is recommended if the maximum conservative treatment fails to improve or prevent renal damage and symptomatic urinary tract infection. In addition, management of urinary incontinence should be considered individually in patients with risk factors for urinary incontinence and decreased quality of life.
Proteolytic activity, degradation, and dissolution of primary and permanent teeth
Authors: Scheffel Debora Lopes Salles , Cury Jaime Aparecido , Tenuta Livia Maria Andaló , Scheffel Régis Henke , Perez Cristina , Soares Diana Gabriela , Basso Fernanda Gonçalves , Costa Carlos Alberto de Souza , Pashley David Henry , Hebling Josimeri
Published: February 2020

Background

Primary and permanent teeth composition may influence dissolution and degradation rates.

Aim

To compare the dissolution and degradation of primary and permanent teeth.

Design

Enamel and dentin powders were obtained from primary molars and premolars and incubated within different pH buffers. Calcium and inorganic phosphate release was quantified in the buffers by atomic absorption and light spectrophotometry. A colorimetric assay was used to assess the MMP activity of primary dentin (PrD) and permanent dentin (PeD). Collagen degradation was assessed by dry mass loss, change in elastic modulus (E), and ICTP and CTX release. Data were submitted to ANOVA and Tukey's tests (α = 0.05).

Results

Similar dissolution was found between PrD and PeD after 256 hours. At pH 4.5, enamel released more minerals than dentin whereas at pH 5.5 the inverse result was observed. MMP activity was similar for both substrates. PrD showed higher dry mass loss after 1 week. In general, greater reduction in E was recorded for PrD. Higher quantities of ICTP and CTX were released from PrD after 1 week.

Conclusions

Primary and permanent teeth presented similar demineralization rates. Collagen degradation, however, was faster and more substantial for PrD.
Review of tellurite glasses purification issues for mid‐IR optical fiber applications
Authors: Désévédavy Frédéric , Strutynski Clément , Lemière Arnaud , Mathey Pierre , Gadret Grégory , Jules Jean‐Charles , Kibler Bertrand , Smektala Frédéric
Published: February 2020

We reviewed the tellurite glass purification studies performed over the last 20 years, in particular dealing with the mid‐infrared (mid‐IR) transmission performances. Best results are obtained under rich O2 atmosphere with platinum crucibles although Gibbs energy calculations show that other crucibles material are possible such as gold or alumina. From the point of view of the thermodynamics of involved oxidation reactions only, we identified the suitable conditions based on Gibbs energy calculations to be a synthesis temperature set above 900 K and a O2 pressure around 105 Pa. The performances of the different purification techniques were also compared. Finally, we analyzed the tellurite fibers recently optimized for mid‐IR which present low attenuation up to 4 µm allowing supercontinuum generation up to 5 µm.
Sympathy as knowledge of the other in need: An investigation into the roles of need for closure and the moral foundations on sympathy toward immigrants
Authors: Baldner Conrad , Di Santo Daniela , Talamo Alessandra , Pierro Antonio
Published: February 2020

Although sympathy is a powerful other‐focused motivation, not all individuals will experience sympathy when it is appropriate. Immigrants, as a disadvantaged out‐group, are especially in need of sympathy and, given the tensions of the immigration debate, are at‐risk for low sympathy. Indeed, past research has found that sympathy is less likely to be experienced toward disliked out‐groups. In the current research, we investigated the role of need for closure (NFC), or the general desire for epistemic certainty, on the experience of sympathy toward immigrants in Italy, a nation where the immigration debate is becoming increasingly fractious. Consistent with past research on the roles of NFC and the binding moral foundations (i.e., a concern for the well‐being of groups) on prejudice toward out‐groups, we propose that individuals with a high NFC, and who endorsed the binding moral foundations (i.e., a concern for the well‐being of groups), would be particularly likely to have decreased sympathy toward immigrants in Italy. In line with past research and our hypotheses, in three studies we found that the binding foundations mediated the NFC effect on decreased sympathy toward immigrants in Italy. Conceptually, these individuals can strongly adopt traditional cultural norms as a way to acquire stable knowledge; this can make sympathy toward immigrants less likely, as they both stand outside “traditional” morality, as well can threaten the stability of natives’ knowledge.
Reentrant para‐Hisian ventricular tachycardia eliminated from the noncoronary cusp: Importance of regional anatomy for vantage‐point ablation
Authors: Nishimura Takuro , Kannan Arun , Tung Roderick
Published: February 2020

We present a rare case of reentrant ventricular tachycardia proven by entrainment maneuvers that was successfully ablated from the noncoronary cusp. The case highlights regional anatomy, pacing maneuvers with multi‐modality images from fluoroscopy, intracardiac echo, and electroanatomical mapping.
hsa_circ_0000092 promotes hepatocellular carcinoma progression through up‐regulating HN1 expression by binding to microRNA‐338‐3p
Authors: Pu Jian , Wang Jianchu , Li Wenchuan , Lu Yuan , Wu Xianjian , Long Xidai , Luo Chunying , Wei Huamei
Published: February 2020

Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR‐338‐3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR‐338‐3p and HN1 was determined by dual‐luciferase reporter, RNA pull‐down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR‐338‐3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR‐338‐3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR‐338‐3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR‐338‐3p to up‐regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR‐338‐3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down‐regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR‐338‐3p‐mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC.
Chronic nodular prurigo: clinical profile and burden. A European cross‐sectional study
Authors: Pereira M.P. , Hoffmann V. , Weisshaar E. , Wallengren J. , Halvorsen J.A. , Garcovich S. , Misery L. , Brenaut E. , Savk E. , Potekaev N. , Lvov A. , Bobko S. , Szepietowski J.C. , Reich A. , Bozek A. , Legat F.J. , Metz M. , Streit M. , Serra‐Baldrich E. , Gonçalo M. , Storck M. , Greiwe I. , Nau T. , Steinke S. , Dugas M. , Ständer S. , Zeidler C. ,   the EPP Consensus Conference Participants 2017
Published: February 2020

Background

Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regarding its clinical characteristics and impact on quality of life is still lacking.

Objectives

Aim of this pan‐European multicentre cross‐sectional study was to establish the clinical profile of CNPG, including its associated burden.

Methods

Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co‐morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed.

Results

A total of 509 patients (210 male, median age: 64 years [52; 72]) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%).

Conclusions

This multicentre cross‐sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.
Carbon dioxide as a novel indicator for bacterial growth in milk
Authors: Cranz Séverine , Valster Sanne , Vulders Roland , Dellimore Kiran
Published: February 2020

Human milk spoils due to bacterial, yeast, or mold contamination. Current domestic methods of assessing milk spoilage are subjective or rely on time and temperature‐based guidelines. A key unmet food safety need remains the objective assessment of human milk spoilage. Experiments were conducted using a simplified human milk spoilage model based on goat's milk as a human milk surrogate, spiked with a single bacterial strain (Staphylococcus epidermidis), in which pH and carbon dioxide (CO2) concentration were measured along with bacteria count over 160 hr. Bacteria count correlated highly with CO2 but not with pH. A 0.21% CO2 concentration threshold could be defined for milk spoilage (correlating to a bacteria count threshold of 105 CFU/ml), with sensitivity and specificity above 84%. These findings suggest that CO2 measurement is a promising method to detect S. epidermidis growth in milk which merits further investigation for the objective and quantitative assessment of milk spoilage.
Comment on: Can Hearing Aids Delay Time to Diagnosis of Dementia, Depression, or Falls in Older Adults?
Authors: Abiola Aanuoluwa O. , Berry Sarah D. , Kim Dae Hyun
Published: February 2020

See the Reply by Mahmoudi et al.
The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges
Authors: Maskos Uwe
Published: February 2020

Nicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome‐Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of ‘positive allosteric modulators’ (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.

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Option Profit and Loss Attribution and Pricing: A New Framework
Authors: CARR PETER , WU LIUREN
Published: February 2020

This paper develops a new top‐down valuation framework that links the pricing of an option investment to its daily profit and loss attribution. The framework uses the Black‐Merton‐Scholes option pricing formula to attribute the short‐term option investment risk to variation in the underlying security price and the option's implied volatility. Taking risk‐neutral expectation and demanding no dynamic arbitrage result in a pricing relation that links an option's fair implied volatility level to the underlying volatility level with corrections for the implied volatility's own expected direction of movement, its variance, and its covariance with the underlying security return.
Optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait
Authors: Nunchai Chanhathai , Sirichotiyakul Supatra , Tongsong Theera
Published: February 2020

Aim

To identify the optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait.

Methods

The database of pregnant women who attended antenatal care clinic at Department of Obstetrics and Gynecology, Chiang Mai University during January 1st, 2015 to December 31st, 2017 was accessed and reviewed. A total of 1264 cases who had MCV ≤80 fL and met the inclusion criteria were enrolled to the study. Cases with hemoglobin level ≤10.0 gm/dL, iron deficiency anemia, chronic medical diseases and other types of thalassemia trait except alpha‐thalassemia 1 trait were excluded.

Results

After exclusion, 438 cases were available for analysis. Of them, 139 were alpha‐thalassemia 1 trait. Based on the receiver operating characteristic curves, the best cutoff value of MCV for screening of alpha‐thalassemia 1 trait was ≤76.15 fL, giving 100% sensitivity, and 60.9% specificity with the area under curve of 0.925. Compared to the conventional cutoff (≤80 fL), the new cutoff gave much less false positive tests (117 vs 299 cases), whereas capability to detect alpha‐thalassemia 1 trait was the same.

Conclusion

With the new MCV cutoff (≤76.15 fL) as a secondary cutoff for screening alpha‐thalassemia 1 carrier, a substantial number of positive cases requiring DNA analysis could be avoided without compromising the detection efficacy.
Future time perspective and affect in daily life across adulthood and old age: Findings from two micro‐longitudinal studies
Authors: Katana Marko , Hill Patrick L. , Allemand Mathias
Published: February 2020

Objective

Future time perspective (FTP) refers to individuals’ perceptions of the future as either open‐ended or limited. Despite well‐documented individual differences in FTP across the adult life span, little is known about short‐term variations of FTP within individuals and the within‐person associations between FTP and affective experiences.

Method

Study 1 used data from a daily diary study over 10 days (N = 564) with a wide age range across the adult life span (M = 48.30). Study 2 used data from an ambulatory assessment study over 10 days (N = 136) obtained from healthy older adults (M = 70.45).

Results

Findings suggest that 10% to 20% of the total variance in FTP was within‐person and 29% to 62% of the total variance in affect was within‐person. Multilevel modeling showed that occasions with a more open‐ended FTP were occasions with more positive affect, energetic arousal, calmness, and positive valence, and less negative affect. Age moderated the within‐person associations between FTP and positive and negative affect as well as energetic arousal, with weaker associations for older adults.

Conclusions

This research demonstrates the importance of looking at both within‐person and between‐person differences with respect to the associations between FTP and affective experiences in daily life.
Current management of non‐alcoholic steatohepatitis
Authors: Muthiah Mark D. , Sanyal Arun J.
Published: February 2020

Non‐alcoholic steatohepatitis (NASH) is the most common cause of liver disease in Western populations, and its prevalence is increasing rapidly. It is part of a multisystem disease affecting other organs such as the kidneys, heart and blood vessels, and is closely associated with the components of the metabolic syndrome. Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients. The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis. In this mini‐review, we discuss the currently available treatment options for NASH, as well as those in late‐stage clinical trials. We discuss the challenges of managing these patients with a limited number of approved therapies, as well as managing advanced‐stage patients with NASH and cirrhosis. We also discuss the specific management of comorbidities in NASH patients, in particular diabetes, hypertension, dyslipidaemia and cardiovascular diseases. Finally, we present the screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in these patients.
The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management
Authors: Berná Genoveva , Romero‐Gomez Manuel
Published: February 2020

A healthy diet together with physical activity could induce weight loss and control the progression of non‐alcoholic fatty liver disease (NAFLD). However, the composition of diet has not been clearly established. Macronutrients such as saturated fatty acids (SFA), trans‐fats, simple sugars and animal proteins have a harmful effect on the liver. On the other hand, monounsaturated fats (MUFAs), polyunsaturated (PUFAs) omega‐3‐fats, plant‐based proteins and dietary fibres are considered to be beneficial to the liver. The impact of specific micronutrients is less well‐known. Nutrients are part of the food we eat. Food makes up our meals, which compose our dietary patterns. Non‐alcoholic fatty liver disease patients usually follow Western diets which are rich in soda, frozen junk food, juice, red meat, lard, processed meats, whole fat dairy foods, fatty snack foods, take‐away foods, cakes and biscuits and poor in cereals, whole grains, fruit, vegetables, extra virgin olive oil (EVOO) and fish. On the other hand, the Mediterranean diet (MD) is beneficial for NAFLD even when it is iso‐caloric or there are no changes in body weight. A new approach, called ‘nutritional geometry’ considers the importance of integrating nutrition, animals and the environment. The goal of this approach is to combine nutrients and foods in a model to understand how food components interact to regulate the properties of diets affecting health and disease. The use of algorithms developed by artificial intelligence (AI) to create a personalized diet for patients can provide customized nutritional counselling to prevent and treat NAFLD.
Natural history of NASH and HCC
Authors: Negro Francesco
Published: February 2020

Widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non‐cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin‐like phospholipase domain‐containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini‐review will discuss the contribution of these factors to NAFLD‐associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.
Can we cure hepatitis B virus with novel direct‐acting antivirals?
Authors: Martinez Maria G. , Villeret François , Testoni Barbara , Zoulim Fabien
Published: February 2020

Current treatments against chronic hepatitis B (CHB) include pegylated interferon alpha (Peg‐IFNα) and nucleos(t)ide analogs (NAs), the latter targeting the viral retrotranscriptase, thus inhibiting de novo viral production. Although these therapies control infection and improve the patient's quality of life, they do not cure HBV‐infected hepatocytes. A complete HBV cure is currently not possible because of the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Current efforts are focused on achieving a functional cure, defined by the loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA levels in serum, and on exploring novel targets and molecules that are in the pipeline for early clinical trials. The likelihood of achieving a long‐lasting functional cure, with no rebound after therapy cessation, is higher using combination therapies targeting different steps in the hepatitis B virus (HBV) replication cycle. Novel treatments and their combinations are discussed for their potential to cure HBV infection, as well as exciting new technologies that could directly target cccDNA and cure without killing the infected cells.
Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues
Authors: Buti Maria , Roade Luisa , Riveiro‐Barciela Mar , Esteban Rafael
Published: February 2020

Management of chronic hepatitis B (CHB) is still considered a challenge in clinical practice. Patients must be carefully evaluated before starting therapy. This includes virology and laboratory assessments, an estimation of fibrosis by invasive and/or noninvasive methods, and an estimation of the risk of hepatocellular carcinoma (HCC). Nucleos(t)ide analogues (NAs) with a high barrier to resistance (tenofovir disoproxil fumarate [TDF], entecavir [ETV] and tenofovir alafenamide [TAF]) are the most frequently used treatments because of their good long‐term efficacy and tolerability. None of these options has been shown to be more effective than the other, but certain factors should be considered when selecting the best therapy for specific populations. Most patients achieve a virological and biochemical response to these agents, with a low rate of emerging resistance during long‐term treatment. However, the rate of hepatitis B surface antigen (HBsAg) loss is low and in most cases NAs therapy is lifelong. Safety concerns for long‐term NA use have become a priority in the management of CHB, in particular, the risk of impaired kidney function and bone marrow density loss described with TDF regimens. The risk of HCC is not completely eliminated by NAs. Thus, patients at higher risk should be identified and provided with appropriate surveillance.
Where medical education meets artificial intelligence: ‘Does technology care?’
Authors: van der Niet Anneke G. , Bleakley Alan
Published: February 2020

‘Cold’ technologies and ‘warm’ hands‐on medicine need to walk hand‐in‐hand

Technologies, such as deep learning artificial intelligence (AI), promise benign solutions to thorny, complex problems; but this view is misguided. Though AI has revolutionised aspects of technical medicine, it has brought in its wake practical, conceptual, pedagogical and ethical conundrums. For example, widespread adoption of technologies threatens to shift emphasis from ‘hands‐on’ embodied clinical work to disembodied ‘technology enhanced’ fuzzy scenarios muddying ethical responsibilities. Where AI can offer a powerful sharpening of diagnostic accuracy and treatment options, ‘cold’ technologies and ‘warm’ hands‐on medicine need to walk hand‐in‐hand. This presents a pedagogical challenge grounded in historical precedent: in the wake of Vesalian anatomy introducing the dominant metaphor of ‘body as machine,’ a medicine of qualities was devalued through the rise of instrumental scientific medicine. The AI age in medicine promises to redouble the machine metaphor, reducing complex patient experiences to linear problem‐solving interventions promising ‘solutionism.’ As an instrumental intervention, AI can objectify patients, frustrating the benefits of dialogue, as patients’ complex and often unpredictable fleshly experiences of illness are recalculated in solution‐focused computational terms.

Suspicions about solutions

The rate of change in numbers and sophistication of new technologies is daunting; they include surgical robotics, implants, computer programming and genetic interventions such as clustered regularly interspaced short palindromic repeats (CRISPR). Contributing to the focus of this issue on ‘solutionism,’ we explore how AI is often promoted as an all‐encompassing answer to complex problems, including the pedagogical, where learning ‘hands‐on’ bedside medicine has proven benefits beyond the technical. Where AI and embodied medicine have differing epistemological, ontological and axiological roots, we must not imagine that they will readily walk hand‐in‐hand down the aisle towards a happy marriage. Their union will be fractious, requiring lifelong guidance provided by a perceptive medical education suspicious of ‘smart’ solutions to complex problems.
A single amino acid substitution in the movement protein enables the mechanical transmission of a geminivirus
Authors: Lee Chia‐Hwa , Zheng You‐Xiu , Chan Chin‐Hsiang , Ku Hsin‐Mei , Chang Chung‐Jan , Jan Fuh‐Jyh
Published: February 2020

Begomoviruses of the Geminiviridae are usually transmitted by whiteflies and rarely by mechanical inoculation. We used tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus, to address this issue. Most ToLCNDV isolates are not mechanically transmissible to their natural hosts. The ToLCNDV‐OM isolate, originally identified from a diseased oriental melon plant, is mechanically transmissible, while the ToLCNDV‐CB isolate, from a diseased cucumber plant, is not. Genetic swapping and pathological tests were performed to identify the molecular determinants involved in mechanical transmission. Various viral infectious clones were constructed and successfully introduced into Nicotiana benthamiana, oriental melon, and cucumber plants by Agrobacterium‐mediated inoculation. Mechanical transmissibility was assessed via direct rub inoculation with sap prepared from infected N. benthamiana. The presence or absence of viral DNA in plants was validated by PCR, Southern blotting, and in situ hybridization. The results reveal that mechanical transmissibility is associated with the movement protein (MP) of viral DNA‐B in ToLCNDV‐OM. However, the nuclear shuttle protein of DNA‐B plays no role in mechanical transmission. Analyses of infectious clones carrying a single amino acid substitution reveal that the glutamate at amino acid position 19 of MP in ToLCNDV‐OM is critical for mechanical transmissibility. The substitution of glutamate with glycine at this position in the MP of ToLCNDV‐OM abolishes mechanical transmissibility. In contrast, the substitution of glycine with glutamate at the 19th amino acid position in the MP of ToLCNDV‐CB enables mechanical transmission. This is the first time that a specific geminiviral movement protein has been identified as a determinant of mechanical transmissibility.
Family happiness among people in a Southeast Asian city: Grounded theory study
Authors: Napa Wilai , Granger Jumpee , Kejkornkaew Siranee , Phuagsachart Pornsiri
Published: February 2020

Happiness is a fundamental human aspiration. However, many families live in places where the cost of living is high, and there is a need for people to balance their lives to maintain happiness. This study explored the characteristics of happiness for families living in a city in Thailand. A grounded theory methodology was used to collect and analyze data. Thirteen participants were recruited into the study by purposive sampling based on a set of inclusion criteria, followed by theoretical sampling. The findings demonstrated that living together without financial problems was a core category of family happiness, which involved close connections, caring for one another and financial security. Families needed to balance these components when facing stress, using coping methods to restore happiness. To enhance family happiness, health professionals should focus on caring and communication within families, including coping techniques to maintain family happiness.
A cornucopia of mutants for understanding plant embryo development
Authors: Ponce María Rosa , Micol José Luis
Published: February 2020

This article is a Commentary on Meinke, 226: 306–325.