bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy
Authors: Zheng Dezhi , Zhang Yong , Hu Yonghe , Guan Jing , Xu Lianbin , Xiao Wenjing , Zhong Qinyue , Ren Chao , Lu Jinfeng , Liang Jiali , Hou Jun
Published: February 2019

Diabetic cardiomyopathy (DCM)—ventricular dysfunction in the absence of underlying heart disease—is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure. Although it is well‐established that the transforming growth factor‐beta signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene reg;ulation of key signaling effectors in DCM‐associated cardiac fibrosis. A recently emerged hotspot in the field of gene regulation is the role of long noncoding RNAs (lncRNAs). Recent evidence indicates that lncRNAs play a critical role in cardiac fibrosis; however, in DCM, the function of these regulatory RNAs have not been studied in depth. In this study, we identified a conserved cardiac‐specific lncRNA named colorectal neoplasia differentially expressed (Crnde). By analyzing 376 human heart tissues, it was found that Crnde expression is negatively correlated with that of cardiac fibrosis marker genes. Moreover, Crnde expression was shown to be enriched in cardiac fibroblasts (CFs). Overexpression of Crnde attenuated cardiac fibrosis and enhanced cardiac function in mice with DCM. Further, in vitro experiments showed that Crnde negatively regulates the myofibroblast differentiation of CFs. The expression of Crnde was activated by SMAD family member 3 (Smad3), shedding light on the underlying molecular mechanism. Interestingly, Crnde also inhibited the transcriptional activation of Smad3 on target genes, thereby inhibiting the expression of myofibroblastic marker genes in CFs. Overall, our data provide valuable insights into the development of potential anti‐cardiac fibrosis strategies centered on lncRNAs, for the treatment of DCM.
Contrasting latitudinal gradients of body size in helminth parasites and their hosts
Authors: Dallas Tad , Gehman Alyssa‐Lois M. , Aguirre A. Alonso , Budischak Sarah A. , Drake John M. , Farrell Maxwell J. , Ghai Ria , Huang Shan , Morales‐Castilla Ignacio
Published: February 2019

Aim

We examined body size scaling relationships for two developmental life stages of parasitic helminths (egg and adult) separately in relationship to latitude (i.e. Bergmann's rule), temperature and temperature seasonality. Given that helminth eggs experience environmental conditions more directly, whereas adults live inside infected host individuals, we predict stronger environmentally driven gradients of body size for eggs than for adults.

Location

Global.

Time period

Present day.

Major taxa studied

Parasitic helminths.

Methods

We compiled egg size and adult body size data (both minimum and maximum) for 265 parasitic helminth species from the literature, along with species latitudinal distribution information using an extensive global helminth occurrence database. We then examined how the average helminth egg and adult body size of all helminth species present (minimum and maximum separately) scaled with latitude, temperature and temperature variability, using generalized linear models.

Results

Both the egg size and the adult body size of helminths tended to decrease towards higher latitudes, although we found the opposite body size scaling pattern for their host species. Helminth sizes were also positively correlated with temperature and negatively, but more weakly, with temperature seasonality.

Main conclusions

Instead of following the body size patterns of their hosts, helminth parasites are more similar to other ectotherms in that they follow the converse Bergmann's rule. This pattern did not differ between helminth developmental stages, suggesting that mean annual temperature and seasonality are unlikely to be related mechanistically to body size variation in this case.
Relationship between jaw‐opening force and neck circumference in healthy older individuals
Authors: Yoshida Saori , Tohara Haruka , Nakagawa Kazuharu , Hara Koji , Yamaguchi Kohei , Nakane Ayako , Yoshimi Kanako , Ariya Chantaramanee , Kurosawa Yukiko , Minakuchi Shunsuke
Published: February 2019

Aim

In recent years, the relationships of arm circumference and calf circumference with swallowing function have been reported. However, the efficacy of using the neck circumference, which is closer to the swallowing‐related muscles, has never been verified. Jaw‐opening force, an indicator of suprahyoid muscle strength, is known to be useful for screening for dysphagia. The aim of the present study was to identify the relationships between neck circumference and swallowing‐related muscle strength, and to clarify the association between these variables in older individuals.

Methods

A total of 104 healthy, independent older individuals, aged ≥65 years (36 men, 68 women, mean age 71.5 ± 4.5 years, range 65–83 years), participated in the study. Neck circumference, arm circumference, calf circumference, jaw‐opening force and repetitive saliva swallowing test scores were measured. Multiple regression analysis was carried out to determine the relationship between neck circumference and jaw‐opening force, between neck circumference and repetitive saliva swallowing test score, and to identify variables affecting jaw‐opening force and neck circumference.

Results

The participants’ mean body mass index was 22.8 ± 2.9 (range 15.8–32.4). Sex and neck circumference, but not arm or calf circumference, were significant independent factors related to jaw‐opening force. Independent factors affecting neck circumference were sex, body mass index, jaw‐opening force and arm circumference, but not repetitive saliva swallowing test score.

Conclusions

In healthy older individuals, neck circumference was more strongly related to jaw‐opening force than were arm or calf circumference. This suggested that neck circumference could be useful for evaluating swallowing‐related muscle strength non‐invasively and easily. Geriatr Gerontol Int 2019; 19: 330–334.
Evolutionary origin of the type 2 corticotropin‐releasing hormone receptor γ splice variant
Authors: De Groef Bert , Wawrzyczek Stanisław K. , Watanabe Yugo , Noy Ellyse B. , Reser David H. , Grommen Sylvia V. H.
Published: February 2019

Many G protein‐coupled receptors have splice variants, with potentially different pharmaceutical properties, expression patterns and roles. The human brain expresses three functional splice variants of the type 2 corticotropin‐releasing hormone: CRHR2α, –β and –γ. CRHR2γ has only been reported in humans, but its phylogenetic distribution, and how and when during mammalian evolution it arose, is unknown. Based on genomic sequence analyses, we predict that a functional CRHR2γ is present in all Old World monkeys and apes, and is unique to these species. CRHR2γ arose by exaptation of an intronic sequence—already present in the common ancestor of primates and rodents—after retrotransposition of a short interspersed nuclear element (SINE) and mutations that created a 5′ donor splice site and in‐frame start codon, 32–43 million years ago. The SINE is not part of the coding sequence, only of the 5′ untranslated region and may therefore play a role in translational regulation. Putative regulatory elements and an alternative transcriptional start site were added earlier to this genomic locus by a DNA transposon. The evolutionary history of CRHR2γ confirms some of the earlier reported principles behind the “birth” of alternative exons. The functional significance of CRHR2γ, particularly in the brain, remains to be showed.
Haemophilia in Côte d’Ivoire (the Ivory Coast) in 2017: Extensive data collection as part of the World Federation of Hemophilia’s twinning programme
Authors: Lambert Catherine , Meité N’Dogomo , Sanogo Ibrahima , Lobet Sébastien , Adjambri Eusèbe , Eeckhoudt Stéphane , Hermans Cedric
Published: February 2019

Introduction

In sub‐Saharan African countries, research on haemophilia is limited. Since 2015, a partnership has been established through the World Federation of Hemophilia (WFH)’s twinning programme between the haemophilia treatment centre (HTC) of the Centre Hospitalier universitaire of Yopougon in Abidjan, Côte d’Ivoire, and the Cliniques universitaires Saint‐Luc of Brussels, Belgium.

Aim

This study sought to collect accurate, and detailed demographic, clinical, and laboratory data on the whole identified Ivorian haemophilia population.

Methods

A prospective study was conducted in 2017 in Yopougon’s HTC. Participants were assessed through multidisciplinary workups including interviews, logbook review, pedigree establishment, clinical examination and laboratory testing.

Results

Data on 81 patients with haemophilia (PWH) (78 severe and moderate) were collected. Postcircumcision bleeding was the most common diagnosis reason (32%). Mouth bleeds and skin wounds accounted for 55.2% of bleeds. Pedigrees revealed 63 deaths in affected relatives among 33 families. Most PWHs (76.5%) were treated on demand, and 21% had never been exposed to clotting factor. Non‐substitutive therapies (tranexamic acid [43%], physiotherapy [11%] and DDAVP [0%]) were underused. Overweight was uncommon. Knees were the most clinically affected joints at the Hemophilia Joint Health Score. Inhibitors were present in 7.8% of previously treated PWHs.

Conclusions

This study highlights the value of simple, feasible and inexpensive tools to collect data in the Ivorian haemophilia population and provides the basis for developing and implementing locally appropriate strategies to improve screening, diagnosis, preventive care, treatment and education. It demonstrated the WFH twinning programme benefits for haemophilia care in the developing world.
Joining of silicon carbide ceramics using a silicon carbide tape
Authors: Kim Yong‐Hyeon , Jang Seung Hoon , Kim Young‐Wook
Published: February 2019

This paper reports the joining of liquid‐phase sintered SiC ceramics using a thin SiC tape with the same composition as base SiC material. The base SiC ceramics were fabricated by hot pressing of submicron SiC powders with 4 wt% Al2O3–Y2O3–MgO additives. The base SiC ceramics were joined by hot‐pressing at 1800‐1900°C under a pressure of 10 or 20 MPa in an argon atmosphere. The effects of sintering temperature and pressure were examined carefully in terms of microstructure and strength of the joined samples. The flexural strength of the SiC ceramic which was joined at 1850°C under 20 MPa, was 343 ± 53 MPa, higher than the SiC material (289 ± 53 MPa). The joined SiC ceramics showed no residual stress built up near the joining layer, which was evidenced by indentation cracks with almost the same lengths in four directions.
Why is optimisation of antimicrobial use difficult at the end of life?
Authors: Broom Jennifer , Broom Alex , Good Phillip , Lwin Zarnie
Published: February 2019

The antibiotic optimisation imperative is now ubiquitous, with national policy frameworks in Organisation for Economic Co‐operation and Development (OECD) countries incorporating the requirement for antimicrobial stewardship within healthcare services. Yet in practice, the optimisation agenda often raises complex ethical‐ and practice‐based dilemmas. Antibiotic use at the end of life is multidimensional. It includes balancing complex issues, such as accuracy of prognostic estimates, benevolence to the individual versus the broader public health, personalised value judgement of time and quality of life and the right to treatment versus the right to die. It also occurs in an emotional context where the clinician and patient (and their family) collectively confront mortality. This provides a scenario where amplification of the already strong social and behavioural forces that drive overuse of antibiotics in many other clinical settings may occur. It therefore offers an important case for illustrating how antibiotic optimisation may be limited by social, value‐based and ethical dilemmas.
A case of persistent fever, cutaneous manifestations and pulmonary and splenic nodules: clinical experience and a literature review
Authors: Xu Ping , Cai Yazhou , Ying Xiaona , Shi Shiqiao , Song Weidong
Published: February 2019

Pyoderma gangrenosum (PG) is a rare and recurrent ulcerating, non‐infectious, inflammatory dermatosis, with occasional concomitant extracutaneous manifestations. The pathogenesis and aetiology of PG are unknown. Moreover, early diagnosis is challenging because there are several visceral manifestations that may occur prior to the skin findings, such that misdiagnosis of PG as an infection is common. Here, we present a case of PG in which pulmonary and spleen lesions preceded the cutaneous manifestations. The correct diagnosis was made 6 months after multiple nodules were detected in the lung and spleen, based on the development of skin wound ulcers. To the best of our knowledge, this is the first report of PG in which pulmonary and splenic involvement preceded the appearance of skin lesions, without systemic disease. The patient was followed up for 5 years, during which time complete clinical and radiographic resolution was confirmed. This case demonstrates the challenges in the diagnosis of PG and the importance of using multiple diagnostic methods to determine the cause of unexplained clinical manifestations.
Lactation ketoacidosis: an easily missed diagnosis
Authors: Azzam Omar , Prentice David
Published: February 2019

Ketoacidosis is uncommon in non‐diabetic women, but occurs in the postpartum period as a rare complication of continuing to breastfeed during periods of acute illness. We report a case of a lactating woman who presented with severe symptomatic ketoacidosis in the early postpartum period. We also review the pathophysiology and management of lactation ketoacidosis.
Plumage coloration follows Gloger's rule in a ring species
Authors: Ribot Raoul F. H. , Berg Mathew L. , Schubert Emanuel , Endler John A. , Bennett Andrew T. D.
Published: February 2019

Aim

Animal coloration is expected to differ between populations in different habitats according to Gloger's rule, with darker animals found in more humid, vegetated or warmer environments. Yet despite considerable support across the globe, the mechanisms behind this biogeographical rule are currently still unclear. Exploiting a ring species with plumage coloration from crimson to pale yellow, we test Gloger's rule and the mechanisms behind phenotypic divergence.

Location

South‐eastern Australia.

Major taxa studied

Crimson rosellas (Platycercus elegans).

Methods

We combined three modelling approaches (spatial regression; random decision forest species distribution and conditional inference tree) to test the association between 10 environmental variables (based on long‐term climate data and remotely sensed reflectance of the land) and plumage coloration across the distribution of P. elegans. We also took in‐situ measurements of background coloration of dominant vegetation to examine the relationship between (a) background coloration measured locally and remotely, (b) P. elegans coloration and (c) known differences in visual sensitivity of the subspecies using species‐specific visual models.

Results

On both a continental and a local scale, the distribution of yellow‐red plumage coloration was strongly predicted by average rainfall, summer temperature and the Earth's reflectance between 620–670 nm. Remotely sensed radiance measures correlated strongly and positively with reflectance of the leaves of the dominant tree species at sites across the P. elegans distribution. Visual modelling indicated that differences in background colour could affect signalling efficacy in dim‐light conditions.

Main conclusions

Our study shows that the highly variable plumage coloration conforms to Gloger's rule, and indicates that background coloration of the vegetation and thermoregulation are likely to be important mechanisms. Our results also show that Gloger's rule can explain variation in pigmentary systems other than melanin, and highlight that selection from environmental variation could be an important force behind the geographic diversity found in ring species.
Endoplasmic reticulum stress‐dependent autophagy inhibits glycated high‐density lipoprotein‐induced macrophage apoptosis by inhibiting CHOP pathway
Authors: Tian Hua , Li Yanyan , Kang Panpan , Wang Zhichao , Yue Feng , Jiao Peng , Yang Nana , Qin Shucun , Yao Shutong
Published: February 2019

This study was designed to explore the inductive effect of glycated high‐density lipoprotein (gly‐HDL) on endoplasmic reticulum (ER) stress‐C/EBP homologous protein (CHOP)‐mediated macrophage apoptosis and its relationship with autophagy. Our results showed that gly‐HDL caused macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase‐like ER kinase (PERK) and eukaryotic translation initiation factor 2α, and CHOP up‐regulation, which were inhibited by 4‐phenylbutyric acid (PBA, an ER stress inhibitor) and the gene silencing of PERK and CHOP. Similar data were obtained from macrophages treated by HDL isolated from diabetic patients. Gly‐HDL induced macrophage autophagy as assessed by up‐regulation of beclin‐1, autophagy‐related gene 5 and microtubule‐associated protein one light chain 3‐II, which were depressed by PBA and PERK siRNA. Gly‐HDL‐induced apoptosis, PERK phosphorylation and CHOP up‐regulation were suppressed by rapamycin (an autophagy inducer), whereas aggravated by 3‐methyladenine (an autophagy inhibitor) and beclin‐1 siRNA. Administration of diabetic apoE−/− mice with rapamycin attenuated MOMA‐2 and CHOP up‐regulation and apoptosis in atherosclerotic lesions. These data indicate that gly‐HDL may induce macrophage apoptosis through activating ER stress‐CHOP pathway and ER stress mediates gly‐HDL‐induced autophagy, which in turn protects macrophages against apoptosis by alleviating CHOP pathway.
Morphology and Molecular Phylogeny of Two New Terrestrial Ciliates, Australocirrus rubrus n. sp. and Notohymena gangwonensis n. sp. (Ciliophora: Oxytrichidae), from South Korea
Authors: Kim Kang‐San , Jung Jae‐Ho , Min Gi‐Sik
Published: February 2019

Two new soil oxytrichids, Australocirrus rubrus n. sp. and Notohymena gangwonensis n. sp., were discovered from South Korea. Morphologically, A. rubrus shares many features with A. australis, and these two species form a single clade in a molecular tree based on nuclear small subunit ribosomal RNA (SSU rRNA) gene sequences. Australocirrus rubrus mainly differs from A. australis in the color (citrine color vs. reddish) and distribution of the cortical granules. Additionally, we confirm that the genus Australocirrus is not a monophyletic group, as A. shii is separated from the clade comprising the other Australocirrus species, being clustered instead with other taxa. Notohymena gangwonensis n. sp. mainly differs from its congeners by the following combination of features: irregularly distributed cortical granules (vs. arranged in groups associated with cirri and dorsal kineties), variable four or five (usually four) transverse cirri (vs. invariable five), and the anteriormost pretransverse cirrus V/2 on 13.2–16.1% of cell length (vs. on or above 18.9% of cell length). Currently, there are no available gene sequences for members of the genus Notohymena, thus we provide SSU rRNA gene sequences from the new species of Notohymena, as well as detailed morphological descriptions of the novel species.
Cryptic diets of forage fish: jellyfish consumption observed in the Celtic Sea and western English Channel
Authors: Lamb Philip D. , Hunter Ewan , Pinnegar John K. , van der Kooij Jeroen , Creer Simon , Taylor Martin I.
Published: February 2019

To establish if fishes’ consumption of jellyfish changes through the year, we conducted a molecular gut‐content assessment on opportunistically sampled species from the Celtic Sea in October and compared these with samples previously collected in February and March from the Irish Sea. Mackerel Scomber scombrus were found to feed on hydrozoan jellyfish relatively frequently in autumn, with rare consumption also detected in sardine Sardina pilchardus and sprat Sprattus sprattus. By October, moon jellyfish Aurelia aurita appeared to have escaped predation, potentially through somatic growth and the development of stinging tentacles. This is in contrast with sampling in February and March where A. aurita ephyrae were heavily preyed upon. No significant change in predation rate was observed in S. sprattus, but jellyfish predation by S. scombrus feeding in autumn was significantly higher than that seen during winter. This increase in consumption appears to be driven by the consumption of different, smaller jellyfish species than were targeted during the winter.
Optimizing the Feasibility and Scalability of a Geriatric Surgery Quality Improvement Initiative
Authors: Hornor Melissa A. , Tang Victoria L. , Berian Julia , Robinson Thomas N. , Coleman JoAnn , Katlic Mark R. , Rosenthal Ronnie A. , Christensen Kataryna , Baker Tracey , Finlayson Emily , Lagoo‐Deenadaayalan Sandhya A. , Ko Clifford Y. , Russell Marcia M.
Published: February 2019

BACKGROUND

The American College of Surgeons Coalition for Quality in Geriatric Surgery is a multidisciplinary stakeholder group that aims to systematically improve the surgical care of older adults by establishing a verifiable quality improvement program with standards based on best evidence. Prior work confirmed the validity of a preliminary set of 308 standards to improve the quality of geriatric surgery, but concerns exist as to whether the standards are feasible for hospitals to implement.

OBJECTIVE

Our aim was to utilize data gained from a multi‐institutional survey and interview to improve the scalability and generalizability of a geriatric quality improvement program.

METHODS

Using a survey followed by a targeted debrief interview, 15 hospitals gathered an interdisciplinary panel to answer whether each standard was already in place at their institution, and if not, the perceived difficulty of implementation according to a five‐point Likert scale (from 1 [very easy] to 5 [very difficult]). The standards were then placed into categories according to the hospital responses. Standards were designated “duplicative” if 11 or more hospitals reported baseline implementation, “prohibitively difficult” if 6 or more hospitals rated the standard as such, and “high potential” if they were neither duplicative nor difficult. A targeted debrief interview was then conducted with each participating hospital.

RESULTS

Fifteen participating hospitals evaluated the feasibility of 108 standards and found 28 (26%) duplicative, 35 (32%) too difficult, and 45 (42%) high potential. Of the 108 standards, 49 (45%) were selected for the next iteration of standards, and 59 were removed. Among the standards that were removed, the majority (64%) were rated duplicative and/or difficult.

CONCLUSION

A multi‐institutional survey and interview successfully identified care standards that were redundant or too difficult to implement on the hospital level. These data will help improve the generalizability and scalability of the program while maintaining the overall goal of improving care. J Am Geriatr Soc 67:1074–1078, 2019.
Monetary Policy Implementation in a Negative Rate Environment
Authors: BOUTROS MICHAEL , WITMER JONATHAN
Published: February 2019

To analyze monetary policy implementation in a negative rate environment, we add the option to exchange central bank reserves for cash to the standard workhorse model of monetary policy implementation (Poole 1968). Importantly, we show that monetary policy can be constrained when the target overnight rate is below the yield on cash. At this point, the overnight rate equals the yield on cash instead of the target rate. Modifications to the implementation framework, such as a reserve requirement that varies with cash withdrawals, can help restore the implementation of monetary policy such that the overnight rate equals the target rate.
Viral vector‐mediated Cre recombinase expression in substantia nigra induces lesions of the nigrostriatal pathway associated with perturbations of dopamine‐related behaviors and hallmarks of programmed cell death
Authors: Rezai Amin Sara , Gruszczynski Carole , Guiard Bruno P. , Callebert Jacques , Launay Jean‐Marie , Louis Franck , Betancur Catalina , Vialou Vincent , Gautron Sophie
Published: February 2019

Cre/loxP recombination is a widely used approach to study gene function in vivo, using mice models expressing the Cre recombinase under the control of specific promoters or through viral delivery of Cre‐expressing constructs. A profuse literature on transgenic mouse lines points out the deleterious effects of Cre expression in various cell types and tissues, presumably by acting on illegitimate loxP‐like sites present in the genome. However, most studies reporting the consequences of Cre‐lox gene invalidation often omit adequate controls to exclude the potential toxic effects of Cre, compromising the interpretation of data. In this study, we report the anatomical, neurochemical, and behavioral consequences in mice of adeno‐associated virus (AAV)‐mediated Cre expression in the dopaminergic nuclei substantia nigra, at commonly used viral titers (3 × 109 genome copies/0.3 μL or 2 × 109 genome copies/0.6 μL). We found that injecting AAV‐eGFP‐Cre into the SN engendered drastic and reproducible modifications of behavior, with increased basal locomotor activity as well as impaired locomotor response to cocaine compared to AAV‐eGFP‐injected controls. Cre expression in the SN induced a massive decrease in neuronal populations of both pars compacta and pars reticulata and dopamine depletion in the nigrostriatal pathway. This anatomical injury was associated with typical features of programmed cell death, including an increase in DNA break markers, evidence of apoptosis, and disrupted macroautophagy. These observations underscore the need for careful control of Cre toxicity in the brain and the reassessment of previous studies. In addition, our findings suggest that Cre‐mediated ablation may constitute an efficient tool to explore the function of specific cell populations and areas in the brain, and the impact of neurodegeneration in these populations.

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Tracking oxytocin functions in the rodent brain during the last 30 years: From push‐pull perfusion to chemogenetic silencing
Authors: Neumann Inga D. , Landgraf Rainer
Published: February 2019

A short overview is provided of the last 30 years of oxytocin (and vasopressin) research performed in our laboratories, starting with attempts to monitor the release of this nonapeptide in the rodent brain during physiological conditions such as suckling in the lactating animal. Using push‐pull perfusion and microdialysis approaches, release patterns in hypothalamic and limbic brain regions could be characterised to occur from intact neuronal structures, to be independent of peripheral secretion into blood, and to respond differentially to various stimuli, particularly those related to reproduction and stress. Parallel efforts focused on the functional impact of central oxytocin release, including neuroendocrine and behavioural effects mediated by nonapeptide receptor interactions and subsequent intraneuronal signalling cascades. The use of a variety of sophisticated behavioural paradigms to manipulate central oxytocin release, along with pharmacological, genetic and pharmacogenetic approaches, revealed multiple consequences on social behaviours, particularly social fear.
A population‐based and cross‐sectional study of the long‐term prognosis in multifocal motor neuropathy
Authors: Al‐Zuhairy Ali , Sindrup Søren H. , Andersen Henning , Jakobsen Johannes
Published: February 2019

A population‐based, cross‐sectional study of patients referred to the Danish hospital system between 1985 and 2006 was conducted to evaluate the long‐term outcome in Danish patients treated for multifocal motor neuropathy (MMN). Thirty‐four MMN patients were identified, three had died of unrelated diseases, 10 were excluded, one did not reply to study request and 20 were included. The median disease duration was 24 years (interquartile range: 18.5‐31.0). Compared to 24 healthy matched control subjects, the Rasch‐built Overall Disability Scale for Multifocal Motor Neuropathy was reduced by 9%, the Neuropathy Impairment Score showed a 3‐fold increase, the isokinetic strength was reduced by 29%, the grip strength by 56%, the Timed 25‐Foot Walk was prolonged by 13% and the EQ‐5D‐5 L‐Index value was impaired by 20%. The isokinetic strength was significantly more impaired at the wrist and ankle as compared to the elbow and knee, and one patient had lost ambulation because of instability at the ankle. Patients were considerably more fatigued and had substantially impaired hand dexterity, while mood, aerobic capacity, social adjustment, and working capacity were not affected. Regression analysis showed that lag‐time until start of initial therapy lead to impaired long‐term outcome without any effect of disease duration. Long‐term prognosis in treated MMN is characterized by moderate to severe impairment primarily affecting dexterity and stability at the ankle. Our observations support previous observations that the long‐term impairment in MMN might be improved following earlier start of therapy and that an effect of disease duration cannot be demonstrated.
THE EFFECTS OF HUMAN CAPITAL INTERVENTIONS ON ENTREPRENEURIAL PERFORMANCE IN INDUSTRIALIZED COUNTRIES
Authors: Hogendoorn Bram , Rud Iryna , Groot Wim , Maassen van den Brink Henriëtte
Published: February 2019

This paper provides a systematic review of studies on the effects of human capital interventions on entrepreneurial performance in industrialized countries. We identify 21 experimental and quasi‐experimental studies published before September 2018. These studies examine the effects of business training, formal education, and entrepreneurship education. Their performance outcomes include firm profits, firm size, and entrepreneurial earnings. The main finding across these studies is that these interventions do not have statistically significant effects. Formal education is the only exception, showing positive effects on firm profits and entrepreneurial earnings, yet these effects are small in magnitude. Evidence is inconclusive regarding effect duration. These findings stand in stark contrast to correlational studies, which tend to find large positive correlations between human capital interventions and entrepreneurial performance. We therefore conclude that correlational studies tend to overestimate the benefits of human capital interventions. Moreover, our estimates show that the interventions are associated with moderately low additionality.
Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes
Authors: Brod Staley A. , Lincoln John A. , Nelson Flavia
Published: February 2019

BACKGROUND AND PURPOSE

There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI).

METHODS

We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center.

RESULTS

There was increased CSF neural cell adhesion molecule (N‐CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N‐CAM and T1 lesion volume was observed. A negative correlation between serum brain‐derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed.

CONCLUSIONS

Increased N‐CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.
Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease
Authors: Alwatban Mohammed , Murman Daniel L. , Bashford Greg
Published: February 2019

BACKGROUND AND PURPOSE

A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO2 as a vasodilatory stimulus. The breath‐hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening.

METHODS

A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid‐β (Aβ) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aβ, and prodromal to mild AD subjects had CDR scores ≥.5 and elevated Aβ. CVR was calculated using two indices: the conventional breath‐holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared.

RESULTS

BHAI was able to distinguish between 9 normal control subjects and 8 preclinical‐AD subjects with high statistical significance (P < .001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects (P < .001).

CONCLUSIONS

In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.
Presidential Address: Religion and Power—A Return to the Roots of Social Scientific Scholarship
Authors: Edwards Korie L.
Published: February 2019

Early social scientists, including Karl Marx, Max Weber, and W. E. B. DuBois, recognized the importance of religion for power systems. Since the beginning of the 20th century, however, there has been a decline in scholars examining how religion matters for power. This address proposes that scholars bring religion back to the center of understanding the production, deconstruction, and distribution of power as religion is critical to the flows of power in the social world. I propose that furthering an agenda that interrogates the role of religion for power means we emphasize that (i) religion is an institution; (ii) religious ideas motivate action; (iii) our epistemology sources theories of power rather than those that invalidate the centrality of religion in societies; and (iv) ground‐breaking theoretical and empirical contributions to the social scientific study of religion and power demand that we broaden and diversify the standpoints from which this knowledge is produced.
Long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure: An observational cohort study
Authors: Lin Su , Zhang Kai , Zhang Junchao , Wang Mingfang , Velani Bharat , Zhu Yueyong
Published: February 2019

Background and Aims

The long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure (HBV‐ACLF) remain unclear. The main aim of the study was to compare the 5‐year survival rate and incidence rate of hepatocellular carcinoma (HCC) between patients with HBV‐ACLF and HBV‐cirrhosis.

Methods

Clinical data of patients with ACLF, compensated cirrhosis and decompensated cirrhosis who survived more than 3 months after diagnosis were collected. The survival rate and cumulative incidence of HCC were compared. The Cox regression was used to evaluate risk factors for outcomes.

Results

A total of 814 patients were included in the analysis, including 122 (14.99%) patients with ACLF, 450 (55.28%) patients with compensated cirrhosis and 242 (29.73%) patients with decompensated cirrhosis. The 5‐year survival rate of patients with ACLF (97.2%) was higher than patients with decompensated cirrhosis (86.0%), but was lower than patients with compensated cirrhosis (99.1%). The 5‐year HCC incidence rate was the highest in the decompensated cirrhosis group (14.6%, P < 0.05), while no statistical differences were found between patients with ACLF (3.5%) and compensated cirrhosis (9.5%). The episode of ACLF did not increase the risk of HCC and the overall survival when compared with patients with cirrhosis. In ACLF subgroup analysis, the age, rather than the presence of cirrhosis, was independently associated with both mortality and incidence of HCC.

Conclusions

ACLF patients who survived the first 3 months had a better long‐term prognosis than decompensated cirrhosis, while the HCC risk was comparable to compensated cirrhosis. HCC surveillance is strongly recommended for these patients.
Pantasma: Evidence for a Pleistocene circa 14 km diameter impact crater in Nicaragua
Authors: Rochette P. , Alaç R. , Beck P. , Brocard G. , Cavosie A. J. , Debaille V. , Devouard B. , Jourdan F. , Mougel B. , Moustard F. , Moynier F. , Nomade S. , Osinski G. R. , Reynard B. , Cornec J.
Published: February 2019

The circa 14 km diameter Pantasma circular structure in Oligocene volcanic rocks in Nicaragua is here studied for the first time to understand its origin. Geomorphology, field mapping, and petrographic and geochemical investigations all are consistent with an impact origin for the Pantasma structure. Observations supporting an impact origin include outward‐dipping volcanic flows, the presence of former melt‐bearing polymict breccia, impact glass (with lechatelierite and low H2O, <300 ppm), and also a possible ejecta layer containing Paleozoic rocks which originated from hundreds of meters below the surface. Diagnostic evidence for impact is provided by detection in impact glass of the former presence of reidite in granular zircon as well as coesite, and extraterrestrial ε54Cr value in polymict breccia. Two 40Ar/39Ar plateau ages with a combined weighted mean age of 815 ± 11 ka (2 σ; P = 0.17) were obtained on impact glass. This age is consistent with geomorphological data and erosion modeling, which all suggest a rather young crater. Pantasma is only the fourth exposed crater >10 km found in the Americas south of N30 latitude, and provides further evidence that a significant number of impact craters may remain to be discovered in Central and South America.
Effectiveness of NGO‐government partnership to prevent and treat child wasting in urban India
Authors: Chanani Sheila , Waingankar Anagha , Shah More Neena , Pantvaidya Shanti , Fernandez Armida , Jayaraman Anuja
Published: February 2019

This study reviews the performance of a community‐based nutrition programme in preventing and treating wasting without complications among children under age three in urban informal settlements of India. Implemented by a non‐profit organization, with national (Integrated Child Development Services [ICDS]) and city‐level (Municipal Corporation of Greater Mumbai [MCGM]) government partners, the programme screened 7,759 children between May 2014 and April 2015. During this period, the programme admitted 705 moderately wasted and 189 severely wasted children into the treatment group and 6,820 not wasted children into the prevention group. Both prevention and treatment groups received growth monitoring, referrals to public health facilities, and home‐based counselling (if <6 months) by community health workers. Treatment groups received additional home‐based counselling and access to medical screenings. Severely wasted children also received access to ready‐to‐use therapeutic food. The study assessed default rates, wasting status, and average weight gain 3 months after admission. Factors associated with growth faltering in the prevention group were explored using logistic regression.

Default rates for the severely wasted, moderately wasted, and prevention group were 12.7%, 20.4%, and 22.1%, respectively. Recovery rate was 42.4% for the severely wasted and 61.3% for the moderately wasted. For the moderately wasted, mean weight gain was 2.1 g/kg/day, 95% confidence interval (CI) [1.6, 2.6], and 4.5 g/kg/day for the severely wasted, 95% CI [3.1, 5.9]. Among prevention group children, 3.6% faltered into wasting—3.2% into moderate and 0.4% into severe. The paper gives insights into ways in which ICDS and MCGM can successfully integrate large‐scale community‐based acute malnutrition programming.
Rethinking integrated nutrition‐health strategies to address micronutrient deficiencies in children under five in Mozambique
Authors: Picolo Melanie , Barros Iracema , Joyeux Mathieu , Gottwalt Allison , Possolo Edna , Sigauque Betuel , Kavle Justine A.
Published: February 2019

In Mozambique, about two thirds of children 6–59 months of age are affected by vitamin A deficiency and anaemia. The objective of this case study is to provide programme considerations for planning, implementing, monitoring, and evaluating vitamin A and iron deficiency interventions within the context of lessons learned to date for vitamin A supplementation, micronutrient powders (MNPs), and food‐based strategies. For 15 years, the Mozambique Ministry of Health implemented twice‐yearly vitamin A supplementation through both campaigns and routine health services. Yet coverage in 2017 (55%) was not much higher than in 2003 (44%). Reaching every district/reaching every child, a strategy adapted from the field of immunization, was used to achieve equitable coverage of vitamin A and for microplanning of outreach services in health facilities, with support from the Maternal and Child Survival Program. In Mozambique, a free or subsidized distribution model for MNPs has been rolled out, yet integration of MNPs into infant and young child feeding programming (i.e., cooking demonstrations) is needed to reinforce “the who, what, and why” of MNPs through culturally sensitive behaviour change communication. Food‐based strategies to promote dietary diversity, such as through complementary feeding recipes, are also critical. To harmonize efforts, the Mozambique government should consider the development of a national strategy for the prevention and control of micronutrient malnutrition, with clear monitoring and evaluation targets. Ongoing monitoring of the prevalence of micronutrient deficiencies and coverage of implemented micronutrient interventions is needed to make evidence‐based decisions to drive nutrition–health programming.
Accelerating progress for complementary feeding in Kenya: Key government actions and the way forward
Authors: Ahoya Brenda , Kavle Justine A. , Straubinger Sarah , Gathi Constance M.
Published: February 2019

Optimal complementary feeding practices, a critical component of infant and young child feeding, has been demonstrated to prevent micronutrient deficiencies, stunting, overweight, and obesity. In Kenya, while impressive gains have been made in exclusive breastfeeding, progress in complementary feeding has been slow, and the country has failed to meet targets. Recent 2014 Kenya Demographic and Health Survey reveal that only 22% of Kenyan children, 6–23 months, met criteria for a minimum acceptable diet. This case study describes key actions for complementary feeding put in place by the Kenya Ministry of Health as well as approaches for improving and monitoring complementary feeding within existing health platforms. Experience from USAID's Maternal and Child Survival Program and Ministry of Health on development of 23 complementary feeding recipes through application of a national guide for recipe development and Trials of Improved Practices is described. Challenges in how to prepare, modify, and cook foods, including meat, for young children 6–23 months of age was relayed by mothers. Addressing cultural beliefs around complementary feeding meant providing reassurance to mothers that young children are developmentally able to digest fruit and vegetables and ready to consume animal‐source protein. Through the Baby Friendly Community Initiative platform, cooking demonstrations and key hygiene actions were integrated with complementary feeding messages. Future programming for complementary feeding should consider development of context specific counselling messages on consumption of animal source foods, strengthen production and use of local foods through agriculture‐nutrition linkages, and include complementary indicators through routine health monitoring systems to track progress.
Strengthening nutrition services within integrated community case management (iCCM) of childhood illnesses in the Democratic Republic of Congo: Evidence to guide implementation
Authors: Kavle Justine A. , Pacqué Michel , Dalglish Sarah , Mbombeshayi Evariste , Anzolo Jimmy , Mirindi Janvier , Tosha Maphie , Safari Octave , Gibson Lacey , Straubinger Sarah , Bachunguye Richard
Published: February 2019

In the Democratic Republic of Congo, 43% of children under 5 years of age suffer from stunting, and the majority (60%) of children, 6–59 months of age, are anaemic. Malaria, acute respiratory infections, and diarrheal diseases are common among children less than 5 years of age, with 31% of children 6–59 months affected by malaria. This qualitative implementation science study aimed to identify gaps and opportunities available to strengthen service delivery of nutrition within integrated community case management (iCCM) at the health facility and community level in Tshopo Province, Democratic Republic of Congo, through the following objectives: (a) examine cultural beliefs and perceptions of infant and young child feeding (IYCF) and child illness, (b) explore the perspectives and knowledge of facility‐based and community‐based health providers on nutrition and iCCM, and (c) gain an understanding of the influence of key family and community members on IYCF and care‐seeking practices. This study involved in‐depth interviews with mothers of children under 5 years of age (n = 48), grandmothers (n = 20), fathers (n = 21), facility‐based providers (n = 18), and traditional healers (n = 20) and eight focus group discussions with community health workers. Study findings reveal most mothers reported diminished quantity and quality of breastmilk linked to child/maternal illness, inadequate maternal diet, and feedings spaced too far apart. Mothers' return to work in the field led to early introduction of foods prior to 6 months of age, impeding exclusive breastfeeding. Moreover, children's diets are largely limited in frequency and diversity with small quantities of foods fed. Most families seek modern and traditional medicine to remedy child illness, dependent on type of disease, its severity, and cost. Traditional healers are the preferred source of information for families on certain child illnesses and breastmilk insufficiency. Community health workers often refer and accompany families to the health centre, yet are underutilized for nutrition counselling, which is infrequently given. Programme recommendations are to strengthen health provider capacity to counsel on IYCF and iCCM while equipping health workers with updated social and behavior change communication (SBCC) materials and continued supportive supervision. In addition, targeting key influencers to encourage optimal IYCF practices is needed through community and mother support groups. Finally, exploring innovative ways to work with traditional healers, to facilitate referrals for sick/malnourished children and provide simple nutrition advice for certain practices (i.e., breastfeeding), would aid in strengthening nutrition within iCCM.