bluuebunny/crossref_metadata_2025 huggingface dataset:
FAR‐RED ELONGATED HYPOCOTYLS3 negatively regulates shade avoidance responses in Arabidopsis
Authors: Ma Lin , Li Yang , Li Xiuxiu , Xu Di , Lin Xueqiao , Liu Mingmei , Li Gang , Qin Xiaochun
Published: July 2019

Light is a key limiting factor of plant growth and development under the canopy. Specific light signals, such as a low ratio of red : far‐red (R:FR) light, trigger the shade avoidance response, which affects hypocotyl, stem, and leaf growth. Although multiple components mediating shade avoidance responses have been identified in the past few decades, the underlying regulatory mechanism remains unclear. In this study, we found that the far‐red elongated hypocotyls 3 (fhy3) mutant exhibited longer hypocotyls and increased expression levels of core shade avoidance response genes under low R:FR shade conditions compared with the wild type No‐0, suggesting that FHY3 negatively regulates shade avoidance responses. Yeast one‐hybrid, chromatin immunoprecipitation, and RT‐qPCR assays revealed that FHY3 directly binds to the promoters and gene body of PHYTOCHROME RAPIDLY REGULATED1 (PAR1) and PAR2 and activates their expression to inhibit shade responses. Furthermore, the overexpression of PAR1 or PAR2 rescued the enhanced shade avoidance responses of fhy3, indicating that both genes are direct downstream targets of FHY3 that mediate shade avoidance responses. Our findings demonstrate that the light‐signalling protein FHY3 positively regulates the transcription of PAR1 and PAR2, which encode two key negative regulators of shade avoidance responses, thus repressing plant responses to shade signals.
Multi‐targeting of viral RNAs with synthetic trans‐acting small interfering RNAs enhances plant antiviral resistance
Authors: Carbonell Alberto , Lisón Purificación , Daròs José‐Antonio
Published: July 2019

RNA interference (RNAi)‐based tools are used in multiple organisms to induce antiviral resistance through the sequence‐specific degradation of target RNAs by complementary small RNAs. In plants, highly specific antiviral RNAi‐based tools include artificial microRNAs (amiRNAs) and synthetic trans‐acting small interfering RNAs (syn‐tasiRNAs). syn‐tasiRNAs have emerged as a promising antiviral tool allowing for the multi‐targeting of viral RNAs through the simultaneous expression of several syn‐tasiRNAs from a single precursor. Here, we compared in tomato plants the effects of an amiRNA construct expressing a single amiRNA and a syn‐tasiRNA construct expressing four different syn‐tasiRNAs against Tomato spotted wilt virus (TSWV), an economically important pathogen affecting tomato crops worldwide. Most of the syn‐tasiRNA lines were resistant to TSWV, whereas the majority of the amiRNA lines were susceptible and accumulated viral progenies with mutations in the amiRNA target site. Only the two amiRNA lines with higher amiRNA accumulation were resistant, whereas resistance in syn‐tasiRNA lines was not exclusive of lines with high syn‐tasiRNA accumulation. Collectively, these results suggest that syn‐tasiRNAs induce enhanced antiviral resistance because of the combined silencing effect of each individual syn‐tasiRNA, which minimizes the possibility that the virus simultaneously mutates all different target sites to fully escape each syn‐tasiRNA.
Multiple steps of leaf thickening during sun‐leaf formation in Arabidopsis
Authors: Hoshino Rina , Yoshida Yuki , Tsukaya Hirokazu
Published: July 2019

Plant morphological and physiological traits exhibit plasticity in response to light intensity. Leaf thickness is enhanced under high light (HL) conditions compared with low light (LL) conditions through increases in both cell number and size in the dorsoventral direction; however, the regulation of such phenotypic plasticity in leaf thickness (namely, sun‐ or shade‐leaf formation) during the developmental process remains largely unclear. By modifying observation techniques for tiny leaf primordia in Arabidopsis thaliana, we analysed sun‐ and shade‐leaf development in a time‐course manner and found that the process of leaf thickening can be divided into early and late phases. In the early phase, anisotropic cell elongation and periclinal cell division on the adaxial side of mesophyll tissue occurred under the HL conditions used, which resulted in the dorsoventral growth of sun leaves. Anisotropic cell elongation in the palisade tissue is triggered by blue‐light irradiation. We discovered that anisotropic cell elongation processes before or after periclinal cell division were differentially regulated independent of or dependent upon signalling through blue‐light receptors. In contrast, during the late phase, isotropic cell expansion associated with the endocycle, which determined the final leaf thickness, occurred irrespective of the light conditions. Sucrose production was high under HL conditions, and we found that sucrose promoted isotropic cell expansion and the endocycle even under LL conditions. Our analyses based on this method of time‐course observation addressed the developmental framework of sun‐ and shade‐leaf formation.
An ‘eFP‐Seq Browser’ for visualizing and exploring RNA sequencing data
Authors: Sullivan Alexander , Purohit Priyank K. , Freese Nowlan H. , Pasha Asher , Esteban Eddi , Waese Jamie , Wu Alison , Chen Michelle , Chin Chih Y. , Song Richard , Watharkar Sneha R. , Chan Agnes P. , Krishnakumar Vivek , Vaughn Matthew W. , Town Chris , Loraine Ann E. , Provart Nicholas J.
Published: July 2019

Improvements in next‐generation sequencing technologies have resulted in dramatically reduced sequencing costs. This has led to an explosion of ‘‐seq’‐based methods, of which RNA sequencing (RNA‐seq) for generating transcriptomic data is the most popular. By analysing global patterns of gene expression in organs/tissues/cells of interest or in response to chemical or environmental perturbations, researchers can better understand an organism's biology. Tools designed to work with large RNA‐seq data sets enable analyses and visualizations to help generate hypotheses about a gene's function. We present here a user‐friendly RNA‐seq data exploration tool, called the ‘eFP‐Seq Browser’, that shows the read map coverage of a gene of interest in each of the samples along with ‘electronic fluorescent pictographic’ (eFP) images that serve as visual representations of expression levels. The tool also summarizes the details of each RNA‐seq experiment, providing links to archival databases and publications. It automatically computes the reads per kilobase per million reads mapped expression‐level summaries and point biserial correlation scores to sort the samples based on a gene's expression level or by how dissimilar the read map profile is from a gene splice variant, to quickly identify samples with the strongest expression level or where alternative splicing might be occurring. Links to the Integrated Genome Browser desktop visualization tool allow researchers to visualize and explore the details of RNA‐seq alignments summarized in eFP‐Seq Browser as coverage graphs. We present four cases of use of the eFP‐Seq Browser for ABI3, SR34, SR45a and U2AF65B, where we examine expression levels and identify alternative splicing. The URL for the browser is https://bar.utoronto.ca/eFP-Seq_Browser/.

Open research badges

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. Tool is at https://bar.utoronto.ca/eFP-Seq_Browser/; RNA‐seq data at https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/ and https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/Klepikova/. Code is available at https://github.com/BioAnalyticResource/eFP-Seq-Browser
Transforming compound leaf patterning by manipulating REVOLUTA in Medicago truncatula
Authors: Zhou Chuanen , Han Lu , Zhao Yang , Wang Hongfeng , Nakashima Jin , Tong Jianhua , Xiao Langtao , Wang Zeng‐Yu
Published: July 2019

Leaves are derived from the shoot apical meristem with three distinct axes: dorsoventral, proximodistal and mediolateral. Different regulators are involved in the establishment of leaf polarity. Members of the class III homeodomain‐leucine zipper (HD‐ZIPIII) gene family are critical players in the determination of leaf adaxial identity mediated by microRNA165/166. However, their roles in compound leaf development are still unclear. By screening of a retrotransposon‐tagged mutant population of the model legume plant Medicago truncatula, a mutant line with altered leaflet numbers was isolated and characterized. Mutant leaves partially lost their adaxial identity. Leaflet numbers in the mutant were increased along the proximodistal axis, showing pinnate pentafoliate leaves in most cases, in contrast to the trifoliate leaves of the wild type. Detailed characterization revealed that a lesion in a HD‐ZIPIII gene, REVOLUTA (MtREV1), resulted in the defects of the mutant. Overexpression of MtMIR166‐insensitive MtREV1 led to adaxialized leaves and ectopic leaflets along the dorsoventral axis. Accompanying the abnormal leaf patterning, the free auxin content was affected. Our results demonstrate that MtREV1 plays a key role in determination of leaf adaxial–abaxial polarity and compound leaf patterning, which is associated with proper auxin homeostasis.
Lipid remodeling regulator 1 (LRL1) is differently involved in the phosphorus‐depletion response from PSR1 in Chlamydomonas reinhardtii
Authors: Hidayati Nur A. , Yamada‐Oshima Yui , Iwai Masako , Yamano Takashi , Kajikawa Masataka , Sakurai Nozomu , Suda Kunihiro , Sesoko Kanami , Hori Koichi , Obayashi Takeshi , Shimojima Mie , Fukuzawa Hideya , Ohta Hiroyuki
Published: July 2019

The elucidation of lipid metabolism in microalgae has attracted broad interest, as their storage lipid, triacylglycerol (TAG), can be readily converted into biofuel via transesterification. TAG accumulates in the form of oil droplets, especially when cells undergo nutrient deprivation, such as for nitrogen (N), phosphorus (P), or sulfur (S). TAG biosynthesis under N‐deprivation has been comprehensively studied in the model microalga Chlamydomonas reinhardtii, during which TAG accumulates dramatically. However, the resulting rapid breakdown of chlorophyll restricts overall oil yield productivity and causes cessation of cell growth. In contrast, P‐deprivation results in oil accumulation without disrupting chloroplast integrity. We used a reverse genetics approach based on co‐expression analysis to identify a transcription factor (TF) that is upregulated under P‐depleted conditions. Transcriptomic analysis revealed that the mutants showed repression of genes typically associated with lipid remodeling under P‐depleted conditions, such as sulfoquinovosyl diacylglycerol 2 (SQD2), diacylglycerol acyltransferase (DGTT1), and major lipid droplet protein (MLDP). As accumulation of sulfoquinovosyl diacylglycerol and TAG were suppressed in P‐depleted mutants, we designated the protein as lipid remodeling regulator 1 (LRL1). LRL1 mutants showed slower growth under P‐depletion. Moreover, cell size in the mutant was significantly reduced, and TAG and starch accumulation per cell were decreased. Transcriptomic analysis also suggested the repression of several genes typically upregulated in adaptation to P‐depletion that are associated with the cell cycle and P and lipid metabolism. Thus, our analysis of LRL1 provides insights into P‐allocation and lipid remodeling under P‐depleted conditions in C. reinhardtii.

Open Research Badges

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The sequencing data were made publicly available under the BioProject Accession number PRJDB6733 and an accession number LC488724 at the DNA Data Bank of Japan (DDBJ). The data is available at https://trace.ddbj.nig.ac.jp/BPSearch/bioproject?acc=PRJDB6733; http://getentry.ddbj.nig.ac.jp/getentry/na/LC488724. The metabolome data were made publicly available and can be accessed at http://metabolonote.kazusa.or.jp/SE195:/; http://webs2.kazusa.or.jp/data/nur/.
Human skeletal muscle nitrate store: influence of dietary nitrate supplementation and exercise
Authors: Wylie Lee J. , Park Ji Won , Vanhatalo Anni , Kadach Stefan , Black Matthew I. , Stoyanov Zdravko , Schechter Alan N. , Jones Andrew M. , Piknova Barbora
Published: July 2019

Key points

Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions.

We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise.

In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high‐intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO.

We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism.

Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise‐induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4‐fold and ∼29‐fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19‐fold) and muscle (∼5‐fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise‐induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.
Computational Wear Prediction for Impact of Kinematics Boundary Conditions on Wear of Total Knee Replacement Using Two Cross-Shear Models
Authors: Zhang Jing , Chen Zhenxian , Gao Yongchang , Zhang Xuan , Guo Lei , Jin Zhongmin
Published: July 2019

Wear particle-induced osteolysis is the main reason for the long-term failure of total knee replacement. Simulator testing is the standard procedure for validating wear performance pre-clinically. The load and kinematics specified in the International Organization for Standardization (ISO) are standard input profiles for wear testing of implants. Directions of internal–external (IE) rotation and anterior–posterior (AP) translation have been modified in the new version of ISO 14243-3 2014. This study focused on investigating the effects of internal–external rotation and anterior–posterior translation on the wear of knee implants. Numerical wear prediction was performed using the finite element model along with two wear models, namely the contact pressure independent model and contact pressure dependent model. Addition of internal–external rotation significantly increased the wear, and the two wear models obtained similar results. The effect of internal–external rotation direction on wear was slight. Forward movement of the tibial insert during flexion decreased the wear under the contact pressure independent model and increased the wear under the contact pressure dependent model. When the AP direction switched, the two models obtained opposite wear tendencies. The results predicted by the contact pressure dependent model were consistent with those of wear tendency experiments reported in the literature. Further investigation of wear physical principles was necessary to gain a more reliable model. This study demonstrated that both internal–external rotation and anterior–posterior translation were pivotal factors influencing the contact mechanism and wear of total knee implants. More realistic kinematics are necessary for accurate wear assessment.
Flagellar Mutants Have Reduced Pilus Synthesis in
Caulobacter crescentus
Authors: Ellison Courtney K. , Rusch Douglas B. , Brun Yves V.
Published: July 2019

Most bacterial species synthesize surface-exposed appendages that are important for environmental interactions and survival under diverse conditions. It is often assumed that these appendages act independently of each other and that mutations in either system can be used to assess functionality in specific processes. However, we show that mutations in flagellar genes can impact the production of type IV pili, as well as alter general RNA transcriptional profiles compared to a wild-type strain. These data demonstrate that seemingly simple mutations can broadly affect cell-regulatory networks.
Primary HIV-1 Strains Use Nef To Downmodulate HLA-E Surface Expression
Authors: van Stigt Thans Thomas , Akko Janet I. , Niehrs Annika , Garcia-Beltran Wilfredo F. , Richert Laura , Stürzel Christina M. , Ford Christopher T. , Li Hui , Ochsenbauer Christina , Kappes John C. , Hahn Beatrice H. , Kirchhoff Frank , Martrus Glòria , Sauter Daniel , Altfeld Marcus , Hölzemer Angelique
Published: July 2019

For almost two decades, it was thought that HIV-1 selectively downregulated the highly expressed HLA-I molecules HLA-A and HLA-B from the cell surface in order to evade cytotoxic-T-cell recognition, while leaving HLA-C and HLA-E molecules unaltered. It was stipulated that HIV-1 infection thereby maintained inhibition of NK cells via inhibitory receptors that bind HLA-C and HLA-E. This concept was recently revised when a study showed that primary HIV-1 strains reduce HLA-C surface levels, whereas the cell line-adapted HIV-1 strain NL4-3 lacks this ability. Here, we demonstrate that infection with distinct primary HIV-1 strains results in significant downregulation of surface HLA-E levels. Given the increasing evidence for HLA-E as an important modulator of CD8+T-cell and NKG2A+NK cell functions, this finding has substantial implications for future immunomodulatory approaches aimed at harnessing cytotoxic cellular immunity against HIV.
Mycobacterium tuberculosis
Metabolism
Authors: Mashabela Gabriel T. , de Wet Timothy J. , Warner Digby F.
Published: July 2019

Mycobacterium tuberculosis
is the cause of tuberculosis (TB), a disease which continues to overwhelm health systems in endemic regions despite the existence of effective combination chemotherapy and the widespread use of a neonatal anti-TB vaccine. For a professional pathogen,
M. tuberculosis
retains a surprisingly large proportion of the metabolic repertoire found in nonpathogenic mycobacteria with very different lifestyles. Moreover, evidence that additional functions were acquired during the early evolution of the
M. tuberculosis
complex suggests the organism has adapted (and augmented) the metabolic pathways of its environmental ancestor to persistence and propagation within its obligate human host. A better understanding of
M. tuberculosis
pathogenicity, however, requires the elucidation of metabolic functions under disease-relevant conditions, a challenge complicated by limited knowledge of the microenvironments occupied and nutrients accessed by bacilli during host infection, as well as the reliance in experimental mycobacteriology on a restricted number of experimental models with variable relevance to clinical disease. Here, we consider
M. tuberculosis
metabolism within the framework of an intimate host-pathogen coevolution. Focusing on recent advances in our understanding of mycobacterial metabolic function, we highlight unusual adaptations or departures from the better-characterized model intracellular pathogens. We also discuss the impact of these mycobacterial “innovations” on the susceptibility of
M. tuberculosis
to existing and experimental anti-TB drugs, as well as strategies for targeting metabolic pathways. Finally, we offer some perspectives on the key gaps in the current knowledge of fundamental mycobacterial metabolism and the lessons which might be learned from other systems.
Carcinoma cervix with cerebellar metastases presenting with pulmonary aspiration: a rare presentation and a rare metastatic site in a common cancer
Authors: Chakrabarti Deep , Resu Abigail Veravolu , Pandey Amit , Gupta Rajeev
Published: July 2019

A 52-year-old woman with cervical cancer stage IIB presented with altered sensorium and breathlessness to the emergency room 5 months after completing primary chemoradiotherapy, which was diagnosed as aspiration pneumonia. She was found to have cerebellar metastases with additional frontal, occipital, and temporal lobe lesions. She had no evidence of extracranial disease. She received supportive care and palliative whole brain radiotherapy and was asymptomatic at 6 months following radiotherapy. Median reported survival is 8–13 months.
Hypertensive urgency in nephrogenic diabetes insipidus with concomitant Hinman syndrome
Authors: Tan Yu Guang , Chan Daniel Wei Keong , Yap Fabian Kok Peng , Yap Te-Lu
Published: July 2019

Diabetes insipidus is a syndrome characterised by the inability to conserve water or concentrate urine, leading to excessive excretion of urine. In congenital nephrogenic diabetes insipidus (CNDI), common presentations include failure to thrive, polydipsia, polyuria and dehydration. The long trajectory of the disease, coupled with psycho-behavioural changes as a child grows, can precipitate a period of non-adherence despite initial optimal control, especially in the adolescent age group. Social inconvenience of repeated voiding and nocturnal disturbances can lead to adapted urine holding behaviour, also known as non-neurogenic neurogenic bladder (Hinman syndrome). Anatomical changes in the urinary system, such as bladder trabeculation and hydroureteronephrosis, can subsequently give rise to functional renal impairment. We present a case of CNDI with concomitant Hinman syndrome, resulting in acute renal impairment and hypertensive emergency. We aim to raise awareness of the association between these two entities.
Cocaine-induced toxic leucoencephalopathy with complete clinical recovery
Authors: Abdilla Ylenia , Cauchi Marija , Vella Norbert
Published: July 2019

A 45-year-old man, a regular cocaine user, presented with confusion and unusual behaviour to the emergency room. On examination he was unable to perform simple tasks or follow commands. He was treated for possible central nervous system infection. MRI of the brain showed multiple bilateral T2 hyperintense periventricular and deep white matter foci, best appreciated on FLAIR with contrast enhancement. He continued deteriorating, eventually becoming catatonic with extensor posturing and increased tone, requiring intensive therapy unit management. Repeat MRIs were also noted to show worsening changes. He was treated for a presumed inflammatory leucoencephalopathy with intravenous methylprednisolone, immunoglobulins, as well as plasmapheresis. After 2 weeks, the patient started to show clinical improvement with eventual transfer to a rehabilitation hospital. A year after his first presentation, the patient scored 30 out of 30 on the MMSE and his neurological examination was normal.
Recanalisation of subclavian-pulmonary artery shunt in adult with tetralogy of Fallot
Authors: Moreno Escobar Eduardo , Segura-Rodriguez Diego , Rodriguez Torres Diego José , Garcia Orta Rocio
Published: July 2019

We report the case of a patient diagnosed with extreme tetralogy of Fallot who received subclavian-pulmonary artery shunt at the age of 3 years and underwent corrective surgery at the age of 16 years. The patient developed progressive effort dyspnea and left ventricular dysfunction from the age of 40 years. The exploratory finding of a continuous jugular and left subclavian murmur prompted an echocardiographic study that evidenced a continuous flow in the suprasternal view. CT study confirmed the patency of the surgical subclavian-pulmonary artery shunt, which was percutaneously embolised with the implantation of an Amplatzer plug, with a good final outcome and no residual flow. The patient showed a satisfactory development with clinical improvement, decreased left ventricular volume and enhanced left ventricular function.
Impact of surgical intervention on seizure and psychiatric symptoms in patients with temporal lobe epilepsy
Authors: Shahani Lokesh , Cervenka Gregory
Published: July 2019

Temporal lobe epilepsy (TLE), a common form of localisation-related epilepsy, is characterised by focal seizures and accompanied by variety of neuropsychiatric symptoms. This form of epilepsy proves difficult to manage as many anticonvulsant and psychotropic medications have little to no effect on controlling the seizure and neuropsychiatric symptoms respectively. The authors, report a patient with TLE and recurrent seizures that were refractory to multiple classes of antiepileptic therapy. Additionally, she exhibited psychosis, depression and irritability that required antipsychotic medication. After several years of poorly controlled seizure disorder, the patient underwent anterior temporal lobectomy and amygdalohippocampectomy, which proved beneficial for seizure control, as well as her neuropsychiatric symptoms. While it is common to treat refractory temporal lobe epilepsy with surgical interventions, there is little literature about it also treating the neuropsychiatric symptoms. This case underscores both the neurological and psychiatric benefits following surgical intervention for patients with TLE.
Successful ROTEM-guided transfusion therapy in a case of rural paediatric trauma
Authors: Choy Kay Tai , Hartslief Merve
Published: July 2019

Massive transfusion therapy in severe paediatric trauma is a challenge. When this occurs in a rural setting, the potential delays in accessing medical services can lead to worse coagulopathy on presentation. We report successful treatment of a child post-traumatic lower limb amputation where treatment was only initiated 3 hours postinjury due to difficulties in access/retrieval. Rotational thromboelastometry (ROTEM)-guided, goal-directed haemostatic therapy perioperatively utilising a blood product ratio of 2:2:1 units of red blood cell:free frozen plasma:platelet reverted his coagulopathy. This report aims to raise awareness of the utility of ROTEM in paediatric trauma.
Radiological evaluation of primary breast sarcoidosis presenting as bilateral breast lesions
Authors: Reis Joana , Boavida Joao , Lyngra Marianne , Geitung Jonn Terje
Published: July 2019

Sarcoidosis is an idiopathic multisystemic inflammatory disease that may exceptionally involve the breast and can have imaging features suspicious for benign or malignant lesions. Biopsy should be required to distinguish between breast sarcoidosis and malignancy, because clinical, mammographic and sonographic findings can be ambiguous or inconclusive. This case discusses the radiological manifestations and the value of different diagnostic features, and names the most relevant differential diagnosis.
Congenital protein C deficiency causing major arterial thrombosis in a neonate
Authors: Chakravarty Sanchari , Acharyya Saugata , Mahapatra Manas Kumar
Published: July 2019

A 9-day-old female baby presented with complaints of progressively worsening respiratory distress and lethargy. The parents were first cousins with history of multiple fetal losses in previous pregnancies. On examination, the baby was noted to be tachypnoeic, tachycardic with poor peripheral perfusion of the lower extremities. Femoral pulses on both sides were barely palpable. Echocardiography was normal. But cardiac catheterisation revealed the presence of an intraluminal obstruction of the distal aorta by a large thrombus. An attempt to dissolve the thrombus with urokinase infusion was unsuccessful. The affected vessels were then surgically explored and a large thrombus from the common iliac artery and distal abdominal aorta was removed. Following this, the child recovered uneventfully with return of lower limb pulsation. A thrombotic profile revealed the underlying diagnosis of congenital protein C deficiency responsible for the arterial thrombosis. This is an extremely unusual presentation, hardly ever been reported before.
Supreme dominance of right coronary artery in a patient with typical angina
Authors: Ahmed A Shaheer , Ghati Nirmal , Sharma Gautam , Malhi Amarinder Singh
Published: July 2019

A 50-year-old woman presented to our hospital with Canadian Cardiovascular Society grade III angina of 4 months duration. Coronary angiography of the patient showed the absence of left main coronary artery from the left coronary sinus. There was a single right coronary artery (RCA) with a super dominant course from right coronary sinus. It also showed a left main coronary and left anterior descending artery arising separately from proximal RCA, with retroaortic and prepulmonic course, respectively. There was another independently arising small septal branch from the proximal RCA that supplied the proximal interventricular septum. The patient was managed with optimal medical therapy and had symptomatic relief.
Posterior reversible encephalopathy syndrome, preeclampsia or stroke? A diagnostic dilemma
Authors: Patel Vikesh , Ramachandran Bhavna , Omar Ifrah
Published: July 2019

When a pregnant woman presents with headaches, visual disturbances, epigastric pain and nausea, preeclampsia quickly springs to mind. This case describes a primigravid 22-year-old female of 32 weeks gestation who presented with the symptoms described but was found to be apparently normotensive. Due to ongoing symptoms and diagnostic uncertainty in the absence of definitive evidence of preeclampsia, the patient was further investigated with an MRI brain scan, which was reported as either an acute stroke or an atypical presentation of posterior reversible encephalopathy syndrome. Together with blood results that showed heterozygosity for Factor V Leiden, we concluded that while the patient’s clinical diagnosis was certainly preeclampsia, her investigations also supported an unexpected diagnosis of silent brain infarction. This report outlines a diagnostic dilemma that required multidisciplinary working between obstetricians, neurologists, radiologists and stroke physicians to manage the patient who went on to make a full recovery and deliver a healthy baby.
Isolated growth hormone deficiency presenting with recurrent hypoglycaemia in a toddler
Authors: Boro Hiya , Goyal Alpesh , Khadgawat Rajesh
Published: July 2019

Hypoglycaemia in infants and children is caused by a number of endocrine and metabolic defects, some of which are unique to this age group. Growth hormone deficiency (GHD) has been rarely reported as a cause of recurrent fasting hypoglycaemia in children. An 18-month-old male child presented to us for evaluation of neuroglycopenic symptoms caused by recurrent episodes of fasting hypoglycaemia. Laboratory evaluation revealed ketotic hypoinsulinaemic hypoglycaemia. The child was diagnosed to have GHD on the basis of two failed stimulation tests. A detailed work-up for metabolic and other hormonal causes of hypoglycaemia was negative. We present the case for its rarity and to highlight the importance of a detailed metabolic and hormonal assessment in evaluation of childhood hypoglycaemia.
Second opinion utilization by healthcare insurance type in a mixed private-public healthcare system: a population-based study
Authors: Shmueli Liora , Shmueli Erez , Pliskin Joseph S , Balicer Ran D , Davidovitch Nadav , Hekselman Igal , Greenfield Geva
Published: July 2019

Objectives

To evaluate the utilisation (overall and by specialty) and the characteristics of second-opinion seekers by insurance type (either health fund or supplementary insurance) in a mixed private-public healthcare.

Design

An observational study.

Setting

Secondary care visits provided by a large public health fund and a large supplementary health insurance in Israel.

Participants

The entire sample included 1 392 907 patients aged 21 years and above who visited at least one specialist over an 18 months period, either in the secondary care or privately via the supplementary insurance.

Outcomes measures

An algorithm was developed to identify potential second-opinion instances in the dataset using visits and claims data. Multivariate logistic regression was used to identify characteristics of second-opinion seekers by the type of insurance they used.

Results

143 371 (13%) out of 1 080 892 patients who had supplementary insurance sought a single second opinion, mostly from orthopaedic surgeons. Relatively to patients who sought second opinion via the supplementary insurance, second-opinion seekers via the health fund tended to be females (OR=1.2, 95% CI 1.17 to 1.23), of age 40–59 years (OR=1.36, 95% CI 1.31 to 1.42) and with chronic conditions (OR=1.13, 95% CI 1.08 to 1.18). In contrast, second-opinion seekers via the supplementary insurance tended to be native-born and established immigrants (OR=0.79, 95% CI 0.76 to 0.84), in a high socioeconomic level (OR=0.39, 95% CI 0.37 to 0. 4) and living in central areas (OR=0.88, 95% CI 0.85 to 0.9).

Conclusions

Certain patient profiles tended to seek second opinions via the supplementary insurance more than others. People from the centre of the country and with a high socioeconomic status tended to do so, as medical specialists tend to reside in central urban areas. Further research is recommended to examine the availability of medical specialists by specialty and residence.
Factors associated with maternal postpartum fatigue: an observationalstudy
Authors: Henderson Jane , Alderdice Fiona , Redshaw Maggie
Published: July 2019

Objectives

To assess the prevalence of postpartum fatigue at 10 days, 1 month and 3 months, and to describe the sociodemographic and clinical characteristics of women with fatigue and the associations with infant characteristics, maternal–infant attachment, and partner and midwifery support.

Setting

Maternity care in England. Secondary analysis of 2014 National Maternity Survey.

Participants

Participants were a random sample of 10 000 women selected by the Office for National Statistics using birth registration records. Women aged less than 16 years or if their baby had died were excluded. Questionnaires were sent to women at 3 months post partum and asked about well-being and care during pregnancy, labour, birth and post partum. Specifically, women were asked whether they experienced fatigue/severe tiredness at 10 days, 1 month or 3 months post partum. Responses were received from 4578 women (47% response rate).

Results

Decreasing but substantial proportions of women, 38.8%, 27.1% and 11.4%, experienced fatigue/severe tiredness at 10 days, 1 month and 3 months, respectively. These figures varied significantly by maternal age, level of deprivation, education and parity. Women reporting depression, anxiety, sleep problems and those breast feeding were at significantly increased risk (eg, OR for depression in women with fatigue at 3 months: 2.99 (95% CI 2.13 to 4.21)). Significantly more negative language was used by these women to describe their babies, and they perceived their baby as more difficult than average (eg, two or more negative adjectives used by women with fatigue at 3 months: OR 1.86 (95% CI 1.36 to 2.54)). Women with postpartum fatigue had greater partner support but were significantly less likely to report seeing the midwife as much as they wanted.

Conclusions

Postpartum fatigue is not inevitable or universal, although early in the postnatal period it affects a substantial proportion of women. Predictors include age and parity, but practical help and support from partners and midwives may be protective factors.
Association of pre-pregnancy BMI and gestational weight gain with fat mass distribution and accretion during pregnancy and early postpartum: a prospective study of Albertan women
Authors: Subhan Fatheema B , Shulman Lisa , Yuan Yan , McCargar Linda J , Kong Linglong , Bell Rhonda C
Published: July 2019

Objectives

To examine the patterns of fat mass gain in pregnancy and fat loss in the early postpartum period relative to women’s pre-pregnancy body mass index (BMI) and by adherence to Institute of Medicine’s gestational weight gain (GWG) recommendations.

Design

Prospective cohort study with three to four study visits.

Setting

This study is a part of the prospective longitudinal birth cohort, ‘The Alberta Pregnancy Outcomes and Nutrition Study’ (APrON) that recruited pregnant women from the cities of Edmonton and Calgary in Alberta.

Participants

1820 pregnant women were recruited and followed through their pregnancy and at 3 months postpartum.

Outcome measures

Body weight and skinfold thicknesses were measured during pregnancy and early postpartum in women. Body density was calculated from sum of skinfold thickness (biceps, triceps, subscapula and suprailiac), and total fat mass accretion during pregnancy was calculated using Van Raaij’s equations and at postpartum using Siri’s equation. Differences in total fat mass gain, fat mass loss and fat retention according to pre-pregnancy BMI categories and GWG categories were tested using two-way analysis of variance and post hoc comparisons.

Results

Most women (64%) had a normal pre-pregnancy BMI, and overall 49% women exceeded the GWG recommendations. Obese women gained significantly less total fat mass, had lower fat mass loss and had lower postpartum fat retention than normal-weight women (p<0.05). Women with excessive GWG gained higher total fat mass and had higher postpartum fat mass retention (p<0.03) than women who met the GWG recommendations. Total GWG was positively correlated with total fat gain (r=0.61, p<0.01) and total fat retention (r=0.31, p<0.05).

Conclusion

Excessive GWG is the significant risk factor for higher fat mass accretion during pregnancy and higher postpartum fat retention, irrespective of pre-pregnancy BMI.
Improving access to primary healthcare for vulnerable populations in Australia and Canada: protocol for a mixed-method evaluation of six complex interventions
Authors: Russell Grant , Kunin Marina , Harris Mark , Levesque Jean-Frédéric , Descôteaux Sarah , Scott Catherine , Lewis Virginia , Dionne Émilie , Advocat Jenny , Dahrouge Simone , Stocks Nigel , Spooner Catherine , Haggerty Jeannie
Published: July 2019

Introduction

Access to primary healthcare (PHC) has a fundamental influence on health outcomes, particularly for members of vulnerable populations. Innovative Models Promoting Access-to-Care Transformation (IMPACT) is a 5-year research programme built on community-academic partnerships. IMPACT aims to design, implement and evaluate organisational innovations to improve access to appropriate PHC for vulnerable populations. Six Local Innovation Partnerships (LIPs) in three Australian states (New South Wales, Victoria and South Australia) and three Canadian provinces (Ontario, Quebec and Alberta) used a common approach to implement six different interventions. This paper describes the protocol to evaluate the processes, outcomes and scalability of these organisational innovations.

Methods and analysis

The evaluation will use a convergent mixed-methods design involving longitudinal (pre and post) analysis of the six interventions. Study participants include vulnerable populations, PHC practices, their clinicians and administrative staff, service providers in other health or social service organisations, intervention staff and members of the LIP teams. Data were collected prior to and 3–6 months after the interventions and included interviews with members of the LIPs, organisational process data, document analysis and tools collecting the cost of components of the intervention. Assessment of impacts on individuals and organisations will rely on surveys and semistructured interviews (and, in some settings, direct observation) of participating patients, providers and PHC practices.

Ethics and dissemination

The IMPACT research programme received initial ethics approval from St Mary’s Hospital (Montreal) SMHC #13–30. The interventions received a range of other ethics approvals across the six jurisdictions. Dissemination of the findings should generate a deeper understanding of the ways in which system-level organisational innovations can improve access to PHC for vulnerable populations and new knowledge concerning improvements in PHC delivery in health service utilisation.
Haemorrhage control in the prehospital setting: a scoping review protocol
Authors: Ezeibe Chibuike , McCarty Justin C , Chaudhary Muhammad A , De Jager Elzerie , Herrera-Escobar Juan , Andriotti Tomas , Jarman Molly P , Ortega Gezzer , Goralnick Eric
Published: July 2019

Introduction

Prehospital haemorrhage control has saved thousands of lives in the military over the last decade. While uncontrolled haemorrhage is a leading cause of preventable injury death in the USA for individuals under 45, military prehospital haemorrhage control techniques have not fully translated to the civilian sector in the USA. The effective implementation of haemorrhage control for civilian prehospital trauma is dependent on a more complex array of system and personnel-level factors than the military.

Objective

This protocol describes the methodology of a scoping review on haemorrhage control strategies in the prehospital setting; specifically, education, logistics and implementation of these strategies. The aim of the review is to identify research gaps and create recommendations for future research surrounding prehospital layperson haemorrhage control.

Methods

The protocol uses the framework published by The Joanna Briggs Institute and Arksey and O’Malley, while following the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols guidelines. The search strategy was refined with the help of a medical librarian. Three peer-reviewed databases (EMBASE, PubMed and Web of Science), databases dedicated to grey literature sources, and reference mining will be used. Two investigators will independently screen and extract data. Discrepancies will be resolved by a third investigator. The extracted data will undergo descriptive analysis of the contextual data and a quantitative analysis using the appropriate statistical methods. In addition, this search strategy will be supplemented by a grey literature search.

Ethics and dissemination

Research ethics approval is not required for this scoping review. This scoping review will serve to highlight existing gaps within the literature to guide further research and develop future strategies to improve prehospital haemorrhage management. The results of this review will be presented at relevant national and international conferences and published in a peer-reviewed journal.
Malnutrition, nutritional interventions and clinical outcomes of patients with acute small bowel obstruction: results from a national, multicentre, prospective audit
Authors: Lee Matthew James , Sayers Adele E , Drake Thomas M , Singh Pritam , Bradburn Mike , Wilson Timothy R , Murugananthan Aravinth , Walsh Ciaran J , Fearnhead Nicola S
Published: July 2019

Objective

The aim of this study was to assess the nutritional status of patients presenting with small bowel obstruction (SBO), along with associated nutritional interventions and clinical outcomes.

Design

Prospective cohort study.

Setting

131 UK hospitals with acute surgical services.

Participants

2069 adult patients with a diagnosis of SBO were included in this study. The mean age was 67.0 years and 54.7% were female.

Primary and secondary outcome measures

Primary outcome was in-hospital mortality. Secondary outcomes recorded included: major complications (composite of in-hospital mortality, reoperation, unplanned intensive care admission and 30-day readmission), complications arising from surgery (anastomotic leak, wound dehiscence), infection (pneumonia, surgical site infection, intra-abdominal infection, urinary tract infection, venous catheter infection), cardiac complications, venous thromboembolism and delirium.

Results

Postoperative adhesions were the most common cause of SBO (49.1%). Early surgery (<24 hours postadmission) took place in 30.0% of patients, 22.0% underwent delayed operation and 47.9% were managed non-operatively. Malnutrition as stratified by Nutritional Risk Index was common, with 35.7% at moderate risk and 5.7% at severe risk of malnutrition. Dietitian review occurred in just 36.4% and 55.9% of the moderate and severe risk groups. In the low risk group, 30.3% received nutritional intervention compared with 40.7% in moderate risk group and 62.7% in severe risk group. In comparison to the low risk group, patients who were at severe or moderate risk of malnutrition had 4.2 and 2.4 times higher unadjusted risk of in-hospital mortality, respectively. Propensity-matched analysis found no difference in outcomes based on use or timing of parenteral nutrition.

Conclusions

Malnutrition on admission is associated with worse outcomes in patients with SBO, and marked variation in management of malnutrition was observed. Future trials should focus on identifying effective and cost-effective nutritional interventions in SBO.
Lorcaserin for prevention and remission of type 2 diabetes mellitus in people with overweight or obesity: protocol for a systematic review and meta-analysis
Authors: Zeng Hai , Luo Meng , Li Zunjiang , Wen Junru , He Guoxin , Jin Yuelin , Fu Wenbin , Zhou Peng
Published: July 2019

Introduction

High body mass index (BMI) is associated with risk of diabetes. Lorcaserin is a selective 5-hydroxytryptamine 2C agonist which exerts robust benefits on long-term weight loss by suppressing appetite among adults with overweight or obesity. The magnitude of efficacy of lorcaserin for preventing and remitting type 2 diabetes mellitus (T2DM) among those people remains undefined. Therefore, we plan to conduct this systematic review and meta-analysis to aggregate data from all published studies with regard to the issue to acquire reliable evidence.

Methods and analysis

We will search various databases for relevant trials published up to June 2019. Randomised controlled trials investigating the efficacy of lorcaserin for preventing and remitting T2DM among overweight and obese population will be included. A standardised data form will be used to complete data search and extraction in duplicate. All discrepancies will be resolved by consensus. The primary outcome will be incidence of T2DM in patients with pre-diabetes. Secondary outcomes will include achievement of normoglycaemia in people with pre-diabetes, remission of hyperglycaemia in patients with diabetes, the proportion of patients with weight loss of at least 5% or 10% and hypoglycaemia incident. Data synthesis and statistical analysis will be performed for each outcome with Stata V.14.0.

Ethics and dissemination

Ethics approval is not required. Results of our study will be submitted to a peer-review journal.

PROSPERO registration number

CRD42019119136.