bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of the Analgesic Efficacy of CT‐Guided Percutaneous Pulsed Radiofrequency Treatment of Gasserian Ganglion in Patients With Idiopathic Trigeminal Neuralgia
Authors: Ren Hao , Zhao Chunmei , Jia Zipu , Bian Jiajia , Luo Fang
Published: May 2020

Aims

Although pulsed radiofrequency (PRF) has few postoperative adverse reactions, its analgesic efficacy for trigeminal neuralgia (TN) is not always guaranteed. The response rate of PRF targeting the Gasserian ganglion for patients with TN varies. This study aims to identify the predictors of the analgesic efficacy of CT‐guided percutaneous PRF in patients with idiopathic TN.

Methods

The patients with idiopathic TN who failed to respond to conservative treatment and underwent CT‐guided percutaneous PRF treatment of the Gasserian ganglion from July 2008 to August 2018 at our pain clinic were screened. A positive response was defined as a ≥50% reduction in the pain numeric rating scale (NRS) score from baseline. The demographics and other pretreatment clinical data were analyzed by logistic regression analysis to identify the predictors of a positive response.

Results

Of the total 102 patients with idiopathic TN who were evaluated in this study, 57 patients (55.9%) were positively responsive to our treatment after 1 year. The binary logistic regression analysis revealed that the positive response to a prior peripheral branch nerve block of the trigeminal nerve with steroid and local anesthetic agents was an independent predictor of the analgesic efficacy of PRF treatment (odds ratio [OR] = 3.685, 95% confidence interval [CI] = 1.583 to 8.577, P = 0.002). The disease duration of TN was also included in the multivariate regression model, although the P value was 0.058 (OR 0.807, 95% CI 0.646 to 1.007).

Conclusion

For patients who previously had positive responses to peripheral branch nerve block of the trigeminal nerve, PRF is likely to have better efficacy.
The photoperiodic response of hypocotyl elongation involves regulation of CDF1 and CDF5 activity
Authors: Martín Guiomar , Veciana Nil , Boix Marc , Rovira Arnau , Henriques Rossana , Monte Elena
Published: May 2020

Hypocotyl elongation relies on directional cell expansion, a process under light and circadian clock control. Under short photoperiods (SD), hypocotyl elongation in Arabidopsis thaliana follows a rhythmic pattern, a process in which circadian morning‐to‐midnight waves of the transcriptional repressors PSEUDO‐RESPONSE REGULATORS (PRRs) jointly gate PHYTOCHROME‐INTERACTING FACTOR (PIF) activity to dawn. Previously, we described CYCLING DOF FACTOR 5 (CDF5) as a target of this antagonistic PRR/PIF dynamic interplay. Under SD, PIFs induce CDF5 accumulation specifically at dawn, when it promotes the expression of positive cell elongation regulators such as YUCCA8 to induce growth. In contrast to SD, hypocotyl elongation under long days (LD) is largely reduced. Here, we examine whether CDF5 is an actor in this photoperiod specific regulation. We report that transcription of CDF5 is robustly induced in SD compared to LD, in accordance with PIFs accumulating to higher levels in SD, and in contrast to other members of the CDF family, whose expression is mainly clock regulated and have similar waveforms in SD and LD. Notably, when CDF5 was constitutively expressed under LD, CDF5 protein accumulated to levels comparable to SD but was inactive in promoting cell elongation. Similar results were observed for CDF1. Our findings indicate that both CDFs can promote cell elongation specifically in shorter photoperiods, however, their activity in LD is inhibited at the post‐translational level. These data not only expand our understanding of the biological role of CDF transcription factors, but also identify a previously unrecognized regulatory layer in the photoperiodic response of hypocotyl elongation.
Recovery of soil phosphorus on former bauxite mines through tropical forest restoration
Authors: Bizuti Denise T. G. , de Marchi Soares Thaís , Duarte Marina M. , Casagrande José C. , de Souza Moreno Vanessa , Peinado Francisco J. M. , Sartorio de Medeiros Simone D. , van Melis Juliano , Schweizer Daniella , Brancalion Pedro H. S.
Published: May 2020

Soil phosphorus (P) is a major driver of forest development and a critically limited nutrient in tropical soils, especially when topsoil is removed by mining. This nutrient can be present in soils in the form of different fractions, which have direct consequences for P availability to plants and, consequently, for restoration success. Therefore, understanding how the stocks of different soil P fractions change over the restoration process can be essential for guiding restoration interventions, monitoring, and adaptive management. Here, we investigated the recovery of soil P fractions by forest restoration interventions on bauxite mine sites in the Brazilian Atlantic Forest. We assessed the concentration of different fractions of soil organic and inorganic P at (1) a bauxite mine prepared for restoration; (2) two former bauxite mines undergoing forest restoration for 6 and 24 years; and (3) an old‐growth forest remnant. Overall, restored areas recovered levels of labile organic P (Po‐NaHCO3) at 5–40 cm and of moderately labile organic P (Po‐NaOH) at different depths, exhibiting concentrations similar to those found in a conserved forest. The use of P‐rich fertilizers and forest topsoil may have greatly contributed to this outcome. Some other fractions, however, recovered only after 24 years of restoration. Other inorganic P fractions did not differ among mined, restored, and conserved sites: nonlabile Pi (residual P and P‐HCl), labile Pi (Pi‐NaHCO3), and moderately labile Pi (Pi‐NaOH). Forest restoration was able to promote efficient recovery of important soil P fractions, highlighting the value of restoration efforts to mitigate soil degradation by mining.
The endosomal sorting complex required for transport complex negatively regulates Erg6 degradation under specific glucose restriction conditions
Authors: Zhang Ao , Meng Ying , Li Qunli , Liang Yongheng
Published: May 2020

Lipid droplets (LDs) are cytosolic fat storage organelles that play roles in lipid metabolism, trafficking and signaling. Breakdown of LDs in Saccharomyces cerevisiae is mainly achieved by lipolysis and lipophagy. In this study, we found that the endosomal sorting complex required for transport (ESCRT) in S. cerevisiae negatively regulated the turnover of a LD marker, Erg6, under both simplified glucose restriction (GR) and acute glucose restriction (AGR) conditions by monitoring the localization and degradation of Erg6. Loss of Vps27, Snf7 or Vps4, representative subunits of the ESCRT machinery, facilitated the delivery of Erg6‐GFP to vacuoles and its degradation depending on the lipophagy protein Atg15 under simplified GR. Additionally, the lipolysis proteins Tgl3 and Tgl4 were also involved in the enhanced vacuolar localization and degradation of Erg6‐GFP in vps4Δ cells. Furthermore, we found that Atg14, which is required for the formation of putatively liquid‐ordered (Lo) membrane domains on the vacuole that act as preferential internalization sites for LDs, abundantly localized to vacuolar membranes in ESCRT mutants. Most importantly, the depletion or overexpression of Atg14 correspondingly abolished or promoted the observed Erg6 degradation in ESCRT mutant cells. We propose that Atg14 together with other proteins promotes Erg6 degradation in ESCRT mutant cells under specific glucose restriction conditions. These results shed new light on the regulation of ESCRT on LD turnover.
Extensive clinical, serologic and molecular studies lead to the first reported Rhmod phenotype in Argentina
Authors: Mufarrege Nicolás , Franco Noelia , Trucco Boggione Carolina , Arnoni Carine , de Paula Vendrame Tatiane , Bartoli Sonia , Ensinck Alejandra , Principi Cintia , Lujan Brajovich Melina , Mattaloni Stella , Riquelme Bibiana , Biondi Claudia , Castilho Lilian , Cotorruelo Carlos
Published: May 2020

BACKGROUND

A highly reduced expression of Rh antigens in the erythrocyte membrane is the main feature of Rhmod, an extremely rare phenotype. Mutations within RHAG gene, which encodes RhAG glycoprotein and modulates Rh antigen expression and Rh complex formation, are the molecular events responsible for the Rhmod phenotype. Here we report a clinical, serologic, and molecular study of an Argentinean proband with Rh‐deficiency syndrome.

MATERIALS AND METHODS

Rh antigens, RhAG and CD47 glycoproteins were studied by serologic methods in the proband, her parents and sister. Osmotic fragility and viscoelastic parameters were also examined. RHD zygosity was analyzed by RFLP‐PCR. RHD, RHCE, and RHAG genes were studied by Sanger sequencing.

RESULTS

No Rh antigens were detected in the proband by standard techniques. However, adsorption‐elution and anti‐RhAG tests showed that the proposita was Rhmod. Reduced expression of CD47, enhanced osmotic fragility, and surface viscosity alterations giving rise to spherocytes were observed in the patient. Sequencing analysis showed that a c.920C>T mutation in RHAG Exon 6 was present in a homozygous state in the proband and in a heterozygous state in the rest of the family. This novel missense mutation caused the p.Ser307Phe amino acid substitution in Transmembrane Segment 10 of the RhAG glycoprotein.

CONCLUSION

This comprehensive study determined the causes of the probandʼs anemia allowing the diagnosis of Rh‐deficiency syndrome.
The effect of body position on intraocular pressure in anesthetized horses
Authors: Meekins Jessica M. , McMurphy Rose M. , Roush James K.
Published: May 2020

Objective

To evaluate the effect of four recumbent body positions on intraocular pressure (IOP) in anesthetized normal horses.

Animals studied

Ten nonglaucomatous adult horses.

Procedures

Intraocular pressure was measured with a rebound tonometer in both eyes of standing sedated horses (baseline), then under general anesthesia during four randomized recumbent body positions, including Trendelenburg (Tr; 15‐degree head down), reverse Trendelenburg (RTr; 15‐degree head up), dorsal, and lateral; only the superior eye was measured in lateral positions. The mean of 3 IOP readings was taken at each position, allowing a minimum of 2 minutes of acclimatization after each position change before obtaining measurements. Repeated Measures Analysis with Newman‐Keuls Multiple Comparison Post hoc was used to compare IOPs in different positions, and linear regression was used to compare IOP with age and weight cofactors.

Results

When compared to baseline, the greatest change in IOP occurred in Tr (increase of 25.63 ± 8.12 mm Hg). When comparing all recumbent positions to baseline, IOP significantly increased in 3 of 4 body positions (P < .001), with no significant difference identified between RTr and baseline. When comparing all body positions to each other, the greatest IOP difference occurred between the Tr and the RTr positions (increase of 26.95 ± 5.41 mm Hg). Age and weight were not correlated with IOP in any position.

Conclusions

Recumbent body position significantly increases IOP in normal eyes of horses under injectable anesthesia.
A novel cancer immunotherapy utilizing autologous tumour tissue
Authors: Park Haemin , Gladstone Matthew , Shanley Crystal , Goodrich Raymond , Guth Amanda
Published: May 2020

Background

With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells.

Materials and methods

We investigated a novel method for inactivating tumour cells that uses UVA/UVB light and riboflavin (vitamin B2) (RF + UV). RF + UV inactivates the tumour cells’ ability to replicate, yet preserves tumour cell integrity and antigenicity.

Results

Our results demonstrate that proteins are preserved on the surface of RF + UV‐inactivated tumour cells and that they are immunogenic via induction of dendritic cell maturation, increase in IFNγ production and generation of tumour cell‐specific IgG. Moreover, when formulated with an adjuvant (‘Innocell vaccine’) and tested in different murine tumour primary and metastatic disease models, decreased tumour growth, decreased metastatic disease and prolonged survival were observed. In addition, immune cells obtained from tumour tissue following vaccination had decreased exhausted and regulatory T cells, suggesting that activation of intra‐tumoural T cells may be playing a role leading to reduced tumour growth.

Conclusions

These data suggest that the RF + UV inactivation of tumour cells may provide an efficacious method for generating autologous whole tumour cell vaccines for use in cancer patients.
Brainstem inflammation modulates the ventilatory pattern and its variability after acute lung injury in rodents
Authors: Hsieh Yee‐Hsee , Litvin David G , Zaylor Abigail R , Nethery David E , Dick Thomas E , Jacono Frank J
Published: May 2020

Key points

Compared with sham rats, rats a week after acute lung injury (ALI) express more pro‐inflammatory cytokines in their brainstem respiratory control nuclei, exhibit a higher respiratory frequency (fR) and breathe with a more predictable pattern.

These characteristics of the respiratory pattern persist in in situ preparations even after minimizing pulmonary and chemo‐afferent inputs.

Interleukin (IL)‐1β microinjected in the nucleus tractus solitarii increases fR and the predictability of the ventilatory pattern similar to rats with ALI.

Intracerebroventricular infusion of indomethacin, an anti‐inflammatory drug, mitigates the effect of ALI on fR and ventilatory pattern variability.

We conclude that changes in the ventilatory pattern after ALI result not only from sensory input due to pulmonary damage and dysfunction but also from neuro‐inflammation.

Acute lung injury (ALI) increases respiratory rate (fR) and ventilatory pattern variability (VPV), but also evokes peripheral and central inflammation. We hypothesized that central inflammation has a role in determining the ventilatory pattern after ALI. In rat pups, we intratracheally injected either bleomycin to induce ALI or saline as a sham control. One week later, we recorded the ventilatory pattern of the rat pups using flow‐through plethysmography, then formed in situ preparations from these pups and recorded their ‘fictive’ patterns from respiratory motor nerves. Compared with the ventilatory pattern of the sham rat pups, injured rat pups had increased fR and predictability. Surprisingly, the fictive patterns of the in situ preparations from ALI pups retained these characteristics despite removing their lungs to eliminate pulmonary sensory inputs and perfusing them with hyperoxic artificial cerebral spinal fluid to minimize peripheral chemoreceptor input. Histological processing revealed increased immunoreactivity of the pro‐inflammatory cytokine Interleukin‐1β (IL‐1β) in the nucleus tractus solitarii (nTS) from ALI but not sham rats. In subsequent experiments, we microinjected IL‐1β in the nTS bilaterally in anaesthetized naïve adult rats, which increased fR and predictability of ventilatory pattern variability (VPV) after 2 h. Finally, we infused indomethacin intracerebroventricularly during the week of survival after ALI. This did not affect sham rats, but mitigated changes in fR and VPV in ALI rats. We conclude that neuro‐inflammation has an essential role in determining the ventilatory pattern of ALI rats.
Numerical Investigation of Combustion Instabilities in a Single-Element Lean Direct Inject Combustor Using Flamelet Based Approaches
Authors: Patwardhan Saurabh Sudhir , Nakod Pravin , Orsino Stefano , Arguinzoni Carlo
Published: May 2020

In this paper, high-fidelity large eddy simulations (LES) along with flamelet-based combustion models are assessed to predict combustion dynamics in low-emission gas turbine combustor. A model configuration of a single-element lean direct injection (LDI) combustor from Purdue University (Huang et al., 2014, “Combustion Dynamics Behavior in a Single-Element Lean Direct Injection (LDI) Gas Turbine Combustor,” 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, Cleveland, OH, July 28–30.) is used for the validation of simulation results. Two combustion models based on the flamelet concept, i.e., steady diffusion flamelet (SDF) model and flamelet generated manifold (FGM) model are employed to predict combustion instabilities. Simulations are carried out for two equivalence ratios of φ = 0.6, and 0.4. The results in the form of mode shapes, peak to peak pressure amplitude and power spectrum density (PSD) are compared with the experimental data of Huang et al. (2014, “Combustion Dynamics Behavior in a Single-Element Lean Direct Injection (LDI) Gas Turbine Combustor,” 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference, Cleveland, OH, July 28–30.). The effect of variation in the time-step size hence acoustic courant number is studied. Further, two numerical solver options, i.e., pressure-based segregated solver and pressure-based coupled solver, are used to understand their effect on the solution convergence regarding the number of time-steps required to reach the limit cycle of the pressure oscillations. A truncated (half) domain simulation is performed by applying an appropriate acoustic impedance boundary condition at the truncated location. Overall, the simulation results compare well with the experimental data and trends are captured accurately in all simulations. It builds confidence in flamelet-based combustion models for the use in combustion instability modeling which is traditionally done using finite rate chemistry models based on reduced kinetics.
The race is on for antibodies that stop the new coronavirus
Authors: Cohen Jon
Published: May 2020

Mass-produced immune proteins may outpace a vaccine.
Meet the psychobiome
Authors: Pennisi Elizabeth
Published: May 2020

Mounting evidence that gut bacteria influence the nervous system inspires efforts to mine the microbiome for brain drugs.
PIRs mediate innate myeloid cell memory to nonself MHC molecules
Authors: Dai Hehua , Lan Peixiang , Zhao Daqiang , Abou-Daya Khodor , Liu Wentao , Chen Wenhao , Friday Andrew J. , Williams Amanda L. , Sun Tao , Chen Jianjiao , Chen Wei , Mortin-Toth Steven , Danska Jayne S. , Wiebe Chris , Nickerson Peter , Li Tengfang , Mathews Lisa R. , Turnquist Hêth R. , Nicotra Matthew L. , Gingras Sebastien , Takayama Eiji , Kubagawa Hiromi , Shlomchik Mark J. , Oberbarnscheidt Martin H. , Li Xian C. , Lakkis Fadi G.
Published: May 2020

Innate immune cells remember

Immunological memory is a phenomenon by which immune cells can quickly recognize an antigen that the host has previously encountered. Certain cells of the innate immune system exhibit memory-like responses know as trained immunity. Rapid, antigen-specific secondary (anamnestic) responses were long thought to be the domain of B and T cells. However, Dai
et al.
report that monocytes and macrophages can acquire memory specific for particular major histocompatibility complex I antigens using paired A-type immunoglobulin-like receptors (PIR-As) (see the Perspective by Dominguez-Andrés and Netea). This pathway contributes to recognition and rejection of allograft-transplanted tissue from a donor of the same species. Genetic depletion or blockade of PIR-As in mice diminished the rejection of kidney and heart allografts. This work, which expands immunological memory to include myeloid cells, points to targets that may improve organ transplantation outcomes in the future.

Science
, this issue p.
1122
; see also p.
1052
Prenatal development of human immunity
Authors: Park Jong-Eun , Jardine Laura , Gottgens Berthold , Teichmann Sarah A. , Haniffa Muzlifah
Published: May 2020

The blood and immune systems develop in parallel during early prenatal life. Waves of hematopoiesis separated in anatomical space and time give rise to circulating and tissue-resident immune cells. Previous observations have relied on animal models, which differ from humans in both their developmental timeline and exposure to microorganisms. Decoding the composition of the human immune system is now tractable using single-cell multi-omics approaches. Large-scale single-cell genomics, imaging technologies, and the Human Cell Atlas initiative have together enabled a systems-level mapping of the developing human immune system and its emergent properties. Although the precise roles of specific immune cells during development require further investigation, the system as a whole displays malleable and responsive properties according to developmental need and environmental challenge.
Sending copper where it is needed most
Authors: Lutsenko Svetlana
Published: May 2020

Elesclomol improves survival in a mouse model of Menkes disease
Harnessing multiple models for outbreak management
Authors: Shea Katriona , Runge Michael C. , Pannell David , Probert William J. M. , Li Shou-Li , Tildesley Michael , Ferrari Matthew
Published: May 2020

Expert elicitation methods and a structured decision-making framework will help account for risk and uncertainty
Combination prevention for COVID-19
Authors: Cohen Myron S. , Corey Lawrence
Published: May 2020

The coronavirus disease 2019 (COVID-19) pandemic has produced the fear and disorder inevitably provoked by emerging pathogens. As such, it should also inspire consideration of our experience with HIV over the past 40 years. As with HIV, the road to reducing infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19), and attendant morbidity and mortality, requires medical and nonmedical strategies. The most important lesson learned from tackling HIV is to use a combination of prevention strategies.
Several Metarhizium Species Produce Ergot Alkaloids in a Condition-Specific Manner
Authors: Leadmon Caroline E. , Sampson Jessi K. , Maust Matthew D. , Macias Angie M. , Rehner Stephen A. , Kasson Matthew T. , Panaccione Daniel G.
Published: May 2020

Our discovery of ergot alkaloids in fungi of the genus
Metarhizium
has agricultural and pharmaceutical implications. Ergot alkaloids produced by other fungi in the family Clavicipitaceae accumulate in forage grasses or grain crops; in this context they are considered toxins, though their presence also may deter or kill insect pests. Our data report ergot alkaloids in
Metarhizium
species and indicate a close association of ergot alkaloid accumulation with insect colonization. The lack of accumulation of alkaloids in spores of the fungi and in plants colonized by the fungi affirms the safety of using
Metarhizium
species as biocontrol agents. Ergot alkaloids produced by other fungi have been exploited to produce powerful pharmaceuticals. The class of ergot alkaloids discovered in
Metarhizium
species (lysergic acid amides) and their secretion into the growth medium make
Metarhizium
species a potential platform for future studies on ergot alkaloid synthesis and modification.
Changes in the Microbiome of Mariculture Feed Organisms after Treatment with a Potentially Probiotic Strain of Phaeobacter inhibens
Authors: Dittmann Karen K. , Rasmussen Bastian Barker , Melchiorsen Jette , Sonnenschein Eva C. , Gram Lone , Bentzon-Tilia Mikkel
Published: May 2020

This work is an essential part of the risk assessment of the application of roseobacters as probiotics in mariculture. It provides insights into the impact of TDA-producing
Phaeobacter inhibens
on the commensal bacteria related to mariculture live feed and fish larvae. Also, the study provides a sequencing-based characterization of the microbiomes related to mariculture-relevant microalga, copepods, and turbot larvae.
A Sensitive Magnetic Arsenite-Specific Biosensor Hosted in Magnetotactic Bacteria
Authors: Dieudonné Anissa , Prévéral Sandra , Pignol David
Published: May 2020

Whole-cell biosensors based on reporter genes can be designed for heavy metal detection but often require the optimization of their sensitivity and specific adaptations for practical use in the field. Magnetotactic bacteria as cellular hosts for biosensors are interesting models, as their intrinsic magnetism permits them to be easily concentrated and entrapped to increase the arsenic-response signal. This paves the way for the development of sensitive and immobilized whole-cell biosensors tailored for use in the field.
Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity
Authors: Zhu Yuanmei , Yu Danwei , Yan Hongxia , Chong Huihui , He Yuxian
Published: May 2020

The COVID-19 pandemic, caused by SARS-CoV-2, presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor binding and membrane fusion, thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein has evolved a high level of activity to mediate cell-cell fusion, significantly differing from the S protein of SARS-CoV that emerged previously. The HR1 sequence in the fusion protein of SARS-CoV-2 adopts a much higher helical stability than the HR1 sequence in the fusion protein of SARS-CoV and can interact with the HR2 site to form a six-helical bundle structure more efficiently, underlying the mechanism of the enhanced fusion capacity. Also, importantly, the design of membrane fusion inhibitors with high potencies against both SARS-CoV-2 and SARS-CoV has provided potential arsenals to combat the pandemic and tools to exploit the fusion mechanism.
Herpes Simplex Virus 1 ICP34.5 Alters Mitochondrial Dynamics in Neurons
Authors: Manivanh Richard , Mehrbach Jesse , Charron Audra J. , Grassetti Andrew , Cerón Stacey , Taylor Sean A. , Cabrera Jorge Rubén , Gerber Scott , Leib David A.
Published: May 2020

Herpes simplex virus persists lifelong in neurons and can reactivate to cause recurrent lesions in mucosal tissues. A key determinant of virulence is the viral protein ICP34.5, of which residues 68 to 87 significantly contribute to neurovirulence through an unknown mechanism. Our report provides evidence that residues 68 to 87 of ICP34.5 are required for binding mitochondrion-associated factors. These interactions alter mitochondrial dynamics in neurons, thereby facilitating viral replication and pathogenesis.
Role of tacrolimus in return of hand function after brachial plexus injury in a lung transplantation patient
Authors: Saffari Tiam M , Arendt Christopher J , Spinner Robert J , Shin Alexander Y
Published: May 2020

We report a patient who has been on tacrolimus for bilateral lung transplantation and presented with a brachial plexus injury (BPI), with unusual improvement of lower trunk innervated hand function. The lower trunk injury with resultant left hand paralysis had developed after his sternotomy 18 months ago. He has been treated with tacrolimus as part of his immunosuppression protocol since the surgery, without severe side effects. Physical examination at 18 months demonstrated unusual excellent grip pattern and full opposition of his thumb with slight claw deformity of his ulnar two digits. While the neurotoxic effects of tacrolimus are more emphasised, the neuroregenerative properties have been recently explored. The recovery in this patient is unique and unusual after BPI and is most likely as a result of the low dose tacrolimus treatment.
Prevalence and sociodemographic determinants of dyspepsia in the general population of Rwanda
Authors: Bangamwabo Jean Bosco , Chetwood John David , Dusabejambo Vincent , Ntirenganya Cyprien , Nuki George , Nkurunziza Arcade , Kieffer Kelly A , Jones Michael , Walker Timothy D
Published: May 2020

Introduction

Dyspepsia accounts for a significant burden of worldwide disease, but there is a relative paucity of data from the sub-Saharan African setting. We undertook to describe the burden, risk factors and severity of dyspepsia across Rwanda.

Methods

We performed a population-based clustered cross-sectional survey between November 2015 and January 2016, nationwide in Rwanda, using the Short Form Leeds Dyspepsia Questionnaire to describe the presence and severity of dyspepsia, and the Short Form Nepean Dyspepsia Index to describe the concomitant quality of life effects. Univariate and multivariate logistic regression models were constructed to correlate measured sociodemographic factors with dyspepsia.

Results

The prevalence of clinically significant dyspepsia in the general Rwandan population was 14.2% (283/2000). The univariate factors that significantly predicted severity were gender, profession, socioeconomic status, and non-steroidal anti-inflammatory drug, aspirin and alcohol use, with gender, current smoking, aspirin use both in the past and currently, and alcohol use in the past remaining significant on multivariate modelling. Dyspeptics had a significantly lower gastrointestinal-related quality of life, though the sociodemographic factors measured did not modify the observed quality of life.

Conclusion

Dyspepsia is prevalent in the Rwandan setting and is associated with a significant burden on quality of life. More work is required to determine the pathological entities involved, and the optimal approach to mitigating this burden.
Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women’s Health Initiative Clinical Trial
Authors: Parikh Nisha I , Kapphahn Kristopher , Hedlin Haley , Olgin Jeffrey E , Allison Matthew A , Magnani Jared W , Ryckman Kelli R , Waring Molly E , Perez Marco Valentin , Howard Barbara V
Published: May 2020

Objectives

Pregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women’s Health Initiative Clinical Trials.

Design

Secondary analysis of multicentre clinical trial.

Setting

USA.

Primary outcome measures

ECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval.

Participants

n=40 687 women (mean age=62 years) participating in the Women’s Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian.

Methods

In primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use.

Results

Among participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (–0.56 to 1.88), 1=0.15 (–0.71 to 1.02), 2–4=0.25 (–0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (−0.07 to –0.01).

Conclusions

An increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life.

Trial registration number

NCT00000611; Post-results.
Impact of maternity waiting homes on facility delivery among remote households in Zambia: protocol for a quasiexperimental, mixed-methods study
Authors: Scott Nancy A , Kaiser Jeanette L , Vian Taryn , Bonawitz Rachael , Fong Rachel M , Ngoma Thandiwe , Biemba Godfrey , Boyd Carol J , Lori Jody R , Hamer Davidson H , Rockers Peter C
Published: May 2020

Introduction

Maternity waiting homes (MWHs) aim to improve access to facility delivery in rural areas. However, there is limited rigorous evidence of their effectiveness. Using formative research, we developed an MWH intervention model with three components: infrastructure, management and linkage to services. This protocol describes a study to measure the impact of the MWH model on facility delivery among women living farthest (≥10 km) from their designated health facility in rural Zambia. This study will generate key new evidence to inform decision-making for MWH policy in Zambia and globally.

Methods and analysis

We are conducting a mixed-methods quasiexperimental impact evaluation of the MWH model using a controlled before-and-after design in 40 health facility clusters. Clusters were assigned to the intervention or control group using two methods: 20 clusters were randomly assigned using a matched-pair design; the other 20 were assigned without randomisation due to local political constraints. Overall, 20 study clusters receive the MWH model intervention while 20 control clusters continue to implement the ‘standard of care’ for waiting mothers. We recruit a repeated cross section of 2400 randomly sampled recently delivered women at baseline (2016) and endline (2018); all participants are administered a household survey and a 10% subsample also participates in an in-depth interview. We will calculate descriptive statistics and adjusted ORs; qualitative data will be analysed using content analysis. The primary outcome is the probability of delivery at a health facility; secondary outcomes include utilisation of MWHs and maternal and neonatal health outcomes.

Ethics and dissemination

Ethical approvals were obtained from the Boston University Institutional Review Board (IRB), University of Michigan IRB (deidentified data only) and the ERES Converge IRB in Zambia. Written informed consent is obtained prior to data collection. Results will be disseminated to key stakeholders in Zambia, then through open-access journals, websites and international conferences.

Trial registration number

NCT02620436; Pre-results.
Direct inpatient costs and influencing factors for patients with rectal cancer with low anterior resection: a retrospective observational study at a three-tertiary hospital in Beijing, China
Authors: Chen Zhishui , Leng Jiahua , Gao Guangying , Zhang Lianhai , Yang Yang
Published: May 2020

Objectives

The aim of the study was to investigate the direct inpatient cost and analyse influencing factors for patients with rectal cancer with low anterior resection in Beijing, China.

Design

A retrospective observational study.

Setting

The study was conducted at a three-tertiary oncology institution.

Participants

A total of 448 patients who underwent low anterior resection and were diagnosed with rectal cancer from January 2015 to December 2016 at Peking University Cancer Hospital were retrospectively identified. Demographic, clinical and cost data were determined.

Results

The median inpatient cost was￥89 064, with a wide range (￥46 711–￥191 329) due to considerable differences in consumables. The material cost accounted for 52.19% and was the highest among all the cost components. Colostomy (OR 4.17; 95% CI 1.79 to 9.71), complications of hypertension (OR 5.30; 95% CI 1.94 to 14.42) and combined with other tumours (OR 2.92; 95% CI 1.12 to 7.60) were risk factors for higher cost, while clinical pathway (OR 0.10; 95% CI 0.03 to 0.35), real-time settlement (OR 0.26; 95% CI 0.10 to 0.68) and combined with cardiovascular disease (OR 0.09; 95% CI 0.02 to 0.52) were protective determinants.

Conclusions

This approach is an effective way to relieve the economic burden of patients with cancer by promoting the clinical pathway, optimising the payment scheme and controlling the complication. Further research focused on the full-cost investigation in different stages of rectal cancer based on a longitudinal design is necessary.
Children’s and caregivers’ perspectives about mandatory reporting of child maltreatment: a meta-synthesis of qualitative studies
Authors: McTavish Jill R , Kimber Melissa , Devries Karen , Colombini Manuela , MacGregor Jennifer C D , Wathen Nadine , MacMillan Harriet L
Published: May 2020

Objective

To systematically synthesise qualitative research that explores children’s and caregivers’ perceptions of mandatory reporting.

Design

We conducted a meta-synthesis of qualitative studies.

Data sources

Searches were conducted in Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Criminal Justice Abstracts, Education Resources Information Center, Sociological Abstracts and Cochrane Libraries.

Eligibility criteria

English-language, primary, qualitative studies that investigated children’s or caregivers’ perceptions of reporting child maltreatment were included. All healthcare and social service settings implicated by mandatory reporting laws were included.

Data extraction and synthesis

Critical appraisal of included studies involved a modified checklist from the Critical Appraisal Skills Programme (CASP). Two independent reviewers extracted data, including direct quotations from children and caregivers (first-order constructs) and interpretations by study authors (second-order constructs). Third-order constructs (the findings of this meta-synthesis) involved synthesising second-order constructs that addressed strategies to improve the mandatory reporting processes for children or caregivers—especially when these themes addressed concerns raised by children or caregivers in relation to the reporting process.

Results

Over 7935 citations were retrieved and 35 articles were included in this meta-synthesis. The studies represent the views of 821 caregivers, 50 adults with histories of child maltreatment and 28 children. Findings suggest that children and caregivers fear being reported, as well as the responses to reports. Children and caregivers identified a need for improvement in communication from healthcare providers about mandatory reporting, offering preliminary insight into child-driven and caregiver-driven strategies to mitigate potential harms associated with reporting processes.

Conclusion

Research on strategies to mitigate potential harms linked to mandatory reporting is urgently needed, as is research that explores children’s experiences with this process.
Prevalence of nocturnal cough in asthma and its potential as a marker for asthma control (MAC) in combination with sleep quality: protocol of a smartphone-based, multicentre, longitudinal observational study with two stages
Authors: Tinschert Peter , Rassouli Frank , Barata Filipe , Steurer-Stey Claudia , Fleisch Elgar , Puhan Milo Alan , Brutsche Martin , Kowatsch Tobias
Published: May 2020

Introduction

Nocturnal cough is a burdensome asthma symptom. However, knowledge about the prevalence of nocturnal cough in asthma is limited. Furthermore, prior research has shown that nocturnal cough and impaired sleep quality are associated with asthma control, but the association between these two symptoms remains unclear. This study further investigates the potential of these symptoms as markers for asthma control and the accuracy of automated, smartphone-based passive monitoring for nocturnal cough detection and sleep quality assessment.

Methods and analysis

The study is a multicentre, longitudinal observational study with two stages. Sensor and questionnaire data of 94 individuals with asthma will be recorded for 28 nights by means of a smartphone. On the first and the last study day, a participant’s asthma will be clinically assessed, including spirometry and fractionated exhaled nitric oxide levels. Asthma control will be assessed by the Asthma Control Test and sleep quality by means of the Pittsburgh Sleep Quality Index. In addition, nocturnal coughs from smartphone microphone recordings will be labelled and counted by human annotators. Relatively unrestrictive eligibility criteria for study participation are set to support external validity of study results. Analysis of the first stage is concerned with the prevalence and trends of nocturnal cough and the accuracies of smartphone-based automated detection of nocturnal cough and sleep quality. In the second stage, patient-reported asthma control will be predicted in a mixed effects regression model with nocturnal cough frequencies and sleep quality of past nights as the main predictors.

Ethics and dissemination

The study was reviewed and approved by the ethics commission responsible for research involving humans in eastern Switzerland (BASEC ID: 2017–01872). All study data will be anonymised on study termination. Results will be published in medical and technical peer-reviewed journals.

Trial registration number

NCT03635710; Pre-results.
Protocol for a mixed-methods exploratory investigation of care following intensive care discharge: the REFLECT study
Authors: Vollam Sarah , Gustafson Owen , Hinton Lisa , Morgan Lauren , Pattison Natalie , Thomas Hilary , Young J Duncan , Watkinson Peter
Published: May 2020

Introduction

A substantial number of patients discharged from intensive care units (ICUs) subsequently die without leaving hospital. It is unclear how many of these deaths are preventable. Ward-based management following discharge from ICU is an area that patients and healthcare staff are concerned about. The primary aim of REFLECT (Recovery Following Intensive Care Treatment) is to develop an intervention plan to reduce in-hospital mortality rates in patients who have been discharged from ICU.

Methods and analysis

REFLECT is a multicentre mixed-methods exploratory study examining ward care delivery to adult patients discharged from ICU. The study will be made up of four substudies. Medical notes of patients who were discharged from ICU and subsequently died will be examined using a retrospective case records review (RCRR) technique. Patients and their relatives will be interviewed about their post-ICU care, including relatives of patients who died in hospital following ICU discharge. Staff involved in the care of patients post-ICU discharge will be interviewed about the care of this patient group. The medical records of patients who survived their post-ICU stay will also be reviewed using the RCRR technique. The analyses of the substudies will be both descriptive and use a modified grounded theory approach to identify emerging themes. The evidence generated in these four substudies will form the basis of the intervention development, which will take place through stakeholder and clinical expert meetings.

Ethics and dissemination

Ethical approval has been obtained through the Wales Research and Ethics Committee 4 (17/WA/0107). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media.

Trial registration number

ISRCTN14658054.
Incidentally diagnosed cancer and commonly preceding clinical scenarios: a cross-sectional descriptive analysis of English audit data
Authors: Koo Minjoung Monica , Rubin Greg , McPhail Sean , Lyratzopoulos Georgios
Published: May 2020

Objectives

Cancer can be diagnosed in the absence of tumour-related symptoms, but little is known about the frequency and circumstances preceding such diagnoses which occur outside participation in screening programmes. We aimed to examine incidentally diagnosed cancer among a cohort of cancer patients diagnosed in England.

Design

Cross-sectional study of national primary care audit data on an incident cancer patient population.

Setting

We analysed free-text information on the presenting features of cancer patients aged 15 or older included in the English National Audit of Cancer Diagnosis in Primary Care (2009–2010). Patients with screen-detected cancers or prostate cancer were excluded. We examined the odds of incidental cancer diagnosis by patient characteristics and cancer site using logistic regression, and described clinical scenarios leading to incidental diagnosis.

Results

Among the studied cancer patient population (n=13 810), 520 (4%) patients were diagnosed incidentally. The odds of incidental cancer diagnosis increased with age (p<0.001), with no difference between men and women after adjustment. Incidental diagnosis was most common among patients with leukaemia (23%), renal (13%) and thyroid cancer (12%), and least common among patients with brain (0.9%), oesophageal (0.5%) and cervical cancer (no cases diagnosed incidentally). Variation in odds of incidental diagnosis by cancer site remained after adjusting for age group and sex.

There was a range of clinical scenarios preceding incidental diagnoses in primary or secondary care. These included the monitoring or management of pre-existing conditions, routine testing before or after elective surgery, and the investigation of unrelated acute or new conditions.

Conclusions

One in 25 patients with cancer in our population-based cohort were diagnosed incidentally, through different mechanisms across primary and secondary care settings. The epidemiological, clinical, psychological and economic implications of this phenomenon merit further investigation.
Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review
Authors: Tatalovic Milos , Lehmann Roger , Cheetham Marcus , Nowak Albina , Battegay Edouard , Rampini Silvana K
Published: May 2020

Objectives

What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy?

Design

We conducted a systematic literature review.

Data sources

We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018.

Eligibility criteria

We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies.

Data extraction and synthesis

We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines.

Results

Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control.

Conclusion

The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control.

PROSPERO registration number

CRD42015024739.