bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats
Authors: Tsai Chung-Min , Chang Shwu-Fen , Chang Hsi
Published: March 2022

Background

Convulsive status epilepticus (CSE) prevention is critical for pediatric patients with epilepsy. Immediate intervention before CSE reduce severity. Despite its wide usage as an anticonvulsant, valproic acid (VPA) results in harmful side effects such as dose-dependent hepatotoxicity. Hence, reducing VPA dosage to minimize side effects while maintaining its efficacy is necessary, and transcranial photobiomodulation (tPBM) add-on therapy could facilitate this. We recently demonstrated for the first time that tPBM at a wavelength of 808 nm attenuated CSE in peripubertal rats. However, the effects of VPA with the add-on therapy of tPBM prior to seizures have not yet been explored. This study investigated whether adding tPBM to VPA exerts synergistic effect for CSE prevention in peripubertal rats.

Methods

A gallium-aluminum-arsenide laser (wavelength of 808 nm with an exposure duration of 100 s and irradiance of 1.333 W/cm2at the target) was applied transcranially 30 min after VPA injection in Sprague Dawley rats. All the rats received 90 mg/kg of pentylenetetrazole (PTZ). Except for the saline (n = 3), tPBM + saline (n = 3), and PTZ group (n = 6), all the rats received a PTZ injection 30 min after VPA injection. The rats received add-on tPBM with PTZ immediately after tPBM. In the VPA + PTZ group, the rats received low-dose (100 mg/kg,n = 6), medium-dose (200 mg/kg,n = 6), and high-dose (400 mg/kg,n = 7) VPA. In the VPA + tPBM + PTZ group, the rats received low (100 mg/kg,n = 5), medium (200 mg/kg,n = 6), and high (400 mg/kg,n = 3) doses of VPA. Seizures were evaluated according to the revised Racine’s scale in a non-blinded manner.

Results

Adding tPBM to low-dose VPA reduced the incidence of severe status epilepticus and significantly delayed the latency to stage 2 seizures. However, adding tPBM to high-dose VPA increased the maximum seizure stage, prolonged the duration of stage 4–7 seizures, and shortened the latency to stage 6 seizures.

Conclusions

Adding tPBM to low-dose VPA exerted a synergistic prevention effect on PTZ-induced seizures, whereas adding tPBM to high-dose VPA offset the attenuation effect.
Workplace health promotion interventions for nurses in Germany: a systematic review based on the RE-AIM framework
Authors: Schaller Andrea , Gernert Madeleine , Klas Teresa , Lange Martin
Published: March 2022

Background

The German health care system is faced with a serious shortage of nurses. This is associated, amongst other things, with difficult working conditions and work-related health burdens. Workplace health promotion (WHP) is considered a promising approach to promote the health of nurses. The present review aims to give an overview on existing interventions in different nursing settings (acute care hospitals, long-term care (LTC) facilities and home-based long-term care) in Germany.

Methods

A systematic literature search was conducted in PubMed and PubPsych. Studies were included if published after 2010 and provided data of intervention studies on workplace health promotion among nurses in Germany (RCTs, non-RCTs, non-controlled intervention studies and pilot studies). The setting in which the study was conducted (acute medical care hospital, inpatient LTC facilities, home-based LTC, cross-setting) as well as the health issue assessed (physical health, mental health and/or violence experience) were extracted. The intervention was reported against the background of the quality criteria for prevention measures of the statutory health insurers in Germany. The results of the studies were presented according to the RE-AIM framework.

Results

Eleven studies on WHP for nurses were included, whereof seven studies were conducted in acute medical care hospitals and four in LTC facilities. No study reported results on WHP for nurses working in the setting of home-based LTC. Most studies aimed at improving mental health. The intervention contents and forms of implementation were heterogeneous. According to the RE-AIM criteria, the reporting of most studies showed several limitations, especially a lack of reporting on Implementation and Adoption. Most studies showed no statistically significant effect on the respective outcomes (Effectiveness). Four studies reported results on Maintenance indicating a sustained effectiveness.

Conclusion

Despite the high relevance for health promotion for nurses, our review showed a striking lack of intervention studies in this field. From this we derive a high need of tailored interventions, taking into account the setting-specific development, implementation of WHP interventions for nurses. With regard to the evaluation, the RE-AIM criteria should be taken more into account in order to meet the requirements of evaluating complex interventions and thus contribute to evidence development of WHP in nursing. In terms of content, the topic of violence prevention and dealing with experiences of violence should also be taken into account. Regarding the settings, the working conditions and health burdens in LTC facilities, home-based LTC and acute medical hospitals must be considered.

Trial registration

PROSPERO registration number: CRD42021231891
Experiences of and resistance to multiple discrimination in health care settings among transmasculine people of color
Authors: Agénor Madina , Geffen Sophia R. , Zubizarreta Dougie , Jones Raquel , Giraldo Shane , McGuirk Allison , Caballero Mateo , Gordon Allegra R.
Published: March 2022

Background

Research shows that transmasculine people experience discrimination based on their gender identity and/or expression (i.e., cissexism) while obtaining health care. However, studies examining the experience of other forms of discrimination in health care settings among diverse subgroups of transmasculine individuals, including those from minoritized racial/ethnic backgrounds, are very limited.

Methods

Guided by intersectionality, we designed a qualitative research study to explore how transmasculine people of color experience—and resist—multiple, intersecting forms of discrimination in health care settings. Guided by a purposive sampling strategy, we selected 19 transmasculine young adults of color aged 18–25 years to participate in 5 mini-focus groups conducted between February and May 2019 in Boston, MA. Focus group transcripts were analyzed using a template style approach to thematic analysis that involved both deductive and inductive coding using a codebook. Coded text fragments pertaining to participants’ experiences of health care discrimination were clustered into themes and sub-themes.

Results

Transmasculine people of color described experiencing notable challenges accessing physical and mental health care as a result of structural barriers to identifying health care providers with expertise in transgender health, finding providers who share one or more of their social positions and lived experiences, and accessing financial resources to cover high health care costs. Further, participants discussed anticipating and experiencing multiple forms of interpersonal discrimination—both independently and simultaneously—in health care settings, including cissexism, racism, weight-based discrimination, and ableism. Moreover, participants described the negative impact of anticipating and experiencing multiple interpersonal health care discrimination on their health care utilization, quality of care, and mental and physical health. Lastly, participants discussed using various strategies to resist the multiple, intersecting forms of discrimination they encounter in health care settings, including setting boundaries with health care providers, seeking care from competent providers with shared social positions, engaging in self-advocacy, drawing on peer support during health care visits, and obtaining health information through their social networks.

Discussion

Efforts are needed to address cissexism, racism, weight-based discrimination, ableism, and other intersecting forms of discrimination in clinical encounters, health care institutions and systems, and society in general to advance the health of transmasculine people of color and other multiply marginalized groups.
Assessing predictors of self-management intentions in people with type 2 diabetes
Authors: Nantha Yogarabindranath Swarna , Shan Tan Yan , Haque Shamsul , Zain Anuar Zaini Md
Published: March 2022

Background

Type 2 diabetes mellitus (T2D) is slowly turning into an international health emergency, evidenced by accelerated growth in prevalence rates worldwide. Experts have now called for greater integration of self-management interventions in clinical practice in light of these worrisome trends, supplanting the prevailing notion of a “glucocentric” approach. In this pilot study designed to complement a novel assessment program currently in development, we describe a concise screening tool designed to stratify the intention to follow through on self-management practices in people with T2D.

Methods

A cross-sectional survey was conducted at 3 regional primary care clinics. Individuals with T2D having the following characteristics were recruited into the study: (i) individuals with T2D between 18 and 65 years, (ii) fluent in English and, and iii) having been diagnosed with T2D for at least 2 years. We assessed the relevance of components in the Theory of Planned Behaviour (TPB) within the context of self-management behaviour in T2D. Participants were requested to complete a questionnaire containing questions related to intention, attitudes subjective norm and perceived behavioural control. Based on their responses, the psychometric properties of the scale were then evaluated using both reliability and validity analysis.

Results

The Cronbach α value for all direct measures of TPB was excellent: intention to adhere to self-management practices (0.98), attitude towards self-management behaviour (0.87), subjective norm (0.83), and perceived behaviour control (0.66). The correlation between intentions and all 3 constructs of TPB was excellent (p < 0.01). Structural equation modeling helped determine attitudes and subjective norms as important predictors of intentions to follow through self-management practices.

Conclusions

By first understanding the dimensions that influence intentions associated with self-management behaviour, clinicians have the opportunity to “triage” individuals with T2D who require greater involvement to bring about better self-care practices. Thus, our research attempts to bridge this gap by devising a psychometric tool suited to a regional setting which allows for an improved person-centered communication between clinicians and patients.
Patients’ and professionals’ perspectives on the consideration of patients’ convenient therapy periods as part of personalised rehabilitation: a focus group study with patients and therapists from inpatient neurological rehabilitation
Authors: Dür Mona , Wenzel Claudia , Simon Patrick , Tucek Gerhard
Published: March 2022

Background

Research on the optimal period for administering health services, especially rehabilitation interventions, is scarce. The aims of this study were to explore the construct of patients’ convenient therapy periods and to identify indicators based on the perspectives of patients and different health professionals from inpatient neurological rehabilitation clinics.

Methods

This study was part of a larger project on patients’ convenient therapy periods following a mixed methods approach. In the current study a grounded theory approach was employed based on the use of focus group interviews. Focus group interviews were conducted in three different inpatient neurological rehabilitation clinics. Patients and therapists from inpatient neurological rehabilitation clinics who were able to speak and to participate in conversations were included.

Results

A total of 41 persons, including 23 patients and 18 therapists, such as music and occupational therapists, participated in a total of six focus group interviews. The analysis of the focus group interviews resulted in the identification of a total of 1261 codes, which could be summarised in fifteen categories. However, these categories could be divided into five indicators and ten impact factors of convenient therapy periods. Identified indicators were verbal and non-verbal communication, mental functions, physiological needs, recreational needs, and therapy initiation.

Conclusions

The results provide initial evidence that convenient therapy periods are clinically relevant for patients and therapists. Different states of patients’ ability to effectively participate in a rehabilitation intervention exist. A systematic consideration of patients’ convenient therapy periods could contribute to a personalised and more efficient delivery of intervention in neurological rehabilitation. To our knowledge, this study is one of the first attempts to research convenient therapy periods.
The impact of an integrated safer use space and safer supply program on non-fatal overdose among emergency shelter residents during a COVID-19 outbreak: a case study
Authors: Lew Brendan , Bodkin Claire , Lennox Robin , O’Shea Timothy , Wiwcharuk Gillian , Turner Suzanne
Published: March 2022

Background

Opioid-related harms, including fatal and non-fatal overdoses, rose dramatically during the COVID-19 pandemic and presented unique challenges during outbreaks in congregate settings such as shelters. People who are deprived of permanent housing have a high prevalence of substance use and substance use disorders, and need nimble, rapid, and portable harm reduction interventions to address the harms of criminalized substance use in an evidence-based manner.

Case study

In February 2021, a COVID-19 outbreak was declared at an emergency men’s shelter in Hamilton, Ontario, Canada. Building on pre-existing relationships, community and hospital-based addictions medicine providers and a local harm reduction group collaborated to establish a shelter-based opioid agonist treatment and safer supply program, and a volunteer run safer drug use space that also distributed harm reduction supplies. In the 4 weeks preceding the program, the rate of non-fatal overdoses was 0.93 per 100 nights of shelter bed occupancy. During the 26 days of program operation, there were no overdoses in the safer use space and the rate of non-fatal overdoses in the shelter was 0.17 per 100 nights of shelter bed occupancy. The odds ratio of non-fatal overdose pre-intervention to during intervention was 5.5 (95% CI 1.63–18.55, p = 0.0059). We were not able to evaluate the impact of providing harm reduction supplies and did not evaluate the impact of the program on facilitating adherence to public health isolation and quarantine orders. The program ended as the outbreak waned, as per the direction from the shelter operator.

Conclusions

There was a significant reduction in the non-fatal overdose rate after the safer drug use and safer supply harm reduction program was introduced. Pre-existing relationships between shelter providers, harm reduction groups, and healthcare providers were critical to implementing the program. This is a promising approach to reducing harms from the criminalization of substance use in congregate settings, particularly in populations with a higher prevalence of substance use and substance use disorders.
Parasagittal dural space and cerebrospinal fluid (CSF) flow across the lifespan in healthy adults
Authors: Hett Kilian , McKnight Colin D. , Eisma Jarrod J. , Elenberger Jason , Lindsey Jennifer S. , Considine Ciaran M. , Claassen Daniel O. , Donahue Manus J.
Published: March 2022

Background

Recent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport.

Methods

We re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20–83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T1-weighted and T2-weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05).

Results

A significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman’s-$$\rho$$
ρ
 = 0.6), CSF volume (p < 0.001, Spearman’s-$$\rho$$
ρ
 = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow.

Conclusions

Findings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.
Exploring ITM2A as a new potential target for brain delivery
Authors: Cegarra Céline , Chaves C. , Déon C. , Do T. M. , Dumas B. , Frenzel A. , Kuhn P. , Roudieres V. , Guillemot J. C. , Lesuisse D.
Published: March 2022

Background

Integral membrane protein 2A (ITM2A) is a transmembrane protein expressed in a variety of tissues; little is known about its function, particularly in the brain. ITM2A was found to be highly enriched in human brain versus peripheral endothelial cells by transcriptomic and proteomic studies conducted within the European Collaboration on the Optimization of Macromolecular Pharmaceutical (COMPACT) Innovative Medicines Initiative (IMI) consortium. Here, we report the work that was undertaken to determine whether ITM2A could represent a potential target for delivering drugs to the brain.

Methods

A series of ITM2A constructs, cell lines and specific anti-human and mouse ITM2A antibodies were generated. Binding and internalization studies in Human Embryonic Kidney 293 (HEK293) cells overexpressing ITM2A and in brain microvascular endothelial cells from mouse and non-human primate (NHP) were performed with these tools. The best ITM2A antibody was evaluated in an in vitro human blood brain barrier (BBB) model and in an in vivo mouse pharmacokinetic study to investigate its ability to cross the BBB.

Results

Antibodies specifically recognizing extracellular parts of ITM2A or tags inserted in its extracellular domain showed selective binding and uptake in ITM2A-overexpressing cells. However, despite high RNA expression in mouse and human microvessels, the ITM2A protein was rapidly downregulated when endothelial cells were grown in culture, probably explaining why transcytosis could not be observed in vitro. An attempt to directly demonstrate in vivo transcytosis in mice was inconclusive, using either a cross-reactive anti-ITM2A antibody or in vivo phage panning of an anti-ITM2A phage library.

Conclusions

The present work describes our efforts to explore the potential of ITM2A as a target mediating transcytosis through the BBB, and highlights the multiple challenges linked to the identification of new brain delivery targets. Our data provide evidence that antibodies against ITM2A are internalized in ITM2A-overexpressing HEK293 cells, and that ITM2A is expressed in brain microvessels, but further investigations will be needed to demonstrate that ITM2A is a potential target for brain delivery.
Perceived impact of the patent linkage system on pharmaceutical market from the viewpoint of the domestic manufacturers in South Korea
Authors: Choi Nahye , Son Kyung-Bok , Byun Joonsoo , Yang Dong-Wook
Published: March 2022

Background

The United States requires a patent linkage system in other countries as part of free trade agreements. However, introducing a patent linkage system could be a significant barrier to the timely approval of generic drugs. This study aimed to evaluate the perceived impact of the patent linkage system in South Korea held by domestic manufacturers and analyze variations in evaluating the system according to the characteristics of domestic manufacturers.

Methods

In 2020, we conducted a questionnaire survey of 39 domestic manufacturers. The survey consisted of perceptions of the system, factors affecting patent challenges, and the perceived impact of the system. A 5-point Likert scale was used to rate each item. Domestic manufacturers were categorized into three groups based on their experience of listing a patent and acquiring first generic exclusivity.

Results

More than half of the manufacturers surveyed had experience of listing a patent. The patent linkage system could protect the involved patents. However, manufacturers perceived that they could successfully challenge the validity of the involved patents and then obtained market approval for generic drugs. Manufacturers responded that market size, expectations for succeeding in litigation, and expectations for manufacturing the drug were the most relevant factors when they initiated patent challenges. Manufacturers reported that the system, in particular the first generic exclusivity, enhanced the research and development capability of generic manufacturers, increased their domestic sales, and improved access to generic drugs.

Conclusions

The perceived impact of the patent linkage system was limited to the domestic market and generic drugs. In narrowing the impact to the effects on the domestic industry, the system had positive impacts of the system on generic manufacturers. The first generic drug exclusivity lies at the center of this positive perception. However, manufacturers perceived that the current system did not provide enough incentives for domestic manufacturers to be granted first generic drug exclusivity through patent challenges.
Lactation in quarantine: The (in)visibility of human milk feeding during the COVID-19 pandemic in the United States
Authors: Cohen Mathilde , Botz Corinne
Published: March 2022

Background

In response to the COVID-19 pandemic, billions of people were asked by their state and local governments not to go to work and not leave the house unless they had to. The goal of this qualitative study was to collect the lived experiences of a small group of parents and lactation professionals in the United States about what it was like to feed babies human milk under these conditions of quarantine.

Methods

This project is a social constructionist analysis of lactation narratives of 24 parents feeding their children human milk and 13 lactation professionals. They were interviewed remotely in 2020–21 via videoconferencing about their experiences and perspectives on the pandemic’s effect on lactation. Additionally, photographs of 16 of the parents are provided to visualize their practices and how they chose to represent them.

Results

Four interrelated themes were identified in participants’ narratives about how they experienced and made sense of human milk feeding during the pandemic: the loneliness of lactation during the pandemic, the construction of human milk as a resource to cope with the crisis, the (in)visibility of lactation amidst heightened multitasking, and the sense of connection created by human milk feeding at a time of unprecedented solitude.

Conclusions

While the pandemic may have had both positive and negative effects on lactation, it exposed continuing inequities in infant feeding, generating new forms of (in)visibility for lactating labor. Going forward, one lesson for policy and lawmakers may be that to adequately support lactation, they should take cues from the families who had positive experiences during the crisis. This would call for systemically overhauling of US laws and policies by guaranteeing: universal basic income, paid parental leave for at least six months, paid lactation leaves and breaks, affordable housing, universal health care, subsidized childcare programs, and equal access to high-quality, non-discriminatory, and culturally appropriate medical care—including lactation counseling—, among other initiatives.
Enablers and inhibitors of exclusive breastfeeding: perspectives from mothers and health workers in Accra, Ghana
Authors: Agyekum Martin Wiredu , Codjoe Samuel N. A. , Dake Fidelia A. A. , Abu Mumuni
Published: March 2022

Background

Despite the health and economic benefits of exclusive breastfeeding, there is evidence of a decline globally and in Ghana. Previous studies addressing this problem are mostly quantitative with only a few of such studies using qualitative or mixed methods to examine the predictors, benefits, ways of improving and managing exclusive breastfeeding, and the challenges associated with exclusive breastfeeding from the perspective of exclusive and nonexclusive breastfeeding mothers, and health workers. This study employs the health belief model to examine the experiences of mothers and health workers regarding exclusive breastfeeding to fill this gap in the literature.

Methods

A cross-sectional qualitative study involving in-depth interviews was conducted among health workers and mothers attending child welfare clinic at two polyclinics in Madina, Accra-Ghana in 2019. Purposive sampling was used to select health facilities and participants for the study. Twenty participants comprising ten exclusive breastfeeding mothers, six non-exclusive breastfeeding mothers and four health workers were interviewed for the study. The data were analyzed based on emerging themes from inductive and deductive coding.

Results

The decision to practice exclusive breastfeeding was based on mothers’ work, advertisement on exclusive breastfeeding and education on breastfeeding provided by health workers. Insufficient flow of breast milk, pressure from family and friends, and insufficient breast milk for infants were among the reasons for discontinuing exclusive breastfeeding. The factors that help improve exclusive breastfeeding include eating healthy food and breastfeeding on demand, while counselling and monitoring, restricting advertisement on infant formula and granting maternity leave for breastfeeding mothers were identified as factors that can  facilitate the practice of exclusive breastfeeding.

Conclusion

Different levels of experience affect and shape exclusive breastfeeding practice in Ghana. The decision to practice exclusive breastfeeding, as well as the challenges and strategies employed in managing exclusive breastfeeding, emanates from mothers’ personal experiences and interactions with institutional factors. In view of this, there should be counselling on the management of challenges associated with exclusive breastfeeding and provision of accurate information on exclusive breastfeeding to enable mothers practice exclusive breastfeeding.
High-throughput estimation of allele frequencies using combined pooled-population sequencing and haplotype-based data processing
Authors: Schneider Michael , Shrestha Asis , Ballvora Agim , Léon Jens
Published: March 2022

Background

In addition to heterogeneity and artificial selection, natural selection is one of the forces used to combat climate change and improve agrobiodiversity in evolutionary plant breeding. Accurate identification of the specific genomic effects of natural selection will likely accelerate transfer between populations. Thus, insights into changes in allele frequency, adequate population size, gene flow and drift are essential. However, observing such effects often involves a trade-off between costs and resolution when a large sample of genotypes for many loci is analysed. Pool genotyping approaches achieve high resolution and precision in estimating allele frequency when sequence coverage is high. Nevertheless, high-coverage pool sequencing of large genomes is expensive.

Results

Three pool samples (n = 300, 300, 288) from a barley backcross population were generated to assess the population's allele frequency. The tested population (BC2F21) has undergone 18 generations of natural adaption to conventional farming practice. The accuracies of estimated pool-based allele frequencies and genome coverage yields were compared using three next-generation sequencing genotyping methods. To achieve accurate allele frequency estimates with low sequence coverage, we employed a haplotyping approach. Low coverage allele frequencies of closely located single polymorphisms were aggregated into a single haplotype allele frequency, yielding 2-to-271-times higher depth and increased precision. When we combined different haplotyping tactics, we found that gene and chip marker-based haplotype analyses performed equivalently or better compared with simple contig haplotype windows. Comparing multiple pool samples and referencing against an individual sequencing approach revealed that whole-genome pool re-sequencing (WGS) achieved the highest correlation with individual genotyping (≥ 0.97). In contrast, transcriptome-based genotyping (MACE) and genotyping by sequencing (GBS) pool replicates were significantly associated with higher error rates and lower correlations, but are still valuable to detect large allele frequency variations.

Conclusions

The proposed strategy identified the allele frequency of populations with high accuracy at low cost. This is particularly relevant to evolutionary plant breeding of crops with very large genomes, such as barley. Whole-genome low coverage re-sequencing at 0.03 × coverage per genotype accurately estimated the allele frequency when a loci-based haplotyping approach was applied. The implementation of annotated haplotypes capitalises on the biological background and statistical robustness.
Sensor-based phenotyping of above-ground plant-pathogen interactions
Authors: Tanner Florian , Tonn Sebastian , de Wit Jos , Van den Ackerveken Guido , Berger Bettina , Plett Darren
Published: March 2022

Plant pathogens cause yield losses in crops worldwide. Breeding for improved disease resistance and management by precision agriculture are two approaches to limit such yield losses. Both rely on detecting and quantifying signs and symptoms of plant disease. To achieve this, the field of plant phenotyping makes use of non-invasive sensor technology. Compared to invasive methods, this can offer improved throughput and allow for repeated measurements on living plants. Abiotic stress responses and yield components have been successfully measured with phenotyping technologies, whereas phenotyping methods for biotic stresses are less developed, despite the relevance of plant disease in crop production. The interactions between plants and pathogens can lead to a variety of signs (when the pathogen itself can be detected) and diverse symptoms (detectable responses of the plant). Here, we review the strengths and weaknesses of a broad range of sensor technologies that are being used for sensing of signs and symptoms on plant shoots, including monochrome, RGB, hyperspectral, fluorescence, chlorophyll fluorescence and thermal sensors, as well as Raman spectroscopy, X-ray computed tomography, and optical coherence tomography. We argue that choosing and combining appropriate sensors for each plant-pathosystem and measuring with sufficient spatial resolution can enable specific and accurate measurements of above-ground signs and symptoms of plant disease.
Development of a controlled-environment assay to induce iron deficiency chlorosis in soybean by adjusting calcium carbonates, pH, and nodulation
Authors: Merry R. , Espina M. J. , Lorenz A. J. , Stupar R. M.
Published: March 2022

Background

Soybean iron deficiency chlorosis (IDC) is an important nutrient stress frequently found in high pH and/or soils high in calcium carbonates. To advance the understanding of IDC resistance in soybean, a rapid (21-day) controlled-environment assay was developed to investigate the effects of nodulation, pH, and calcium carbonate levels on soybean iron deficiency traits. This system was tested on four genotypes known to exhibit differences in iron efficiency, including two standard IDC check cultivars and a pair of near-isogenic lines exhibiting variation at an IDC resistance quantitative trait locus. Visual score, chlorophyll content, plant height, root dry mass, and shoot dry mass were measured to quantify iron stress.

Results

Calcium carbonate levels and nodulation were found to have the greatest effects on IDC severity. Increasing calcium carbonate levels worsened IDC symptoms, while nodulation reduced symptoms in all genotypes. Higher pH levels increased iron deficiency symptoms in check genotypes ‘Corsoy 79’ and ‘Dawson’, but did not induce iron deficiency symptoms in near-isogenic lines. A significant interaction was observed between genotype, nodulation, and calcium carbonate level, indicating that a specific treatment level could discern IDC symptoms between genotypes differing in resistance to IDC.

Conclusions

IDC symptoms were successfully induced in the Check Genotypes Experiment as well as the NIL Experiment, indicating the success of using this assay for inducing IDC in controlled environments. However, our results suggest that treatment levels that best differentiate genotypes for their IDC resistance may need to be determined for each experiment because of the unique way in which different genotypes display symptoms and respond to iron deficiency conditions.
Outcomes of proton therapy for non-small cell lung cancer in patients with interstitial pneumonia
Authors: Hashimoto Shingo , Iwata Hiromitsu , Hattori Yukiko , Nakajima Koichiro , Nomura Kento , Hayashi Kensuke , Toshito Toshiyuki , Yamamori Eiko , Akita Kenji , Mizoe Jun-etsu , Ogino Hiroyuki , Shibamoto Yuta
Published: March 2022

Background

Interstitial pneumonia (IP) is a disease with a poor prognosis. In addition, IP patients are more likely to develop lung cancer. Since IP patients frequently develop toxicities during cancer treatment, minimally invasive cancer treatment is warranted for such patients to maintain their quality of life. This study retrospectively investigated the efficacy and safety of proton therapy (PT) for non-small cell lung cancer (NSCLC) in patients with IP.

Methods

Twenty-nine NSCLC patients with IP were treated with PT between September 2013 and December 2019. The patients had stage IA to IIIB primary NSCLC. Ten of the 29 patients exhibited the usual interstitial pneumonia pattern. The prescribed dose was 66–74 Grays (relative biological effectiveness) in 10–37 fractions.

Results

The median follow-up period was 21.1 months [interquartile range (IQR), 15.6–37.3] for all patients and 37.2 months (IQR, 24.0–49.9) for living patients. The median patient age was 77 years (IQR, 71–81). The median planning target volume was 112.0 ml (IQR, 56.1–246.3). The 2-year local control, progression-free survival, and overall survival rates were 85% (95% confidence interval: 57–95), 30% (15–47), and 45% (26–62), respectively. According to the Common Terminology Criteria for Adverse Events (version 4.0), grade 3 acute radiation pneumonitis (RP) was observed in 1 patient. Two patients developed grade 3 late RP, but no other patients experienced serious toxicities. The patients’ quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 and SF-36) scores had not changed after 3 months.

Conclusions

﻿PT may be a relatively safe treatment for NSCLC patients with IP, without deteriorating quality of life scores within 3 months.
Sex differences in the relationship of hip strength and functional performance to chronic ankle instability scores
Authors: Lu Junlan , Wu Zhigang , Adams Roger , Han Jia , Cai Bin
Published: March 2022

Background

While decreased hip abductor strength, functional performance, and self-reported instability scores have all been shown in association with CAI, any sex difference in the relationship between these indicators is unclear. This study was to determine whether sex differences are present in the relationship between these indicators in individuals with CAI.

Methods

Thirty-two women and twenty-nine men with unilateral CAI took part. Hip abductor strength and functional performance were respectively assessed using a hand-held dynamometer and the figure-8-hop test. All 61 participants scored the Cumberland Ankle Instability Tool (CAIT) for self-reported ankle instability. Independent sample t-tests and correlation analysis were conducted.

Results

Normalized hip abductor strength and functional performance measures for females were lower than for males. The self-reported ankle instability CAIT score, where higher values represent less instability, was significantly and positively correlated with both normalized hip abductor strength (p = 0.003) and functional performance (p = 0.001) on the affected side in females, but not in males (p = 0.361 and p = 0.192 respectively).

Conclusions

Sex differences were observed in that there were significant relationships between normalized hip abductor strength, functional performance, and CAIT scores in female CAI participants, but not males, suggesting that CAI evaluation and rehabilitation strategies should be sex-specific.

Highlights

In females with CAI, hip abductor strength and functional performance showed significant relationships with self-reported instability scores.

Correspondingly, in clinical practice with individuals with CAI, evaluation criteria may be formulated according to these observed sex differences.

Sex differences should be factored into the evaluation and treatment of CAI individuals.

Hip strength assessment should be employed with CAI individuals.

Hip strengthening and functional hopping may be recommended for the rehabilitation of CAI, especially in female patients.
Hemorrhagic pericardial effusion resulting in constriction in hereditary hemorrhagic telangiectasia
Authors: Chung Joshua S. , Bylsma Ryan , Denham Laura J. , Hu Huayong , Mamdani Nirav , Bharadwaj Aditya , Rabkin David G.
Published: March 2022

Background

We report the first ante-mortem diagnosis of hemorrhagic pericardial effusion in hereditary hemorrhagic telangiectasia resulting in constriction; the case also demonstrates the unusual but well-described complication of right-sided heart failure requiring extracorporeal membrane oxygenation (ECMO) support after pericardiectomy.

Case presentation

A previously healthy 48 year old man with a strong family history of Osler–Weber–Rendu disease presented to our institution with signs and symptoms of advance heart failure. His workup demonstrated a thickened pericardium and constrictive physiology. He was brought to the operating room where old clot and inflamed tissue were appreciated in the pericardial space and he underwent complete pericardiectomy under cardiopulmonary bypass. Separation from bypass, hampered by the development of right ventricular dysfunction and profound vasoplegia, required significant pressor and inotropic support. The right heart dysfunction and vasoplegia worsened in the early postoperative period requiring a week of ECMO after which his right ventricle recovered and he was successfully de-cannulated.

Conclusion

Given the poor outcome of severe postoperative right ventricular failure after pericardiectomy, with high central venous pressure, a low gradient between central venous and pulmonary artery pressures and high vasopressor requirements, ECMO should be instituted promptly.
Complete recovery of deep venous thrombosis from Coombs (+) thrombotic thrombocytopenic purpura: case report
Authors: Zhou Mi , Yin Jie
Published: March 2022

Background

Acute thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic microangiopathy that if not treated, can have a 90% mortality rate. Timely, extensive plasma exchange (PEX) has been indicated to reduce the mortality rate to < 10%, but its side effects are not well-known. We present here a case of a patient presented with Comb (+) TTP and developed catheter-associated deep vein thrombosis (DVT).

Case presentation

A 27-year-young man presented with persistent thrombocytopenia and Coombs positive anemia was firstly diagnosed with Evans syndrome. However, he was refractory to a methylprednisolone pulse therapy with a combination of platelet transfusion and eventually developed microangiopathy of central nerve system. Several pathological manifestations of the disease were prevented by PEX. The immediate start of PEX (1500 mL/d) induced a complete remission of acquired TTP and disappearance of neurological signs and symptoms. However, external iliac and femoro-popliteal venous thrombosis was diagnosed subsequently, inferior vena cava filter (IVC) filter was immediately implanted accompanied with anticoagulation therapy. Meanwhile, PEX session was sustained as well as oral anticoagulant (rivaroxaban). 14 days later, the patient got full recovery.

Conclusions

Catheter-related DVT under the setting of TTP should be cautious. It is necessary to start anticoagulation and antiplatelet therapy for thrombosis early, especially in such cases when PLT count > 50 × 109/L.
Development of a patient journey map for people living with cervical dystonia
Authors: Benson Monika , Albanese Alberto , Bhatia Kailash P. , Cavillon Pascale , Cuffe Lorraine , König Kathrin , Reinhard Carola , Graessner Holm
Published: March 2022

Background

Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment.

Methods

The CDPJM was developed in 2 stages; a patient survey (open questions and multichoice) of 15 patients with CD was conducted to inform the design of the CDPJM, which was then refined and validated by an expert-patient focus group.

Results

Qualitative analysis of the patient survey supported five key stages of the patient journey: symptom onset, diagnosis and therapeutic relationship with healthcare professionals, initiation of care for CD, start of CD treatment, and living with treated CD. Following symptom onset, survey respondents described having multiple visits to their family doctor who prescribed strong pain killers and muscle relaxants and referred their patient to up to 10 different specialists for diagnosis. Over half (53.3%) of respondents had received ≥ 1 misdiagnosis. Respondents reported relief at having a diagnosis but a lack of understanding of the prognosis and treatment options; 46.7% said their neurologist did not spend enough time addressing their concerns. Survey respondents reported using a variety of alternative sources of information, including the internet (86.7%), self-help groups (66.7%) and information leaflets provided by health care professionals (60.0%). While botulinum toxin (BoNT) was consistently discussed as the main treatment option, some neurologists also mentioned physiotherapy, counselling, and other complementary approaches. However, patients were often left to seek complementary services themselves. Patients reported a ‘rollercoaster’ of relief with BoNT treatment with symptoms (and subsequent impact on daily life) returning towards the end of an injection cycle. “When BoNT works well I can return to an almost normal life … when the injections stop working so well, I have to rest more and avoid going to work and experience life restrictions.”

Conclusions

We present the first patient journey map for CD that can be used to guide local service mapping and to compare current provision with what patients say they want and need.
Symptoms and impacts of aromatic l-amino acid decarboxylase (AADC) deficiency among individuals with different levels of motor function
Authors: Williams Kate , Skrobanski Hanna , Buesch Katharina , Acaster Sarah
Published: March 2022

Background

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare neurological disorder associated with a range of symptoms and functional impairments. The aim of this study was to describe the experience of AADC deficiency across five different motor milestone health states.

Methods

Qualitative interviews were conducted with caregivers of individuals with AADC deficiency in Italy, Spain, Portugal and the United States. An interview guide was developed with input from clinical experts and caregivers, and explored the symptoms and impacts of AADC deficiency. Interviews were conducted by telephone and were recorded and transcribed. Data were analysed using thematic analysis and the symptoms and impacts were compared across health states.

Results

Fourteen caregivers took part, who provided care to 13 individuals with AADC deficiency aged 1–15 years. Six individuals were in the ‘no motor function’ health state, one in the ‘sitting unsupported’ health state, one in the ‘standing/stepping when fully supported’ health state and five in the ‘walking with minimal support’ health state. The results highlight a substantial impact of AADC deficiency, even among those who were able to walk with minimal support. Overall, those with better motor function also had better functional hand use, communication skills, ability to eat and perform other activities independently, and interact with their peers. The burden of caring was high across all health states, but caregivers of individuals in the walking health state were better able to participate in social and leisure activities.

Conclusion

Individuals with higher levels of motor function had less severe symptoms and were better able to perform their daily, leisure and social activities. Treatments which improve motor function have the potential to improve other aspects of the lives of individuals with AADC deficiency and their caregivers.
A brief history of MECP2 duplication syndrome: 20-years of clinical understanding
Authors: Ta Daniel , Downs Jenny , Baynam Gareth , Wilson Andrew , Richmond Peter , Leonard Helen
Published: March 2022

MECP2duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene—a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000. The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features—although these comorbidities are not yet understood with sufficient granularity. This review has covered the past two decades of MDS case studies and series since the discovery of the disorder in 1999. After comprehensively reviewing the reported characteristics, this review has identified areas of limited knowledge that we recommend may be addressed by better phenotyping this disorder through an international data collection. This endeavour would also serve to delineate the clinical overlap between MDS and RTT.