bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a menstrual hygiene intervention in urban and rural schools in Bangladesh: a pilot study
Authors: Alam Mahbub-Ul , Sultana Farhana , Hunter Erin C. , Winch Peter J. , Unicomb Leanne , Sarker Supta , Mahfuz Mehjabin Tishan , Al-Masud Abdullah , Rahman Mahbubur , Luby Stephen P.
Published: June 2022

Girls’ menstrual experiences impact their social and educational participation, physical and psychological health. We conducted a pilot study to assess the acceptability and feasibility of a multi-component intervention intended to support menstruating girls; improve menstrual care knowledge, practices, and comfort; and increase school attendance.

We conducted a pre/post evaluation of a 6-month pilot intervention in four schools (2 urban, 2 rural) in Dhaka, Bangladesh. We selected 527 schoolgirls (grades 5 to 10; aged 10 to 17 years) for a baseline survey and 528 girls at endline. The intervention included: 1) Menstrual Hygiene Management (MHM) packs– reusable cloth pads, underwear, carry bags and menstrual cycle tracking calendars, 2) education curriculum- pictorial flipcharts, puberty related-booklets, and teachers’ training to deliver puberty and MHM sessions, 3) maintenance- improvements to school sanitation, provision of disposable pads in the school office, provision of chute disposal systems for disposable pads, and gender committees to promote a gender-friendly school environment and maintenance of intervention facilities. We estimated intervention uptake and intervention effect by calculating prevalence differences and 95% confidence intervals using fixed-effects logistic regression.

The intervention uptake was more than 85% for most indicators; 100% reported receiving puberty education, 85% received MHM packs, and 92% received booklets. Reusable cloth pads uptake was 34% by endline compared with 0% at baseline. Knowledge about menstrual physiology and knowledge of recommended menstrual management practices significantly improved from baseline to endline. Reported improvements included more frequent changing of menstrual materials (4.2 times/day at endline vs. 3.4 times/day at baseline), increased use of recommended disposal methods (prevalence difference (PD): 8%; 95% Confidence Interval: 1, 14), and fewer staining incidents (PD: − 12%; 95% CI: − 22, − 1). More girls reported being satisfied with their menstrual materials (59% at endline vs. 46% at baseline, p < 0.005) and thought school facilities were adequate for menstrual management at endline compared to baseline (54% vs. 8%, p < 0.001). At endline, 64% girls disagreed/strongly disagreed that they felt anxious at school due to menstruation, compared to 33% at baseline (p < 0.001). Sixty-five percent girls disagreed/strongly disagreed about feeling distracted or trouble concentrating in class at endline, compared to 41% at baseline (p < 0.001). Self-reported absences decreased slightly (PD: − 8%; 95% CI: − 14, − 2).

Uptake of cloth pads, improved maintenance and disposal of menstrual materials, and reduced anxiety at school suggest acceptability and feasibility of the intervention aiming to create a supportive school environment.
Delayed-onset radiculopathy caused by a retropulsed bone fragment after percutaneous kyphoplasty: report of four cases and literature review
Authors: Lee Yi-Hsuan , Chen Po-Quang , Wu Chung-Ting
Published: June 2022

Background

Vertebral compression fractures caused by osteoporosis are common in elderly patients and are often encountered by clinical physicians. Percutaneous balloon kyphoplasty (PKP) is widely accepted as a minimally invasive procedure for effectively relieving pain and correcting deformities, but complications may occur. Radiculopathy with a delayed onset caused by a retropulsed bone fragment has not been adequately described in the literature. Thus, this article presents a case report of four cases of retropulsed bone fragment-related radiculopathy after PKP.

Case presentation

In this article, we reported that four out of 251 patients developed radiculopathy after PKP between January 2012 and January 2019 despite experiencing substantial improvements in back pain. All patients with radiculopathy were female and diagnosed with osteoporosis, and their ages ranged from 68 to 89 years. Radiculopathy occurred from 2 to 16 weeks after PKP. All four patients underwent another operation (posterior decompression and instrumentation). Three patients recovered completely, and one died of postoperative intracranial haemorrhage. A detailed imaging study with pre- and postoperative magnetic resonance imaging (MRI) revealed that retropulsed bone fragments that impinged on the corresponding root after PKP were responsible for this complication, and all four patients developed a disrupted posterior vertebral rim preoperatively. No leakage of cement or pedicle track violations were observed.

Conclusion

Although PKP is a safe and effective treatment for painful osteoporotic vertebral compression fractures, a risk of catastrophic neurological injury remains. Radiculopathy with delayed onset caused by a retropulsed bone fragment after kyphoplasty is rare and challenging to treat, and the integrity of the posterior vertebral cortex should be carefully evaluated preoperatively to prevent this complication.
A finite element model of the shoulder: application to the changes of biomechanical environment induced by postoperative malrotation of humeral shaft fracture
Authors: Wang Cheng , Ma Xiao-yuan , Lu Lin-tao , Guo Zheng , Dai Guo-feng
Published: June 2022

Objectives

The humerus fracture is one of the most commonly occurring fractures. In this research, we attempted to evaluate and compare the extent of malrotation and biomechanical environment after surgical treatment of humeral shaft fractures.

Methods

A finite element (FE) model of the shoulder was built based on Computed Tomography (CT) data of a patient with a humeral shaft fracture. The muscle group around the shoulder joint was simulated by spring elements. The changes of shoulder stresses under rotation were analyzed. The biomechanics of the normal shoulder and postoperative malrotation of the humeral shaft was analyzed and compared.

Results

During rotations, the maximum stress was centered in the posterosuperior part of the glenoid for the normal shoulder. The von Mises shear stresses were 4.40 MPa and 4.89 MPa at 40° of internal and external rotations, respectively. For internal rotation deformity, the shear contact forces were 7–9 times higher for the shoulder internally rotated 40° than for the normal one. For external rotation deformity, the shear contact forces were about 3–5 times higher for the shoulder with 40° external rotation than the normal one.

Conclusion

Postoperative malrotation of humeral shaft fracture induced the changes of the biomechanical environment of the shoulders. The peak degree of malrotation was correlated with increased stresses of shoulders, which could be paid attention to in humeral shaft fracture treatment. We hoped to provide information about the biomechanical environment of humeral malrotation.
A hierarchy of needs for remote undergraduate medical education: lessons from the medical student experience
Authors: Besche Henrike C. , Onorato Sarah , Pelletier Stephen , Ashrafzadeh Sepideh , Joshi Ashwini , Nelsen Brenna , Yoon Jaewon , Zhou Joyce , Schwartz Andrea , Cockrill Barbara A.
Published: June 2022

Purpose

The disruption of undergraduate medical education (UME) by the COVID-19 pandemic has sparked rapid, real-time adjustments by medical educators and students. While much is known about online teaching in general, little guidance is available to medical educators on how to adapt courses not originally designed for the online environment. To guide our faculty in this transition we conducted a needs assessment of students enrolled in virtual courses across all 4 years of UME training.

Methods

Using a mixed-methods approach, we conducted a single-institution virtual learning needs assessment in May and June of 2020. We developed and disseminated a survey to assess student experiences with virtual learning. We conducted quantitative and qualitative analysis of responses (n = 255 or 39%) to identify emergent themes.

Results

We identified six interdependent themes that need to be met for medical students to fully reach their learning potential: access to stable internet and quiet study spaces, flexible course design with asynchronous, self-paced components, clear expectations for engagement with content and each other, a sense of connectedness with faculty and peers, synchronous classes that maximize interactivity, and assessments that foster a sense of learning over performance. Interpersonal relationships with faculty and peers affected students’ sense of learning more than any other factor.

Conclusions

Based on our findings we propose a hierarchy of needs for virtual learning that provides guidance on adapting existing medical school courses to the remote setting and overcoming common challenges. We highlight opportunities for how virtual elements may enrich in-person courses going forward, including in the clinical setting. Although the solutions required to meet the threshold of need at each level may differ based on the context, attending to these same fundamental needs can be extrapolated and applied to learners across a range of environments beyond the virtual.
Developing and validating the nursing presence scale for hospitalized patients
Authors: Atashzadeh-Shoorideh Foroozan , Parvizy Soroor , Hosseini Meimanat , Raziani Yosra , Mohammadipour Fatemeh
Published: June 2022

Aim

We developed and psychometrically tested the Nursing Presence Scale.

Background

Nursing presence is a foundation for professional nursing practice; therefore, it is critical to measure this concept.

Introduction

This instrument development study was designed to generate an itemized scale and psychometric testing using a sample of Iranian patients.

Methods

Based on both a concept development and literature review, and finally face and content validity 44-item draft scale was generated. During November 2018–2019, 774 patients were surveyed. Exploratory and confirmatory factor analyses were used to evaluate the scale’s construct validity; concurrent and predictive reliability of the nursing presence scale were also evaluated. We also examine the weighting to scale items.

Results

The analyses yielded a 36-item, 4-factor scale that adequately fit the data. Cronbach’s alpha coefficient for the whole instrument was 0.94. The intra class correlation coefficient was 0.91. Nursing Presence Scale scores were positively correlated with Revised Humane Caring Scale and predicted 25% of missed nursing care.

Conclusion

This 36-item has good reliability and validity, making it useful for measuring the current condition of nursing presence.

Implications for Nursing and Health Policy

Measuring the frequency of nursing presence allows for data-driven planning and upgrading the inpatient care services.
Inherent constraints on a polyfunctional tissue lead to a reproduction-immunity tradeoff
Authors: Gupta Vanika , Frank Ashley M. , Matolka Nick , Lazzaro Brian P.
Published: June 2022

Background

Single tissues can have multiple functions, which can result in constraints, impaired function, and tradeoffs. The insect fat body performs remarkably diverse functions including metabolic control, reproductive provisioning, and systemic immune responses. How polyfunctional tissues simultaneously execute multiple distinct physiological functions is generally unknown. Immunity and reproduction are observed to trade off in many organisms but the mechanistic basis for this tradeoff is also typically not known. Here we investigate constraints and trade-offs in the polyfunctional insect fat body.

Results

Using single-nucleus sequencing, we determined that theDrosophila melanogasterfat body executes diverse basal functions with heterogenous cellular subpopulations. The size and identity of these subpopulations are remarkably stable between virgin and mated flies, as well as before and after infection. However, as an emergency function, the immune response engages the entire tissue and all cellular subpopulations produce induce expression of defense genes. We found that reproductively active females who were given bacterial infection exhibited signatures of ER stress and impaired capacity to synthesize new protein in response to infection, including decreased capacity to produce antimicrobial peptides. Transient provision of a reversible translation inhibitor to mated females prior to infection rescued general protein synthesis, specific production of antimicrobial peptides, and survival of infection.

Conclusions

The commonly observed tradeoff between reproduction and immunity appears to be driven, inD. melanogaster, by a failure of the fat body to be able to handle simultaneous protein translation demands of reproductive provisioning and immune defense. We suggest that inherent cellular limitations in tissues that perform multiple functions may provide a general explanation for the wide prevalence of physiological and evolutionary tradeoffs.
Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity
Authors: Ziko Laila , AbdelRaheem Omnia , Nabil Marina , Aziz Ramy K. , Siam Rania
Published: June 2022

Background

The search for novel antimicrobial agents is crucial as antibiotic-resistant pathogens continue to emerge, rendering the available antibiotics no longer effective. Likewise, new anti-cancer drugs are needed to combat the emergence of multi-drug resistant tumors. Marine environments are wealthy sources for natural products. Additionally, extreme marine environments are interesting niches to search for bioactive natural compounds. In the current study, a fosmid library of metagenomic DNA isolated from Atlantis II Deep Lower Convective Layer (ATII LCL), was functionally screened for antibacterial activity as well as anticancer effects.

Results

Two clones exhibited antibacterial effects against the marine Bacillus Cc6 strain, namely clones 102-5A and 88-1G and they were further tested against eleven other challenging strains, including six safe relatives of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter  spp.), a safe relative to Mycobacterium tuberculosis and four resistant clinical isolates. Clone 88-1G resulted in clear zones of inhibition against eight bacterial strains, while clone 102-5A resulted in zones of inhibition against five bacterial strains. The whole cell lysates of clone 88-1G showed 15% inhibition of Mtb ClpP protease -Mycobacterium tuberculosis drug target-, while whole cell lysates of clone 102-5A showed 19% inhibition of Mtb ClpP protease. Whole cell lysates from the selected clones exhibited anticancer effects against MCF-7 breast cancer cells (cell viability at 50% v/v was 46.2% ± 9.9 for 88-1G clone and 38% ± 7 for 102-5A clone), U2OS osteosarcoma cells (cell viability at 50% v/v was 64.6% ± 12.3 for 88-1G clone and 28.3% ± 1.7 for 102-5A clone) and 1BR hTERT human fibroblast cells (cell viability at 50% v/v was 74.4% ± 5.6 for 88-1G clone and 57.6% ± 8.9 for 102-5A clone). Sequencing of 102-5A and 88-1G clones, and further annotation detected putative proteases and putative biosynthetic genes in clones 102-5A and 88-1G, respectively.

Conclusions

The ATII LCL metagenome hosts putative peptidases and biosynthetic genes that confer antibiotic and anti-cancer effects. The tested clones exhibited promising antibacterial activities against safe relative strains to ESKAPE pathogens and Mycobacterium tuberculosis. Thus, searching the microbial dark matter of extreme environments is a promising approach to identify new molecules with pharmaceutical potential use.
Engineered Bacillus subtilis for the de novo production of 2′-fucosyllactose
Authors: Zhang Quanwei , Liu Zhenmin , Xia Hongzhi , Huang Ziyang , Zhu Yonglian , Xu Linfeng , Liu Yanfeng , Li Jianghua , Du Guocheng , Lv Xueqin , Liu Long
Published: June 2022

Background

The most abundant human milk oligosaccharide in breast milk, 2′-fucosyllactose (2′-FL), has been approved as an additive to infant formula due to its multifarious nutraceutical and pharmaceutical functions in promoting neonate health. However, the low efficiency of de novo synthesis limits the cost-efficient bioproduction of 2′-FL.

Results

This study achieved 2′-FL de novo synthesis in a generally recognized as safe (GRAS) strain Bacillus subtilis. First, a de novo biosynthetic pathway for 2′-FL was introduced by expressing the manB, manC, gmd, wcaG, and futC genes from Escherichia coli and Helicobacter pylori in B. subtilis, resulting in 2′-FL production of 1.12 g/L. Subsequently, a 2′-FL titer of 2.57 g/L was obtained by reducing the competitive lactose consumption, increasing the regeneration of the cofactor guanosine-5′-triphosphate (GTP), and enhancing the supply of the precursor mannose-6-phosphate (M6P). By replacing the native promoter of endogenous manA gene (encoding M6P isomerase) with a constitutive promoter P7, the 2′-FL titer in shake flask reached 18.27 g/L. The finally engineered strain BS21 could produce 88.3 g/L 2′-FL with a yield of 0.61 g/g lactose in a 3-L bioreactor, without the addition of antibiotics and chemical inducers.

Conclusions

The efficient de novo synthesis of 2′-FL can be achieved by the engineered B. subtilis, paving the way for the large-scale bioproduction of 2′-FL titer in the future.
A review on the role of PTENP1 in human disorders with an especial focus on tumor suppressor role of this lncRNA
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Taheri Mohammad , Akbari Dilmaghani Nader
Published: June 2022

PTENP1 is a long non-coding RNA which has been regarded as a pseudogene of thePTENtumor suppressor gene. However, it has been shown to be a biologically active transcript that can function as a competing endogenous RNA and enhance expression of PTEN protein. This lncRNA has two transcripts, namely PTENP1-202 and PTENP1-202 with sizes of 3996 and 1215 bps, respectively. PTENP1 acts as a sponge for some PETN-targeting miRNAs, such as miR-17, miR-20a, miR-19b, miR-106b, miR-200c, miR-193a-3p, miR-499-5p and miR-214. Besides, it can affect miR-20a/PDCD4, miR-27a-3p/EGR1, miR-17‐5p/SOCS6 and miR-19b/TSC1 axes. This long non-coding RNA participates in the pathoetiology of several types of cancers as well as non-malignant conditions such as alcohol-induced osteopenia, insulin resistance, osteoporosis, sepsis-associated cardiac dysfunction and spinal cord injury. In the current review, we elucidate the role of PTENP1 in human disorders, particularly malignant conditions based on evidence acquired from cell line assays, animal studies and investigations on human samples.
Using ecological observations to improve malaria control in areas where Anopheles funestus is the dominant vector
Authors: Kahamba Najat F. , Finda Marceline , Ngowo Halfan S. , Msugupakulya Betwel J. , Baldini Francesco , Koekemoer Lizette L. , Ferguson Heather M. , Okumu Fredros O.
Published: June 2022

The most important malaria vectors in sub-Saharan Africa areAnopheles gambiae, Anopheles arabiensis, Anopheles funestus, andAnopheles coluzzii. Of these,An. funestuspresently dominates in many settings in east and southern Africa. While research on this vector species has been impeded by difficulties in creating laboratory colonies, available evidence suggests it has certain ecological vulnerabilities that could be strategically exploited to greatly reduce malaria transmission in areas where it dominates. This paper examines the major life-history traits ofAn. funestus, its aquatic and adult ecologies, and its responsiveness to key interventions. It then outlines a plausible strategy for reducing malaria transmission by the vector and sustaining the gains over the medium to long term. To illustrate the propositions, the article uses data from south-eastern Tanzania whereAn. funestusmediates over 85% of malaria transmission events and is highly resistant to key public health insecticides, notably pyrethroids. Both male and femaleAn. funestusrest indoors and the females frequently feed on humans indoors, although moderate to high degrees of zoophagy can occur in areas with large livestock populations. There are also a few reports of outdoor-biting by the species, highlighting a broader range of behavioural phenotypes that can be considered when designing new interventions to improve vector control. In comparison to other African malaria vectors,An. funestusdistinctively prefers permanent and semi-permanent aquatic habitats, including river streams, ponds, swamps, and spring-fed pools. The species is therefore well-adapted to sustain its populations even during dry months and can support year-round malaria transmission. These ecological features suggest that highly effective control ofAn. funestuscould be achieved primarily through strategic combinations of species-targeted larval source management and high quality insecticide-based methods targeting adult mosquitoes in shelters. If done consistently, such an integrated strategy has the potential to drastically reduce local populations ofAn. funestusand significantly reduce malaria transmission in areas where this vector species dominates. To sustain the gains, the programmes should be complemented with gradual environmental improvements such as house modification to maintain biting exposure at a bare minimum, as well as continuous engagements of the resident communities and other stakeholders.
Egocentric network characteristics of people who inject drugs in the Chicago metro area and associations with hepatitis C virus and injection risk behavior
Authors: Mackesy-Amiti Mary Ellen , Falk Joshua , Latkin Carl , Kaufmann Maggie , Williams Leslie , Boodram Basmattee
Published: June 2022

Background

Hepatitis C (HCV) infection has been rising in the suburban and rural USA, mainly via injection-based transmission. Injection and sexual networks are recognized as an important element in fostering and preventing risky behavior; however, the role of social support networks has received somewhat less attention.

Methods

Using baseline data from an ongoing longitudinal study, we examined the composition and structure of injection drug use (IDU), sex, and social support networks of young people who inject drugs (aged 18–30) and their injection network members. Lasso logistic regression was used to select a subset of network characteristics that were potentially important predictors of injection risk behaviors and HCV exposure.

Results

Several measures of IDU, sexual, and support network structure and composition were found to be associated with HCV exposure, receptive syringe sharing (RSS), and ancillary equipment sharing. Gender and sexual relationships were important factors for all risk behaviors. Support network characteristics were also important, notably including a protective effect of majority Hispanic support networks for RSS and HCV exposure. Both IDU network residence heterogeneity and support network geography were associated with injection equipment sharing.

Conclusions

The associations of IDU and support network geography with equipment sharing highlight the need to extend harm reduction efforts beyond urban areas. Greater understanding of support network influences on risk behavior may provide important insights to strengthen the benefits of harm reduction. In considering the probability of HCV transmission, it is important to consider setting and network structures that promote propagation of risk.
The safety of a novel single-drape cover for sterile back tables in the operating room compared to the standard two-drape method: an experimental study
Authors: Zarei Mohammadreza , Babajani-Vafsi Saeed , Kazemi-Galougahi Mohammad Hassan , Bakhshi Ashraf , Ajorpaz Neda Mirbagher , Ghorbani Mahdi
Published: June 2022

Background

Covering the prepared sterile back tables (PSBTs) during periods of nonuse and during active surgeries may decrease contamination of sterile surgical instruments that have direct contact to surgical wound. The Association of periOperative Registered Nurses (AORN) declared that an easy method for covering and removing the drape will ultimately be most effective (e.g. standard two-drape method). Hence, this study was designed to test the hypothesis that using a novel single-drape cover had more efficiency and safety in decreasing airborne bacteria-carrying particles (ABCPs) settling on the PSBTs during static and dynamic periods than the standard two-drape method.

Methods

This experimental study was conducted with using 918 agar plates to detect contamination of the PSBTs with ABCPs on two conditions (static and dynamic) at an academic medical center in Kashan, Iran, from September 25, 2021, to January 20, 2022. The contamination of PSBTs was evaluated by 6 agar settle plates (n = 918 in total) on each PSBT in static and dynamic operating room (OR) conditions. At each time-point, this set-up was repeated on two occasions else during data collection, establishing 81 PSBTs in total. Tested groups included the PSBTs covered with the standard two-drape method, the novel single-drape cover, or no cover. The plates were collected after 15, 30, 45, 60, 120, 180, 240 min and 24 h. The primary outcome measured was comparison of mean bioburden of ABCPs settling on covered PSBTs on two conditions by using agar settle plates. The secondary outcomes measured were to determine the role of covering in decreasing contamination of PSBTs and the estimation of time-dependent surgical instrument contamination in the uncovered PSBTs on two conditions by using agar settle plates.

Results

Covering the PSBTs during static and dynamic OR conditions lead to a significantly decreased bioburden of ABCPs on them (P < 0.05). No differences were seen between the standard two-drape method and the novel single-drape cover (P > 0.05).

Conclusions

We found that there is no preference for using the novel single-drape cover than the standard two-drape method. Our results showed a significant decrease in bioburden of ABCPs on the PSBTs when those were covered during static and dynamic OR conditions, indicating the efficiency for covering the PSBTs during periods of nonuse and during active surgery.
The PRMT5-LSD1 axis confers Slug dual transcriptional activities and promotes breast cancer progression
Authors: Zhang Jianchao , Fan Xiaokai , Zhou Yunfan , Chen Liang , Rao Hai
Published: June 2022

Background

Downregulation of epithelial markers and upregulation of mesenchymal markers are the characteristics of the epithelial to mesenchymal transition (EMT) program, which provides the metastatic advantage of breast cancer. However, the mechanism underlying the switch of EMT markers remains poorly understood.

Methods

In this study, we used the affinity purification and mass spectrometry coupled approach to identify the interactome of Slug. CoIP, GST-pulldown, ChIP, Re-ChIP, qPCR and Immunoblot were used to investigate the underlying mechanism of Slug-PRMT5-LSD1 complex. The role of PRMT5 and LSD1 in breast cancer progression was evaluated both in vivo and in vitro.

Results

Here we found that the transcription factor Slug associates with PRMT5 and LSD1 in a complex and facilitates the breast cancer invasion in vitro. Mechanistically, PRMT5 and LSD1 work with Slug to exert dual transcriptional activities to inhibit E-cadherin expression by PRMT5-catalyzed H4R3me2s and LSD1-mediated demethylation of H3K4me2 on the E-cadherin (CDH1) promoter, and activate vimentin (VIM) expression via PRMT5-driven H3R2me2s and LSD1-mediated removal of H3K9me2. Importantly, PRMT5 and LSD1 are coordinately expressed in breast cancer patients and pharmacologic perturbation of both PRMT5 and LSD1 shows a synergetic effect on the inhibition of breast tumor growth and metastasis in vivo.

Conclusions

Our study suggests that PRMT5 and LSD1 function as a dual epigenetic modifier to promote Slug induced EMT program, suggesting that the inhibition of PRMT5 and LSD1 presents a potential therapeutic strategy against cancer metastasis.
The Project ENABLE Cornerstone randomized controlled trial: study protocol for a lay navigator-led, early palliative care coaching intervention for African American and rural-dwelling advanced cancer family caregivers
Authors: Bechthold Avery C. , Azuero Andres , Pisu Maria , Pierce Jennifer Young , Williams Grant R. , Taylor Richard A. , Wells Rachel , Curry Kayleigh , Reed Rhiannon D. , Harrell Erin R. , Gazaway Shena , Mollman Sarah , Engler Sally , Puga Frank , Bakitas Marie A. , Dionne-Odom J. Nicholas
Published: June 2022

Background

Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer.

Methods

This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin’s Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20–60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient’s death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient’s death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated.

Discussion

Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances.

Trial registration

ClinicalTrials.gov NCT04318886. Registered on 20 March, 2020.
Tolerating bad health research: the continuing scandal
Authors: Pirosca Stefania , Shiely Frances , Clarke Mike , Treweek Shaun
Published: June 2022

Background

At the 2015 REWARD/EQUATOR conference on research waste, the late Doug Altman revealed that his only regret about his 1994 BMJ paper ‘The scandal of poor medical research’ was that he used the word ‘poor’ rather than ‘bad’. But how much research is bad? And what would improve things?

Main text

We focus on randomised trials and look at scale, participants and cost. We randomly selected up to two quantitative intervention reviews published by all clinical Cochrane Review Groups between May 2020 and April 2021. Data including the risk of bias, number of participants, intervention type and country were extracted for all trials included in selected reviews. High risk of bias trials was classed as bad. The cost of high risk of bias trials was estimated using published estimates of trial cost per participant.

We identified 96 reviews authored by 546 reviewers from 49 clinical Cochrane Review Groups that included 1659 trials done in 84 countries. Of the 1640 trials providing risk of bias information, 1013 (62%) were high risk of bias (bad), 494 (30%) unclear and 133 (8%) low risk of bias. Bad trials were spread across all clinical areas and all countries. Well over 220,000 participants (or 56% of all participants) were in bad trials. The low estimate of the cost of bad trials was £726 million; our high estimate was over £8 billion.

We have five recommendations: trials should be neither funded (1) nor given ethical approval (2) unless they have a statistician and methodologist; trialists should use a risk of bias tool at design (3); more statisticians and methodologists should be trained and supported (4); there should be more funding into applied methodology research and infrastructure (5).

Conclusions

Most randomised trials are bad and most trial participants will be in one. The research community has tolerated this for decades. This has to stop: we need to put rigour and methodology where it belongs — at the centre of our science.
Persistent hyperlactatemia in decompensated type I diabetes with hepatic glycogenosis and hepatomegaly: Mauriac syndrome: a case report
Authors: Dolip Waheed , Bourmanne Eric , Van Homwegen Charlotte , Van Nuffelen Marc
Published: June 2022

Background

We describe a case of Mauriac syndrome, which is a rare complication of poorly controlled type I diabetes that combines glycogenosis, hepatomegaly, growth retardation with a Cushingoid appearance that is most often present in children but also in young adults. Here we also describe another finding with this syndrome, which is hyperlactatemia.

Case presentation

The case is of a 16-year-old female of North African ethnicity with history of poorly controlled type I diabetes who was brought to the emergency department for dyspnea and tachycardia, treated initially for diabetic ketoacidosis. Her persistent hyperlactatemia helped to reveal a more subtle condition known as Mauriac syndrome after multiple examinations and follow-up.

Conclusions

This case reports shows that Mauriac syndrome is a rare condition that should be considered in a setting of poorly controlled type I diabetes, hepatomegaly, Cushingoid appearance, and hyperlactatemia. The current treatment of this condition is a strict control of blood glucose levels with an attempt to achieve an acceptable glycated hemoglobin value.
Jail-based treatment for opioid use disorder in the era of bail reform: a qualitative study of barriers and facilitators to implementation of a state-wide medication treatment initiative
Authors: Krawczyk Noa , Bandara Sachini , Merritt Sydney , Shah Hridika , Duncan Alexandra , McEntee Brendan , Schiff Maria , Ahmad N. Jia , Whaley Sara , Latimore Amanda , Saloner Brendan
Published: June 2022

Background

Until recently, few carceral facilities offered medications for opioid use disorder (MOUD). Although more facilities are adopting MOUD, much remains to be learned about addressing implementation challenges related to expansion of MOUD in carceral settings and linkage to care upon re-entry. This is particularly important in jails, where individuals cycle rapidly in and out of these facilities, especially in jurisdictions beginning to implement bail reform laws (i.e., laws that remove the requirement to pay bail for most individuals). Increasing access to MOUD in these settings is a key unexplored challenge.

Methods

In this qualitative study, we interviewed staff from county jails across New Jersey, a state that has implemented state-wide efforts to increase capacity for MOUD treatment in jails. We analyzed themes related to current practices used to engage individuals in MOUD while in jail and upon re-entry; major challenges to delivering MOUD and re-entry services, particularly under bail reform conditions; and innovative strategies to facilitate delivery of these services.

Results

Jail staff from 11 New Jersey county jails participated in a baseline survey and an in-depth qualitative interview from January–September 2020. Responses revealed that practices for delivering MOUD varied substantially across jails. Primary challenges included jails’ limited resources and highly regulated operations, the chaotic nature of short jail stays, and concerns regarding limited MOUD and resources in the community. Still, jail staff identified multiple facilitators and creative solutions for delivering MOUD in the face of these obstacles, including opportunities brought on by the COVID-19 pandemic.

Conclusions

Despite challenges to the delivery of MOUD, states can make concerted and sustained efforts to support opioid addiction treatment in jails. Increased use of evidence-based clinical guidelines, greater investment in resources, and increased partnerships with health and social service providers can greatly improve reach of treatment and save lives.
Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus–response in spinal muscular atrophy
Authors: Deng Chunchu , Reinhard Sebastian , Hennlein Luisa , Eilts Janna , Sachs Stefan , Doose Sören , Jablonka Sibylle , Sauer Markus , Moradi Mehri , Sendtner Michael
Published: June 2022

Background

Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn (survival of motor neuron) deficiency that could contribute to axonopathy and presynaptic dysfunction in SMA.

Methods

Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation.

Results

We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In addition, in axon terminals of Smn-deficient motoneurons, ribosomes failed to respond to the brain-derived neurotrophic factor stimulation, and did not undergo rapid association with the axonal ER in response to extracellular stimuli.

Conclusions

These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.
On using a double-thin-shell approach and TEC perturbation component to sound night-time mid-latitude E–F coupling
Authors: Fu Weizheng , Yokoyama Tatsuhiro , Ssessanga Nicholas , Yamamoto Mamoru , Liu Peng
Published: June 2022

Observations and theoretical analysis on the night-time mid-latitude ionospheric irregularities support the postulation of frequently coupled E and F regions. In this paper, we attempt at asserting this notion while using total electron content (TEC) measurements. The TECs are from a dense GNSS receiver network over Japan with more than 1200 stations and a mean distance of ~ 25 km between receivers; thus, ideal for analyzing small-scale perturbations in ionospheric electron density. We take an ansatz that mid-latitude night-time plasma instabilities concentrate at E and F layers. Then the integrated three-dimensional density perturbations are parameterized with a double-thin-shell model. At each shell, perturbation components are assumed identical at any point within a given grid block. Two days with events of night-time medium-scale traveling ionospheric disturbances (MSTIDs), but with different amplitudes, were investigated. Results show that the newly developed technique can infer several horizontal characteristics on E–F coupled instabilities; the coexistence of northwest–southeast (NW–SE) aligned irregular structures in E and F regions is evident. Both E- and F-region irregularities share similar propagation parameters, a shred of clear evidence of strong coupling.

Graphical Abstract
Waveform inversion of the ultra-long-period seismic event associated with ground tilt motion during an eruption of Mount Kusatsu–Shirane, Japan, on January 23, 2018
Authors: Takahashi Ryohei , Maeda Yuta , Watanabe Toshiki
Published: June 2022

We conducted waveform inversions of an ultra-long-period (~ 240-s) event associated with the phreatic eruption of Mount Kusatsu–Shirane on January 23, 2018. We used broadband seismic and tilt records from three stations surrounding the eruption site. The horizontal components of the broadband seismic records were severely contaminated by tilt motions. We applied a waveform inversion algorithm to account for both the translational and tilt motions. To reduce the number of free parameters, we assumed a tensile crack source and conducted grid searches for the centroid location and orientation of the crack. The results showed a rapid inflation of 105 m3 of the crack, followed by a slow deflation starting 8–11 s prior to the onset of the eruption. The source location and crack orientation were not uniquely determined. The most likely source is a north–south-opening sub-vertical crack near the eruptive craters. This ultra-long-period event may represent volcanic fluid migration from depth to the surface through a vertical crack during the eruption.

Graphical abstract
Impact of interventions by a community pharmacist on care burden for people with dementia: development and randomized feasibility trial of an intervention protocol
Authors: Nanaumi Yoko , Yoshitani Atsushi , Onda Mitsuko
Published: June 2022

Background

Traditionally, the role of pharmacists has been to manage and monitor pharmacotherapy for patients with dementia. However, additional intervention by community pharmacists to collect and share patient information with other professionals may help reduce the care burden among caregivers. The aims of this study were to examine (1) the feasibility of a designed community pharmacist working procedure in dementia care and (2) the expected impact of pharmacist intervention on care burden.

Methods

This was a randomized, open-label, parallel-group feasibility study, involving eight Nara City pharmaceutical association member pharmacies that provided consent to participate. These pharmacies were assigned to an intervention group or a control group at a 1:1 ratio. The subjects were patients with dementia and their primary caregivers that visited the participating pharmacies and provided consent to participate. Pharmacists in the intervention group actively collected information from the patients’ family physicians and care managers and intervened to address medication-related problems, while those in the control group only performed their normal duties. The primary endpoint was a change in the caregiver’s score on the Japanese version of Zarit Caregiver Burden interview (J-ZBI) from the baseline to after 5 months of follow-up. The changes in mean J-ZBI scores from the beginning to the end of the study period of the two groups were compared.

Results

Obtaining consent from caregivers was certainly difficult, but possible. Pharmacists managed to fill out the survey form while practising pharmaceutical care. Totally, nine patients and nine caregivers in the intervention group and nine patients and eight caregivers in the control group completed the study. The changes in J-ZBI scores could be calculated for seven cases in the intervention group and five cases in the control group. The J-ZBI scores were found to decrease by 1.0 in the intervention group and increase by 3.0 in the control group.

Conclusions

The protocol presented was considered feasible, but, the intervention process needs to be simplified in order to conduct a large study. Also, improvements are needed in the various survey forms and in the explanatory documents for caregivers. Although the sample size was small, the effect sizes suggested that community pharmacist interventions for patient with dementia may reduce the care burden for caregivers.

Trial registration

UMIN000039949 (registration date: 1 April 2020, retrospectively registered)
Quality of patient- and proxy-reported outcomes for children with impairment of the upper extremity: a systematic review using the COSMIN methodology
Authors: Kalle J. P. Ruben , Saris Tim F. F. , Sierevelt Inger N. , Eygendaal Denise , van Bergen Christiaan J. A.
Published: June 2022

Background

As patient-reported outcome measures (PROMs) have become of significant importance in patient evaluation, adequately selecting the appropriate instrument is an integral part of pediatric orthopedic research and clinical practice. This systematic review provides a comprehensive overview of PROMs targeted at children with impairment of the upper limb, and critically appraises and summarizes the quality of their measurement properties by applying the COnsensus-based Standards for selection of health Measurement INstruments (COSMIN) methodology.

Methods

A systematic search of the MEDLINE and EMBASE databases was performed to identify relevant publications reporting on the development and/or validation of PROMs used for evaluating children with impairment of the upper extremity. Data extraction and quality assessment (including a risk of bias evaluation) of the included studies was undertaken by two reviewers independently and in accordance with COSMIN guidelines.

Results

Out of 6423 screened publications, 32 original articles were eligible for inclusion in this review, reporting evidence on the measurement properties of 22 self- and/or proxy-reported questionnaires (including seven cultural adaptations) for various pediatric orthopedic conditions, including cerebral palsy (CP) and obstetric brachial plexus palsy (OBPP). The measurement property most frequently evaluated was construct validity. No studies evaluating content validity and only four PROM development studies were included. The methodological quality of these development studies was either ‘doubtful’ or ‘inadequate’. The quantity and quality of the evidence on the other measurement properties of the included questionnaires varied substantially with insufficient sample sizes and/or poor methodological quality resulting in significant downgrading of evidence quality.

Conclusion

This review provides a comprehensive overview of currently available PROMs for evaluation of the pediatric upper limb. Based on our findings, none of the PROMs demonstrated sufficient evidence on their measurement properties to justify recommending the use of these instruments. These findings provide room for validation studies on existing pediatric orthopedic upper limb PROMs (especially on content validity), and/or the development of new instruments.