bluuebunny/crossref_metadata_2025 huggingface dataset:
Sentinel lymph node mapping with superparamagnetic iron oxide for melanoma: a pilot study in healthy participants to establish an optimal MRI workflow protocol
Authors: Aldenhoven Loeki , Frotscher Caroline , Körver-Steeman Rachelle , Martens Milou H. , Kuburic Damir , Janssen Alfred , Beets Geerard L. , van Bastelaar James
Published: October 2022

Background

Current pre-operative Sentinel Lymph Node (SLN) mapping using dual tracing is associated with drawbacks (radiation exposure, logistic challenges). Superparamagnetic iron oxide (SPIO) is a non-inferior alternative for SLN mapping in breast cancer patients. Limited research has been performed on SPIO use and pre-operative MRI in melanoma patients to identify SLNs. 

Methods

Healthy participants underwent MRI-scanning pre- and post SPIO-injection during 20 min. Workflow protocols varied in dosage, massage duration, route of administration and injection sites. The first lymph node showing a susceptibility artefact caused by SPIO accumulation was considered as SLN.

Results

Artefacts were identified in 5/6 participants. Two participants received a 0.5 ml subcutaneous injection and 30-s massage, of which one showed an artefact after one hour. Four participants received a 1.0 ml intracutaneous injection and two-minute massage, leading to artefacts in all participants. All SLNs were observed within five minutes, except after lower limb injection (30 min).

Conclusion

SPIO and pre-operative MRI-scanning seems to be a promising alternative for SLN visualization in melanoma patients. An intracutaneous injection of 1.0 ml SPIO tracer, followed by a two-minute massage seems to be the most effective technique, simplifying the pre-operative pathway. Result will be used in a larger prospective study with melanoma patients.

Trial registration

ClinicalTrials.gov (NCT05054062) – September 9, 2021.
Overall survival of individuals with metastatic cancer in Sweden: a nationwide study
Authors: Bütepage Greta , Carlqvist Peter , Jacob Johanna , Toft Hornemann Asbjørn , Vertuani Simona
Published: October 2022

Aims

Consistent improvements for overall survival (OS) have been reported for individuals with metastatic cancer. Swedish population-based registers allow national coverage and long follow-up time. The aim of this study was to estimate and explore long-term OS of individuals diagnosed with metastatic cancer using Swedish nationwide health registers.

Methods

Individuals with metastatic breast (MBC), non-small cell lung (MNSCLC), ovary (MOC) or colorectal cancer (MCRC) or metastatic malignant melanoma (MMM) were identified in the Swedish national cancer register and national patient registers. Survival was estimated and stratified by available variables. Potential cure fractions were estimated using mixture cure models.

Results

In total, approximately 69,000 individuals were identified. The most common cancers were MCRC (36.2%) and MNSCLC (29.5%). Men were more frequently diagnosed with MNSCLC, MCRC, and MMM compared to women. Except for MOC, about 50% of individuals were 70 years or older at diagnosis. Throughout the study period survival differed across cancers. The longest median OS was observed for individuals with MOC and MBC. At 10 years of follow-up, the survival curves flatten at a survival rate of approximately 10% for all cancers except MNSCLC. The youngest age groups had the longest median OS. Increased survival was also observed for individuals diagnosed in 2015 and 2018 compared to individuals diagnosed during earlier years. The estimated cure fractions were 4% for MBC, 1.5% for MNSCLC, 6.8% for MCRC, 8.6% for MOC and MMM.

Conclusions

Long-term survival has been assessed across all indications except for NSCLC.. The findings may be relevant for healthcare planning to meet the needs of future patients and potential long-term survivors.
Development of a community-based COVID-19 intervention in rural Ghana: a document analysis
Authors: Frimpong Shadrack Osei , Seidu Moro , Hilton Sam Kris , Ransome Yusuf , Paintsil Elijah , Talbert-Slagle Kristina , Dorcoo-Attipoe Sharon , Brayne Carol
Published: October 2022

Background

The COVID-19 pandemic has caused the loss of millions of lives and economic breakdowns in many countries across the globe. Despite the limited availability of vaccines and the challenges of poor health infrastructure, few interventions have been developed and implemented for those who live in rural areas, particularly in sub-Saharan Africa. In response, Cocoa360, a global health nonprofit in rural Ghana designed an intervention called Cocoa360’s COVID-19 Preparedness and Outbreak Prevention Plan (CoCoPOPP). This paper aimed to examine the extent to which CoCoPOPP’s design aligned with the Promoting Action on Research Implementation in Health Services (PARIHS) framework.

Methods

We reviewed documents influencing CoCoPOPP’s design between March and June 2021. A total of 11 documents were identified for analysis. Using the Promoting Action on Research Implementation in Health Services (PARIHS) framework as a guide, thematic analysis was done to analyze the extracted data.

Results

Overall, CoCoPOPP’s design aligned with the evidence, context, and facilitation domains of the PARIHS framework. It positioned CoCoPOPP as an intervention that considered the unique context of a rural Ghanaian setting. It was guided by robust and high-quality published and non-published evidence and engaged external and internal stakeholders during its implementation. CoCoPOPP’s context-dependent nature positions it for potential replication in sub-Saharan Africa’s rural communities with similar farming contexts. Specific areas that were less well and/or not addressed were the unintended negative consequences of community engagement, the absence of primary data in the guiding evidence, and the lack of a facilitation continuum coupled with the role of power during the facilitation process.

Conclusion

CoCoPOPP, Cocoa360’s response to the COVID-19 pandemic in rural Ghana, is an evidence-driven, context-dependent public health intervention that has been designed to reduce COVID-19 infections and prevent potential deaths. This study underscores the importance of considering the unique community and cultural contexts, employing evidence, and engaging local and external actors as facilitators when designing interventions to respond to global health pandemics.
Restoration and maintenance of segment lordosis in oblique lumbar interbody fusion
Authors: Gong Ke , Lin Yang , Wang Zhibin , Li Feng , Xiong Wei
Published: October 2022

Purpose

Restoration of the segment lordosis angle (SLA) can effectively reduce the risk of adjacent segment degeneration. This study aimed to perform a comprehensive multifactor analysis of the risk factors affecting restoration and maintenance of the SLA in oblique lumbar interbody fusion (OLIF).

Methods

Seventy-three patients (93 segments) who underwent OLIF with posterior pedicle screw fixation due to lumbar degenerative disease between January 2015 and December 2019 were included. Radiographic parameters including the middle disc height (MDH), segment lordosis angle (SLA), cage center point ratio (CPR), cage subsidence, and L1 CT Hounsfield Unit (HU) were measured.

Results

The postoperative SLA increased from 3.5° to 8.7°, and decreased to 6.7° at the last follow-up. Multivariate analysis showed that preoperative SLA, CPR and cage subsidence were significantly correlated with SLA restoration. The significant correlations were between restoration of SLA with pre-operative SLA (r=-0.575, adjusted R2 = 0.323, P < 0.01) and between SLA restoration and CPR (r = 0.526, adjusted R2 = 0.268, P < 0.01). Cage subsidence was found in 12.9% (12/93) of segments and was the main factor affecting SLA loss (4.2 ± 1.0° versus 1.7 ± 2.1°, P < 0.01). Logistic regression analysis showed that CPR < 50%, L1 CT HU < 110 and cage height > preoperative MDH were risk factors for cage subsidence. Cages placed anteriorly (CPR ≥ 50%) showed a large SLA increase and lower incidence of cage subsidence than those placed posteriorly (5.9 ± 3.9° versus 4.2 ± 3.2°, P < 0.05; 1.8% versus 28.9%, P < 0.05, respectively).

Conclusion

SLA restoration is dependent on preoperative SLA, cage subsidence and cage position in OLIF. Cage position is the key determinant of SLA restoration and placement of the cage at the anterior position (CPR ≥ 50%) can achieve better restoration of the SLA and reduce the incidence of cage subsidence.
Pingyin rose essential oil alleviates LPS-Induced inflammation in RAW 264.7 cells via the NF-κB pathway: an integrated in vitro and network pharmacology analysis
Authors: Raka Rifat Nowshin , Zhiqian Ding , Yue Yuan , Luchang Qiao , Suyeon Park , Junsong Xiao , Hua Wu
Published: October 2022

Background

Rosa rugosa cv. Plena, a cultivar of Rosa rugosa, has a history of more than 1300 years of application in both medicine and food in China. The essential oil of Rosa rugosa cv. Plena (PREO) is one of the most frequently used additives in food, cosmetics and aromatherapy. PREO exhibits some anti-inflammation, antioxidant and nerve alleviating effects. However, the mechanisms behind these effects are still unclear.

Methods

The composition of PREO was determined by GC‒MS. Network pharmacology was performed to predict the possible compound-target network and analyze the possible targets against inflammation and oxidative stress. An inflammatory immune cell model was constructed by exposing RAW 264.7 cells to LPS. A series of experiments, including biochemical assays, RT‒PCR, and western blotting, were conducted to investigate the anti-inflammatory and antioxidative effects of PREO.

Results

PREO treatment significantly (p < 0.05) alleviated inflammatory and oxidative biomarkers such as NO, ROS, and MDA and preserved SOD and CAT activities. GC‒MS analysis revealed that PREO consists of 57 compounds, mainly monoterpenoids. Network pharmacology revealed that citronellol, farnesol, ethyl octanoate, geranyl acetate, and methyl eugenol were active components interacting with several inflammatory pathway proteins. By measuring the gene and protein expression of possible targets by qRT‒PCR and western blotting, PREO anti-inflammatory responses in LPS-treated RAW 264.7 cells might be associated with the regulation of NF-κB signaling. Molecular docking showed that PREO components can interact with different proteins involved in the NF-κB pathway.

Conclusion

The integrated study of molecular analysis and network pharmacology suggested that PREO might be a potential anti-inflammatory agent to treat inflammation and oxidative stress.
Creating an online educational intervention to improve knowledge about systematic reviews among healthcare workers: mixed-methods pilot study
Authors: Krnic Martinic Marina , Malisa Snjezana , Aranza Diana , Civljak Marta , Marušić Ana , Sapunar Damir , Poklepovic Pericic Tina , Buljan Ivan , Tokalic Ruzica , Cavic Dalibor , Puljak Livia
Published: October 2022

Background

Lack of knowledge about systematic reviews (SRs) could prevent individual healthcare workers (HCWs) from using SRs as a source of information in their clinical practice or discourage them from participating in such research. In this study, we aimed to explore in-depth the opinion of a sample of HCWs about the newly created online educational intervention designed to improve knowledge about SRs.

Methods

We created a brief online educational intervention on SRs, consisting of 11 textual modules. We evaluated it among practicing HCWs who graduated from a university-level health sciences program using a mixed-methods pilot study that consisted of pre- and post-intervention questionnaires and qualitative evaluation via semi-structured interviews. We assessed participants’ knowledge about SR methodology before and after the intervention, and compared the responses. We sought their opinions about the characteristics of SRs. Also, the participants were presented with four scientific abstracts, where they were asked to distinguish whether those abstracts presented summaries of a systematic or a non-systematic review.

Results

Twelve participants took part in the study. In the pilot study, the participants’ knowledge about SRs was improved after the intervention compared to the baseline. Participants provided positive feedback regarding the educational intervention. Suggestions to improve the educational intervention were to provide more details about the forest plot, add more digital content or images, provide more details about the methodological steps of an SR, add descriptions about practical applications of SRs and provide links to additional educational materials. The participants suggested that HCWs could be motivated to take part in such an education if it is offered as continuing medical education (CME) course or credit for academic/career advancement.

Conclusion

HCWs provided positive feedback about the newly designed online educational intervention on SRs; they considered it an appropriate tool for learning about SRs and resulted in increased knowledge about SRs. In addition, participants gave suggestions for improving education, which can be used to tailor the education for end-users. In future studies, it would be useful to examine the effectiveness of the modified educational intervention on increasing knowledge in a larger sample and in the form of a randomized controlled trial.
Do in-service training materials for midwifery care providers in sub-Saharan Africa meet international competency standards? A scoping review 2000–2020
Authors: Welsh Joanne , Hounkpatin Hashim , Gross Mechthild M. , Hanson Claudia , Moller Ann-Beth
Published: October 2022

Background

Levels of maternal and neonatal mortality remain high in sub-Saharan Africa, with an estimated 66% of global maternal deaths occurring in this region. Many deaths are linked to poor quality of care, which in turn has been linked to gaps in pre-service training programmes for midwifery care providers. In-service training packages have been developed and implemented across sub-Saharan Africa in an attempt to overcome the shortfalls in pre-service training. This scoping review has aimed to summarize in-service training materials used in sub-Saharan Africa for midwifery care providers between 2000 and 2020 and mapped their content to the International Confederation of Midwives (ICM) Essential Competencies for Midwifery Practice.

Methods

Searches were conducted for the years 2000–2020 in Cumulative Index of Nursing and Allied Health Literature, PubMed/MEDLINE, Social Science Citation Index, African Index Medicus and Google Scholar. A manual search of reference lists from identified studies and a search of grey literature from international organizations was also performed. Identified in-service training materials that were accessible freely on-line were mapped to the ICM Essential Competencies for midwifery practice.

Results

The database searches identified 1884 articles after removing duplicates. After applying exclusion criteria, 87 articles were identified for data extraction. During data extraction, a further 66 articles were excluded, leaving 21 articles to be included in the review. From these 21 articles, six different training materials were identified. The grey literature yielded 35 training materials, bringing the total number of in-service training materials that were reviewed to 41. Identified in-service training materials mainly focused on emergency obstetric care in a limited number of sub-Saharan Africa countries. Results also indicate that a significant number of in-service training materials are not readily and/or freely accessible. However, the content of in-service training materials largely met the ICM Essential Competencies, with gaps noted in the aspect of woman-centred care and shared decision making.

Conclusion

To reduce maternal and newborn morbidity and mortality midwifery care providers should have access to evidence-based in-service training materials that include antenatal care and routine intrapartum care, and places women at the centre of their care as shared decision makers.
Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients
Authors: Wong Carlos King Ho , Lui David Tak Wai , Xiong Xi , Chui Celine Sze Ling , Lai Francisco Tsz Tsun , Li Xue , Wan Eric Yuk Fai , Cheung Ching Lung , Lee Chi Ho , Woo Yu Cho , Au Ivan Chi Ho , Chung Matthew Shing Hin , Cheng Franco Wing Tak , Tan Kathryn Choon Beng , Wong Ian Chi Kei
Published: October 2022

Background

In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset.

Methods

We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves’ disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression.

Results

A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670–1.114; CoronaVac: IRR 0.707, 95% CI 0.549–0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716–1.159; CoronaVac: IRR 0.778, 95% CI 0.618–0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744–1.023; CoronaVac: IRR 0.830, 95% CI 0.713–0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838–1.199; CoronaVac: IRR 0.963, 95% CI 0.807–1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770–1.227; CoronaVac: IRR 0.879, 95%CI 0.693–1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833–1.246; CoronaVac: IRR 0.768, 95% CI 0.613–0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899–1.201; CoronaVac: IRR 0.911, 95% CI 0.786–1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794–1.102; CoronaVac: IRR 0.945, 95% CI 0.799–1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines.

Conclusions

Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.
Non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD in type 2 diabetic patients
Authors: Zhang Ziyin , Zhang Lu , Jiang Wangyan , Du Tingting , Yuan Gang
Published: October 2022

Background

Non-obese non-alcoholic fatty liver disease (NAFLD) has been reported to share clinical outcomes with its obese counterpart in the general population. However, conflicting results have been observed regarding the cardio-metabolic risk profile of non-obese NAFLD as compared to obese NAFLD. Moreover, in the context of type 2 diabetes mellitus (T2DM), this issue has been even less addressed. We hence aimed to examine the association of NAFLD with the cardio-metabolic risk profile in patients with T2DM according to their obesity status.

Methods

A total of 2,708 patients with T2DM who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed.

Results

The prevalence of NAFLD was 49.3%. NAFLD was found in 34.1% of non-obese patients and 66.0% of obese patients. Non-obese NAFLD patients had more and worse metabolic disorders than obese patients without NAFLD in both men and women. Comparable cardio-metabolic risk profiles were noted between non-obese and obese NAFLD subjects. The associations of worse cardio-metabolic risk profiles with NAFLD were overall stronger in non-obese than in obese subjects among women with T2DM, while more pronounced in obese than in non-obese subjects among men with T2DM.

Conclusion

In patients with T2DM, non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD. The associations of metabolic disorders with NAFLD were stronger in non-obese than in obese patients in women patients with T2DM.
Identification of a flavonoid C-glycosyltransferase from fern species Stenoloma chusanum and the application in synthesizing flavonoid C-glycosides in Escherichia coli
Authors: Ni Rong , Liu Xin-Yan , Zhang Jiao-Zhen , Fu Jie , Tan Hui , Zhu Ting-Ting , Zhang Jing , Wang Hai-Long , Lou Hong-Xiang , Cheng Ai-Xia
Published: October 2022

Background

Flavonoid C-glycosides have many beneficial effects and are widely used in food and medicine. However, plants contain a limited number of flavonoid C-glycosides, and it is challenging to create these substances chemically.

Results

To screen more robust C-glycosyltransferases (CGTs) for the biosynthesis of flavonoid C-glycosides, one CGT enzyme from Stenoloma chusanum (ScCGT1) was characterized. Biochemical analyses revealed that ScCGT1 showed the C-glycosylation activity for phloretin, 2-hydroxynaringenin, and 2-hydroxyeriodictyol. Structure modeling and mutagenesis experiments indicated that the glycosylation of ScCGT1 may be initiated by the synergistic action of conserved residue His26 and Asp14. The P164T mutation increased C-glycosylation activity by forming a hydrogen bond with the sugar donor. Furthermore, when using phloretin as a substrate, the extracellular nothofagin production obtained from the Escherichia coli strain ScCGT1-P164T reached 38 mg/L, which was 2.3-fold higher than that of the wild-type strain. Finally, it is proved that the coupling catalysis of CjFNS I/F2H and ScCGT1-P164T could convert naringenin into vitexin and isovitexin.

Conclusion

This is the first time that C-glycosyltransferase has been characterized from fern species and provides a candidate gene and strategy for the efficient production of bioactive C-glycosides using enzyme catalysis and metabolic engineering.
Attitude changes following short-form opioid overdose video education: a pilot study
Authors: Galiher Mika V. , Huffman Miranda
Published: October 2022

Background

Opioid overdose response training (OORT) and the need for its rapid expansion have become more significant as the opioid epidemic continues to be a health crisis in the USA. Limitation of funding and stigmatization often hinders expansion of OORT programs. Primarily due to the COVID-19 pandemic, there has been widespread transition from in-person to virtual communication. However, OORT programs may benefit from long-term use of this modality of education if it can be as effective.

Objective

To measure the change in participant attitude after a brief, virtual OORT.

Methods

A 6.5-min OORT video explained recognition of opioid overdose, appropriate response and proper administration of intranasal naloxone. Pre- and post-video scores from a 19-item survey were used to determine the video's impact on participants’ self-perceived competence and readiness to administer naloxone to a person with a suspected opioid overdose. Paired t tests were used in the analysis of pre- and post-video scores. Mann–Whitney U and Kruskal–Wallis H testing were used to compare variance between several demographic subgroups of interest.

Results

A sample of 219 participants had a significant mean difference of 15.12 (SD 9.48; 95% CI 13.86–16.39, p < 0.001) between pre- and posttest scores. Improvements were found to be greatest in content-naïve participants with lower levels of education and non-health care-related jobs than participants endorsing previous content awareness, formal naloxone training, masters, doctorate or professional degrees and health care-related jobs.

Conclusion

This pilot study demonstrated encouraging evidence that a brief, virtual, pre-recorded educational intervention improved participant-rated competence and readiness to administer intranasal naloxone in a suspected opioid overdose. Due to scalability and ability to overcome common healthcare accessibility barriers, short-form videos focused on key facts about naloxone and the benefits of its use could be part of a strategy for rapid expansion of OORT programs to mitigate opioid overdose fatalities.
Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress
Authors: Gao Junling , Lei Tong , Wang Hongyun , Luo Kai , Wang Yuanli , Cui Bingqing , Yu Zhuoran , Hu Xiaoqi , Zhang Fang , Chen Yingjie , Ding Wenjun , Lu Zhongbing
Published: October 2022

Background

Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM2.5-induced lung injury has not been investigated.

Methods

Ddah1−/− and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM2.5 (mean daily concentration ~ 50 µg/m3) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined.

Results

Ddah1−/− mice developed more severe lung injury than WT mice after long-term PM2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In the lungs of PM2.5-exposed mice, Ddah1 deficiency increased protein expression of p-p65, iNOS and Bax, and decreased protein expression of Bcl-2, SOD1 and peroxiredoxin 4. Conversely, DDAH1 overexpression significantly alleviated lung injury, attenuated pulmonary oxidative stress and inflammation, and exerted opposite effects on those proteins in PM2.5-exposed mice. In addition, exogenous ADMA administration could mimic the effect of Ddah1 deficiency on PM2.5-induced lung injury, oxidative stress and inflammation. In PM2.5-exposed macrophages, ADMA aggravated the inflammatory response and oxidative stress in an iNOS-dependent manner.

Conclusion

Our data revealed that DDAH1 has a marked protective effect on long-term PM2.5 exposure-induced lung injury.
HINT1 neuropathy in Lithuania: clinical, genetic, and functional profiling
Authors: Malcorps Matilde , Amor-Barris Silvia , Burnyte Birute , Vilimiene Ramune , Armirola-Ricaurte Camila , Grigalioniene Kristina , Ekshteyn Alexandra , Morkuniene Ausra , Vaitkevicius Arunas , De Vriendt Els , Baets Jonathan , Scherer Steven S. , Ambrozaityte Laima , Utkus Algirdas , Jordanova Albena , Peeters Kristien
Published: October 2022

Background

Recessive loss-of-function variations in HINT1 cause a peculiar subtype of Charcot-Marie-Tooth disease: neuromyotonia and axonal neuropathy (NMAN; OMIM[#137200]). With 25 causal variants identified worldwide, HINT1 mutations are among the most common causes of recessive neuropathy. The majority of patients are compound heterozygous or homozygous for a Slavic founder variant (c.110G>C, p.Arg37Pro) that has spread throughout Eurasia and America.

Results

In a cohort of 46 genetically unresolved Lithuanian patients with suspected inherited neuropathy, we identified eight families with HINT1 biallelic variations. Most patients displayed sensorimotor or motor-predominant axonal polyneuropathy and were homozygous for the p.Arg37Pro variant. However, in three families we identified a novel variant (c.299A>G, p.Glu100Gly). The same variant was also found in an American patient with distal hereditary motor neuropathy in compound heterozygous state (p.Arg37Pro/p.Glu100Gly). Haplotype analysis demonstrated a shared chromosomal region of 1.9 Mb between all p.Glu100Gly carriers, suggesting a founder effect. Functional characterization showed that the p.Glu100Gly variant renders a catalytically active enzyme, yet highly unstable in patient cells, thus supporting a loss-of-function mechanism.

Conclusion

Our findings broaden NMAN’s genetic epidemiology and have implications for the molecular diagnostics of inherited neuropathies in the Baltic region and beyond. Moreover, we provide mechanistic insights allowing patient stratification for future treatment strategies.
Comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from SCLC: study protocol for a randomized controlled trial
Authors: Zhang Xiaofang , Wang Tianlu , Wang Chen Yu , Zhao Peng , Huang Bo , He Lei , Song Ying Qiu
Published: October 2022

Background

This study is in regard to the comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from small cell lung cancer (SCLC). Therapeutically, they have notably varying dose distributions. Based on theoretical and model studies, it has long been speculated that these modes may result in different prognostic outcomes. We aim to assess the efficacy of tomotherapy in the treatment of SCLC brain metastases while protecting the key functional area, the hippocampus, and minimizing any neurocognitive impairments incurred by radiation.

Methods

This is a randomized, controlled, prospective study including 102 SCLC patients with brain metastases randomized (1:1) to the experimental (whole brain radiation therapy for synchronous brain metastases with irradiation to protect the hippocampus) or control (whole brain radiotherapy for sequential brain metastases to boost irradiation) group. The sample size is calculated through a single-sided test; 102 participants will be required for the main results to have statistical and clinical significance. We aim to provide clinical trial data support for better prognostic treatment options in patients with SCLC and brain metastases. The clinical trial data include both the primary and secondary outcomes; the primary outcome is the intracranial progression-free survival time after the new technology application. The secondary study outcomes include the assessment of neurological function, the quality of life, and the overall survival rate. Follow-up consultations will be conducted every 2 months. After the final patient completes follow-up, the Statistical Product and Service Solutions software will be used for scientific and rigorous data analysis. Version 1.0 of the protocol was implemented on January 1, 2021; the recruitment process for this clinical trial commenced on April 1, 2021, and will end on March 31, 2024.

Discussion

The study will provide high-quality clinical evidence to support the efficacy and safety of whole brain radiation therapy for synchronous brain metastases with dose irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases with push volume irradiation for the treatment of patients who have lung cancer as well as brain metastases. This has not been previously reported.

Trial registration

This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900027539; November 17, 2019) (URL: https://www.chictr.org.cn/hvshowproject.aspx?id=20515).
The effect of an 8-week treatment program using a novel foot neuromuscular electrical stimulator on physical function, leg pain, leg symptoms, and leg blood flow in community-dwelling older adults: a randomized sham-controlled trial
Authors: Kumaran Binoy , Targett Darren , Watson Tim
Published: October 2022

Background

Neuromuscular electrical stimulation (NMES) is an established therapy that has been widely used for many decades to improve circulation in the legs. However, studies using NMES devices in an elderly, ambulant, and otherwise apparently healthy population are lacking; this is despite the use of such devices being indicated for lower leg symptoms (such as aches, pain, and cramps) that are frequently seen in older individuals. The main purpose of this study is to evaluate the effect of non-invasive foot NMES (administered using Revitive Medic©) on such symptoms compared to a sham in a 12-week period.

Methods

This is a single-center, single (participant)-blind, parallel-group, randomized, placebo-controlled (sham group), interventional study. Participants will be randomized to 1 of 3 groups (1:1:1) with each study group receiving a different type of foot NMES: Revitive sham; Revitive Medic© Program 1; or Revitive® Program 2. Each participant will be instructed to self-administer the foot NMES device for 30 min twice daily for 8 weeks. During the study, all participants will continue with their normal life, activities, medications, and diet with no restrictions. Following the 8-week NMES treatment program participants will be assessed for Canadian Occupational Performance Measure performance (COPM-P) and satisfaction (COPM-S) scores, lower leg pain, lower leg symptoms (heaviness, tiredness, aching and cramps), and blood flow volume and intensity.

Discussion

Revitive® foot NMES has been proven to increase blood circulation in the legs during use, which may help to relieve symptoms such as pain, heaviness, cramps, and tiredness. When NMES is applied to the plantar surface of the feet it indirectly induces contraction of the calf muscle, activating the musculo-venous pump and thus improving circulation. This study aims to provide data informing on the applicability of foot NMES for the management of leg symptoms that are likely to be indicative of poor circulation in an elderly (> 65 years) community population.

Trial registration

ISRCTN10576209.
Restored intestinal integrity, nutrients transporters, energy metabolism, antioxidative capacity and decreased harmful microbiota were associated with IUGR piglet's catch-up growth before weanling
Authors: Cui Chang , Wu Caichi , Wang Jun , Ma Ziwei , Zheng Xiaoyu , Zhu Pengwei , Wang Nuan , Zhu Yuhua , Guan Wutai , Chen Fang
Published: October 2022

Background

Intrauterine growth restriction (IUGR) is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth (CUG) before weanling could significantly restore this negative influence. But there was limited knowledge about the underlying mechanism of CUG occurrence.

Methods

Eighty litters of newborn piglets were divided into normal birth weight (NBW) and IUGR groups according to birth weight. At 26 d, those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG, and the piglets with IUGR still below average body weight were considered as NCUG. This study was conducted to systemically compare the intestinal difference among NBW, CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.

Results

The results indicated that the mRNA expression of nutrients (amino acids, glucose, and fatty acids) transporters, and mitochondrial electron transport chain (ETC) I were upregulated in CUG piglets’ gut with improved morphology compared with those NCUG, as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism. Meanwhile, CUG piglet’s gut showed higher antioxidative capacity with increased SOD and GSH-Px activity, decreased MDA levels, as well as higher mRNA expressions of Nrf2, Keap1, SOD, and GSH-Px. Furthermore, inflammatory parameters including TNF-α, IL-1β, IL-6, and IL-12 factors, and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine, while the protein expression of ZO-1, Occludin and Claudin-1 was reduced. The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets, and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.

Conclusions

CUG piglet’s intestine showed comprehensive restoration including higher nutrients transport, energy metabolism, antioxidant capacity, and intestinal physical barrier, while lower oxidative stress, inflammatory response, and pathogenic microbiota.
Characteristics of physical properties of the sliding and its surrounding layers in landslides caused by the 2018 Hokkaido Eastern Iburi Earthquake
Authors: Istiyanti Mega Lia , Goto Satoshi
Published: October 2022

A 6.6-Mw earthquake struck the Iburi region of Hokkaido, Japan, in 2018, triggering massive landslides. Most of these landslides were shallow and occurred mostly in the Atsuma and Abira towns. Ta-c and Ta-d tephra layers have been found in the Towa landslide at Atsuma from the Tarumai volcano, while Ta-d, En-a, and Spfa-1 tephra layers have been found in the Mizuho landslide at Abira from the Tarumai and Eniwa volcanos, as well as the Shikotsu caldera. Field observations from previous studies revealed that the sliding layers were located in the Ta-d and En-a layers at the Towa and Mizuho landslides, respectively. Unlike previous research on earthquake-induced landslides, which were investigated using mechanical properties, this study investigates the characteristics of physical properties, saturated permeability properties, and content of clay minerals on sliding and surrounding tephra layers. Results from this study reveal that the physical properties of sliding layers from two landslides demonstrated the same characteristics: non-plastic soil with a low density of soil particles, void ratio, and dry density; these characteristics could influence earthquake-induced landslides. It also reveals a relationship between the plasticity chart and the age of tephra materials, including the relationship between the weathering process and density of soil particles and the dissimilarity in characteristics of saturated permeability properties in tephra materials.
Systemic protothecosis in an immunocompetent patient
Authors: Trespalacios Sierra Alvano , Arroyo-Salgado Bárbara , Rodriguez-Blanco Jesús , Tibocha Gordon Ingrid , Martínez-Ávila María Cristina
Published: October 2022

Background

Although uncommon, there is increasing interest and public health concerns of the pathogenPrototheca spp, a ubiquitous achlorophilic microalgae that can affect both humans and animals. High mortality rates have been reported in immunocompromised patients with disseminated infection, but no data is available in the immunocompetent population.

Case Presentation

We present the case of a 59-year-old man from rural area of Colombia who was admitted to the intensive care unit due to decompensated heart failure that was difficult to medically manage, with development of septic shock and isolation ofPrototheca wickerhamiifrom blood culture. Fluconazole and Amphotericin B were given with successful outcome.

Conclusions

To date, protothecosis and its virulence factors and pathogenesis remain to be fully understood, in our case the isolation of this microalga and its implication of exacerbating chronic conditions such as heart failure is unclear. The medical-scientific community is invited to study this microorganism to determine effective management strategies, as well as its timely identification, treatment, and control, to avoid fatal outcomes.
A novel cell-free intrathecal approach with PRP for the treatment of spinal cord multiple sclerosis in cats
Authors: Farid Mariam F. , Abouelela Yara S. , Yasin Noha A. E. , Mousa Mohamed R. , Ibrahim Marwa A. , Prince Abdelbary , Rizk Hamdy
Published: October 2022

Background

Multiple sclerosis (MS) is a progressive autoimmune demyelinating disease of the central nervous system. To date, there is no effective therapy for it. Our study aimed to determine the potential role of platelet-rich plasma (PRP) in the treatment of MS in cats.

Methods

The current study was conducted on 15 adult Persian cats that were divided into three groups: control negative, control positive (ethidium bromide (EB)-treated group), and PRP co-treated group (EB-treated group intrathecally injected with PRP on day 14 post-spinal cord injury). PRP was obtained by centrifuging blood on anticoagulant citrate dextrose and activating it with red and green laser diodes. The Basso–Beattie–Bresnahan (BBB) scores were used to assess the motor function recovery on days 1, 3, 7, 14, 20, and 28 following 14 days from EB injection. Moreover, magnetic resonance imaging (MRI) analysis, histopathological investigations, transmission electron microscopy (TEM) studies, and immunohistochemical analysis were conducted, and the gene expressions of nerve growth factors (NGFs), brain-derived neurotrophic factors (BDNF), and stromal cell-derived factors (SDF) were evaluated.

Results

Our results indicated that PRP had a significant ameliorative effect on the motor function of the hindlimbs as early as day 20 and so on. MRI revealed that the size and intensity of the lesion were significantly reduced in the PRP co-treated group. The histopathological and TEM investigations demonstrated that the PRP co-treated group had a significant improvement in the structure and organization of the white matter, as well as a high remyelination capacity. Furthermore, a significant increase in myelin basic protein and Olig2 immunoreactivity as well as a reduction in Bax and glial fibrillar acidic protein immune markers was observed. NGFs were found to be upregulated by gene expression.

Conclusion

As a result, we concluded that the intrathecal injection of PRP was an effective, safe, and promising method for the treatment of MS.
Violence against healthcare workers during coronavirus (COVID-19) pandemic in Egypt: a cross-sectional study
Authors: Elsaid Noha M. Abu Bakr , Ibrahim Omneya , Abdel-Fatah Zeinab F. , Hassan Hend A. , Hegazy MennatAllah H. , Anwar Marwa M. , Soliman Hanan H.
Published: October 2022

Background

Healthcare workers are on the front lines of COVID-19 and are subject to risks. A rise in the cases of violence and aggressiveness against HCWs has been observed worldwide, adding to the already existing burnout. The purpose of this research is to determine the prevalence of workplace violence, its risk variables, and the pattern of violence directed towards healthcare workers in the context of COVID-19 pandemic. The research used a cross-sectional analytic design. Purposive sampling was utilized to identify research participants using an online survey. Form’s link was distributed to accessible social media groups such as Facebook and WhatsApp from July 2020 to the end of October 2020. A self-administered structured survey was adapted from the World Health Organization survey questionnaire about violence in healthcare settings. The Google Form’s link was distributed to the social media groups until the total sample of 405 was collected.

Results

During the COVID-19 pandemic, workplace violence against Egyptian healthcare workers was prevalent (63.2%). The most prevailing type of violence among the exposed participants was verbal violence (87.9%). Violence is more common in the (< 40 years old) age group (80.9% of exposed healthcare workers). Violence was more statistically significant against females (60.5% of the exposed healthcare workers) (p-value = 0.023). Regarding the work specialty, violence was more committed against physicians (84.3% of exposed healthcare workers) than nurses (12.8% of exposed healthcare workers). The primary perpetrators of violence were the patient’s family (74.6%). The majority of the exposed HCWs (96%) reported no physical injury from the violent event, and 71.5% deemed the violent incident preventable. The majority (90.6%) of HCWs exposed to violent incidents declared non-reporting.

Conclusions

Effective risk communication at all levels of society is critical for reducing fear, stigma, and ultimately workplace violence, as recent assaults on healthcare institutions demonstrate. To reduce violence and safeguard the safety of the medical profession, the government, health policymakers, media organizations, and community engagement groups must collaborate for healthcare workers’ safety.
Life table parameters of the predatory mite, Blattisocius mali Oudemans (Mesostigmata: Blattisociidae), fed on eggs and larvae of the stored product mite, Tyrophagus putrescentiae (Schrank)
Authors: Asgari Faeze , Safavi Seyed Ali , Moayeri Hamid Reza Sarraf
Published: October 2022

Background

The predatory mite, Blattisocius mali Oudemans (Mesostigmata: Blattisociidae), feeds on various species of storage mites such as Tyrophagous putresentiae (Schrank). In this study, life table parameters and consumption rates of B. mali were determined when fed on the eggs and larvae of T. putrescentiae as the prey under laboratory conditions.

Results

Based on the age-stage two-sex life table analysis, the total pre-ovipositional period (TPOP) of the predator was considerably lower by feeding on host larvae than that on eggs. Also, mean fecundity (eggs/female) of the B. mali was 2.60-fold higher on host larvae than its eggs. Moreover, the intrinsic rate of increase (r), as the most important parameter was 0.272 and 0.357 day−1, respectively, by host mite eggs and larvae as food. This showed the significantly greater influence of T. putrescentiae larvae than eggs on mass production of the predatory mite. The same trend was observed in finite rate of increase (λ), net reproductive rate (R0), gross reproductive rate. But mean generation times (T) were statistically the same by feeding both host stages. Maximum longevity of male and female individuals was, respectively, 21 and 22 days when eggs were fed. By feeding on larvae as prey, maximum longevity was lowered to 20 days in both predator sexes. However, the net predation rate (C0) and transformation rate from prey population to predator offspring (QP) were significantly higher by feeding on host eggs (97.420 and 3.049) than its larvae (41.3936 and 0.5575), respectively.

Conclusion

From practical biocontrol view, both eggs and larvae of T. putrescentiae can be consumed and therefore controlled by the predatory mite, B. mali. From mass production view, larvae of T. putrescentiae produced a better fitness in the predatory mite than its eggs and can be used in augmentation programs of B. mali.