bluuebunny/crossref_metadata_2025 huggingface dataset:
BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease
Authors: Guo Yifan , Wang Mengdi , Liu Yufei , Pang Yanyu , Tian Lei , Zhao Jingwen , Liu Mengchao , Shen Cun , Meng Yuan , Wang Yuefen , Cai Zhen , Zhao Wenjing
Published: March 2023

Background

Mitochondrial dysfunction is considered to be an important contributor in podocyte injury under diabetic conditions. The BaoShenTongLuo (BSTL) formula has been shown to reduce podocyte damage and postpone the progression of diabetic kidney disease (DKD). The potential mechanisms underlying the effects of BSTL, however, have yet to be elucidated. In this study, we aimed to investigate whether the effects of BSTL are related to the regulation of mitochondrial biogenesis via the adenosine monophosphate-activated protein kinase (AMPK) pathway.

Methods

High-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer (HPLC–ESI–MS) analysis was performed to investigate the characteristics of pure compounds in BSTL. db/db mice and mouse podocyte clone-5 (MPC5) cells were exposed to high glucose (HG) to induce DKD and podocyte damage. Body weight, random blood glucose, urinary albumin/creatinine ratio (UACR), indicators of renal function and renal histological lesions were measured. Markers of podocyte injury, mitochondrial morphology, mitochondrial deoxyribonucleic acid (mtDNA) content, mitochondrial respiratory chain complexes activities, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) levels were assessed. Protein expressions of AMPK, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), transcription factor A (TFAM), mitochondrial fusion protein 2 (MFN2) and dynamin-related protein 1 (DRP1) were also detected. MPC5 cells were transfected with AMPKα small interfering RNA (AMPKα siRNA) to determine the underlying mechanisms of BSTL improvement of mitochondrial function under diabetic conditions.

Results

In vivo, treatment with BSTL reduced the UACR levels, reversed the histopathological changes in renal tissues, and alleviated the podocyte injury observed in db/db mice. After BSTL treatment, the decreased mtDNA content and mitochondrial respiratory chain complex I, III, and IV activities were significantly improved, and these effects were accompanied by maintenance of the protein expression of p-AMPKαT172, PGC-1α, TFAM and MFN2. The in vitro experiments also showed that BSTL reduced podocyte apoptosis, suppressed excessive cellular ROS production, and reversed the decreased in MMP that were observed under HG conditions. More importantly, the effects of BSTL in enhancing mitochondrial biogenesis and reducing podocyte apoptosis were inhibited in AMPKα siRNA-treated podocytes.

Conclusion

BSTL plays a crucial role in protecting against podocyte injury by regulating the AMPK-mediated mitochondrial biogenesis in DKD.
Carbon stock potential of highland bamboo plantations in northwestern Ethiopia
Authors: Jember Ayana A. , Taye Mintesinot A. , Gebeyehu Getaneh , Mulu Gashaw , Long Trinh Thang , Jayaraman Durai , Abebe Shiferaw
Published: March 2023

Background

In Ethiopia, highland bamboo has been cultivated in various niches: farmlands, riverbanks, woodlot boundaries, and homesteads, and agroforestry systems. However, the biomass and carbon storage of potential of bamboo forests across niches is not well characterized in Ethiopia. Therefore, this study was conducted to estimate the biomass and carbon storage potential of highland bamboo plantations in northwestern Ethiopia. To this end, a total of 60 circular plots measuring 100 m2 with a radius of 5.64 m were randomly established on the homestead, woodlot, and riverbank plantation niches to conduct the inventory. The biomass storage of bamboo was calculated based on previously published allometric equations. Biomass and carbon stock variations among age-classes and niches of bamboo forests were analyzed using analysis of variance (ANOVA) and subsequent pairwise means comparisons of carbon stocks among niches were performed via post hoc Tukey test at p < 0.05.

Results

Results showed that the mean aboveground biomass (AGB) ranged from 150.18 – 191.42 Mg ha−1 in the entire niches. The highest amount of AGB was stored in the homestead niche (191.42 Mg ha−1) followed by the woodlot (180.11 Mg ha−1) and riverbank niche (150.17 Mg ha−1), respectively. The highest carbon stock (111.56 Mg C ha−1) was found in the homestead niche while the smallest amount was recorded in the riverbank niche (87.52 Mg ha−1). The homestead bamboo plantation has the highest biomass storage due to the application of manure and natural fertilizer, regular harvesting and management of culms, and protection from illegal harvesting and grazing.

Conclusion

This study highlights the importance of bamboo plantations in climate change mitigation. Hence, bamboo plantation should be promoted; and natural resource management and forestry departments of the government, Universities, research centers, the International Bamboo and Rattan Organization (INBAR), and other partners should work with local communities to expand bamboo plantation on their homesteads and degraded lands.
GLUT1-DS Italian registry: past, present, and future: a useful tool for rare disorders
Authors: Varesio Costanza , De Giorgis Valentina , Veggiotti Pierangelo , Nardocci Nardo , Granata Tiziana , Ragona Francesca , Pasca Ludovica , Mensi Martina Maria , Borgatti Renato , Olivotto Sara , Previtali Roberto , Riva Antonella , Mancardi Maria Margherita , Striano Pasquale , Cavallin Mara , Guerrini Renzo , Operto Francesca Felicia , Pizzolato Alice , Di Maulo Ruggero , Martino Fabiola , Lodi Andrea , Marini Carla
Published: March 2023

Background

GLUT1 deficiency syndrome is a rare, genetically determined neurological disorder for which Ketogenic Dietary Treatment represents the gold standard and lifelong treatment. Patient registries are powerful tools providing insights and real-world data on rare diseases.

Objective

To describe the implementation of a national web-based registry for GLUT1-DS.

Methods

This is a retrospective and prospective, multicenter, observational registry developed in collaboration with the Italian GLUT1-DS association and based on an innovative, flexible and configurable cloud computing technology platform, structured according to the most rigorous requirements for the management of patient’s sensitive data. The Glut1 Registry collects baseline and follow-up data on the patient’s demographics, history, symptoms, genotype, clinical, and instrumental evaluations and therapies.

Results

Five Centers in Italy joined the registry, and two more Centers are currently joining. In the first two years of running, data from 67 patients (40 females and 27 males) have been collected. Age at symptom onset was within the first year of life in most (40, 60%) patients. The diagnosis was formulated in infancy in almost half of the cases (34, 51%). Symptoms at onset were mainly paroxysmal (mostly epileptic seizure and paroxysmal ocular movement disorder) or mixed paroxysmal and fixed symptoms (mostly psychomotor delay). Most patients (53, 79%) are currently under Ketogenic dietary treatments.

Conclusions

We describe the principles behind the design, development, and deployment of the web-based nationwide GLUT1-DS registry. It represents a stepping stone towards a more comprehensive understanding of the disease from onset to adulthood. It also represents a virtuous model from a technical, legal, and organizational point of view, thus representing a possible paradigmatic example for other rare disease registry implementation.
The era of cryptic exons: implications for ALS-FTD
Authors: Mehta Puja R. , Brown Anna-Leigh , Ward Michael E. , Fratta Pietro
Published: March 2023

TDP-43 is an RNA-binding protein with a crucial nuclear role in splicing, and mislocalises from the nucleus to the cytoplasm in a range of neurodegenerative disorders. TDP-43 proteinopathy spans a spectrum of incurable, heterogeneous, and increasingly prevalent neurodegenerative diseases, including the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum and a significant fraction of Alzheimer’s disease. There are currently no directed disease-modifying therapies for TDP-43 proteinopathies, and no way to distinguish who is affected before death. It is now clear that TDP-43 proteinopathy leads to a number of molecular changes, including the de-repression and inclusion of cryptic exons. Importantly, some of these cryptic exons lead to the loss of crucial neuronal proteins and have been shown to be key pathogenic players in disease pathogenesis (e.g., STMN2), as well as being able to modify disease progression (e.g., UNC13A). Thus, these aberrant splicing events make promising novel therapeutic targets to restore functional gene expression. Moreover, presence of these cryptic exons is highly specific to patients and areas of the brain affected by TDP-43 proteinopathy, offering the potential to develop biomarkers for early detection and stratification of patients. In summary, the discovery of cryptic exons gives hope for novel diagnostics and therapeutics on the horizon for TDP-43 proteinopathies.
Surgical dose and the clinical outcome in the treatment of mammary gland tumours in female dogs: a literature review
Authors: Hörnfeldt Maria Bennet , Mortensen Jacob Kvesel
Published: March 2023

Mammary gland tumours are the most frequent tumours in intact female dogs and surgery remains the main treatment modality. Surgery is traditionally performed according to the lymphatic drainage of the mammary glands, but robust evidence is still lacking on what surgical dose is the smallest and results in the best outcome. The objective of the study was to investigate whether choice of surgical dose influences treatment outcome in dogs with mammary tumours and to identify current gaps in research that need to be filled in future studies for identifying the smallest surgical dose with the best possible outcome. Articles for entrance into the study were identified in online databases. Information regarding outcome following use of different surgical doses was extracted for analysis. Also, known prognostic factors were mapped for each study to discuss their impact on treatment outcome. Twelve articles were identified and included. Surgical dose applied ranged from lumpectomy to radical mastectomy. Radical mastectomy was most often analysed [11/12 (92%) articles]. Less invasive surgical doses were used less often in decreasing order of invasiveness. Outcomes analysed were most often survival time [7/12 (58%) articles], frequency of recurrences [5/12 (50%) studies] and time to recurrence [5/12 (42%) studies)]. No studies demonstrated any significant association between surgical dose and outcome. Gaps in the research could be categorised as data that was not available for extraction, for example known prognostic factors. Other factors related to study design were also identified, for example small groups of dogs included into the study. No studies showed a clear benefit of choosing one surgical dose over the other. Choice of surgical dose should be based on known prognostic factors and risks for complications rather than on lymphatic drainage. In future studies all prognostic factors should be included when investigating how choice of surgical dose influences treatment outcome.
Survival of livestock-associated methicillin-resistant Staphylococcus aureus CC398 on different surface materials
Authors: Tuominen Krista , Frosth Sara , Pedersen Karl , Rosendal Thomas , Sternberg Lewerin Susanna
Published: March 2023

Background

Zoonotic livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widely spread in pig herds in many countries. However, the knowledge regarding the survival of LA-MRSA in the pig farm environment is currently limited. The aim of this study was to assess the survival of LA-MRSA on different surface materials found in the farm environment. The study investigated the survival of two different LA-MRSA strains belonging to the clonal complex (CC) 398 on four different surfaces: stainless steel, polypropylene plastic, K30 concrete and commercial concrete disk coupons. The survival of the bacteria over time was determined by the viable count method and, where possible, fitting a model to the observed data by using nonlinear least squares method to calculate the half-life ($${t}_{1/2}$$

t

1
/
2

) for different strain and material combinations.

Results

The study showed that the half-life of the bacteria was longer on polypropylene plastic ($${t}_{1/2}$$

t

1
/
2

=11.08–15.78 days) than on stainless steel ($${t}_{1/2}$$

t

1
/
2

=2.45–7.83 days). On these materials, both LA-MRSA strains survived through the 14 week observation period. The bacterial decay was fastest on the concrete surfaces, where LA-MRSA became undetectable after 3–9 weeks.

Conclusions

The survival of LA-MRSA in the pig farm environment may be affected by different surface materials. A more frequent sampling protocol (< 7 days) is needed to determine the half-life on concrete surfaces.
Prevalence and multi-level factors associated with acute malnutrition among children aged 6–59 months from war affected communities of Tigray, Northern Ethiopia, 2021: a cross-sectional study
Authors: Gebretsadik Gebretsadkan Gebremedhin , Abraha Mahlet , Bereket Tedros , Hailemariam Ferehiwot , Gebrearegay Freweini , Hagos Tigist , Assefa Mizan , Berhe Kidanemaryam , Gebregziabher Hadush , Adhanu Amaha Kahsay , Haileselassie Mekonnen , Gebregziabher Mulugeta , Mulugeta Afework
Published: March 2023

Background

Armed conflicts greatly affect the health, nutrition, and food security of conflict affected settings particularly children. However, no empirical data exist regarding context specific factors contributing towards acute malnutrition in the war-torn Tigray, Ethiopia. Thus, this study aimed to identify individual and community level factors associated with acute malnutrition among children aged 6–59 months from armed conflict affected settings of Tigray, Ethiopia.

Methods

A community based cross-sectional study was conducted among 3,614 children aged 6–59 months in Tigray, from July 15 to Aug 15, 2021. Study participants were selected using a two-stage random sampling method. A structured questionnaire was used to collect data by interviewing mothers/caregivers. Mid upper arm circumference (MUAC) measurements were taken from upper left arm of the children using MUAC tapes. Multivariable multilevel logistic regression analysis was used to determine factors associated with acute malnutrition. Adjusted Odds ratio (AOR) with 95% CI were estimated to describe the strength of associations at p < 0.05.

Results

More than half (52.5%) of the sampled children were males in sex. Immediately after the first nine months into the conflict, the prevalence of severe, moderate, and global acute malnutrition was very high (5.1%, 21.8%, and 26.9%, respectively) in Tigray. The lowest and highest burden of child acute malnutrition was reported from Mekelle zone (13.3%) and Southeastern zone (36.7%), respectively. Individual-level factors such as older child age (AOR = 0.13, 95% CI: 0.10, 0.18), female child sex (AOR = 1.24, 95% CI 1.05, 1.480.95), Vitamin-A supplementation (AOR = 1.3, 95% CI: 1.05, 1.65), and history of diarrhea (AOR = 1.22, 95%CI: 1.02, 1.53) and community-level factors like unimproved drinking water source (AOR = 1.31, 95%CI: 1.08, 1.58), unimproved toilet facility (AOR = 1.24, 95% CI: 1.01, 1.52), and severe food insecurity (AOR = 1.55, 95% CI: 1.16. 2.07) were significantly associated with childhood acute malnutrition.

Conclusions

The burden of acute malnutrition is a severe public health problem in Tigray. To prevent the untimely suffering and death of children, regular nutrition screening, speedy, and appropriate referral of all malnourished children to nutritional services and large-scale humanitarian assistance including access to food; nutrition supplies; water, sanitation and hygiene supplies; and health care in a timely manner are required. In the prevailing armed conflict, these have been very difficult to achieve. Thus, immediate international intervention is needed.
Are complications related to the perineal post on orthopaedic traction tables for surgical fracture fixation more common than we think? A systematic review
Authors: Attenasio Andrea , Kraeutler Matthew J. , Hong Ian S. , Baskar Suriya , Patel Deepak V. , Wright Craig , Jankowski Jaclyn M. , Liporace Frank A. , Yoon Richard S.
Published: March 2023

Background

Traction tables have long been utilized in the management of fractures by orthopaedic surgeons. The purpose of this study was to systematically review the literature to determine the complications inherent to the use of a perineal post when treating femur fractures using a traction table.

Methods

A systematic review was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) using PubMed, EMBASE, and Cochrane Library. The search phrase used was “fracture” AND “perineal” AND “post” AND (“femur” OR “femoral” OR “intertrochanteric” OR “subtrochanteric”). Inclusion criteria for this review were: level of evidence (LOE) of I – IV, studies reporting on patients surgically treated for femur fractures, studies reporting on patients treated on a fracture table with a perineal post, and studies that reported the presence or absence of perineal post-related complications. The rate and duration of pudendal nerve palsy were analyzed.

Results

Ten studies (2 prospective and 8 retrospective studies; 2 LOE III and 8 LOE IV) were included consisting of 351 patients of which 293 (83.5%) were femoral shaft fractures and 58 (16.5%) were hip fractures. Complications associated with pudendal nerve palsies were reported in 8 studies and the mean duration of symptoms ranged between 10 and 639 days. Three studies reported a total of 11 patients (3.0%) with perineal soft tissue injury including 8 patients with scrotal necrosis and 3 patients with vulvar necrosis. All patients that developed perineal skin necrosis healed through secondary intention. No permanent complications relating to pudendal neurapraxia or soft tissue injuries were reported at final follow-up timepoints.

Conclusion

The use of a perineal post when treating femur fractures on a fracture table poses risks for pudendal neurapraxia and perineal soft tissue injury. Post padding is mandatory and supplemental padding may also be required. Appropriate perineal skin examination prior to use is also important. Occurring at a higher rate than previously thought, appropriate post-operative examination for any genitoperineal soft tissue complications and sensory disturbances should not be ignored.
Experience-dependent changes in affective valence of taste in male mice
Authors: Hamada Shun , Mikami Kaori , Ueda Shuhei , Nagase Masashi , Nagashima Takashi , Yamamoto Mikiyasu , Bito Haruhiko , Takemoto-Kimura Sayaka , Ohtsuka Toshihisa , Watabe Ayako M.
Published: March 2023

Taste plays an essential role in the evaluation of food quality by detecting potential harm and benefit in what animals are about to eat and drink. While the affective valence of taste signals is supposed to be innately determined, taste preference can also be drastically modified by previous taste experiences of the animals. However, how the experience-dependent taste preference is developed and the neuronal mechanisms involved in this process are poorly understood. Here, we investigate the effects of prolonged exposure to umami and bitter tastants on taste preference using two-bottle tests in male mice. Prolonged umami exposure significantly enhanced umami preference with no changes in bitter preference, while prolonged bitter exposure significantly decreased bitter avoidance with no changes in umami preference. Because the central amygdala (CeA) is postulated as a critical node for the valence processing of sensory information including taste, we examined the responses of cells in the CeA to sweet, umami, and bitter tastants using in vivo calcium imaging. Interestingly, both protein kinase C delta (Prkcd)-positive and Somatostatin (Sst)-positive neurons in the CeA showed an umami response comparable to the bitter response, and no difference in cell type-specific activity patterns to different tastants was observed. Meanwhile, fluorescence in situ hybridization with c-Fos antisense probe revealed that a single umami experience significantly activates the CeA and several other gustatory-related nuclei, and especially CeA Sst-positive neurons were strongly activated. Intriguingly, after prolonged umami experience, umami tastant also significantly activates the CeA neurons, but the Prkcd-positive neurons instead of Sst-positive neurons were highly activated. These results suggest a relationship between amygdala activity and experience-dependent plasticity developed in taste preference and the involvement of the genetically defined neural populations in this process.
In-vivo oogenesis of oogonial and mesenchymal stem cells seeded in transplanted ovarian extracellular matrix
Authors: Mirzaeian Leila , Eivazkhani Farideh , Saber Maryam , Moini Ashraf , Esfandiari Fereshteh , Valojerdi Mojtaba Rezazadeh , Fathi Rouhollah
Published: March 2023

Objective (s)

One way to overcome the recurrence of cancer cells following ovarian tissue transplantation is to use decellularized tissues as a scaffold that does not have any cellular components. These cell-free scaffolds can be seeded with different type of stem cells for ovarian restoration.

Materials and methods

OSCs, PMSCs and BMSCs (oogonial, peritoneal and bone marrow mesenchymal stem cells, respectively) were seeded into human decellularized ovarian tissue as 4 groups: Scaffold + OSCs (SO), Scaffold + OSC + PMSCs (SOP), Scaffold + OSC + BMSCs (SOB) and Scaffold + OSC + PMSCs + BMSCs (SOPB). The produced grafts were transplanted into the sub-peritoneal space of ovariectomized NMRI mice as artificial ovary (AO). The expression of Vegf, CD34, Gdf9, Zp3, Ddx4, Amh and Lhr genes in AOs were measured by qRT-PCR. Also, histotechniques were considered to detect the anti GFP, PCNA, VEGF, GDF9, ZP3 and AMH proteins.

Results

H & E staining showed follicle-like structures in all groups; the number of these structures, in the SOP and SOB groups, were the highest. In SO group, differentiation ability to oocyte and granulosa cells was observed. Endothelial, oocyte, germ, and granulosa cell-like cells were specially seen in SOP and angiogenesis capability was more in SOB group. However, angiogenesis ability and differentiation to theca cell-like cells were more often in SOPB group. While none of the groups showed a significant difference in AMH level, estradiol levels were significantly higher in SOPB group.

Conclusion

Integration of OSCs + PMSCs and those OSCs + BMSCs were more conducive to oogenesis.
Airway registries in primarily adult, emergent endotracheal intubation: a scoping review
Authors: Meulendyks Sarah , Korpal Daniel , Jin Helen Jingshu , Mal Sameer , Pace Jacob
Published: March 2023

Background

Emergency Department (ED) airway registries are formalized methods to collect and document airway practices and outcomes. Airway registries have become increasingly common in EDs globally; yet there is no consensus of airway registry methodology or intended utility. This review builds on previous literature and aims to provide a thorough description of international ED airway registries and discuss how airway registry data is utilized.

Methods

A search of Medline, Embase, Scopus, Cochrane Libraries, Web of Science, and Google Scholar was performed with no date limitations applied. English language full-text publications and grey literature from centres implementing an ongoing airway registry to monitor intubations performed in mainly adult patients in an ED setting were included. Non-English publications and publications describing airway registries to monitor intubation practices in predominantly paediatric patients or settings outside of the ED were excluded. Study screening for eligibility was performed by two team members individually, with any disagreements resolved by a third team member. Data was charted using a standardized data charting tool created for this review.

Results

Our review identified 124 eligible studies from 22 airway registries with a global distribution. We found that airway registry data is used for quality assurance, quality improvement, and clinical research regarding intubation practices and contextual factors. This review also demonstrates that there is a great deal of heterogeneity in definitions of first-pass success and adverse events in the peri-intubation period.

Conclusions

Airway registries are used as a crucial tool to monitor and improve intubation performance and patient care. ED airway registries inform and document the efficacy of quality improvement initiatives to improve intubation performance in EDs globally. Standardized definitions of first-pass success and peri-intubation adverse events, such as hypotension and hypoxia, may allow for airway management performance to be compared on a more equivalent basis and allow for the development of more reliable international benchmarks for first-pass success and rates of adverse events in the future.
Changes in liver enzymes are associated with changes in insulin resistance, inflammatory biomarkers and leptin in prepubertal children with obesity
Authors: Valle-Martos Rosario , Jiménez-Reina Luis , Cañete Ramón , Martos Rosario , Valle Miguel , Cañete María Dolores
Published: March 2023

Background

Non-alcoholic fatty liver disease is associated with obesity. A subclinical inflammation state, endothelial dysfunction, and parameters related to metabolic syndrome (MetS), have been documented in children with obesity. We aimed to determine the changes that occur in liver enzymes levels in response to the standard treatment of childhood obesity, also assessing any associations with liver enzyme levels, leptin, and markers of insulin resistance (IR), inflammation, and parameters related to MetS in prepubertal children.

Methods

We carried out a longitudinal study in prepubertal children (aged 6–9 years) of both sexes with obesity; a total of 63 participants were recruited. Liver enzymes, C-reactive protein (CRP), interleukin-6, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), soluble intercellular adhesion molecule-1 (sICAM-1), leptin, homeostasis model assessment for IR (HOMA-IR), and parameters related to MetS were measured.

Results

After standard treatment for 9 months, children who lowered their standardised body mass index (SDS-BMI) had significantly lower systolic blood pressure (p = 0.0242), diastolic blood pressure (p = 0.0002), HOMA-IR (p = 0.0061), and levels of alanine aminotransferase (ALT) (p = 0.0048), CRP (p = 0.0001), sICAM-1 (p = 0.0460), and IL-6 (p = 0.0438). There was a significant association between the changes that occur with treatment, in the ALT levels, and changes in leptin (p = 0.0096), inflammation biomarkers [CRP (p = 0.0061), IL-6 (p = 0.0337), NLR (p = 0.0458), PLR (p = 0.0134)], and HOMA-IR (p = 0.0322).

Conclusion

Our results showed that a decrease in ALT levels after the standard treatment for 9 months was associated with favourable changes in IR markers (HOMA-IR) and inflammation (IL-6, CRP, NLR, and PLR).
Paracetamol and ibuprofen combination for the management of acute mild-to-moderate pain in children: expert consensus using the Nominal Group Technique (NGT)
Authors: Parri Niccolò , Silvagni Davide , Chiarugi Alberto , Cortis Elisabetta , D’Avino Antonio , Lanari Marcello , Marchisio Paola Giovanna , Vezzoli Cesare , Zampogna Stefania , Staiano Annamaria
Published: March 2023

Background

Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia.

Methods

An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn.

Results

The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management.

Conclusions

The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.
Pathological complete response to neoadjuvant chemotherapy in triple negative breast cancer – single hospital experience
Authors: Sivina Elina , Blumberga Lubova , Purkalne Gunta , Irmejs Arvids
Published: March 2023

Background

Triple-negative breast cancer is a heterogeneous molecular subtype of BC. Pathological complete response (pCR) is an important surrogate marker for recurrence-free and overall survival.

Aim of study

The aim of this study was to evaluate clinical and pathological factors that are associated with complete pathological response status in triple-negative breast cancer patients receiving neoadjuvant chemotherapy.

Materials and methods

Eighty triple-negative breast cancer patients who underwent neoadjuvant chemotherapy followed by surgery at Pauls Stradins Clinical University Hospital between January 2018 and January 2020 were retrospectively analysed. Twenty-six patients (32.5%) were BRCA1/2 pathogenic variant carriers.

Results

A total of 32.5% (n = 26) of patients in all study groups and 57.7% (n = 15) of patients with BRCA1/2 pathogenic variants achieved pCR. Forty-seven patients received platinum-based neoadjuvant chemotherapy, and 19 patients (40.4%) achieved complete pathological response. Patients in the pCR group presented with significantly higher Ki-67 scores (p = 0.007), BRCA1/2 pathogenic variants (p = 0.001) and younger age (p = 0.02) than those in the non-pCR group. pCR did not significantly impact recurrence-free survival (RFS) or overall survival (OS). Multivariate analysis revealed that pretreatment N stage (clinical nodal status) was an independent prognostic factor for RFS and OS.

Conclusions

BRCA1 pathogenic variants, high Ki67 score and young age were predictors of pathological complete response, while clinical nodal status predicted survival outcomes in triple-negative breast cancer.
Metagenomic Sequencing in the ICU for Precision Diagnosis of Critical Infectious Illnesses
Authors: Neyton Lucile P. A. , Langelier Charles R. , Calfee Carolyn S.
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Host Response Biomarkers for Sepsis in the Emergency Room
Authors: Turgman Oren , Schinkel Michiel , Wiersinga Willem Joost
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Quality improvement in the determination of death by neurologic criteria around the world
Authors: Lewis Ariane , Kirschen Matthew P. , Badenes Rafael
Published: March 2023

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Embracing complexity in sepsis
Authors: Schuurman Alex R. , Sloot Peter M. A. , Wiersinga W. Joost , van der Poll Tom
Published: March 2023

Sepsis involves the dynamic interplay between a pathogen, the host response, the failure of organ systems, medical interventions and a myriad of other factors. This together results in a complex, dynamic and dysregulated state that has remained ungovernable thus far. While it is generally accepted that sepsis is very complex indeed, the concepts, approaches and methods that are necessary to understand this complexity remain underappreciated. In this perspective we view sepsis through the lens of complexity theory. We describe the concepts that support viewing sepsis as a state of a highly complex, non-linear and spatio-dynamic system. We argue that methods from the field of complex systems are pivotal for a fuller understanding of sepsis, and we highlight the progress that has been made over the last decades in this respect. Still, despite these considerable advancements, methods like computational modelling and network-based analyses continue to fly under the general scientific radar. We discuss what barriers contribute to this disconnect, and what we can do to embrace complexity with regards to measurements, research approaches and clinical applications. Specifically, we advocate a focus on longitudinal, more continuous biological data collection in sepsis. Understanding the complexity of sepsis will require a huge multidisciplinary effort, in which computational approaches derived from complex systems science must be supported by, and integrated with, biological data. Such integration could finetune computational models, guide validation experiments, and identify key pathways that could be targeted to modulate the system to the benefit of the host. We offer an example for immunological predictive modelling, which may inform agile trials that could be adjusted throughout the trajectory of disease. Overall, we argue that we should expand our current mental frameworks of sepsis, and embrace nonlinear, system-based thinking in order to move the field forward.
Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19
Authors: Jalkanen Juho , Khan Sofia , Elima Kati , Huttunen Teppo , Wang Ning , Hollmén Maija , Elo Laura L. , Jalkanen Sirpa
Published: March 2023

Background

The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN β) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial results showed deleterious effects of glucocorticoids when administered together with IFN β, and therefore, we aimed at finding the reason behind this.

Methods

We first sequenced the genes encoding the IFN α/β receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier: NCT02622724, November 24, 2015) in which the patients were randomized to receive an intravenous injection of IFN β-1a (144 patients) or placebo (152 patients). Genetic background was analyzed against clinical outcome, concomitant medication, and pro-inflammatory cytokine levels. Thereafter, we tested the influence of the genetic background on IFN α/β receptor expression in lung organ cultures and whether, it has any effect on transcription factors STAT1 and STAT2 involved in IFN signaling.

Results

We found a novel disease association of a SNP rs9984273, which is situated in the interferon α/β receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and interleukin-6 (IL-6) levels and better outcome in IFN β treated patients with ARDS, while the major allele associates with a poor outcome especially under concomitant IFN β and glucocorticoid treatment. Moreover, the minor allele of rs9984273 associates with a less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database.

Conclusions

The distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids.

Graphical abstract
Impact of breast cancer care pathways and related symptoms on the return-to-work process: results from a population-based French cohort study (CONSTANCES)
Authors: Rolland Anne-Lise , Porro Bertrand , Kab Sofiane , Ribet Céline , Roquelaure Yves , Bertin Mélanie
Published: March 2023

Background

Breast cancer (BC) treatments and related symptoms may affect return to work (RTW). The objective of this study was to investigate the impact of BC care pathways (timing and sequence of treatments) and related symptoms on RTW.

Methods

The study population included working-age women with BC who were enrolled in the French CONSTANCES cohort from 2012 to 2018. BC treatments, antidepressant/anxiolytic and antalgic drug deliveries (used as proxies of depression and pain, respectively) and statutory sick pay (used to estimate RTW and time to RTW) were assessed monthly using data from the French national healthcare system database. BC care pathways were identified with the sequence analysis method. Cox models with time-dependent covariates were used to investigate the impact of BC care pathways and related symptoms on RTW and time to RTW, after adjusting for age and socioeconomic characteristics.

Results

73.2% (231/303) of women returned to work within 2 years after BC diagnosis. Five BC care pathway patterns were identified: (i) BC surgery only, (ii) BC surgery and radiotherapy, (iii) BC surgery and chemotherapy, (iv) BC surgery and chemotherapy and radiotherapy, and (v) BC surgery and long-term alternative chemotherapy/radiotherapy. The hazards ratios of non-RTW were significantly higher for women who received BC surgery and long-term alternative chemotherapy/radiotherapy and for > 55-year-old women. Time to RTW was significantly longer in women who received chemotherapy (patterns iii to v) and in women with antidepressant/anxiolytic and antalgic drug deliveries.

Conclusion

This study highlights the value of considering the dynamic, cumulative and temporal features of BC care pathways and related symptoms to facilitate the RTW of women with BC.
Genetic mapping and molecular mechanism behind color variation in the Asian vine snake
Authors: Tang Chen-Yang , Zhang Xiaohu , Xu Xiao , Sun Shijie , Peng Changjun , Song Meng-Huan , Yan Chaochao , Sun Huaqin , Liu Mingfeng , Xie Liang , Luo Shu-Jin , Li Jia-Tang
Published: March 2023

Background

Reptiles exhibit a wide variety of skin colors, which serve essential roles in survival and reproduction. However, the molecular basis of these conspicuous colors remains unresolved.

Results

We investigate color morph-enriched Asian vine snakes (Ahaetulla prasina), to explore the mechanism underpinning color variations. Transmission electron microscopy imaging and metabolomics analysis indicates that chromatophore morphology (mainly iridophores) is the main basis for differences in skin color. Additionally, we assemble a 1.77-Gb high-quality chromosome-anchored genome of the snake. Genome-wide association study and RNA sequencing reveal a conservative amino acid substitution (p.P20S) inSMARCE1, which may be involved in the regulation of chromatophore development initiated from neural crest cells.SMARCE1knockdown in zebrafish and immunofluorescence verify the interactions amongSMARCE1, iridophores, andtfec, which may determine color variations in the Asian vine snake.

Conclusions

This study reveals the genetic associations of color variation in Asian vine snakes, providing insights and important resources for a deeper understanding of the molecular and genetic mechanisms related to reptilian coloration.
Gene expression in organoids: an expanding horizon
Authors: Smirnov Artem , Melino Gerry , Candi Eleonora
Published: March 2023

Recent development of human three-dimensional organoid cultures has opened new doors and opportunities ranging from modelling human development in vitro to personalised cancer therapies. These new in vitro systems are opening new horizons to the classic understanding of human development and disease. However, the complexity and heterogeneity of these models requires cutting-edge techniques to capture and trace global changes in gene expression to enable identification of key players and uncover the underlying molecular mechanisms. Rapid development of sequencing approaches made possible global transcriptome analyses and epigenetic profiling. Despite challenges in organoid culture and handling, these techniques are now being adapted to embrace organoids derived from a wide range of human tissues. Here, we review current state-of-the-art multi-omics technologies, such as single-cell transcriptomics and chromatin accessibility assays, employed to study organoids as a model for development and a platform for precision medicine.
Effects of an 8-week multimodal exercise program on ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder
Authors: Dehghani Mahrokh , Jafarnezhadgero Amir Ali , Darvishani Mohamad Abdollahpour , Aali Shirin , Granacher Urs
Published: March 2023

Background

Autism spectrum disorder is a developmental disability with first signs appearing in children aged 3 years and younger. Given that autism spectrum disorder is accompanied by a broad range of symptoms such as impaired sensory, neurological, and neuromotor functions, it appears plausible to argue that an intervention program focusing on multimodal exercise rather than single-mode exercise might be more effective in treating this wide variety of symptoms.

Objective

The aim of this study was to evaluate the effects of a multimodal exercise program entitled Sports, Play, and Active Recreation for Kids on variables of ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder.

Methods

Twenty-four autism spectrum disorder boys aged 7–11 years were recruited and randomly allocated into an intervention or a waiting control group. Sports, Play, and Active Recreation for Kids was conducted over a period of 8 weeks with three weekly sessions. This training protocol includes aerobic dance and jump rope exercises as well as running games. Pre- and post-training, ground reaction forces and plantar pressure variables were recorded while walking at a constant walking speed of 0.9 m/s using a foot scan embedded in a 15-m walkway.

Results

Significant group-by-time interactions were found for the first peak of vertical ground reaction force, loading rate, and peak pressure at the medial heel region (all p = 0.001–0.49, d = 0.89–1.40). Post-hoc analyses showed significant pre-post decreases for the first peak of vertical ground reaction force (p = 0.001, d = 1.27), loading rate (p = 0.009, d = 1.11), and peak pressure at the medial heel region (p = 0.021, d = 1.01).

Conclusions

Our results suggest that a joyful and multimodal exercise program has positive effects on kinetic walking characteristics of autism spectrum disorder boys. Accordingly, we recommend to implement this type of exercise in prepubertal autism spectrum disorder boys to improve gait kinetics.

Trial registration

Iranian Registry of Clinical Trials IRCT20170806035517N4. Registered on November 8, 2021. This study was approved by the Ethical Committee of the University of Mohaghegh Ardabili, Ardabil, Iran (IR.UMA.REC.1400.019). The study was conducted in accordance with the latest version of the Declaration of Helsinki.
The integration of rapid qualitative research in clinical trials: reflections from the ward-based goal-directed fluid therapy (GDFT) in acute pancreatitis feasibility trial
Authors: Vindrola-Padros Cecilia , Froghi Farid , Gopalan Vignesh , Maruthan Sachan , Filipe Helder , McNeil Margaret , Garcia Sara Mingo , Davidson Brian ,   on behalf of the GAP trial team
Published: March 2023

Background

There has been an increase in the integration of qualitative studies in randomised controlled trials. The purpose of this article is to reflect on our experience of carrying out a rapid qualitative study during a feasibility trial of goal-directed fluid therapy (GDFT) in patients with acute pancreatitis, including our sharing of emerging findings and the use of these findings by the trial team.

Methods

The study was designed as a rapid feedback evaluation and combined interviews with staff and patients who took part in the trial.

Findings

The rapid qualitative study pointed to common problems in trial recruitment among multiple sites, where lack of engagement of clinical teams across sites might impact negatively on patient recruitment. The article describes how the use of rapid feedback loops can be used as the trial is ongoing to inform changes in implementation. It also covers the potential challenges of working rapidly and collaborative with the trial team.

Conclusions

Rapid feedback evaluations can be used to generate findings across all stages of trial design and delivery. Additional research is required to explore the implementation of this research design in other settings and trial designs.
Master protocol to assess the long-term safety in kidney transplant recipients who previously received Medeor’s cellular immunotherapy products: the MDR-105-SAE
Authors: Kant Sam , Kaufman Dixon B. , Micsa Lenuta , Brennan Daniel C.
Published: March 2023

Background

Immunosuppression in transplantation continues to be associated with a multitude of adverse effects. Induction of immune tolerance may be a viable strategy to reduce dependence on immunosuppression. Various trials are currently underway to assess the efficacy of this strategy. However, long-term safety data for these immune tolerance regimes has yet to be established.

Methods/design

At the completion of primary follow-up of various Medeor kidney transplant studies, subjects receiving cellular immunotherapy products will be followed annually as per protocolized schedule for up to an additional 84 months (7 years) to evaluate long-term safety. Long-term safety will be assessed by summarizing incidence of serious adverse events, adverse events leading to study withdrawal and hospitalization rates.

Discussion

This extension study will be an important step in evaluating safety issues pertaining to immune tolerance regimens, long-term effects of which are largely unknown. These data are essential for furthering an unrealized goal of kidney transplantation- graft longevity without the adverse effects from long-term immunosuppression. The study design utilizes the methodology of a master protocol, wherein multiple therapies can be assessed simultaneously with accompanied gathering of long-term safety data.