bluuebunny/crossref_metadata_2025 huggingface dataset:
Insufficient Bone Mineralization to Sustain Mechanical Load of Weight in Obese Boys: A Cross-Sectional Study
Authors: Emeriau Fabienne , Amsellem-Jager Jessica , Bouhours-Nouet Natacha , Donzeau Aurelie , Rouleau Stephanie , Rerat Solène , Labarre Emmanuelle , Levaillant Lucie , Coutant Régis
Published: January 2024

Context

The increase in bone mineral content (BMC) and density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in obese children may not sustain the mechanical load associated with weight, and the factors influencing bone mineralization are not well known.

Objective

We described bone mineralization in boys with overweight/obesity and leanness in relation to body composition.

Methods

Cross-sectional study in the Pediatric Endocrinology Unit of Angers University Hospital with 249 overweight/obese boys aged 8-18 who underwent DXA and insulin, testosterone, and IGF-1 measurements. Bone mineralization was compared with data from 301 lean boys of similar age and height from NHANES 2011-2015, using the same DXA model. Path analyses were performed to evaluate factors associated with total body less head (TBLH) BMC.

Results

The mean age- and height-adjusted difference in TBLH BMC between obese and lean boys was 241 ± 20 g/cm2. Each 1 kg/m2 increase in BMI was associated with +39 ± 6 g of TBLH BMC in lean subjects vs + 25 ± 3 g in obese subjects (P < .05). Each 1 kg/m2 increase in lean BMI (LBMI) was associated with +78 ± 5 g of TBLH BMC in lean and obese boys, and each 1 kg/m2 increase in fat mass index (FMI) was associated with a decrease of 9 ± 3 g of TBLH BMC. The TBLH BMC was directly positively influenced by LBMI and indirectly and positively influenced by IGF-1, testosterone, and insulin (mediated through height and LBMI). FMI indirectly influenced TBLH BMC, both positively through LBMI and negatively through its negative impact on IGF-1 and testosterone.

Conclusion

The increase in bone mineralization in obese children does not adapt to the increase in body mass.
Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines
Authors: Fitz Victoria , Graca Sandro , Mahalingaiah Shruthi , Liu Jing , Lai Lily , Butt Ali , Armour Mike , Rao Vibhuti , Naidoo Dhevaksha , Maunder Alison , Yang Guoyan , Vaddiparthi Vaishnavi , Witchel Selma F , Pena Alexia , Spritzer Poli Mara , Li Rong , Tay Chau , Mousa Aya , Teede Helena , Ee Carolyn
Published: January 2024

Context

Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate.

Objective

To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS.

Data Sources

Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022.

Study Selection

Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included.

Data Extraction

Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second.

Data Synthesis

Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited.

Conclusion

The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.
Accidental Cushing Syndrome
Authors: Kousoula Konstantina , Ragnarsson Oskar , Trimpou Penelope
Published: January 2024

We present a patient with Cushing syndrome secondary to accidental intake of corticosteroid tablets—a 66-year-old woman with a history of well-controlled hypertension, who over the course of a few weeks developed full-blown Cushing syndrome with uncontrolled blood pressure, typical central fat accumulation, and easy bruising. The clinical features further worsened upon increase of the dosage of her antihypertensive medication because of rising blood pressure. Biochemical analyses showed low cortisol and ACTH concentrations. Inspection of the patient's medications revealed that she had accidentally been taking corticosteroids tablets, prescribed for her husband, instead of antihypertensives, ie, dexamethasone 4 mg and then 8 mg, instead of candesartan at the same dose.

This case highlights the necessity of a thorough review of the medications taken by patients suspected to have exogenous Cushing syndrome, including inspection of the original packaging, and not just relying on information from the patient and electronic health records. This case also highlights the need of special labeling on the packaging for the easy identification of corticosteroid-containing medications given their widespread availability.
Epidermal tyrosine catabolism is crucial for metabolic homeostasis and survival against high-protein diets in Drosophila
Authors: Kosakamoto Hina , Miura Masayuki , Obata Fumiaki
Published: January 2024

The insect epidermis forms the exoskeleton and determines the body size of an organism. How the epidermis acts as a metabolic regulator to adapt to changes in dietary protein availability remains elusive. Here, we show that the Drosophila epidermis regulates tyrosine (Tyr) catabolism in response to dietary protein levels, thereby promoting metabolic homeostasis. The gene expression profile of the Drosophila larval body wall reveals that enzymes involved in the Tyr degradation pathway, including 4-hydroxyphenylpyruvate dioxygenase (Hpd), are upregulated by increased protein intake. Hpd is specifically expressed in the epidermis and is dynamically regulated by the internal Tyr levels. Whereas basal Hpd expression is maintained by insulin/IGF-1 signalling, Hpd induction on high-protein diet requires activation of the AMP-activated protein kinase (AMPK)–forkhead box O subfamily (FoxO) axis. Impairment of the FoxO-mediated Hpd induction in the epidermis leads to aberrant increases in internal Tyr and its metabolites, disrupting larval development on high-protein diets. Taken together, our findings uncover a crucial role of the epidermis as a metabolic regulator in coping with an unfavourable dietary environment.
Atuação do enfermeiro para promoção a participação do pai no pré-natal
Authors: Marques Rafaelle Barboza , Salatiek Alisson , Júnior Antônio
Published: January 2024

Objetivo: apontar as ações do enfermeiro para promover a participação do pai no cuidado pré-natal. Métodos: Trata de um estudo descritivo, qualitativo, realizado com 10 enfermeiros de Unidades Básicas de Saúde do interior do Ceará, por meio de entrevista semiestruturada e análise de conteúdo. Resultados: Os profissionais envolvidos na pesquisa relataram entender a importância da participação do pai no pré-natal, no entanto a maioria dos entrevistados demonstrou não ter um conhecimento prévio adequado sobre o assunto, assim como não relatou medidas efetivas de captação desses homens para a consulta. Conclusão: Percebeu-se que os maiores desafios para a efetivação da participação dos pais no pré-natal se encontram nas barreiras sociais e culturais, na falta de preparo teórico dos
Stoic Consolations
Authors: Sherman Nancy
Published: January 2024

In this paper I explore the Stoic view on attachment to external goods, or what the Stoics call “indifferents.” Attachment is problematic, on the Stoic view, because it exposes us to loss and exacerbates the fragility that comes with needing others and things. The Stoics argue that we can build resilience through a robust reeducation of ordinary emotions and routine practice in psychological risk management techniques. Through a focus on selected writings of Seneca as well as Cicero’s Tusculan Disputations and Marcus Aurelius’s Meditations, I nonetheless ask whether Stoicism leaves any room for grief and distress. I argue that it does, and that consolation comes not from a retreat to some inner citadel, but from the support and sustenance of social connections.
Αντιλήψεις και εμπειρίες γυναικών Σχολικών Κοινωνικών Λειτουργών για τη χρήση του Κινηματογράφου ως εργαλείου παρέμβασης στην εκπαίδευση
Authors: Νικολαΐδου Σοφία
Published: January 2024

Το άρθρο αυτό στηρίζεται σε έρευνα, η οποία εξετάζει τις αντιλήψεις και τις εμπειρίες των σχολικών κοινωνικών λειτουργών σχετικά με τη χρήση του κινηματογράφου ως εργαλείο παρέμβασης σχολικής κοινωνικής εργασίας, με σκοπό την ανάδειξη των ωφελημάτων και των δυσκολιών που ενέχει η χρήση του. Για τη μέθοδο συλλογής και ανάλυσης της παρούσας έρευνας επιλέχθηκε η ποιοτική μεθοδολογία, όπου η συλλογή των δεδομένων έγινε μέσα από δώδεκα ημι- δομημένες συνεντεύξεις σε γυναίκες κοινωνικούς λειτουργούς, με εμπειρία σε ελληνικά δημόσια σχολεία από δέκα μήνες έως εφτά έτη. Οι συνεντεύξεις διεξήχθησαν διαδικτυακά και σε διάστημα δύο μηνών μεταξύ Νοέμβριου-Δεκεμβρίου 2021. Η ανάλυση των δεδομένων έγινε μέσω θεματικής ανάλυσης, όπου αναδείχθηκαν οφέλη τόσο για τους συμμετέχοντες της παρέμβασης όσο και για τους ίδιους τους σχολικούς κοινωνικούς λειτουργούς. Με τους πρώτους, αναδείχθηκε κυρίως η έκφραση των συναισθημάτων,  η καλλιέργεια ενσυναίσθησης και κοινωνικών δεξιοτήτων, η θετική αλλαγή στάσεων, καθώς  και η ενίσχυση ψυχικής ανθεκτικότητας. Έπειτα, οι σχολικοί κοινωνικοί λειτουργοί συνέβαλαν ώστε να αναδειχθεί σημαντικότατα η διευκόλυνση εκτίμησης, εξατομίκευσης και αξιολόγησης περιπτώσεων, επαγγελματικής  εξέλιξης  κ.α. Από την ανάλυση, προέκυψαν και οι δυσκολίες, όπως, ο ελάχιστος διαθέσιμος χρόνος για την παρέμβαση σε σχέση με τον χρόνο που απαιτείται για τη χρήση ταινιών ή βίντεο, η έλλειψη πόρων και υποστήριξης από  το εκπαιδευτικό πλαίσιο, οι δυσκολίες εφαρμογής της παρέμβασης κ.α. Επιπλέον, προέκυψε πως ο κινηματογράφος ως εργαλείο παρέμβασης μπορεί να χρησιμοποιηθεί σε ομαδικές, ατομικές και κάτω από συγκεκριμένες θεματολογικές παρεμβάσεις, έχοντας υπόψιν  στα σημεία που χρήζουν προσοχής κατά τη χρήση του. Τέλος, μέσα από τα ευρήματα της παρούσας έρευνας, αναδείχθηκε ο κινηματογράφος ως μία ιδιαίτερα χρήσιμη προσθήκη στις παρεμβάσεις της σχολικής κοινωνικής εργασίας.
The Sacraments at the Service of Communion in Unity with the Eucharist
Authors: Kwiatkowski Dariusz
Published: January 2024

Sakramenty w służbie komunii w jedności z Eucharystią
Artykuł ukazuje jedność teologiczną i celebracyjną Eucharystii z sakramentami w służbie Komunii, czyli z sakramentem święceń i sakramentem małżeństwa. Sprawowanie tych sakramentów w jednej celebracji liturgicznej wynika nie tyle z przepisów rubrycystycznych ale z ich ontologicznej jedności. Jest to bardzo czytelne w przypadku sakramentu święceń, gdyż został on ustanowiony wspólnie z Eucharystią. Źródłem łaczącym oba sakramenty jest Jezus Chrystus – Najwyższy Kapłan i jednocześnie Ofiara złożona przez Niego na krzyżu. Nie może być Eucharystii bez kapłaństwa i kapłaństwa bez Eucharystii. Sakrament małżeństwa będący znakiem Nowego Przymierza również prowadzi do Eucharystii, która to przymierze celebruje i uobecnia w sakramentalnych znakach. Miłość Chrystusa uobecniająca się w Eucharystii, umacnia i uświęca miłość nowożeńców, wyznawaną w sakramencie małżeństwa. Oznacza to, że nigdy nie powinno się traktować mszy świętej jako specjalnego dodatku do celebracji sakramentu małżeństwa. Komunia eucharystyczna bowiem tworzy i buduje komunię małżeńską.
Homogeneous eigenvalue problems in Orlicz-Sobolev spaces
Authors: Bonder Julián Fernández , Salort Ariel , Vivas Hernán
Published: January 2024

In this article we consider a homogeneous eigenvalue problem ruled
by the fractional $g$-Laplacian operator whose Euler-Lagrange equation
is obtained by minimization of a quotient involving Luxemburg norms.
We prove existence of an infinite sequence of variational eigenvalues
and study its behavior as the fractional parameter $s\uparrow 1$ among
other stability results.
On the operator of center of distances between the spaces of closed subsets of the real line
Authors: Bartoszewicz Artur , Filipczak Małgorzata , Horbaczewska Grażyna , Lindner Sebastian , Prus-Wiśniowski Franciszek
Published: January 2024

We study properties of an operator $S$ which assigns to compact subsets
of $[0,1]$ their centers of distances.
We consider its continuity points and its upper semicontinuity points as well
as orbits and fixed points of this operator. We also compute centers of distances
of some classic sets. Using properties of operator $S$ we show that the family of
achievement sets is of the first category in the space of compact subsets of $[0,1]$.
Framing y Política. Aportaciones empíricas desde iberoamérica
Authors: Gomes Barbosa Marcos Paulo
Published: January 2024

El presente trabajo trata de una reseña de la obra "Framing y Política. Aportaciones empíricas desde iberoamérica", coordinada por Carlos Muñiz y publicada en 2022 por Tirant Humanidades en Ciudad de México (México).
Una mejor comunicación para un mundo mejor
Authors: Rizo Garcia Marta
Published: January 2024

Reseña del libro: García-Jiménez, Leonarda (2019). En defensa de la comunicación, Tirant Humanidades, Valencia.
Improving high school students' research skills through light diffraction experiments using the problem-based learning model
Authors: Muthaharoh Siti , Sukarelawan Moh. Irma
Published: January 2024

This research aims to improve students' research skills through light diffraction experiments using the problem-based learning model. This research is included in the type of classroom action research. The research took place in two cycles. The respondents were 33 class XII Science students from SMAN 1 Tanjung. Students' research skills are reviewed in three aspects: skills in using tools, compiling reports, and presenting results. The rating scale used is a 4-point Likert rating scale. Research skills were analyzed using the Wilcoxon Signed Rank Test, stacking analysis, and racking. The results of the analysis show that there is a significant difference between students' research skills in cycles 1 and 2. After learning in cycle 2, it was identified that students to gain research skills in the low category. Of the three aspects of research skills studied, the skill of presenting results experienced the highest increase compared to the other two aspects. So, applying PBL learning through two-cycle PTK research has improved the research skills of class XII Science students at SMAN 1 Tanjung.
Prevalence of Work Musculoskeletal Disorder in Patients Handling Tasks Among Nursing Staff in Critical Care-Unit
Authors: Mebarki Bouhafs , Zaoui Brahim , Mokdad Mohamed , Mebarki Imed Eddine
Published: January 2024

Awkward postures imposed by nursing duties are a main source of work-related musculoskeletal disorders among nursing staff. The purpose of this article is to describe the prevalence of work-related musculoskeletal disorders among critical care nurses, in two patient handling tasks, transferring and repositioning of patients, and assess their training level and acquaintance of ergonomics rules and principles in patients’ handling tasks. Results of the study revealed a large number of nurses in intensive care unit exhibit musculoskeletal disorders symptoms. Nurses knowledge of safe patients handling technics are superficial and lacking basic human factors /ergonomics principles. The study recommended the immediate hiring of an adequate number of physically able nursing staff and providing the necessary work equipment to assist nurses perform patient handling tasks. In the near future, a human factors/ergonomics intervention program should be launched, incorporating a "Safe Patient Handling Training Program” for the critical care-unit staff
Çoklu Konjenital Anomali Vakası: Parsiyel Trizomi 14 ve Parsiyel Trizomi 22
Authors: GENÇ Aslı , CEYLAN Ahmet Cevdet , SİYAH Betül , KILIÇ Esra
Published: January 2024

Bu yazıda intrauterin gelişme geriliği, dismorfik yüz bulguları ve konjenital kalp anomalisine sahip bir yenidoğanda tespit edilen kısmi trizomi 14 ve kısmi trizomi 22 vakası tartışılmıştır. Canlı doğumlarda konjenital anomali görülme sıklığı %2-6 olup, bunların %60-80’inden genetik nedenlerin sorumlu olduğu düşünülmektedir. Kromozomal değişiklikler, konjenital anomalilerin %25-35’inde görülür. Resiprokal translokasyonlar, bu kromozomal yeniden düzenlemelerin en yaygın nedenidir. Yapılan incelemelerde hastanın tekrarlayan düşük öyküsüne sahip ebeveynlerinde 46, XY t(14;22) (q24;q11.2) dengeli resiprokal translokasyon taşıyıcılığı tespit edilmiştir. Bu gibi durumlarda ebeveynlere genetik danışmanlık sağlamak ve sonraki gebelikler için doğum öncesi tanı seçeneklerini tartışmak oldukça önemlidir.
APRESENTAÇÃO / PRESENTATION
Authors: Rosário Ivo da Costa do , Torres de Aguiar Milena Torres de , Svobodová Iva
Published: January 2024

Apresentação
Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports
Authors: Fang Ling-Zhi , Jin Hui-Xin , Zhao Na , Wu Yu-Pei , Shi Ying-Qin
Published: January 2024

BACKGROUND

Glucose imbalance is common in total parenteral nutrition (TPN). Hypoglycemia seems to be less frequent than hyperglycemia, but it influences the clinical outcome to a greater extent. Therefore, it should be effectively prevented and treated. However, there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury.

CASE SUMMARY

We present three patients with liver cell injury who developed severe hypoglycemia during or after TPN infusion. The causes of severe hypoglycemia and glucose-raising strategies were discussed. According to the physiological characteristics of the hepatocellular injury, the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases. We simultaneously reduced the dose of insulin and fat emulsion, and increased the dose of glucose in TPN. The blood glucose level was restored to normal range and clinical symptoms were eliminated.

CONCLUSION

When hypoglycemia occurs during or after TPN in patients with hepatocellular injury, physicians need to simultaneously reduce insulin and fat emulsion, and increase glucose, and correct severe hypoglycemia in time to reduce its adverse consequences.
Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction
Authors: Yang Ming , Huang Yuan-Tao , Hu Xi-Wen , Wu Chun-Ling
Published: January 2024

BACKGROUND

Cardiovascular disease, particularly myocardial infarction (MI) profound impact on patients' quality of life (QOL) and places a substantial burden on the healthcare and economy systems. Developments in medical technology have led to the emergence of coronary intervention as an essential method for treating MI.

AIM

To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.

METHODS

This study included a total of 180 patients with MI during the period from June 2022 to July 2023. Selected patients were divided into two groups: An observation group, which receiving cardiac rehabilitation care; a control group, which receiving conventional care. By comparing multiple observation indicators such as cardiac function indicators, blood pressure, exercise tolerance, occurrence of adverse cardiac events, and negative emotion scores between the two groups of patients. All the data were analyzed and compared between two groups.

RESULTS

There were 44 males and 46 females in the observation group with an average age of 36.26 ± 9.88 yr; there were 43 males and 47 females in the control group, with an average age of 40.87 ± 10.5 yr. After receiving the appropriate postoperative nursing measures, the results of the observation group showed significant improvement in several indicators compared with the control group. Indicators of cardiac function, such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group (P < 0.05). Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group (P < 0.01). In addition, the incidence of adverse cardiac events was significantly lower in the observation group, and negative mood scores were significantly reduced (P < 0.05).

CONCLUSION

Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery. This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.
A Synopsis of the Causes, Hypotheses, Progression, and Genes Associated with Breast Cancer
Authors: Ali Alatawi Hanan
Published: January 2024

Cancers are widespread among women, and breast cancer is considered one of the deadliest cancers among women. Due to early detection of breast cancer and appropriate treatment, the recovery rate among women increases, reaching 80% in developed countries. There are various genes linked to breast cancer as well as cancer stem cells. Genetic and epigenetic changes that result in abnormal gene function are involved in breast cancer. The genes associated with breast and ovarian cancer are BRCA1 and BRCA2. They are tumour suppressor genes because they play a role in DNA repair procedures. Furthermore, different malignancies exhibit dysregulation of the MYC oncogene family, which is typically associated with a bad prognosis for tumours. HER receptors are found in many tissues of epithelial, mesenchymal, and neuronal origin, where they control a variety of vital processes such as cell migration, programmed cell death (apoptosis), cell differentiation, and abnormal cell growth. Our understanding of the mechanisms that give birth to breast cancer has been significantly impacted by recent advances in genomics research. This understanding has in turn prompted the development of novel diagnostic and treatment techniques. This review will focus on the concept of breast cancer and related genes.
A Comparative Study on Macronutrients Content and Antioxidant Activity of Four Wild and Cultivated Seaweeds from the Moroccan Atlantic Coast
Authors: El-Majnaoui Samira , Lekrati Mounia , El Broudi Said , Benkhalti Fatiha , Zehhar Naima , Belmouden Ahmed , Houari Abdellah , El-Kadmiri Nadia
Published: January 2024

ABSTRACT: Extensive harvest of seaweeds in Morocco has caused overexploitation of these resources. Four Moroccan common seaweed species, wild and cultivated, were studied to assess the cultivated species' potential in comparison to their wild counterparts. The macronutrient composition, total phenolic compounds (TPC), as well as potential antioxidant activity (DPPH and FRAP), were established. Seaweeds contained a wide range of proteins (5–16% of DW), lipids (1–3% of DW), carbohydrates (20–59% of DW), and total polyphenols (3-6 mg EAG/g of DW). Red seaweeds contained high levels of polysaccharides (47–59% of DW), mainly the cultivated Gigartina pistillata, and important amounts of proteins, especially Gelidium sesquipedale (14–15% of DW), whereas the cultivated type was richer in proteins. Gracilaria gracilis and wild Gelidium sesquipedale are characterized by notable antioxidant activity, particularly the cultivated Gracilaria gracilis (TPC: 6.807 mg GAE/g of DW; low values of IC50 of DPPH: 53.863μg/mL and FRAP: 67.033μg/mL). Besides, the green seaweed Ulva lactuca is poor in carbohydrates but contains essential amounts of proteins and phenolics. This work highlights the significant potential of cultivating Moroccan seaweeds through algaculture to achieve more sustainable production with enhanced nutrient and bioactive molecule content.
Statistical Optimization of Fast Dissolving Tablet Contains Isosorbide Dinitrate for the Treatment of Angina Pectoris
Authors: Salam Sabeel , Fathima Reshma , Sreelekha P. P. , Kavya M. , Anjali E.
Published: January 2024

ABSTRACT: The ultimate objective about this experiment was to create a fast-dissolving tablet Isosorbide dinitrate that released its medication quickly. The physical properties of tablets, such as hardness, angle of repose, weight variation, and friability were assessed. In-vitro release was investigated, and a 22-factorial design was created. The results show that the in-vitro release shows that the F2 formulation has the highest release at 20 min. Tablet disintegration time ranges from 31 to 48 s. The hardness ranges from 6-7 kg/cm3. The friability test shows the range from 0.49-0.68%. The weight variation test shows that all the formulation passes the tests. ANOVA statistical analysis revealed that the generated formulations are statistically significant. It is concluded that FDT formulations have optimum and reproducible disintegration time and increased dissolve characteristics, resulting in higher patient compliance.
Drug Repurposing against Anhydro-N-acetylmuramic Acid Kinase of Multi-Drug Resistant Acinetobacter baumannii: An in Silico Approach
Authors: Gupta* Debdoot , Mondal Priya
Published: January 2024

ABSTRACT: Acinetobacter baumannii, a gram-negative coccobacillus is accountable for different nosocomial diseases. It has been enlisted in the ‘critical’ category in WHO published list depending on the urgency for novel drug development as it becomes multidrug resistant (MDR). The aim of this study was to find a drug which can be repurposed against any drug target of these bacteria and thus the time and cost required for typical drug development procedure can be bypassed. In this study, Anhydro-N-acetylmuramic acid kinase (AnmK) of Acinetobacter baumannii was analyzed to be a good drug target which is responsible for the structural integrity of the cell wall of these bacteria. The expression probability of the protein is high with 0.916. PROTPARAM analysis shows that it is a thermostable, non polar protein with molecular weight of 41.7 kDa and pI in the acidic range. The structure prediction was done with SWISS-MODEL (with 46.71% identity with the template) and was found reliable with 91.8% amino acid in allowable region. This predicted structure was used for dug repurposing in which drugs are screened from ZINC15 database (containing FDA approved drug) to find their effective binding (if any) with this protein. PyRx software was used for the docking process which found Ergotamine as the most promising repurposed drug in terms of binding energy(-10.5 kcal/mole) and vina score(-10.3 kcal/mole). Molecular Dynamics Simulation shows that binding of this drug with the protein target is stable over picoseconds time scale.
Isolation and Production of Cellulase from Bacteria Using Agro Waste
Authors: Chavda Nikita R. , Patel Priti. H. , Chaudhary Roshani K.
Published: January 2024

ABSTRACT: The development of appropriate procedures for the efficient treatment and utilization of wastes containing cellulose as an inexpensive carbon source has grown to be of substantial economic relevance. Cellulase enzyme, which is known to be produced by bacteria is responsible for degrading cellulose. Thus, isolation of Bacteria producing cellulase was performed using soil sample that were identified as Bacillus subtilis, Pseudomonas aeruginosa, Enterobacter cloacae using CMC medium. The medium for fermentation was optimized for maximum cellulase to be produced by the potential isolate. Various parameters like the time of Incubation, temperature, pH, nitrogen sources and carbon sources, were considered for optimization. The culture condition was optimized and found to be 40°C at pH 7 with maximum activity in the presence of ammonium sulphate and lactose as nitrogen and carbon sources respectively. Amongst these isolates the maximum cellulase activity was shown by Enterobacter cloacae followed by Pseudomonas aeruginosa and Bacillus subtilis by comparative study. The supplement for the medium was various agricultural waste added as an alternate source of carbon to produce cellulase. The medium with the presence of rice husk (1.76 IU/ml), followed by wheat husk(1.51 IU/ml) and castor seed waste (0.65 IU/ml), had the highest cellulase activity. Thus, this work aimed to compare the potential of all the above-mentioned isolates to use agro-waste for production of cellulase at optimized parameters.
HOW COULD MSC-POLARIZED MACROPHAGES PROMOTE CARTILAGE REPAIR?
Authors: Macmillan A. , Muhammad H. , Hosni R. Al , Alkhayref M. , Hotchen A. , Robertson-Waters E. , Strangmark E. , Gompels B. , Wang J.H. , McDonnell S. , Khan W. , Clatworthy M. , Birch M. , McCaskie A.
Published: January 2024

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.
PATIENT-SPECIFIC CONTACT MECHANICS IN SYNDESMOTIC ANKLE LESIONS
Authors: Peiffer M.
Published: January 2024

Syndesmotic ankle lesions involve disruption of the osseous tibiofibular mortise configuration as well as ligamentous structures stabilizing the ankle joint. Incomplete diagnosis and maltreatment of these injuries is frequent, resulting in chronic pain and progressive instability thus promoting development of ankle osteoarthritis in the long term. Although the pathogenesis is not fully understood, abnormal mechanics has been implicated as a principal determinant of ankle joint degeneration after syndesmotic ankle lesions. Therefore, the focus of this presentation will be on our recent development of a computationally efficient algorithm to calculate the contact pressure distribution in patients with a syndesmotic ankle lesion, enabling us to stratify the risk of OA development in the long term and thereby guiding patient treatment.
CHARACTERIZATION OF CLINICAL DATA FOR IN MODERATE OSTEOARTHRITIS WITH SUPPORT VECTOR MACHINES AND REGULATORY NETWORK MODELS
Authors: Segarra-Queralt M. , Galofré M. , Tio L. , Monfort J. , Monllau J.C. , Piella G. , Noailly J.
Published: January 2024

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors.

Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia.
SUBJECT-SPECIFIC KNEE JOINT MODELLING BETWEEN YOUNG AND ELDERLY
Authors: Han S.K. , Yoo Y.W. , Choi H. , Lee K.K. , Korhonen R.K. , Esrafilian A.
Published: January 2024

It is known that the gait dynamics of elderly substantially differs from that of young people. However, it has not been well studied how this age-related gait dynamics affects the knee biomechanics, e.g., cartilage mechanical response. In this study, we investigated how aging affects knee biomechanics in a female population using subject-specific computational models.

Two female subjects (ages of 23 and 69) with no musculoskeletal disorders were recruited. Korea National Institute for Bioethics Policy Review Board approved the study. Participants walked at a self-selected speed (SWS), 110% of SWS, and 120% of SWS on 10 m flat ground. Three-dimensional marker trajectories and ground reaction forces (Motion Analysis, USA), and lower limbs’ muscle activities were measured (EMG, Noraxon USA). Knee cartilage and menisci geometries were obtained from subjects’ magnetic resonance images (3T, GE Health Care). An EMG-assisted musculoskeletal finite element modeling workflow was used to estimate knee cartilage tissue mechanics in walking trials. Knee cartilage and menisci were modeled using a transversely isotropic poroviscoelastic material model.

Walking speed in SWS, 110%, and 120% of SWS were 1.38 m/s, 1.51 m/s, and 1.65 m/s for the young, and 1.21 m/s, 1.34 m/s and 1.46 m/s for the elderly, respectively. The maximum tensile stress in the elderly tibial cartilage was ~25%, ~33%, and ~32% lower than the young at SWS, 110%, and 120% of SWS, respectively. These preliminary results suggest that the cartilage in the elderly may not have enough stimulation even at 20% increases in walking speed, which may be one reason for tissue degeneration. To enhance these findings, further study with more subjects and different genders will investigate how age-related gait dynamics affects knee biomechanics.

Acknowledgments: Australian NHMRC Ideas Grant (APP2001734), KITECH (JE220006)
3D PRINTING OF PCL TO FABRICATE POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING APPLICATIONS
Authors: Aydin M.S. , Luciani T. , Mohamed-Ahmed S. , Yassin M.A. , Mustafa K. , Rashad A.
Published: January 2024

The aim of this study is to print 3D polycaprolactone (PCL) scaffolds at high and low temperature (HT/LT) combined with salt leaching to induced porosity/larger pore size and improve material degradation without compromising cellular activity of printed scaffolds. PCL solutions with sodium chloride (NaCl) particles either directly printed in LT or were casted, dried, and printed in HT followed by washing in deionized water (DI) to leach out the salt. Micro-Computed tomography (Micro-CT) and scanning electron microscope (SEM) were performed for morphological analysis. The effect of the porosity on the mechanical properties and degradation was evaluated by a tensile test and etching with NaOH, respectively. To evaluate cellular responses, human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) were cultured on the scaffolds and their viability, attachment, morphology, proliferation, and osteogenic differentiation were assessed. Micro-CT and SEM analysis showed that porosity induced by the salt leaching increased with increasing the salt content in HT, however no change was observed in LT. Structure thickness reduced with elevating NaCl content. Mass loss of scaffolds dramatically increased with elevated porosity in HT. Dog bone-shaped specimens with induced porosity exhibited higher ductility and toughness but less strength and stiffness under the tension in HT whereas they showed decrease in all mechanical properties in LT. All scaffolds showed excellent cytocompatibility. Cells were able to attach on the surface of the scaffolds and grow up to 14 days. Microscopy images of the seeded scaffolds showed substantial increase in the formation of extracellular matrix (ECM) network and elongation of the cells. The study demonstrated the ability of combining 3D printing and particulate leaching together to fabricate porous PCL scaffolds. The scaffolds were successfully printed with various salt content without negatively affecting cell responses. Printing porous thermoplastic polymer could be of great importance for temporary biocompatible implants in bone tissue engineering applications.
NOVEL INSIGHTS FROM THE GUT-JOINT AXIS: MICROBIAL CONTRIBUTION TO SKELETAL HOMEOSTASIS
Authors: Wang F.-S.
Published: January 2024

Osteoporosis (OP) and osteoarthritis (OA) are leading causes of musculoskeletal dysfunction in elderly, with chondrocyte senescence, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability as prominent features. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Not surprisingly, the development of OP and OA correlate with dysregulations of the gut microflora in rodents and humans. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes to regulate joint homeostasis. Modulating the abundance of specific gut bacteria, like Lactobacillus and Bifidobacterium, by probiotics or fecal microbiota transplantation appears to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue and holds potential to slow down OP development. The talk will highlight treatment options with probiotics or metabolites for modulating the progression of OA and OP.
OMICS-BASED PRECLINICAL MODELS OF MUSCULOSKELETAL REGENERATION
Authors: Wehrle E.
Published: January 2024

Despite the major advances in osteosynthesis after trauma, there remains a small proportion of patients (<10%) who exhibit delayed healing and/or eventual progression to non-union. While known risk factors exist, e.g. advanced age or diabetes, the exact molecular mechanism underlying the impaired healing is largely unknown and identifying which specific patient will develop healing complications is still not possible in clinical practice. The talk will cover our novel multimodal approaches in small animals, which have the potential to precisely capture and understand biological changes during fracture healing on an individual basis. Via combining emerging omics technologies with our recently developed femur defect loading equipment in mice, we provide a platform to precisely link mechanical and molecular analyses during fracture healing.
TRANSFECTION OF HMSCS WITH CHEMICALLY MODIFIED MRNA CODING FOR BMP-7 ENHANCES OSTEOGENESIS
Authors: Runzer C.D.T. , Sadowska J. , Plank C. , O'Brien F.J. , van Griensven M. , Balmayor E.R.
Published: January 2024

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production.1 The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use.2 Furthermore, BMP-7 was removed from the market.3 These complications are related to the high doses used (1.5-40 miligrams per surgery)2 compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range).4 In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones.5 Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA.6 BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration.

Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790.
A NOVEL SELECTIVE PROSTAGLANDIN-RECEPTOR EP4-AGONIST PROMOTES SPINAL FUSION IN RATS
Authors: Vater C. , Tian X. , Findeisen L. , Raina D.B. , Kern H. , Bolte J. , Straßburger L. , Matuszewski L.-M. , Modler N. , Gottwald R. , Winkler A. , Schaser K.-D. , Disch A.C. , Zwingenberger S.
Published: January 2024

A novel EP4 selective agonist (KMN-159) was developed [1] and has been proven that it can act as an osteopromotive factor to repair critical-size femoral bone defects in rats at a dose-dependent manner [2]. Based on its osteopromotive properties, we hypothesized that KMN-159 could also aid in bone formation for spinal fusion. Therefore, the aim of this study was to investigate its spinal fusion effect in a dorsolateral spinal fusion model in rats. This study was performed on 192, 10-week-old male Wistar rats. The rats were randomized into 8 groups (n = 12 per group): 1) SHAM (negative control), 2) MCM (scaffold only), 3) MCM + 20 µg BMP-2 (positive control), 4-8) MCM + 0.2, 2, 20, 200 or 2000 µg KMN-159. A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds (see above) or left empty in the SHAM group (protocol no. 25-5131/474/38). Animals were euthanized after 3 weeks and 6 weeks for µCT and biomechanical testing analysis. The results showed that KMN-159 promoted new bone formation in a dose-dependent manner at 3 weeks and 6 weeks as verified by µCT. The biomechanical testing showed that the dose of 20, 200 and 2000 µg KMN-159 groups obtained comparable strength with BMP-2 group, which higher than SHAM, MCM and lower doses of 0.2 and 2 µg KMN-159 groups. In conclusion, KMN-159 could be a potential replacement of BMP-2 as a novel osteopromotive factor for spinal fusion.

Acknowledgements: We are grateful to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).
MECHANICAL STIMULATION OF PIEZOELECTRIC SCAFFOLDS PROMOTES CELL OSTEOGENIC DIFFERENTIATION
Authors: Tavernaraki N.N. , Platania V. , Chatzinikolaidou M.
Published: January 2024

Bone is a dynamic tissue that undergoes continuous mechanical forces. Mechanical stimuli applied on scaffolds resembling a part of the human bone tissue affects the osteogenesis [1]. Poly(3,4-ethylenedioxythiophene) (PEDOT) is a piezoelectric material that responds to mechanical stimulation producing an electrical signal, which in turn promotes the osteogenic differentiation of bone-forming cells by opening voltage-gated calcium channels [2]. In this study we examined the biological behavior of pre-osteoblastic cells seeded onto lyophilized piezoelectric PEDOT-containing scaffolds applying uniaxial compression.

Two different concentrations of PEDOT (0.10 and 0.15% w/v) were combined with a 5% w/v poly(vinyl alcohol) (PVA) and 5% w/v gelatin, casted into wells, freeze dried and crosslinked with 2% v/v (3-glycidyloxypropyl)trimethoxysilane and 0.025% w/v glutaraldehyde. The scaffolds were physicochemically characterized by FTIR, measurement of the elastic modulus, swelling ratio and degradation rate. The cell-loaded scaffolds were subjected to uniaxial compression with a frequency of 1 Hz and a strain of 10% for 1 h every second day for 21 days. The loading parameters were selected to resemble the in vivo loading situation [3]. Cell viability and morphology on the PEDOT/PVA/gelatin scaffolds was determined. The alkaline phosphatase (ALP) activity, the collagen and calcium production were determined.

The elastic modulus of PEDOT/PVA/gelatin scaffolds ranged between 1 and 5 MPa. The degradation rate indicates a mass loss of 15% after 21 days. The cell viability assessment displays excellent biocompatibility, while SEM images display well-spread cells. The ALP activity at days 3, 7 and 18 as well as the calcium production are higher in the dynamic culture compared to the static one. Moreover, energy dispersive spectroscopy analysis revealed the presence of calcium phosphate in the extracellular matrix after 14 days. The results demonstrate that PEDOT/PVA/gelatin scaffolds promote the adhesion, proliferation, and osteogenic differentiation of pre-osteoblastic cells under mechanical stimulation, thus favoring bone regeneration.