bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell‐based therapy for diabetic cardiovascular complications: Prospects and challenges
Authors: Li Jia‐Peng , Fu Meng‐Meng , Li Xiao‐Xue , Xu Ming
Published: July 2024

Diabetes mellitus is a long‐term metabolic condition characterized by high blood glucose levels. This disorder is closely associated with a range of complications affecting small and large blood vessels, including conditions like retinopathy, nephropathy and neuropathy, as well as ischaemic heart disease, peripheral vascular disease and cerebrovascular disease. These complications cause organ and tissue damage in an estimated 33% to 50% of individuals with diabetes. The management of these complications in patients with diabetes is confronted with significant clinical challenges. Present treatment modalities for cardiovascular complications secondary to diabetes are limited and exhibit suboptimal efficacy. Cell‐based therapies has shown great promise in regenerative medicine and improving cardiovascular function in individuals with diabetic complications, attributed to their potential for multilineage differentiation and regenerative capacity. In this review, we focus on diabetic cardiovascular complications and provide a brief introduction to the application of cell‐based therapies, including the use of stem cells and progenitor cells, their mechanisms of action and the prospects and challenges.
Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals
Authors: Baliza Larissa R. S. P. , Freitas Túlio R. , Gonçalves Edward K. S. , Antunes Gabriel R. , Souza Ana J. F. , Yoneda Julliane , Duarte Caique Lopes , Andrade Silmara N. , de Paula Sabino Adriano , Varotti Fernando P. , Sangi Diego P.
Published: July 2024

N‐heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N‐heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug‐like compounds and showed potential to interact with HDAC8 and ERK1 cancer‐related targets.
The formation of a “model city in the Anatolian steppes”: Leapfrogging effects of spatial fix in Eskişehir, Turkey
Authors: Civelek Cansu
Published: July 2024

The prevalence of neoliberalism has produced varied effects on cities ranging from rapid growth to gradual disempowerment. Instead of considering neoliberal urbanization as a fixed, predetermined process, I discuss the possibility of leapfrogging in urban repositioning. Particularly, I examine Eskişehir's repositioning process in response to disempowerment, placing particular emphasis on the “spatial fix.” Rather than being passive recipients of neoliberalization, local ruling elites might develop political agency to not only counter but also capitalize on disempowerment. To overcome financial and political constraints vital for the spatial fix, Eskişehir's mayor leveraged multiscalar networking strategies and symbolic revitalizations at particular historical conjunctures. Accordingly, Eskişehir's municipality, ruled by the center‐left opposition party, sought to redefine the city as a stronghold of secularism with the claims of Europeanization and modernization. They introduced the “Eskişehir model” as a contrasting narrative to the ruling AKP's urban vision rooted in Islamist‐nationalist agenda. These mechanisms reveal that ideological‐political clashes at the national level can serve as windows of opportunity for local ruling elites to counter disempowerment. As the ethnographic research shows, these mechanisms had leapfrogging effects not only on repositioning and fostering political power but also dissembling existing inequalities, disparities, and segregation beneath the celebrated Eskişehir model.
Targeting MS4A4A: A novel pathway to improve immunotherapy responses in glioblastoma
Authors: Shao Guangcai , Cui Xiangguo , Wang Yiliang , Luo Shuyan , Li Chuanyu , Jiang Yu , Cai Dasheng , Li Nu , Li Xiang
Published: July 2024

Introduction

Glioblastoma (GBM) remains a challenging brain tumor to treat, with limited response to PD‐1 immunotherapy due to tumor‐associated macrophages (TAMs), specifically the M2 phenotype. This study explores the potential of MS4A4A (membrane spanning four domains, subfamily A, member 4A) inhibition in driving M2 macrophage polarization toward the M1 phenotype via the ferroptosis pathway to enhance the effectiveness of immunotherapy in GBM.

Methods

Single‐cell RNA sequencing and spatial transcriptomic analyses were employed to characterize M2 macrophages and MS4A4A expression in GBM. In vitro studies utilizing TAM cultures, flow cytometry, and western blot validations were conducted to assess the impact of MS4A4A on the tumor immune microenvironment and M2 macrophage polarization. In vivo models, including subcutaneous and orthotopic transplantation in mice, were utilized to evaluate the effects of MS4A4A knockout and combined immune checkpoint blockade (ICB) therapy on tumor growth and response to PD‐1 immunotherapy.

Results

Distinct subsets of GBM‐associated macrophages were identified, with spatial distribution in tumor tissue elucidated. In vivo experiments demonstrated that inhibiting MS4A4A and combining ICB therapy effectively inhibited tumor growth, reshaped the tumor immune microenvironment by reducing M2 TAM infiltration and enhancing CD8+ T‐cell infiltration, ultimately leading to complete tumor eradication.

Conclusion

MS4A4A inhibition shows promise in converting M2 macrophages to M1 phenotype via ferroptosis, decreasing M2‐TAM infiltration, and enhancing GBM response to PD‐1 immunotherapy. These findings offer a novel approach to developing more effective immunotherapeutic strategies for GBM.
Significant Long‐Term Prevention of High Sensitization After Kidney Allograft Failure by Maintaining Calcineurin Inhibitor‐Based Immunosuppression
Authors: Allesina Anna , Lavacca Antonio , Fop Fabrizio , Giraudi Roberta , Giovinazzo Gloria , Deaglio Silvia , Caorsi Cristiana , Dolla Caterina , Gallo Ester , Mella Alberto , Biancone Luigi
Published: July 2024

Introduction

Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF).

Methods

Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127).

Results

Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications.

Conclusions

CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.
Diabetes misconceptions, seriousness, motivation, self‐efficacy and stigma: A cross‐sectional comparison of eight Australian diabetes communication campaign videos
Authors: Holmes‐Truscott Elizabeth , Hateley‐Browne Jessica L. , Charalambakis Elizabeth , Ventura Adriana D. , Ripper Annette , Scibilia Renza , Speight Jane
Published: July 2024

Aim

This study examines potential intended (attitudes, motivation and self‐efficacy) and unintended (stigmatisation of diabetes) consequences of past Australian National Diabetes Week campaign videos. Further, outcomes are compared by the extent to which participants perceived their allocated video as stigmatising diabetes.

Methods

In this cross‐sectional, ten‐arm study, participants (adults with or without diabetes; 1:2 ratio) were randomly allocated to view one of eight archival diabetes campaign videos (intervention), or either an active or passive control group. Post‐exposure, study‐specific scales measured diabetes Misconceptions and Seriousness, General and Diabetes Risk‐Reduction Motivation and Self‐efficacy, and perceptions of video Stigmatisation of diabetes. Scores were compared by condition (intervention vs. control) and by campaign Stigma (highest vs. lowest tertile score), separately by cohort (with or without diabetes).

Results

The sample included n = 1023 without diabetes; and n = 510 with diabetes (79% type 2 diabetes). No significant differences in outcomes were observed between conditions (intervention vs. control), with one exception: a modest effect on General Self‐efficacy among those without diabetes only. Those perceiving high campaign Stigma (15%), relative to low Stigma (60%), reported significantly greater diabetes Misconceptions, lower perceived Seriousness and (among those without diabetes only) lower General Motivation but higher Diabetes Risk Reduction Motivation.

Conclusion

Though limited to a single‐exposure, we found little meaningful positive influence of past diabetes campaign videos on diabetes attitudes, behavioural intentions or self‐efficacy. Further, campaign videos were perceived as stigmatising by a minority—a potential harmful impact. This novel study has implications for the design, implementation and evaluation of future diabetes campaigns.
Applied human neuroscience: Fostering and designing inclusive environments with the 3E‐Cognition perspective
Authors: Parada Francisco J. , Grasso‐Cladera Aitana , Rossi Alejandra , Soto‐Icaza Patricia , Arenas‐Pérez Maritza , Errázuriz María Constanza
Published: July 2024

The conventional medical paradigm often focuses on deficits and impairments, failing to capture the rich tapestry of experiences and abilities inherent in neurodiversity conditions. In this article, we introduce the 3E‐Cognition perspective, offering a paradigm shift by emphasizing the dynamic interplay between the brain, body, and environment in shaping cognitive processes. The perspective fosters a more inclusive and supportive understanding of neurodiversity, with potential applications across various domains such as education, workplace, and healthcare. We begin by introducing the 3E‐Cognition principles: embodied, environmentally scaffolded, and enactive. Then, we explore how the 3E‐Cognition perspective can be applied to create inclusive environments and experiences for neurodiverse individuals. We provide examples in the realms of education, workplace, and healthcare. In all of these domains, spaces, methodologies, epistemologies, and roles that cater to diverse needs and strengths can be designed using the 3E principles. Finally, we discuss the challenges and benefits of implementing the 3E‐Cognition perspective. We focus on the need for technological advancements and research in complex real‐world scenarios; we suggest mobile brain/body imaging is a possible solution. We furthermore highlight the importance of recognizing and valuing the diverse manners of experiencing and interacting with the world, the promotion of diverse well‐being, and the facilitation of innovation and creativity. Thus, we conclude that the 3E‐Cognition perspective offers a groundbreaking approach to understanding and supporting neurodiversity: by embracing the inherent interconnectedness of the brain, body, and environment, we can create a more inclusive and supportive world.
Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations
Authors: Bendary Mahmoud M. , Elmanakhly Arwa R. , Mosallam Farag M. , Alblwi Noaf Abdullah N. , Mosbah Rasha A. , Alshareef Walaa A. , Selim Heba M. R. M. , Alhomrani Majid , Alamri Abdulhakeem S. , Safwat Nesreen A. , Hamdan Ahmed M. E. , Elshimy Rana
Published: July 2024

Background

Antimicrobial‐resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin‐resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti‐Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano‐gold emulsion, and curcumin nanoemulsion.

Methods

The antimicrobial activities of the investigated compounds, both individually and in combination with other anti‐Helicobacter drugs, were evaluated. Their antibiofilm and anti‐virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis.

Results

We observed high anti‐Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti‐biofilm and anti‐virulence compound among the examined substances. The biofilm‐correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post‐treatment with curcumin nanoemulsion. On the protein level, the anti‐virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination.

Conclusion

The anti‐Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher  minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub‐MIC levels could enhance the anti‐Helicobacter activity of azithromycin and exhibit anti‐virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.
Efficacy of a water flosser compared to an interdental brush on gingival bleeding and gingival abrasion: A 4 week randomized controlled trial
Authors: Mancinelli‐Lyle Deborah , Van der Weijden Fridus (G. A.) , Slot Dagmar E.
Published: July 2024

Aim

To determine the efficacy of a water flosser (WF) compared to an interdental brush (IDB) in reducing gingival inflammation. Additionally, the products were compared on the incidence of gingival abrasion.

Methods

Young adults with moderate gingivitis and ≥4 accessible interdental spaces by IDB in each quadrant were selected for this study. Participants were randomly assigned a WF or an IDB as an adjunct to manual toothbrushing. Clinical signs of inflammation were measured in two randomly assigned contralateral quadrants by bleeding on pocket probing (BOPP) or bleeding on marginal probing (BOMP). Gingival Abrasion Score (GAS) was assessed per quadrant. Data was recorded at the baseline, 2 weeks and 4 weeks.

Results

Both groups WF (n = 40) and IDB (n = 38) showed a significant reduction (p = 0.000) in BOMP and BOPP from the baseline to 4 weeks for all sites and the interdental sites only. At 4 weeks the WF group compared to the IDB group showed significantly lower BOPP (p = 0.030) and BOMP scores (p = 0.003) for all sites. For the interdental sites WF showed compared to IDB for BOMP significant (p = 0.019) lower values but not for BOPP (p = 0.219). There were no differences between the groups for GAS at any time point.

Conclusion

In patients with moderate gingivitis, after 4 weeks use the WF is more effective than the IDB in obtaining marginal gingival health.
Investigation of quality of life and anxiety level of patients who have undergone pigtail placement
Authors: Rikos Nikos , Titomichelaki Athena , Katsalaki Maria , Assargiotaki Maria , Kourlaba Georgia , Linardakis Manolis
Published: July 2024

Worldwide, nephrolithiasis is a disease with an increased frequency of presence and symptoms. This study aimed to investigate the quality of life (QoL) and the factors influencing it in patients who have undergone pigtail catheter placement. Α cross‐sectional study was implemented in 85 patients from the Urology Clinic/University General Hospital of Crete, Greece, recruited during November 2022 and January 2023. Patients' demographic and medical history profile were recorded and their QoL and state anxiety status assessed using the SF‐36 and State–Trait Anxiety Inventory (STAI‐S) scales based on multiple logistic regression analysis. The majority of patients were female (55.3%) and the mean age of all was 53.7 years (±11.5). QoL was moderate to high while 30.6% and 35.3% of patients presented high quality of Physical and Mental Components, respectively. For Anxiety, moderate mean scores were found while 62.4% presented high anxiety. Patients with low/moderate State Anxiety compared with their counterparts had better QoL in the SF‐36 subscales (p < 0.05). In the Physical Component, higher odds of high QoL appear to be found in females versus males (odds ratio, OR = 8.68, p = 0.008), in higher income categories (OR = 5.74, p < 0.001) and in patients with low/moderate anxiety (OR = 12.87, p < 0.001), while in the Mental Component higher odds were found for higher income categories (OR = 2.19, p = 0.018) and patients with low/moderate anxiety (OR = 7.20, p = 0.001). Better QoL in patients with nephrolithiasis and pigtail is associated with female gender, higher living standards and lower state anxiety, allowing more effective interventions by health professionals to alleviate patients' symptoms and empower them.
A software‐based observational coding approach for evaluating paediatric dental pain, anxiety, and fear
Authors: Bocklage Clare , Selden Raven , Tumsuden Olivia , Nanney Eleanor , Sawicki Caroline , Rapolla Allen , Cass Katelyn , Lee Jessica , Ginnis Jeannie , Strauman Timothy , Graves Christina , Divaris Kimon , Hodges Eric , Jacox Laura Anne
Published: July 2024

Background

Dental practitioners desire non‐pharmacological methods to alleviate anxiety, fear, and pain in children receiving dental care; high‐quality evidence, however, is required to evaluate methods' efficacy.

Aim

This study aimed to develop and validate an observation‐based coding approach (paediatric dental pain, anxiety, and fear coding approach [PAFCA]) to evaluate non‐pharmacological behavior management techniques for anxiety, fear, and pain.

Design

Objective (video‐based) and subjective (self‐reported) anxiety, fear, and pain data were collected from a pilot clinical trial evaluating animal‐assisted therapy (AAT) in paediatric dentistry, in which 37 children aged 7–14 were assigned to AAT or control before dental treatment (restorations or extractions). A coding approach utilizing a codebook, a gold standard calibration video, and a user training guide was developed. Trained examiners coded the gold standard video for inter‐rater agreement, and masked, calibrated examiners analyzed videos using the Noldus Observer XT software.

Results

A novel, software‐based coding approach was developed, with moderately high inter‐rater agreement. Using PAFCA, we found children reporting higher levels of pain, fear, and anxiety exhibited treatment‐interfering behaviors, including crying/moaning, attempts to dislodge instruments, and more upper and lower body movements.

Conclusion

PAFCA shows promise as a reliable tool for assessing anxiety, pain, and fear in behavioral research for paediatric dentistry.
Molecular Biological Aspects of Inhibitor Development
Authors: Tuddenham E.G.D.
Published: July 2024

Mutation genotype studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development. Searchable information on mutations, phenotype data, models, etc., are available on the internet at http://europium.mrc.rpms.ac.uk. A relatively high incidence of inhibitors occurs in patients with deletion mutations. Stop mutations are also associated with a high incidence of inhibitors, although there is anomalous distribution of the inhibitors associated with different stop codons. Inhibitors have been associated with a small number of missense mutations. Missense mutations are of great interest from the structure/function viewpoint; in many instances, a missense mutation which results in reduced function of a circulating protein can be mapped onto a model structure and inferences can be made about the effects on the functionality of the protein. A model of the A domains of FVIII is available, but as yet, no structure is available on which to model the C domain of FVIII. Stop codons appear to have a different incidence of inhibitor formation compared to other types of mutations. It is concluded that while genotype mutation studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development, though more questions have been raised than answers provided to date.
Epitope Specificity and Inactivation Mechanisms of Factor VIII Inhibitor Antibodies
Authors: Scandella Dorothea
Published: July 2024

The domain specificity of anti‐factor VIII (FVIII) inhibitor antibodies was determined in assays using FVIII domains generated by thrombin cleavage or expressed as recombinant polypeptides to neutralise the inhibitor. The results revealed the existence of three major types of inhibitors, and various combinations of these antibodies were found in haemophilic and autoantibody patients. Anti‐A2 domain inhibitors prevent normal function of the FVIII/factor IXa (FIXa)/phospholipid complex in an unknown manner. Binding of FVIII to phospholipid and to von Willebrand factor is blocked by anti‐C2 domain antibodies, and the binding of FVIII to FIXa is prevented by anti‐A3 domain antibodies. A rare type of inhibitor prevents release of activated FVIII from von Willebrand factor (vWf), and another probably interferes with FVIII binding to factor X (FX) because it shares the epitope of a monoclonal antibody with this property.
Anti‐ldiotypic Antibodies: From Regulation to Therapy of Factor VIII Inhibitors
Authors: Saint‐Remy Jean‐Marie R. , Jacquemin Marc G. , Gilles Jean Guy
Published: July 2024

Evidence has recently accumulated showing that antiidiotype antibodies specific to anti‐FVIII antibodies are present in the plasma of healthy individuals and of haemophilia A patients with or without inhibitors, where they can neutralise the FVIII inhibitory activity. Additionally, patients successfully desensitised towards FVIII have an increased production of anti‐idiotypic antibodies with no significant reduction in anti‐FVIII antibodies. We review here possible strategies for modulating the anti‐FVIII immune response by idiotypic interactions.
Comparison of the International Immune Tolerance Registry and the North American Immune Tolerance Registry
Authors: Kroner Barbara L.
Published: July 2024

Two immune tolerance registries – the International Immune Tolerance Study Group (ITSG) and North American Immune Tolerance Study (NAITS) – are compared and findings from combined data reported. The registries differed with respect to data collection tools, location, host and environmental factors, start date distribution and treatment products. The success and failure rates were similar in the two studies. There was a highly significant association between maximum historical titre and immune tolerance success; the success rate decreased as the historical titre increased. There was a significant association between inhibitor titre immediately prior to treatment and the probability for treatment success, and between outcome and time from diagnosis to treatment in the ITSG (of borderline significance in the NAITS). There was a significant association between outcome and dose, though the direction of the associations was not the same. In the ITSG, success was associated with doses greater than or equal to 200 IU/kg/day, while in the NAITS, greater success was observed with doses of less than 50 IU/kg/day. There was no association between outcome and treatment product. Data from the two registries were combined to produce a table for calculating the chance of successful treatment by historical titre, pretreatment titre, and dose.
Induction of Immune Tolerance in Haemophilia A Inhibitor Patients by the ‘Bonn Protocol‘: Predictive Parameter for Therapy Duration and Outcome
Authors: Oldenburg J. , Schwaab R. , Brackmann H.H.
Published: July 2024

The treatment of inhibitors is one of the most challenging fields in haemophilia care. The present study reports the results of 60 haemophilia A inhibitor patients treated according to the ‘Bonn Protocol’ and evaluates predictors for the duration and outcome of therapy. Successful immune tolerance could be achieved in 52 patients (86.7%) while the therapy failed in eight patients (13.3%). The immune tolerance achieved was longlasting in all 52 patients, with no inhibitor relapse in up to 20‐years follow‐up. The course of ITT was influenced by several factors. Interruptions of treatment during the ITT course led to a substantial prolongation of ITT duration (median 39.9 months vs 14.1 months in continuously treated patients). Infections of intravenous central lines appeared to be frequently coincided with ITT prolongation and sometimes even ITT failure. Further negative predictors towards the ITT duration were high inhibitor titres at enrolment or during ITT. There was also a tendency towards longer ITT duration in patients exhibiting the prevalent intron 22 inversion. As a consequence of our data treatment interruptions and infections of intravenous central lines should be avoided during the course of ITT. Furthermore our data suggest, that ITT should be started at low inhibitor titres preferably with a high factor VIII dosage protocol.
Immune Tolerance Protocols Using Low‐Dose Factor VIII: A Review of the Literature
Authors: Sultan Y.
Published: July 2024

Low‐dose immune tolerance protocols use doses of factor VIII of less than 50 IU/kg/day to induce immune tolerance. Such protocols are chosen for a variety of reasons including cost, patient acceptability and ease of administration. Early published reports of low‐dose protocols appeared in 1981, described small numbers of patients and moderate success. It was proposed that such protocols might modify inhibitor responses from high to low. Later reports are sparse and clinical success is again moderate. Useful treatment and expectation guidelines have emerged from experience with these protocols, and improvements for patients with inhibitors can be achieved. Consideration of immunological success, however, raises doubts about whether real immune tolerance is achieved with such protocols.
Extracorporeal Immunoadsorption for the Treatment of Haemophilia Patients with Inhibitors to Factor VIII or IX
Authors: Knöbl Paul , Derfler Kurt
Published: July 2024

Background and Objectives: This article reviews the relevance of immunoadsorption in the treatment of haemophilic patients with inhibitors. Materials and Methods: Immunosorba (sepharose‐bound staphylococcal protein A) and Ig‐Therasorb (sepharose‐bound polycional sheep antibodies to human immunoglobulin) columns are suitable for the clinical use of immunoadsorption. They allow the processing of large plasma volumes (>7,000 ml) without relevant side‐effects. Results: A haemophilic patient was treated with the Malmö protocol, another was admitted with intracerebral bleeding. Immunoadsorption reduced the inhibitor titer by 70–90%. Conclusions: Immunoadsorption can be used in cases of acute bleeding, before surgery, acquired factor VIII (FVIII) antibodies, and before the start of immune tolerance therapy. We suggest the inclusion of this method in immune tolerance protocols in order to improve levels, recovery, and half‐life of FVIII and to save concentrates.
Successful Immune Tolerance Treatment with Monoclonal or Recombinant Factor VIII Concentrates in High Responding Inhibitor Patients
Authors: Rocino Angiola , de Biasi Raffaello
Published: July 2024

Very high purity factor VIII (FVI1I) concentrates (plasma‐derived or produced by recombinant‐DNA technology) were used to achieve immune tolerance in five patients with high‐responding inhibitors to FVIII. The mean time required for inhibitor disappearance was 5 months. Four out of five patients showed normalisation of the half‐life of infused FVIII after 8–18 months of treatment with 100 IU FVIII/kg body weight administered once daily. Highly purified FVIII products thus appear to be suitable for achieving immune tolerance without negative effects on endogenous von Willebrand factor levels and activity.
The incidence and pathophysiology of atopic dermatitis
Authors: Thestrup‐Pedersen Kristian
Published: July 2024

Aim

To review our present knowledge about atopic dermatitis and try to formulate a working hypothesis about disease mechanisms.

Subject

Atopic dermatitis and disease mechanisms.

Methods

Literature review.

Results

Atopic dermatitis is a skin disorder which develops within the first years of life, is active for a number of years and then resolves in most affected individuals. Although no single disease‐associated gene locus has been found, observations among monozygous and dizygous twins suggest that atopic dermatitis is first and foremost a genetically determined disease. Atopic dermatitis is associated with an abnormal dryness of the skin due to a deficient skin barrier function. Although it seems to be a genetically determined ectodermal disorder, it includes immune deviations such as T lymphocyte accumulation in the skin leading to chronic relapsing eczema. In some patients increased serum IgE is found and type 1 allergies are common. However, the immune deviations are not always associated with type I or type IV allergies. If allergies were of primary importance for disease development, it is hard to explain why the eczema disappears despite the presence of environmental allergens. Some kind of “maturation step” is likely involved in the down‐regulation of eczema.

Many epidemiological studies indicate that the incidence of atopic dermatitis has doubled or tripled over the last two decades. This is difficult to explain, if the disease is mostly genetically determined. However, it could be explained, if atopic dermatitis is considered a dysmaturation of the immune system and that the expression of a genetically determined dysmaturation can be influenced by the age of the mother ‐ comparable to what is found concerning the risk of developing Down's syndrome.

Conclusion

This review summarizes known facts and puts foreward a working hypothesis that atopic dermatitis may be a genetically determined dysmaturation of the T lymphocyte system. T lymphocytes mature primarily in the thymus via positive and negative selection processes. This includes contact between pre‐T cells and the thymic epithelium, which is derived from the ectoderm. We hypothesize that the maturation of the T cell immune system is disturbed, resulting in a faulty selection of T lymphocytes in the thymus. “Dys”‐matured T cells leave the thymus to continue growth in the skin. The cells are eventually eradicated by immune surveillance in the patient. Because of the increased proliferation of “dysmature” T cells, a cytokine imbalance occurs, and in some patients this leads to the development of type 1 allergies.
The role of the staphylococci in dermatology
Authors: Noble W.C.
Published: July 2024

Aim

To describe the prevalence of Staphylococcus aureus in atopic dermatitis.

Subject

Atopic dermatitis and Staphylococcus aureus.

Results

Amongst the staphylococci, only S. aureus is implicated in skin infection. Much localised infection, such as folliculitis or furunculosis, is endogenous, that is the result of infection with organisms carried in the nose or at specific skin sites. In contrast impetigo and scalded skin syndrome are chiefly exogenous in origin. Secondary infection, for example in atopic dermatitis, is also associated with nasal and skin carriage. Much remains to be learned of the pathogenesis of staphylococcal infection and much current interest derives from the superantigenic activity of the exotoxins and toxic shock toxin.

Conclusion

Staphylococcus aureus occurs with increased incidence on the skin of patients with atopic dermatitis. It could be responsible for activating eczema via secretion of exotoxins.
The treatment of atopic dermatitis with topical fusidic acid and hydrocortisone acetate
Authors: Ramsay Colin A. , Savoie J.M. , Gilbert Martin , Gidon Martie , Kidson Paul
Published: July 2024

Aim

To compare the clinical efficacy of a cream combination containing 2% fusidic acid and 1% hydrocortisone acetate in the treatment of patients with mild to moderate atopic dermatitis.

Subject

Atopic dermatitis and efficacy of antibacterial and antiinflammatory topical therapy.

Methods

Randomized, double blind, prospective, parallel group trials.

Results

Study 1, involving 186 patients, compared the combination 2% fusidic acid and 1% hydrocortisone acetate with 1% hydrocortisone cream. Analysis was performed on patients who had pathogens at entry and on the total patient population. Study II, involving 68 patients, compared the combinaison 2% fusidic acid and 1% hydrocortisone acetate with 2% fusidic acid cream. Analysis was the same as in study I.

Results of study I in patients with pathogens at baseline showed a significant difference in favour of the combination (P = 0.04) in terms of the primary efficacy criterion which was a combination of clinical and bacteriological efficacy measures. When all patients in the study were analyzed there was no significant difference between the two groups. The combination was significantly more effective in removing pathogens than 1% hydrocortisone cream (P < 0.0001).

Results of study II in all patients showed that the combination was significantly better than 2% fusidic acid cream (P = 0.04) in terms of the primary efficacy criterion, Both preparations were highly successful in eradicating pathogens.

Pooled analysis of studies 1 and II showed a difference with respect to the primary efficacy criterion among the 3 preparations in the order Fucidin 2% plus HC 1% cream > HC 1% cream > Fucidin 2% cream in all patients and in those with pathogens (P = 0.007 for all patients and P = 0.01 for those with pathogens). Similarly, regarding the reduction in sign/symptom score a significant difference among the 3 preparations existed (P = 0.009 for all patients and P = 0.01 for those with pathogens). Adverse events with the combination were minimal.

Conclusion

2% fusidic acid and 1% hydrocortisone acetate cream is an effective therapy in patients with mild to moderate degrees of atopic dermatitis.
The role of Staphylococcus aureus in atopic eczema: treatment strategies
Authors: Cork Michael J.
Published: July 2024

Subject

Therapy of atopic dermatitis.

Aim

To outline treatment strategies for atopic dermatitis patients.

Methods

Description of therapeutic principles of atopic dermatitis.

Results

Atopic eczema arises as a result of the interaction of environmental factors with an abnormal immune system in a genetically predisposed individual. Also the skin of patients with atopic eczema carries high levels of Staphylococcus aureus, which correlate with the severity of the eczema. Staphylococcus aureus releases a toxin with superanligenic actions which initiates a vicious circle in atopic eczema. Therapy of atopic eczema will he more effective if it breaks the vicious circle at two points. Topical steroids inhibit the action and production of pro‐inflammatory mediators breaking the circle at one point. Intensive emollient therapy and antibiotic steroid combinations reduce the number of Staphylococcus aureus and the penetratioin of the toxins through the skin, thereby breaking the circle at a second point.

Conclusion

Using the approach of reducing both the effects of cytokines and of superantigens, it is possible to reduce the potency and quantity of topical steroids applied and therefore their cutaneous adverse effects.
The role of ‘familiarity’ and ‘normality’ in supporting transition to end of life care in paediatric oncology: A qualitative study
Authors: Kelly Daniel , Closs Mia , McAndrew Rachel , Smith Pam
Published: July 2024

Aim

The aim of this study was to explore factors that helped when a child with cancer transitioned to end of life care in a hospital setting.

Design

Qualitative exploratory design using reflexive thematic analysis.

Methods

In‐depth, semi‐structured interviews were carried out with 7 sets of bereaved parents and 10 health professionals from one specialist paediatric oncology centre. Results were shared with professionals to help shape services in a new children's hospital.

Results

Three themes were identified: ‘change and facing the unknown’, ‘the comfort of feeling normal’ and ‘knowing and being known’. Bereaved parents described a gradual awareness of the deterioration of their child's condition and the need for trust in health professionals. Professionals described the process as challenging but were guided by the needs of children and parents. Supportive and trusting relationships with professionals helped parents to cope with the transition.

Conclusion

We identified practices that helped create a culture that supported parents and professionals involved in caring for children facing death from cancer. These were rooted in feeling supported and working to provide the best end of life care for children.

Summary Statement

Given that the death of a child is a uniquely challenging event, this study indicates that the clinical setting can assist via the promotion of familiarity (supporting families over time) and normality (allowing family‐focused activities). These were helpful to parents and to professionals. However, professionals need emotional support when working with these families.

Reporting Method

The study adhered to the Consolidated Criteria for Reporting Qualitative Research.

Patient or Public Contribution

The project steering group included one bereaved parent (who was not involved in the study), one consultant paediatric oncologist and one hospital chaplain.
An international survey of recalcitrant and recurrent tinea of the glabrous skin—A potential indicator of antifungal resistance
Authors: Khan Sidra S. , Hay Roderick , Saunte Ditte Marie L.
Published: July 2024

Background

There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases.

Objectives

This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally.

Methods

An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years.

Results

A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance.

Conclusions

The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over‐the‐counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.
The genome history of Bacillus thuringiensis subsp. tenebrionis: From discovery to present day product
Authors: Schäfer Lea , Jehle Johannes A. , Kleespies Regina G. , Wennmann Jörg T.
Published: July 2024

Bacillus thuringiensis subsp. tenebrionis (Btt) was discovered in 1982 and has been used as a biological control agent against the Colorado potato beetle (Leptinotarsa decemlineata) since the early 1990s. In this study, we sequenced, assembled and analysed the genome of strain DSM 2803, which is the patent deposit of the original Btt isolate BI 256‐82. A high‐quality reference genome is provided that allows investigating the genomic changes throughout the commercial history of Btt. Strain DSM 2803 (BI 256‐82) is particularly interesting since the subspecies description of ‘tenebrionis’ is based on it and because it represents the genomic origin of the commercial Btt strain currently used in plant protection. Comparative genome analysis of six Btt strains derived from BI 256‐82 revealed that the genomes were generally highly similar. However, some plasticity in the profile of extrachromosomal elements was detected, including recombination‐dependent plasmid differences and the presence/absence of a circular plasmid‐like prophage.
The role of Anchoviella spp. as forage species in different stages of reservoir development in the upper Tocantins River, Central Brazil
Authors: Ferreira Vitor Manuel Barros , Albrecht Míriam Pilz
Published: July 2024

We report the spatiotemporal increase in abundance of Anchoviella spp. (Engraulidae) through the diet of fish consumers after reservoir formation in the upper Tocantins River, Central Brazil. The increase in the abundance of this planktivorous fish evidences the growing importance of autochthonous herbivory food chains as the reservoir stabilized in this novel lentic ecosystem. These changes would otherwise remain unnoticed only through fish sampling, highlighting the importance of assessing trophic interactions to understand responses to damming at the community and ecosystem levels.
Treatment of masseter muscle hypertrophy with botulinum toxin type A injection: A review of adverse events
Authors: Nishikawa Ayaka , Aikawa Yoshiyuki , Kono Taro
Published: July 2024

Background

The popularity of noninvasive botulinum toxin type A (BTX‐A) injections for masseter muscle hypertrophy is increasing among Asian individuals with a square‐shaped lower face.

Aims

This study aimed to analyze the adverse events (AEs) caused by BTX‐A injections into the masseter muscle.

Patients/Methods

This observational study retrospectively evaluated 46 250 patients who underwent BTX‐A injections into the masseter muscle in 2022. The inclusion criteria were the diagnosis of an AE by the physician at the return visit and subsequent follow‐up of progress (n = 223). The patients who were lost to follow‐up (n = 40) were excluded from the study.

Results

Among the 223 patients with AEs, the most common AE was paradoxical bulging (88.3%, n = 197/223). The average period from treatment until confirmation of improvement was 159.6 ± 113.6 days (range 13–667 days) for all AEs, all of which were temporary. The period until improvement was 166.1 days in the intervention group (n = 122) and 151.9 days in the observation group (n = 101) (p = 0.24). As the period until improvement of AEs included the period until the patients visited the clinics and the improvements were confirmed by physicians, the actual period was likely to have been shorter.

Conclusions

(1) All AEs were temporary. (2) All AEs improved within 22.2 months (within 5.3 ± 3.8 months on average). (3) There was no significant difference between the intervention and observation groups in the period until the improvement of AEs.
Association of proteinuria at time of diagnosis with survival times in dogs with lymphoma
Authors: Skinner Stephanie M. , Specht Andrew J. , Cicchirillo Victoria , Fox‐Alvarez Stacey , Harris Autumn N.
Published: July 2024

Background

Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited.

Hypothesis

To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I‐V) or type (B vs T) were associated with the presence of proteinuria.

Animals

Eighty‐six client‐owned dogs with a new diagnosis of lymphoma between 2008 and 2020.

Methods

This was a retrospective cross‐sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti‐neoplastic, or anti‐proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan‐Meier estimator and log‐rank testing.

Results

There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I‐V) or types (B and T).

Conclusions and Clinical Importance

Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.