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Abstract Background Diastrophic dysplasia is a rare autosomal recessive disorder characterized by abnormalities in bone and cartilage development, caused by pathogenic variants in the SLC26A2 gene. Case presentation This article presents a clinical case of preimplantation genetic testing for monogenic disorders (PGT-M) conducted for a family with two previous pregnancy losses due to diastrophic dysplasia in the fetus. We report a previously uncharacterized variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. We detail the approach to performing PGT-M in the absence of material from the proband and close relatives from one partner for analysis. A testing system was developed to analyze pathogenic variants in the SLC26A2 gene, alongside with indirect markers such as short tandem repeats and single nucleotide polymorphisms. This allowed us to identify linkage groups associated with the analyzed pathogenic variants during the in vitro fertilization cycle with PGT-M, enabling the selection of an embryo that did not inherit pathogenic variants from either parent. The transfer of this embryo resulted in a successful pregnancy, resulting in the birth of a healthy child. Conclusion To our knowledge, this is a first report of variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. The successful application of PGT-M enabled the selection of an embryo free from inherited pathogenic variants from both parents, highlighting the importance of PGT-M in improving reproductive outcomes for affected families.

Abstract Background Needle procedures, such as vaccinations, blood draws, and intravenous cannulation, are the most frequent source of childhood pain, causing fear and reducing the uptake of medical procedures. Every child has the right to expect pain relief, and we have evidence-based tools to reduce needle procedure-related pain. Therefore, the lack of analgesic provision for needle pain is not justified. We argue that better informed and motivated healthcare professionals and families can advocate for appropriate pain relief in every child, every time. Observations Engaging communication campaigns are needed to educate our healthcare professionals. Evidence-based modalities such as topical anaesthesia, sucrose or breastfeeding, comfort positioning, and age-appropriate distractions should be available for every child during needle procedures. However, high-quality information is not enough to change behaviour—healthcare professionals need to be motivated, encouraged, and inspired. Parents and carers should be empowered to advocate for their children and be aware that their child has the right to receive pain relief during these procedures. Conclusions and relevance This is a call to action—we need collaboration between academics, healthcare professionals, industry and charities, to expedite behavioural change and parental advocacy through high-quality communication strategies. Effective pain management in infants and children can play a crucial role in promoting the uptake of vaccinations and medical procedures and can influence future attitudes to pain.

Abstract Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards, especially in the perichondrium, the stem cell layer surrounding developing limbs essential for bone formation. Lrp1 deficiency in these stem cells causes joint fusion, malformation of cartilage/bone template and markedly delayed or lack of primary ossification. These abnormalities, which resemble phenotypes associated with Wnt signalling pathways, result in severe and persistent skeletal defects including a severe deficit in hip joint and patella, and markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Mechanistically, we show that LRP1 regulates core non-canonical Wnt/planar cell polarity (PCP) components that may explain the malformation of long bones. LRP1 directly binds to Wnt5a, facilitates its cell-association and endocytic degradation and recycling. In the developing limbs, LRP1 partially colocalises with Wnt5a and its deficiency alters abundance and distribution of Wnt5a and Vangl2. Finally, using Xenopus as a model system, we show the regulatory role for LRP1 in Wnt/PCP signalling. We propose that in skeletal progenitors, LRP1 plays a critical role in formation and maturity of multiple bones and joints by regulating Wnt signalling, providing novel insights into the fundamental processes of morphogenesis and the emergence of skeletal pathologies.

Abstract Background In recent years, there has been a growing number of case reports documenting delayed seroma in patients with a history of breast surgery and reconstruction. The occurrence of these seromas has been associated with prior SARS-CoV-2 infection or SARS-CoV-2 vaccination. So far, there are few systematic analyses on postoperative complications in breast surgery since the emergence of the SARS-CoV-2 pandemic. Study design We conducted a multicenter retrospective analysis to assess the incidence of postoperative complications in two major university breast care centers in Germany during the SARS-CoV-2 pandemic (August 1st, 2021, to January 31st, 2022) compared to a reference period (August 1st, 2019, to January 31st, 2020) before the pandemic. Results A total of 987 patients were included in this retrospective analysis, with 492 patients during the SARS-CoV-2 pandemic and 495 patients in the reference period. There was no significant difference in the incidence rate of seroma after breast surgery. However, complications such as erythema, wound infection, and wound healing disorders were notably more frequent during the SARS-CoV-2 pandemic. Multivariate analysis revealed that increasing patient age, smoking, breast implant reconstruction, axillary lymph node dissection, and previous radiation were significant clinical risk factors for seroma development. Conclusion While our findings did not indicate an elevated incidence of seroma during the SARS-CoV-2 pandemic, we observed increased rates of erythema, wound healing disorders, and wound infection. Additional real-world evidence is needed for understanding both early and late complications following breast surgery in the context of the ongoing SARS-CoV-2 endemic.

The article presents an analysis and assessment of the Republic of Tyva as one of the largest producers of meat and meat products in Russia. The Republic has regional characteristics that are associated with climatic, environmental features, as well as economic and political factors. Recently, in Russia there has been an increase in the consumption of meat industry products, while this figure lags significantly behind developed countries: 120 kg/person in the USA, 80 kg/person in the EU, 63 kg/person in Russia. In recent years, there has been a positive trend in terms of import substitution of meat and meat products, however, a high share of imports still remains, exceeding the threshold level of food security. Therefore, special attention should be paid to the development of industrial production, as well as increasing the competitiveness of meat industry enterprises, especially at the regional level. The article examines the current state of the meat industry in the Republic and the factors that determine its competitiveness. Purpose: to conduct a study of the current state and identify factors that determine the competitiveness of meat industry enterprises in the Republic of Tyva. Methods: analytical methods were used in the research process. Results. The results of the study show that in order to develop and increase the competitiveness of meat industry enterprises in the Republic of Tyva, it is necessary to introduce effective management methods at enterprises, introduce modern innovative equipment and technologies, as well as provide government support. Scope of results. The article offers a number of recommendations for managers of meat industry enterprises in the republic who want to improve the performance of their enterprises and increase competitiveness, which includes investing in sustainable initiatives, establishing clear goals and objectives and using modern digital solutions, interacting with regional executive authorities.

The purpose of this article is to explore the concept of “life” as understood by F.A. Iskander and to explain the genre specificity of his later works through a content analysis of metaphorical structures in the collections of essays, notes, and short stories by the writer. If his earlier works are mostly collections of short stories and novel-in-short stories, then later in his career he turns to such genres as collections of essays and notes. The focus of this study will be on the collections “A little about a lot” and “From notebooks”, the essays “Stalin and Vuchetich”, “State and conscience”, “Poets and kings”, “Mozart and Salieri”, and “Reflections of a writer”, as well as the short story “The plot of existence”. Life is not contrasted with death, and Iskander does not insist on the triumph of the positive over the negative in his work. Through this research, the author will draw the following conclusions. In his later work, Iskander departs from the conceptual metaphor of “life as wholeness”. He argues that only the depiction of life through art or theory can be considered complete, while life itself is inherently fragmented. He believes that only ideas founded on humanistic principles can bring some harmony to the chaotic nature of life. The main feature of Iskander’s later writings is fragmentation, which is based on associative thinking.

In this article, based on the analysis of data from a comprehensive sociological study, the features of the memory policy of the Republic of Azerbaijan were identified in comparison with similar ones in other “post-Soviet” Caspian republics in the context of constructing new national identities. It was concluded that the memory policy of the Republic of Azerbaijan, the “core” of which is the concept of “trauma”, plays an important role in constructing the country’s new national identity. In this case, trauma is represented by a whole complex of memory markers combined with ideas about the genesis of Azerbaijanis’ own national identity in the confrontation with the Armenian people (deportation, wars). These events left a deep mark on the collective memory of the Azerbaijani people, especially due to mass losses, forced displacement, and destruction. The state actively uses the memory of traumatic events to strengthen national identity, to unite the society and to mobilize the nation around the idea of restoring territorial integrity.

Although Eastern Canadian liberal arts universities are portrayed as progressive work environments that cultivate inclusivity and diversity, the corporatisation of these public spaces has transformed them from institutions that once encouraged pluralism and acceptance among all social groups to spaces that unevenly distribute privileges among faculty and students based on ascribed characteristics, social class, and adherence to cisnormative and heteronormative expectations. Under neoliberal reforms, universities and unions adopt their own policies and procedures that legitimate institutional power abuse over marginalised women Contract Limited Term (CLT) assistant professors. Using material evidence from complaints filed with a province's Human Rights Commission and Labour Board, this critical autoethnographic case study explores the institutionalised responses to a disenfranchised woman CLT's discrimination and harassment by a student, departmental chair, faculty and university staff. A theory of genocidal mobbing is developed to conceptualise the organisational processes and practices that maintain the status quo of white heteropatriarchy and disentitle women CLTs to safety, equality and fair representation by their unions. Genocidal mobbing is efficient, because misogynistic administrators only require weaponising one disgruntled student, and effective, because administrators utilise the most fatal and insidious of gendered narcissistic abuse: "gaslighting." The current neoliberal climate within academia puts marginalised women faculty at increased risk of genocidal mobbing from those with institutional power and from students with ethnic/racial and/or economic privilege. This article illuminates the union's culpability in the genocidal mobbing of women CLTs disenfranchised by multiple marginalised intersectional identities. Implications for future research and on policy are presented.

Background and objectivesThe aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults.MethodsAutopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated.ResultsThe 90+ Study participants (n = 414) were older (mean age at death = 97.7 years) and had higher amyloid/tau burden than ACT

(1) Background: American Indians are disproportionately affected by air pollution, an important risk factor for dementia. However, few studies have investigated the effects of air pollution on the risk of dementia among American Indians. (2) Methods: This retrospective cohort study included a total of 26,871 American Indians who were 55+ years old in 2007, with an average follow-up of 3.67 years. County-level average air pollution data were downloaded from land-use regression models. All-cause dementia was identified using ICD-9 diagnostic codes from the Indian Health Service’s (IHS) National Data Warehouse and related administrative databases. Cox models were employed to examine the association of air pollution with dementia incidence, adjusting for co-exposures and potential confounders. (3) Results: The average PM2.5 levels in the IHS counties were lower than those in all US counties, while the mean O3 levels in the IHS counties were higher than the US counties. Multivariable Cox regressions revealed a positive association between dementia and county-level O3 with a hazard ratio of 1.24 (95% CI: 1.02–1.50) per 1 ppb standardized O3. PM2.5 and NO2 were not associated with dementia risk after adjusting for all covariates. (4) Conclusions: O3 is associated with a higher risk of dementia among American Indians.

The brain evolved as a sensory-motor machine that drives behavior while being linked to the world through sensors. Human cognition abstracts from these sensory-motor roots but retains intimate ties. The brain's structure reflects this history. How do neural processes at different distances from the sensory and motor surfaces integrate to achieve meaningful and grounded cognition? This is a challenge given the time-continuous and graded nature of sensory-motor processing, which enables continuous online updating. It is also a major challenge to understanding development and autonomous learning, in which the coupling across functional boundaries evolves under the influence of online activation patterns.

We investigate the relation between conceptual and syntactic structure by focusing on the phenomenon of circumstantial metonymy e.g., “Table #6 wants another pizza”. We hypothesize that the construal of a metonymic interpretation is facilitated when the metonymized argument e.g., “Table #6” is retrieved before the metonymy-trigger e.g., “wants”, since this gives the processor more time to build the event structure that metonymy demands. This predicts greater cost of metonymy composition when the argument is in object position (after the trigger) relative to subject position (before the trigger). An acceptability task shows a main effect of metonymy for both syntactic positions. A self-paced reading task demonstrates a cost for metonymy only in object position. This indicates that the cost of metonymy composition is rooted in the requirement that the conceptual structure for the metonymic argument be fully retrieved, a process constrained by the order of lexical retrieval provided by syntactic structure.

IntroductionDigital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the diagnostic yield of DT in identifying predefined anatomic structures in feline cadaver heads, comparing it with conventional intraoral dental radiography (DR).MethodsA total of 16 feline cadaver heads were utilized to evaluate 19 predefined clinically relevant anatomic structures using both DR and DT. A semi-quantitative scoring system was employed to characterize the ability of each imaging method to identify these structures.ResultsDT demonstrated a significantly higher diagnostic yield compared to DR for all evaluated anatomic structures. Orthogonal DT imaging identified 13 additional anatomic landmarks compared to a standard 10-view feline set obtained via DR. Moreover, DT achieved statistically significant higher scores for each of these landmarks, indicating improved visualization over DR.DiscussionThese findings validate the utility of DT technology in reliably identifying clinically relevant anatomic structures in the cat skull. This validation serves as a foundation for further exploration of DT imaging in detecting dentoalveolar and other maxillofacial bony lesions and pathologies in cats.