In-vivo neuronal dysfunction by Aß and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer's disease.

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aß) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aß- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aß and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant's real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aß-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aß and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aß and tau's synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aß-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

Role of Anteromedial Cortical Support for Unstable Intertrochanteric Fractures Being Treated With Cephalomedullary Nails.

INTRODUCTION: Reduction quality is of paramount importance for an optimal outcome in unstable pertrochanteric fractures. The non-anatomical functional anteromedial buttress is proposed to prevent impending mechanical complications. We aimed to evaluate the role of anteromedial cortical support in preventing mechanical complications following fixation with the cephalomedullary nail. MATERIALS AND METHODS: A prospective, single-arm interventional study was conducted in the Orthopaedics Department of a Combined Military Hospital (CMH) in Rawalpindi. The duration of the study was 24 months. Patients were recruited by the purposive sampling technique as per inclusion/exclusion criteria. Preoperatively, the reduction was categorized as per Baumgartner's and Chang's criteria. Post-operatively, weight bearing as tolerated was advised. Radiographs prior to discharge for loss of reduction were evaluated. Follow-up radiographic measurements of neck length, neck shaft angle, and their loss as per protocol were done at three and six months. RESULTS: A total of 202 patients were operated on from October 21 until August 23. Mortality at six months in 39 patients (19.3%) and loss to follow-up in 31 patients (15.3%) resulted in 132 patients with complete follow-up and having developed complications in 12 patients (9.09%). The mean age was 76.3 ± 7.98 years; males were 105 (79.5%), and females were 27 (20.5%). Closed reduction was 58 (43.9%), and additional manoeuvres were required in 74 (56.1%). The mean tip apex distance (TAD) was 24.56 ± 2.76, and the Calcar gap was 5.16 ± 1.27. Cleveland zone centre-centre in 54 (40.9%), inferior-centre in 65 (49.2%), and inferior-posterior (9.9%) were statistically significant for mechanical complications (p≤0.001). There was a significant association between the grading of Chang's and Baumgartner's poor groups for the development of mechanical complications (p≤0.001). The mean time to full weight bearing without support was 21 ± 1.22 weeks. The mean Hip Harris score at six months was 69.27 ± 7.68. CONCLUSION: Results suggest that anteromedial cortical support can lead to fewer potential mechanical complications at six months. A higher Chang's grade drives surgeons to engage in additional manoeuvres. Anteromedial cortical support is worth consideration for unstable pertrochanteric fractures.

Cardiac Tamponade Caused by Campylobacter ureolyticus Purulent Effusion.

A male in his 60s presented to the emergency department with a seven-day history of progressively worsening malaise, dyspnea, nausea, and vomiting. The patient quickly developed septic and obstructive shock, with the ensuing investigation significant for a purulent pericardial effusion causing cardiac tamponade. Subsequent cultures grew Campylobacter ureolyticus, which is commonly associated with the gastrointestinal tract and is one of many microorganisms that cause diarrhea. Yet, studies have identified this pathogenic organism in oral infections, infectious meningitis, and soft tissue infections, but not pericardial effusions. This organism is an emerging pathogen and warrants renewed research efforts.

Single-nucleus RNA velocity reveals critical synaptic and cell-cycle dysregulations in neuropathologically confirmed Alzheimer's disease.

Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer's disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions.

Twisted van der Waals Quantum Materials: Fundamentals, Tunability, and Applications.

Twisted van der Waals (vdW) quantum materials have emerged as a rapidly developing field of two-dimensional (2D) semiconductors. These materials establish a new central research area and provide a promising platform for studying quantum phenomena and investigating the engineering of novel optoelectronic properties such as single photon emission, nonlinear optical response, magnon physics, and topological superconductivity. These captivating electronic and optical properties result from, and can be tailored by, the interlayer coupling using moiré patterns formed by vertically stacking atomic layers with controlled angle misorientation or lattice mismatch. Their outstanding properties and the high degree of tunability position them as compelling building blocks for both compact quantum-enabled devices and classical optoelectronics. This paper offers a comprehensive review of recent advancements in the understanding and manipulation of twisted van der Waals structures and presents a survey of the state-of-the-art research on moiré superlattices, encompassing interdisciplinary interests. It delves into fundamental theories, synthesis and fabrication, and visualization techniques, and the wide range of novel physical phenomena exhibited by these structures, with a focus on their potential for practical device integration in applications ranging from quantum information to biosensors, and including classical optoelectronics such as modulators, light emitting diodes, lasers, and photodetectors. It highlights the unique ability of moiré superlattices to connect multiple disciplines, covering chemistry, electronics, optics, photonics, magnetism, topological and quantum physics. This comprehensive review provides a valuable resource for researchers interested in moiré superlattices, shedding light on their fundamental characteristics and their potential for transformative applications in various fields.

Assessment of COVID-19 Morbidity and Mortality Among Patients With Autoimmune Diseases at King Abdulaziz University Hospital.

Background The coronavirus disease 2019 (COVID-19) pandemic has raised significant concerns about the effects of the virus on patients with autoimmune diseases. Therefore, understanding the COVID-19 outcomes in this population is crucial for effective prevention and management. Objective This study aimed to investigate the association between autoimmune diseases and the severity of COVID-19 in terms of mortality and morbidity. Despite substantial advancements in pandemic-related research concerning COVID-19 and autoimmune diseases, there remain noteworthy gaps in our comprehension of this association, particularly due to limited investigations conducted in Saudi Arabia. Methods This was a retrospective record review of a tertiary center from January 2020 to January 2022. We included 120 patients, among whom 40 were diagnosed with autoimmune diseases, and 80 were age- and sex-matched controls. Afterward, we assessed their demographics, year of admission, intensive care unit (ICU) admission, health status, length of hospitalization, comorbidities, diagnosis of autoimmune diseases, and type of immunosuppressant therapy. Results Most of the included patients (mean age: 45.4 years) were females (65.8%). The ratio of non-autoimmune diseases to autoimmune diseases was 2:1, the mean length of hospitalization was 8.83 ± 8.16 days, and the median was seven days (interquartile range (IQR) = 3 to 11 days). Among them, 17.5% were admitted to the ICU and 10% died. The prevalence of autoimmune diseases was higher in women than in men (77.5%). The most common diseases were systemic lupus erythematosus (40%), rheumatoid arthritis (20%), and ankylosing spondylitis (10%). Regarding COVID-19 outcomes, ICU admissions were higher among patients with autoimmune diseases than those with non-autoimmune diseases (35% vs. 8.8%) (p<0.05). This trend was also observed in mortality, with a higher percentage of deaths among patients with autoimmune diseases (27.5% vs. 1.7%) (p<0.05). In addition, there were no significant differences between genders in terms of ICU admission, health status outcomes, or length of hospitalization among patients with autoimmune diseases (p>0.05). Notably, 25 patients were administered immunosuppressants. Of these, 18 (72%) used steroids only, while seven (28%) used both biological and steroid therapy. However, no significant associations were observed between the type of treatment used and outcomes such as ICU admission, health status at discharge, and length of hospitalization (p>0.05).  Conclusion This study suggests that individuals with autoimmune diseases have more severe COVID-19 outcomes, as shown by ICU admission and mortality rates, than patients with non-autoimmune diseases. Furthermore, we observed that the use of immunosuppressant medications among patients with autoimmune diseases showed no noticeable effect on these outcomes.

Patient reported outcomes of emergency general surgery procedures.

BACKGROUND: Emergency general surgery (EGS) involves care of a patient's often previously unknown disease in the setting of an unplanned interaction with the healthcare system. This leads to challenges collecting and interpreting patient reported outcome measures (PROMs). METHODS: We performed a qualitative and mixed methods study using semi-structured interviews during the index hospitalization and at 6-12 months to capture peri-operative patient experiences. We compared interview findings to clinical characteristics. RESULTS: Among 30 patients, two-thirds reported feeling no choice but to pursue emergency surgery with many reporting exclusion from decision-making. Females reported these themes more commonly. Patients with minor complications less frequently reported trust in their team and discussed communication issues and delays in care (all p â€‹< â€‹0.05). Patients with major complications more frequently reported confidence in their team and gratefulness, but also communication limitations (all p â€‹< â€‹0.05). Patients not admitted to the ICU more frequently discussed good communication and expeditious treatment. CONCLUSIONS: PROMs developed for EGS patients should consider patient outcomes and reflections that they felt excluded from decision-making. Severity of complications may also differentially impact PROMs.

Tailoring parenting styles and family-based interventions cross-culturally as an effective prevention strategy for youth substance use: a scoping review.

Background: The challenge of substance use among youth continues to be a highly concerning public health issue across the globe. The notion that parenting lifestyles and family-based intervention can help in the prevention of adolescent substance use have received robust attention from policy makers, researchers' clinicians and general public, nonetheless, there is scarcity of high quality evidence to support these concepts. Objective: To review available literature which assessed the effects of parenting styles and family-based interventions on the prevention of adolescent substance use. Methods: A scoping review of literature to identify studies published in English between 2012 and 2022 was conducted searching Scopus, MEDLINE, PsychInfo, and CINAHL databases focused on effects of parenting styles and family-based interventions in the prevention of adolescent substance use.Keywords of family-based intervention strategies and possible outcomes of parenting styles on youth substance use were coded from the results, discussion, or conclusion. Strategies were inductively categorized into themes according to the focus of the strategy. Results: A total of 47 studies, published between 2012 and 2022 in English language included. Narrative synthesis illustrated that parental involvement, restriction of mature-rated content, parental monitoring, authoritative parenting styles, and parental support and knowledge can help in the prevention of adolescent substance use. On the contrary, poor parent-child bonding, overprotection, permissive parenting, parental frustrations, authoritarian and harsh parenting styles promoted adolescent substance use disorders. Proximal risk factors like peer influence, previous use of other substances, and risky behaviours had more effect than just parenting styles. Culturally tailored family-based intervention strategies such as "Preventive Parenting", "Parent Training", and "Parent Involvement", with focus on "Technology Assisted Intervention", particularly "SMART "(Substance Misuse among Adolescents in Residential Treatment) are found as effective family-based intervention strategies to mitigate substance use in youth. Conclusion: Culturally tailored family-based behavioural strategies psychosocial intervention strategies can be considered of the most effective strategies to prevent substance use disorders in youth.

Antimicrobial effect of chamomile-containing over-the-counter ear and eye drops.

Chamomile (Matricaria chamomilla) is a plant with known antimicrobial, anti-inflammatory, and analgesic properties. Homeopathic drops containing chamomile extract are often used for ear pain and chronic ear infections. We aimed to evaluate the antimicrobial effect of over-the-counter eardrops containing chamomile against organisms causing bacterial conjunctivitis and otitis externa. Liquid cultures of Streptococcus aureus and Pseudomonas aeruginosa were exposed to increasing concentrations of eardrops containing chamomile extract. Liquid cultures of S. aureus and Streptococcus pneumoniae were exposed to increasing concentrations of chamomile eye drops for 5, 10, 15, and 45 min. Colony forming units (CFUs) were assessed after 18 h. Viability assays for these organisms were performed using the resazurin microdilution assay. We observed a reduction in the number of P. aeruginosa CFUs when the bacteria were exposed to any of the three concentrations of the chamomile drops as early as 5 min, with maximal reduction upon exposure to the 30% concentration at 45 min. Reduction in S. aureus CFUs, on the other hand, was observed for all three concentrations as maximal in the 5 min of exposure. We observed a marked reduction in the number of S. aureus CFUs upon exposure to any of the three preparations of chamomile-containing eye drops, which was almost immediate at 10% concentration. Streptococcus pneumoniae reduction happened at 5 min and continued through the 45-min observation period for all three concentrations. Our findings suggest that over-the-counter ear drops containing chamomile extract could potentially be used as a non-prescription treatment for mild cases of otitis externa and bacterial conjunctivitis.

A Case of Saphenous Vein Graft Aneurysm Treated With Percutaneous Coiling.

In adults, coronary artery bypass grafting (CABG) is a commonly performed surgery. Oftentimes, saphenous veins from the lower extremity are used as the graft vessels. A rare complication of this procedure is the formation of saphenous vein graft (SVG) aneurysms. We present the case of a 63-year-old male who presented to a referring emergency department with left-sided chest pain after falling off a ladder. The patient's initial chest X-ray revealed a suprahilar mass that was suspicious for being an aneurysm. A computerized tomography coronary angiogram indicated a large aneurysm. The patient was transferred to our facility for specialist evaluation. The patient's history was positive for two CABG procedures and a sternal wound infection, so a repeat sternotomy was not advisable. The SVG aneurysm was treated with percutaneous coiling. The patient tolerated the procedure well and was discharged home the next day.

The Use of Abatacept for the Treatment of Felty Syndrome in Rheumatoid Arthritis.

Felty syndrome is characterized by a triad of rheumatoid arthritis, neutropenia, and splenomegaly that typically occurs in patients with seropositive rheumatoid arthritis. We report a case of an 81-year-old man with a 22-year history of rheumatoid arthritis who developed pancytopenia and neutropenia for one month. An abdominal ultrasound revealed splenomegaly. A bone marrow biopsy excluded large granular lymphocytic leukemia, thus Felty Syndrome was diagnosed. He was treated with a maximum tolerated dose of methotrexate (15 mg once a week) for two months with no improvement in absolute neutrophil count. The patient was given abatacept 1000 mg intravenously every four weeks with improvement in hemoglobin, leukocyte, and platelet counts and absolute neutrophil counts from 0.2 to 2.4 K/µl.

Pre-transarterial Radioembolization of Tumoral Arteriovenous Fistula Associated With Recanalized Umbilical Vein Shunt in a Case of Hepatocellular Carcinoma With Hepatic Vein and Inferior Vena Cava Invasion.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a propensity to develop arteriovenous fistulas with the surrounding vasculature, making targeted intravascular treatment more difficult. HCC can oftentimes be accompanied by portal hypertension and liver cirrhosis, which can, in turn, cause recanalization of the umbilical vein. In rare circumstances, arteriovenous fistula formation and shunting into the recanalized and enlarged umbilical vein can occur. In the following presented case of HCC, an arteriovenous shunt between the anterior division of the right hepatic artery and a recanalized umbilical vein is demonstrated. Subsequent successful endovascular coil embolization of the fistula was performed to avoid shunting and non-target embolization of the radiation particles in the umbilical vein territory. Post-embolization angiogram with DynaCT and lack of Tc-99m macroaggregated albumin deposition in the umbilical vein distribution confirmed the resolution of the shunt. The patient then received targeted Y-90 transarterial radioembolization locoregional therapy in combination with systemic therapy.

Correction: Pretreatment Embolization of Tumoral Arteriovenous Fistula Associated With Recanalized Umbilical Vein Shunt in a Case of Hepatocellular Carcinoma With Hepatic Vein and Inferior Vena Cava Invasion.

[This corrects the article DOI: 10.7759/cureus.44784.].

Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson's disease.

Parkinson's disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent neurotransmitter receptor-mediated mechanisms contributing to Parkinson's disease progression. Combining the spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, we detect a diverse set of receptors influencing gray matter atrophy, functional activity dysregulation, microstructural degeneration, and dendrite and dopaminergic transporter loss. Inter-individual variability in receptor mechanisms correlates with symptom severity along two distinct axes, representing motor and psychomotor symptoms with large GABAergic and glutamatergic contributions, and cholinergically-dominant visuospatial, psychiatric and memory dysfunction. Our work demonstrates that receptor architecture helps explain multi-factorial brain re-organization, and suggests that distinct, co-existing receptor-mediated processes underlie Parkinson's disease.

A Rare Case of Captopril-Induced Parotid Gland Enlargement.

The use of captopril has been linked to scarce adverse events characterized by parotid glands enlargement. We report a case of captopril-induced parotid enlargement in a patient with uncontrolled hypertension. A 57-year-old male presented to the emergency department (ED) with an acute state of headache. The patient has a background of untreated hypertension for which he was managed in the emergency department (ED) by the administration of captopril 12.5 mg sublingually to control his blood pressure. Shortly after the drug administration, he started to experience bilateral painless enlargement of parotid glands that resolved a few hours after the drug was withdrawn.

Biomimicry in Architecture: A Review of Definitions, Case Studies, and Design Methods.

Biomimicry, as a field of science, is mainly defined as a solution for design problems inspired by natural models, systems, and elements. For the built environment, using nature as a guide can enhance sustainability or even go beyond that and generate a regenerative approach. This is important in the building sector to evolve towards a sustainable and circular economy and reduce CO2 emissions in terms of energy-use. While several biomimicry-related keywords exist, scholars and practitioners in architecture have given varying interpretations to the term biomimicry depending on the use and goal. There has been increasing interest in biomimicry in architecture (BIA), yet the field has become more fragmented. This study aims to highlight differences and similarities through an extended literature survey and analysis that explores case studies, classification systems, and methodological frameworks related to biomimicry in architecture as a way to contribute to reduce the fragmentation in the field. To provide the necessary context and avoid confusion regarding the many concepts and terms that refer to nature-based design, biomimicry-related keywords and interpretations of the word biomimicry are first clarified. Ultimately, the discussion is an integrative effort at defining the field, and highlights the significance and impact of employing BIA in terms of sustainability and usability, as well as showcasing the opportunities for further research.

A morphological study comparing heart size measurement on chest radiograph with echocardiography in local population.

OBJECTIVE: To investigate heart size on chest X-ray via cardiothoracic ratio, and to correlate it with echocardiographic measurements. METHODS: The comparative analytical, cross-sectional study was conducted at the Pakistan Navy Station Shifa Hospital, Karachi, between January 2021 and July 2021. The radiological parameters were measured on chest X-rays posterior-anterior view, and the echocardiographic parameters were measured using 2-dimensional transthoracic echocardiography. The absence or presence of cardiomegaly on both imaging modalities was modelled as a binary categorical variable and compared. Data was analysed using SPSS 23. RESULTS: Of the 79 participants, 44(55.7%) were males and 35(44.3%) were females. The mean age of the sample was 52.71±14.54 years. There were 28(35.44%) enlarged hearts on chest X-ray and 46(58.22%) on echocardiography. The sensitivity and specificity of chest X-ray were 54.35% and 90.90%, respectively. The positive and negative predictive values were 89.28% and 58.82%, respectively. The accuracy of chest X-ray in identifying an enlarged heart was 69.62%. CONCLUSIONS: The cardiac silhouette on a chest X-ray could demonstrate heart size through simple measurements with high specificity and reasonable accuracy. However, a normal heart size on chest X-ray may not have a normal function.

Enhancing Protein Adsorption for Improved Lateral Flow Assay on Cellulose Paper by Depleting Inert Additive Films Using Reactive Plasma.

Paper-based platforms are ideal for on-site surveillance of infectious diseases in low-resource settings due to their simplicity, self-containment, and low cost. The two most popular materials used in paper-based platforms are nitrocellulose and cellulose. The nitrocellulose membrane has a high protein binding affinity, but its high price is an issue. Cellulose paper is inexpensive and allows intricate fluidic control for more sophisticated biochemical reactions, but it has a low protein binding affinity. By examining the microstructure of cellulose paper, we discover that cellulose fibers in the paper matrix are covered by thin films, which possibly result from the additives used in the paper-making process. Our finding suggests that the thin films are inert to protein adsorption. By selectively depleting the inert films with reactive plasma, we were able to enhance the protein adsorption to the cellulose paper and improve the performance of lateral flow assays. The performance of certain lateral flow assays on the plasma-treated cellulose paper is equivalent to or better than that on the nitrocellulose membrane. This leads us to believe that cellulose paper with a microstructure exclusively designed for protein binding, either by refined paper manufacturing process or by post-manufacture modification such as the plasma treatment presented herein, can potentially replace nitrocellulose as a less expensive paper substrate for point-of-care rapid test kits.