Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens.

There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine. Our study provides evidence for cross-reactive IgG antibodies specific to eight different spike (S) variants. Furthermore, the specificities of these cross-variant IgG antibody titers were associated to some extent with spike S1- and S2-subunit-derived epitopes P1 and P2, respectively. In addition, nucleocapsid (N)- and membrane (M)-specific IgG antibody titers correlated with N- and M-derived epitopes conserved across beta-CoVs, P3-7. This study reveals conserved epitopes of viral antigens, targeted by natural and/or vaccine-induced human immunity, for future designs of next-generation COVID-19 vaccines.

Reduced voluntary wheel running behaviour in Kiss1r knockout mice.

Kisspeptin and its receptor, Kiss1r, are novel players in the central balance of energy intake and expenditure. Recent evidence also indicates that kisspeptin signalling is important in thermoregulation and generation of the circadian rhythm. We used global Kiss1r knockout mice (Kiss1r KO), which are hypogonadal and develop obesity, to determine the impact of kisspeptin on circadian related behaviour. Voluntary wheel running was examined in Kiss1r KO and wild-type (WT) mice, using gonad intact and gonadectomised (GDX) mice to account for the effects of kisspeptin on gonadal sex steroids. Intact male and female Kiss1r KO mice covered only 10% and 30% of the distance travelled each day by their respective WT controls. In all mice, most of the running activity occurred during the dark phase. GDX WT mice ran significantly less during dark periods than the intact WT. GDX Kiss1r KO male mice ran significantly less than the GDX WT male mice, but the decrease was attenuated compared to intact mice. There was no difference between the female GDX Kiss1r KO and GDX WT. In contrast to the obese phenotype that develops in Kiss1r KO mice, body mass at the end of the study was significantly lower in the GDX Kiss1r KO than it was in the GDX WT mice. The difference in wheel running activity was not associated with any histological change in WAT, BAT, or muscle diameter. No difference in immunohistochemistry expression was seen in lateral hypothalamic orexin neurons or dopamine neurons in the ventral tegmental area / substantia nigra. We observed increased Iba1 expression (activation of microglia) in the arcuate nucleus of male Kiss1r KO mice. Overall, the circadian locomotor activity in male Kiss1r KO mice appears dependant on kisspeptin signalling and the obese phenotype does not develop in Kiss1r KO mice when they engage in voluntary activity.

Infant bronchial tree simulator: Success of a built-from-scratch model for single lung isolation.

BACKGROUND: One-lung ventilation in infants is a high-risk procedure. Complications include endotracheal tube occlusion, with grave consequences. Although there are commercially available bronchoscopy simulators, there are no realistic models of infant patients. This limits access to training opportunities that would ensure safe and efficient lung isolation. To bridge this gap, we developesd a realistic infant bronchial tree model for single lung intubation and evaluated preliminary validity evidence of its features and clinicians' ability to perform critical skills associated with pediatric one-lung ventilation. METHODS: Using computed tomography imaging, a stereolithography file of an infant airway was generated to 3D print a model. This model was inserted into a commercially available airway trainer to allow lung isolation using standard bronchoscopy techniques. Ten experienced pediatric anesthesiologists independently evaluated the simulator's physical attributes, realism, value, and relevance using a 29-item paper survey and rated using 4-point rating scales (4 = highest). Participants' ability to complete 5 critical tasks was self-reported using 5-point rating scales (5 = too easy). Item and domain mean ratings were calculated, and comments reviewed. RESULTS: Overall, reviews were positive, with mean scores indicating adequate realism and high value. Specific challenges were associated with right mainstem bronchus and upper lobe takeoff. Performance scores indicated that most tasks were "somewhat easy to perform," suggesting that the model's anatomy did not hinder physicians' ability to perform one-lung ventilation. CONCLUSION: Preliminary findings indicate that the novel simulator holds promise for training in lung isolation techniques after refinement. Future research will target refinement, expanding evaluation, and developing a comprehensive curriculum and competency assessment program.

Stability-indicating green HPLC method for fixed-dose tablets containing remogliflozin etabonate and teneligliptin: an AQbD approach.

BACKGROUND: In June 2021, the Central Drug Standards Control Organization approved a fixed-dose combination tablet containing remogliflozin etabonate (100 mg) and teneligliptin (10 mg) to manage type II diabetes. OBJECTIVE: This study aims to develop a stability-indicating RP-HPLC method for quantifying remogliflozin etabonate and teneligliptin in tablet formulations via analytical quality by design (AQbD) principles. METHODS: Risk assessment, Plackett-Burman design, and central composite design were employed to understand the impact of independent variables on critical analytical attributes. The stationary phase was a HyperClone BDS C18 column, and the mobile phase consisted of acetonitrile and phosphate buffer (20 mM, pH 5) at a 45:55% (v/v) ratio. RESULTS: The method, validated per ICH Q2 (R1), resulted in retention times of 3.395 and 12.308 min for teneligliptin and remogliflozin etabonate, respectively. Forced degradation studies confirmed robustness, with clear peak separation and no interference from degradation products. The AGREE score of 0.65 supports its green applicability for tablet analysis in quality control. CONCLUSION: The AQbD-assisted RP-HPLC method developed in this study offers environmental friendliness, efficient separation with well-defined peaks, and simple mobile phase combination.

An Unusual and Discrepant Presentation of a Skull Base Paraganglioma.

Paragangliomas are rare tumors of neuroendocrine origin. Within the head and neck, these tumors are slow-growing and locally destructive, with a small malignant potential. Vagal paragangliomas (VPs) originate from paraganglia around the vagus nerve, typically at the level of the skull base. Cranial nerve deficits are common at presentation, with the vagus nerve and hypoglossal nerves being most affected. Similarly, hypoglossal paragangliomas (HPs) originate from around the hypoglossal nerve but are extremely rare and less documented. We describe the case of a patient presenting with an isolated hypoglossal nerve palsy in the setting of a tumor that radiologically represents a VP. A descriptive literature review was conducted to highlight presentation, management, and outcomes related to this pathology. A 65-year-old male presented to the clinic with tongue fasciculations and several years of dysarthria. Physical examination showed intermittent right tongue fasciculations in addition to ipsilateral hemi-atrophy. A computed tomography scan with contrast revealed an enhancing skull base mass inferior to the right carotid space. Subsequently, magnetic resonance imaging with contrast further delineated its anatomic involvement and site of origin, allowing for the diagnosis of a VP. After further discussion with the patient about his clinical findings, the decision was made to proceed with observation and serial imaging. Skull base paragangliomas are a rare pathologic entity that may pose a challenging multidisciplinary approach to optimize management strategies. Treatment may vary on a case-by-case basis and is dependent on patient and tumor characteristics.

Joint British Association for Sexual Health and HIV and Royal College of Obstetricians and Gynaecologists national UK guideline for the management of herpes simplex virus (HSV) in pregnancy and the neonate (2024 update).

This updated national UK guideline offers recommendations on the management of genital herpes simplex virus (HSV) in mothers and pregnant people during pregnancy and within 4 weeks following birth. It includes recommendations for first episode and recurrent HSV, HSV in preterm pre-labour rupture of membranes and in co-infection with HSV and HIV. Recommendations around management of the neonate are made, on prevention of postnatal transmission, management of breastfeeding, and the management of clinically discordant couples. This guideline is aimed at healthcare professionals working in sexual health clinics, maternity units, and those working on postnatal wards and neonatal units in the UK. However, the principles of the recommendations should be adopted across all services, including community care.

Restoration with a posterior CAD/CAM onlay after failure of a direct resin-based composite restoration: a case report.

A conservative approach to restoration assists in preserving the remaining tooth structure of extensively destroyed vital teeth. This case report describes a single-appointment chairside technique for placement of ceramic restorations in posterior teeth. A patient presented for treatment of her mandibular right first molar, which had a fractured resin-based composite restoration. Due to the presence of vital pulp, extent of the restoration, and presence of caries in the tooth, the following treatment plan was proposed: placement of a lithium disilicate glass-ceramic onlay fabricated with a computer-aided design/computer-aided manufacturing workflow. After the dentist removed the restoration and performed selective caries removal, structural analysis guided the reduction of the buccal cusps. Immediate dentin sealing was performed with a 2-step self-etching adhesive system, and a 1-mm-thick layer of flowable resin-based composite was placed as a resin coating. A digital impression was obtained, the onlay restoration was designed, and a lithium disilicate block was milled and subsequently crystallized. When the onlay was completed, the tooth preparation was sandblasted, selectively etched, and coated with a universal adhesive. The intaglio surface of the onlay was cleaned and primed, the onlay was bonded with dual-cure resin cement, and occlusal adjustments were completed. Follow-up examinations at 1 and 4 months revealed the clinical success of the case. From start to finish, it takes approximately 2.5 hours to produce a single-appointment chairside restoration. The technique used in this case offers a fast-paced workflow that is comfortable and practical for the patient and provides a predictable clinical outcome without the need for a temporary restoration.

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? - A population pharmacokinetic analysis.

BACKGROUND: Clinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin. OBJECTIVE: To derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics. METHOD: Edoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function. RESULTS: Data from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min. CONCLUSIONS: Our population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

FDG-PET in the diagnosis of primary progressive aphasia: a systematic review.

Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer's disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions.

Injectable Hydrogels in Cardiovascular Tissue Engineering.

Heart problems are quite prevalent worldwide. Cardiomyocytes and stem cells are two examples of the cells and supporting matrix that are used in the integrated process of cardiac tissue regeneration. The objective is to create innovative materials that can effectively replace or repair damaged cardiac muscle. One of the most effective and appealing 3D/4D scaffolds for creating an appropriate milieu for damaged tissue growth and healing is hydrogel. In order to successfully regenerate heart tissue, bioactive and biocompatible hydrogels are required to preserve cells in the infarcted region and to bid support for the restoration of myocardial wall stress, cell survival and function. Heart tissue engineering uses a variety of hydrogels, such as natural or synthetic polymeric hydrogels. This article provides a quick overview of the various hydrogel types employed in cardiac tissue engineering. Their benefits and drawbacks are discussed. Hydrogel-based techniques for heart regeneration are also addressed, along with their clinical application and future in cardiac tissue engineering.

Groove pancreatitis: From enigma to future directions-A comprehensive review.

Groove pancreatitis (GP) is a rare and clinically distinct form of chronic pancreatitis affecting the pancreaticoduodenal groove comprising the head of the pancreas, duodenum, and the common bile duct. It is more prevalent in individuals in their 4-5th decade of life and disproportionately affects men compared with women. Excessive alcohol consumption, tobacco smoking, pancreatic ductal stones, pancreatic divisum, annular pancreas, ectopic pancreas, duodenal wall thickening, and peptic ulcers are significant risk factors implicated in the development of GP. The usual presenting symptoms include severe abdominal pain, nausea, vomiting, diarrhea, weight loss, and jaundice. Establishing a diagnosis of GP is often challenging due to significant clinical and radiological overlap with numerous benign and malignant conditions affecting the same anatomical location. This can lead to a delay in initiation of treatment leading to increasing morbidity, mortality, and complication rates. Promising research in artificial intelligence (AI) has garnered immense interest in recent years. Due to its widespread application in diagnostic imaging with a high degree of sensitivity and specificity, AI has the potential of becoming a vital tool in differentiating GP from pancreatic malignancies, thereby preventing a missed or delayed diagnosis. In this article, we provide a comprehensive review of GP, covering the etiology, pathogenesis, clinical presentation, radiological and endoscopic evaluation, management strategies, and future directions. This article also aims to increase awareness about this lesser known and often-misdiagnosed clinical entity amongst clinicians to ultimately improve patient outcomes.

Comparative assessment of treatment technologies for minimizing reverse osmosis concentrate volume for industrial applications: A review.

Desalination of seawater, brackish water, and reclaimed water is becoming increasingly prevalent worldwide to supplement and diversify fresh water supplies. However, particularly for industrial wastewater, the need for environment-friendly and economically viable alternatives for concentrate management is the major impediment to deploying large-scale desalination. This review covers various strategies and technologies for managing reverse osmosis concentrate (ROC) and also includes their disposal, treatment, and potential applications. Developing energy-efficient, economical, and ecologically sound ROC management systems is essential if desalination and wastewater treatment are being implemented for a sustainable water future, particularly for industrial wastewater. The limitations and benefits of various concentrate management strategies are examined in this review. Moreover, it explores the potential of innovative technologies in reducing concentrate volume, enhancing water recovery, eliminating organic pollutants, and extracting valuable resources. This review critically discusses concentrate management approaches and technologies, including disposal, treatment, and reuse, including new technologies for reducing concentrate volume, boosting water recovery, eliminating organic contaminants, recovering valuable commodities, and minimizing energy consumption.

Exploring the Impact of Artificial Intelligence and Machine Learning in the Diagnosis and Management of Esthesioneuroblastomas: A Comprehensive Review.

Esthesioneuroblastomas (ENBs) present unique diagnostic and therapeutic challenges due to their rare and complex clinical presentation. In recent years, artificial intelligence (AI) and machine learning (ML) have emerged as promising tools in various medical specialties, revolutionizing diagnostic accuracy, treatment planning, and patient outcomes. However, their application in ENBs remains relatively unexplored. This comprehensive literature review aims to evaluate the current state of AI and ML technologies in ENB diagnosis, radiological and histopathological imaging, and treatment planning. By synthesizing existing evidence and identifying gaps in knowledge, this review aims to showcase the potential benefits, limitations, and future directions of integrating AI and ML into the multidisciplinary management of ENBs.

Loss of control of herpes suppression following bariatric surgery.

We report a 42-year-old female with confirmed recurrent genital herpes (HSV-2), which was well controlled on suppressive antiviral therapy with aciclovir 400 mg twice daily. The patient required bariatric surgery in order to manage what was deemed a dangerously high BMI. A Roux-en-Y procedure was performed which effectively reduced her weight; however, herpes suppression become ineffective post operatively, with serious herpes related complications, despite increasing the total dose of aciclovir and the frequency from twice daily to three times a day. Complete herpes control was restored by changing therapy to valaciclovir 500 mg twice daily. The Roux-en-Y procedure is the most common form of bariatric surgery. Consequences on the efficacy of different herpes antivirals can be predicted from what is known of their properties and sites of absorption. Similar problems with herpes virus suppression may be avoided by an anticipated change in therapy preoperatively.

Ruptured Ovarian Artery Aneurysm in a Postmenopausal Female: Case Report.

Introduction: Ovarian artery aneurysm is a rare diagnosis, primarily associated with late pregnancy and the postpartum period. It can cause life-threatening hemorrhage when ruptured. Even more rare are ovarian artery aneurysms in postmenopausal women. Case Report: We present a case of a postmenopausal female presenting to the emergency department with flank pain. Point-of-care ultrasound showed free fluid in the abdomen. She was diagnosed with an ovarian artery aneurysm on computed tomography angiography and treated successfully with embolization. Conclusion: Ruptured ovarian artery aneurysm is an uncommon cause of intra-abdominal hemorrhage in women.

Trends in cannabis use in New Jersey: Effects of COVID-19 and cannabis legalization.

Objectives: With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis-related harm in both adult and pediatric cannabis-related visits at a tertiary care academic institution. Methods: We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results: We found that adult cannabis ED-related visits significantly increased during the COVID-19 pandemic and remained higher than pre-pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis-related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0-12 years were related to accidental cannabis exposures-often a household member's edibles-whereas most visits for older children stemmed from intentional cannabis use. Conclusion: This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID-19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider.