Discovery of VU6024578/BI02982816: An mGlu Positive Allosteric Modulator with Efficacy in Preclinical Antipsychotic and Cognition Models.

Herein, we report progress toward a metabotropic glutamate receptor subtype 1 (mGlu) positive allosteric modulator (PAM) clinical candidate and the discovery of VU6024578/BI02982816. From a weak high-throughput screening hit (VU0538160, EC > 10 μM, 71% Glu), optimization efforts improved functional potency over 185-fold to deliver the selective (inactive on mGlu) and CNS penetrant (rat K = 0.99, K = 0.

The Reconstruction of Mandible Defects in War Injuries: Systematic Review and Meta-Analysis.

Study Design: Systematic Review and Meta-Analysis.

Objective: There has been an increasing trend in maxillofacial injuries associated with combat trauma. Within the maxillofacial complex, the mandible is the most likely structure to be damaged during combat.

Balancing the scales of safety: the criminal law's impact on patient safety and error reduction.

The chance of death from medical error within the hospital setting is 33,000 times greater than dying in an aircraft crash. Despite patient safety being central to healthcare delivery across the world, medical errors and patient harm remain prevalent. This review evaluates the role of the criminal law in regulating healthcare across England and Wales, using prior legal case studies, and focussing on the offence of gross negligence manslaughter (GNM).

Use of human acellular dermal matrix in rhinoplasty: a systematic review of the literature and meta-analysis.

Alloplastic implants such as acellular dermal matrix (ADM) have been used for various aesthetic and reconstructive purposes since the 1990s. Rhinoplasty addresses both aesthetic and functional nasal impairments, often involving the adoption of grafting materials. Currently, autologous grafts, such as those using septal cartilage, are the gold standard.

Malignant Middle Cerebral Artery Infarct Caused by Eagle's Syndrome.

Eagle's syndrome is characterised by elongation of the styloid process. The elongated styloid process can cause symptoms like dysphagia, facial or neck pain, syncope, visual changes, etc. In severe cases, it may cause a rupture or dissection of the carotid artery, which can lead to intracranial thrombo-embolism and ischemic stroke.

Reconstruction of head and neck oncological soft tissue defects post-resection using robotic surgery: a systematic review of the current literature.

Head and neck cancer (HNC) resection often leaves soft tissue defects and exposure of vital structures. In recent years, there has been an increase in the use of robotic surgery for HNC resections. This allows for achieving smaller defects by using a tissue-sparing approach.

Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts.

Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells.

Are foundation doctors equipped with the skills necessary for the assessment and referral of a patient presenting with a suspected facial skin malignancy?

Background: The incidence of skin cancer (SC) has increased in recent years with it being the most common cancer within the UK. The management of SC requires a multidisciplinary approach involving dermatologists and surgical specialities.

Objectives: To assess the confidence of current foundation trainees (FTs) in the assessment of facial SC and referral for surgical management and reconstruction.

Use of biomaterials in the reconstruction of posterior lamellar eyelid defects: a systematic review and meta-analysis.

Eyelid defects can occur secondary to tumours, trauma, burns, and congenital factors. Among the most challenging aspects of eyelid reconstruction is the rebuilding of a tarsal substitute due to its delicate and multi-layered tissue composition. Attempts to use biomaterials for posterior lamellar reconstruction are intended to provide an alternative to traditional autograft reconstructions.

Can we support second degree students by incorporating non-surgical facial aesthetics into undergraduate dentistry during the first degree?

Non-surgical facial aesthetics (NSFA) are cosmetic procedures intended to reduce signs of ageing and provide facial rejuvenation. There is currently no recommendation for NSFA to be included in the undergraduate dental curriculum globally. This study aims to gain the views of final year dental students about pursuing a career in NSFA.

Pushing the Boundaries of Scientific Research with the use of Artificial Intelligence tools: Navigating Risks and Unleashing Possibilities.

The language of science is communicated through various modes, such as lectures, informal discussions, conferences, and peer-reviewed publications. Artificial Intelligence (AI) based writing tools, like ChatGPT, have recently become increasingly popular due to natural language processing technology advancements. ChatGPT is an AI language model that can generate text close to human writing, making it suitable for tasks such as summarizing literature, composing essays, and producing statistical studies.

What are the concerns of second-degree medical students entering specialty OMFS training?

Oral and maxillofacial surgery (OMFS) applicants are faced with numerous challenges. Previous research has demonstrated that financial burden, length of OMFS training, and impact on personal life are cited as major drawbacks to pursuing the specialty, with trainees having concerns about the Membership of the Royal College of Surgeons (MRCS) examinations. The current study aimed to explore second-degree medical students' concerns about obtaining a specialty training post in OMFS.

Synthesized bioactive lignin nanoparticles/polycaprolactone nanofibers: A novel nanobiocomposite for bone tissue engineering.

The use of artificial biomaterial with enhanced bioactivity for osteostimulation is a major research concern at present days. In this research, antibacterial and osteostimulative core-shell lignin nanoparticles (LgNP) were synthesized from alkali lignin using tetrahydrofuran (THF) as solvent via a simultaneous pH and solvent shifting technology. Later, LgNP-loaded polycaprolactone (PCL) composite nanofibers were fabricated via the electrospinning technique.

Facial trauma education within two English medical schools.

Facial trauma accounts for 5%-10% of all presentations to emergency departments (ED) in the UK, and it is often referred to the oral and maxillofacial surgery (OMFS) department by ED physicians. Undergraduate medical students often have limited exposure to OMFS, and this is likely to translate to reduced exposure to facial trauma. We investigated the exposure of undergraduate clinical medical students to facial trauma teaching and asked about their confidence to manage facial lacerations and their ability to diagnose common facial fractures.

Are clinical medical students confident about their head and neck anatomy knowledge?

Anatomy is a pillar of medical knowledge and essential for safe medical and surgical practice. The literature highlights concerns regarding anatomy knowledge, and knowledge of the head and neck in particular, in medical students and newly qualified doctors. We investigated medical students' confidence to be assessed on head and neck anatomy, the amount of teaching they received, and its mode of delivery, through an online survey completed by 185 medical students across two English Universities (122 (66%) students from University A and 63 (34%) from University B).

Are medical students confident in assessing the patient presenting with a neck lump?

Neck lumps are a common clinical presentation in both primary care, the emergency department and in specialist clinics. Foundation doctors and final year medical students are often not confident in the assessment of patients presenting with head and neck symptoms. We evaluated medical students confidence in performing a systematic neck lump examination, formulation of differential diagnosis and presentation to senior colleagues.

Attitude of clinical medical students to Oral and Maxillofacial Surgery as a career: a perspective from two English Medical Schools.

Oral and Maxillofacial Surgery (OMFS) has been increasing in popularity amongst medicine first trainees. Despite this, there is still limited exposure at the undergraduate level. This study aimed to: evaluate the experience of medical students in the field of OMFS, the awareness of medical students to OMFS resources/societies and to determine the greatest motivators and deterrents for students in pursuing a career in OMFS.

Neurocutaneous Melanosis with Hydrocephalus and Dandy-Walker Variant.

Neurocutaneous melanosis (NCM) is one of the rare, congenital, noninheritable phakomatoses characterized by the presence of large and/or multiple congenital melanocytic cutaneous nevi associated with intracranial leptomeningeal melanocytosis. NCM usually presents before 2 years of age. So far 302 cases have been reported in literature.

Expanded substrate specificity supported by P1' and P2' residues enables bacterial dipeptidyl-peptidase 7 to degrade bioactive peptides.

Dipeptide production from extracellular proteins is crucial for Porphyromonas gingivalis, a pathogen related to chronic periodontitis, because its energy production is entirely dependent on the metabolism of amino acids predominantly incorporated as dipeptides. These dipeptides are produced by periplasmic dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11. Although the substrate specificities of these four DPPs cover most amino acids at the penultimate position from the N terminus (P1), no DPP is known to cleave penultimate Gly, Ser, Thr, or His.

SARS-CoV-2 infection pattern, transmission and treatment: Multi-center study in low to middle-income districts hospitals in Punjab, Pakistan.

Pakistan has reported a substantial number of COVID-19 cases since 2020. A multicenter observational study was conducted to identify the pattern of SARS-CoV-2 infection, transmission, and treatment in patients admitted to seven low to middle-income district hospitals in the Province of Punjab, Pakistan from March to June 2020. A total of 102 patients were recruited.

Preferential dipeptide incorporation of Porphyromonas gingivalis mediated by proton-dependent oligopeptide transporter (Pot).

Multiple dipeptidyl-peptidases (DPPs) are present in the periplasmic space of Porphyromonas gingivalis, an asaccharolytic periodontopathic bacterium. Dipeptides produced by DPPs are presumed to be transported into the bacterial cells and metabolized to generate energy and cellular components. The present study aimed to identify a transporter responsible for dipeptide uptake in the bacterium.

Characterization of substrate specificity and novel autoprocessing mechanism of dipeptidase A from Prevotella intermedia.

Prevotella intermedia, a Gram-negative anaerobic rod, is frequently observed in subgingival polymicrobial biofilms from adults with chronic periodontitis. Peptidases in periodontopathic bacteria are considered to function as etiological reagents. Prevotella intermedia OMA14 cells abundantly express an unidentified cysteine peptidase specific for Arg-4-methycoumaryl-7-amide (MCA).

The Urgency to Mitigate the Spread of Hepatitis C in Pakistan Through Blood Transfusion Reform.

Blood transfusions are contributing to a higher rate of hepatitis C virus (HCV) in Pakistan. Half of all blood transfusions in Pakistan are not screened for hepatitis C, hepatitis B or HIV. Family members donate blood that is likely not tested due to social stigma attached to HCV.