Basic Science and Pathogenesis.

Background: In tauopathies, such as Frontotemporal Dementia (FTD), tau loses association with microtubules (MTs) and forms neurofibrillary tangles. Tau is an abundant MT-associated protein in neurons, which essentially regulate MT properties. Because pathological tau binds less avidly to MTs, which was thought to reduce the levels and stability of axonal MTs.

Germline deletion of Rgs2 and/or Rgs5 in male mice does not exacerbate left ventricular remodeling induced by subchronic isoproterenol infusion.

Sympathoexcitation is a hallmark of heart failure, with sustained β-adrenergic receptor (βAR)-G protein signaling activation. βAR signaling is modulated by regulator of G protein signaling (RGS) proteins. Previously, we reported that Gα regulation by RGS2 or RGS5 is key to ventricular rhythm regulation, while the dual loss of both RGS proteins results in left ventricular (LV) dilatation and dysfunction.

Pituitary adenylate cyclase-activating polypeptide (PACAP)overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.

Strategic Acyl Carrier Protein Engineering Enables Functional Type II Polyketide Synthase Reconstitution In Vitro.

Microbial polyketides represent a structurally diverse class of secondary metabolites with medicinally relevant properties. Aromatic polyketides are produced by type II polyketide synthase (PKS) systems, each minimally composed of a ketosynthase-chain length factor (KS-CLF) and a phosphopantetheinylated acyl carrier protein (-ACP). Although type II PKSs are found throughout the bacterial kingdom, and despite their importance to strategic bioengineering, type II PKSs have not been well-studied .

Cushing's Disease Clinical Phenotype and Tumor Behavior Vary with Age: Diagnostic and Perioperative Implications.

Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging.

Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes.

Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023.

Infectious Disease Management in Pediatric Emergency Departments in Low- and Middle-Income Countries: A Review of Diagnostic Tools, Treatment Protocols, and Preventive Measures.

Pediatric Emergency Departments (PEDs) in low- and middle-income countries (LMICs) face significant challenges in managing infectious diseases due to limited resources, poor infrastructure, and socioeconomic barriers. This review explores the burden of infectious diseases in pediatric populations, the diagnostic tools available, treatment protocols, and preventive measures implemented in LMIC PEDs. We emphasize the need for an integrated approach to improve health outcomes, focusing on enhancing healthcare infrastructure, training healthcare workers, and promoting public health awareness.

Opioid-Prescribing Trends in Dermatology From 2014 to 2020 in the United States.

Introduction The opioid epidemic is a critical public health crisis, with opioid overdose deaths being a leading cause of injury-related deaths in the United States. Dermatology, though a small contributor to overall opioid prescriptions, still accounts for over 700,000 opioid pills annually. Reducing opioid prescribing in this specialty has been challenging due to limited comprehensive research.

Haloperidol-Induced Laryngeal Dystonia: A Case Report on an Antipsychotic-Associated Airway Emergency.

Acute dystonia is a neurological condition characterized by involuntary muscle contractions that can affect various parts of the body. It is commonly triggered by the use of antipsychotic medications, especially within the first few days after administration. Respiratory acute laryngeal dystonia, a particularly severe form of this condition and a very subtype of laryngeal dystonia, can lead to respiratory distress and airway obstruction if not promptly treated.

Reducing Intubations and Related Risks in Neonates with Retinopathy of Prematurity Undergoing Laser Photocoagulation.

Introduction: Although associated with respiratory morbidity, elective endotracheal intubation (ETI) for laser photocoagulation for retinopathy of prematurity (ROP) is the standard practice at our institution, with 100% of patients undergoing preoperation ETI. To mitigate this risk, we strove to reduce the percentage of infants intubated for laser photocoagulation by 30% by June 2022.

Methods: We assembled a multidisciplinary team and implemented a deep sedation guideline utilizing dexmedetomidine, fentanyl, and midazolam with noninvasive ventilation support for laser photocoagulation in January 2020.

Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications.

Although antiretroviral therapy (ART) has dramatically improved the outlook of the HIV/AIDS pandemic, people living with HIV (PLWH) on suppressive therapy are still at higher risk for a range of comorbidities including cardiovascular disease (CVD) and HIV-associated neurocognitive disorders (HAND), among others. Chronic inflammation and immune activation are thought to be an underlying cause of these comorbidities. Many of the factors thought to drive chronic inflammation and immune activation in HIV overlap with factors known to induce trained immunity.

Ocular and Systemic Abnormalities in Punctal Agenesis.

Background: Punctal agenesis (PA) is a rare congenital anomaly that can occur in isolation or as part of an underlying syndrome. The benefit of genetic assessment in individuals with PA and clinical features that should prompt molecular workup has not been systematically studied. The aim of this study was to identify ocular and extraocular features associated with PA and determine its association with an underlying syndrome.

Management of dyslipidaemia in patients with comorbidities - facing the challenge Value and limitations of lipid lowering drugs in liver disease Effects/Interactions of lipid-lowering agents on/with the liver.

Objectives: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.

Methods And Results: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health.

Showcasing diversity, equity, and inclusion in neurological surgery: a comparative analysis of neurological surgery residency program websites in the United States.

Residency websites can often be crucial for influencing neurosurgery applicants' first impressions of programs. This study explores the representation of diversity on neurological surgery residency program websites and evaluates the impact of Diversity, Equity, and Inclusion (DEI) statements. The websites of 117 neurological surgery residency programs were evaluated for the presence of 12 diversity and inclusion elements.

Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease.

Background: Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear.

Severe Transverse Myelitis Following Ankle Surgery Potentially Unmasking Late-Onset Systemic Lupus Erythematosus.

A 70-year-old female underwent open reduction and internal fixation (ORIF) of her right ankle following a mechanical trip and fell two weeks before hospital admission. Two weeks following surgery, the patient experienced sudden-onset bilateral anterior thigh paresthesias and burning mid-back pain. Over the ensuing two days, the patient developed bilateral lower extremity weakness, bilateral lower extremity numbness, and urinary retention with constipation, which led to hospital presentation.

A Case of Fulminant Cerebral Edema Leading to Death After Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment of refractory B-cell malignancies; however, treatment puts patients at risk for side effects secondary to the amplified immune response it induces. Fulminant cerebral edema (FCE) is one of the rarest, yet most devastating side effects following CAR T-cell therapy. Due to this rarity, FCE has not been well characterized and the risk factors associated with its development are not fully understood.

Fidgetin binds spastin to attenuate the microtubule-severing activity.

Microtubule-severing enzymes such as spastin, katanin, and fidgetin, characterized by their AAA ATPase domains, are pivotal in modulating microtubule dynamics and behavior across various cellular processes. While spastin and katanin are recognized for their predominant and robust severing of stable microtubules, thereby enhancing microtubule turnover, fidgetin exhibits comparatively weaker severing activity and selectively targets labile microtubules. The interplay among these enzymes and their mutual regulatory mechanisms remains inadequately understood.

Imaging of gallstones and complications.

Gallbladder pathologies caused by gallstones are commonly encountered in clinical practice, making accurate diagnosis critical for effective patient management. Radiologists play a key role in differentiating these conditions through imaging interpretation, ensuring that appropriate treatment is initiated. The imaging features of gallstone associated diseases are classified into various categories, such as inflammatory conditions, benign lesions, malignant tumors, and associated complications.

The 5-factor modified frailty index as a prognostic factor following stereotactic radiosurgery for metastatic disease to the brain from non-small cell lung cancer: A multi-center cohort analysis.

Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), complicating management. We have shown that increasing frailty is associated with decreased overall survival (OS) and central nervous system progression free survival (PFS) for patients undergoing stereotactic radiosurgery (SRS) to BMs. Leveraging the International Radiosurgery Research Foundation, we sought to expand upon these findings, in NSCLC specifically.

Clinical Outcomes of Therapeutic Interventions for Autoimmune Retinopathy: A Meta-analysis and Systematic Review.

Topic: Autoimmune retinopathy (AIR) is a group of rare inflammatory diseases treated with immunosuppression; however, there is no treatment consensus. This meta-analysis and review aims to investigate treatment effectiveness in slowing AIR progression.

Clinical Relevance: Autoimmune retinopathy is a group of diseases characterized by progressive vision loss that is both difficult to diagnose and treat.

Endoscopic and microscopic video modules are effective for teaching middle ear anatomy.

Objectives: To evaluate the efficacy of video modules in improving trainees' objective knowledge of middle ear anatomy and to compare the efficacy of using the endoscope to the microscope in video modules.

Methods: Medical students and residents were recruited. Two videos reviewing middle ear anatomy were developed.

Cervical Epidural Steroid Injection for Cervical Radicular Pain in a Patient with Fractured Cervical Hardware.

Cervical radicular pain following anterior cervical discectomy and fusion (ACDF) is a challenging condition, particularly in the presence of hardware complications. This case report discusses the successful use of a cervical interlaminar steroid injection to alleviate radicular pain in a patient who presented with a fractured screw following C6/7 ACDF. The patient's symptoms, treatment plan, and outcome are reviewed, highlighting the success of an interlaminar steroid injection in managing radicular pain until the patient could receive corrective surgery.