Extracellular vesicles: essential agents in critical bone defect repair and therapeutic enhancement.

Bone serves as a fundamental structural component in the body, playing pivotal roles in support, protection, mineral supply, and hormonal regulation. However, critical-sized bone injuries have become increasingly prevalent, necessitating extensive medical interventions due to limitations in the body's capacity for self-repair. Traditional approaches, such as autografts, allografts, and xenografts, have yielded unsatisfactory results.

Defining the Optimal Dose for 3-Dimensional Conformal Accelerated Partial Breast Irradiation: 15-Year Follow-Up of a Dose-Escalation Trial.

Purpose: Randomized trials have demonstrated similar local tumor control in patients treated with accelerated partial-breast irradiation (APBI) compared with whole-breast irradiation. However, the optimal APBI dose for maximizing tumor control and minimizing toxicity is uncertain.

Methods And Materials: We enrolled patients ≥18 years of age with grade 1 or 2 ductal carcinoma in situ or stage I invasive breast cancer and resection margins ≥2 mm between 2003 and 2011 to a sequential dose-escalation trial using 3-dimensional conformal external beam APBI giving twice daily 4 Gy fractions with total doses of 32 Gy, 36 Gy, and 40 Gy.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.

Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.

New Insights Into Hepatic Impairment (HI) Trials.

Hepatic impairment (HI) trials are traditionally part of the clinical pharmacology development to assess the need for dose adaptation in people with impaired metabolic capacity due to their diseased liver. This review aimed at looking into the data from dedicated HI studies, cluster these data into various categories and connect the effect by HI with reported pharmacokinetics (PK) properties in order to identify patterns that may allow waiver, extrapolations, or adapted HI study designs. Based on a ratio ≥ 2 or ≤ 0.

Aggressive Digital Papillary Adenocarcinoma: A Meta-Analysis of the Presentation, Treatment, and Outcomes of a Rare Hand Tumor.

Background: Aggressive digital papillary adenocarcinoma (ADPA) is a rare skin adnexal tumor with a predilection for the hand. The presentation, treatment, and outcomes of ADPA remain poorly defined due to the scarcity of reports and low-level evidence of published findings.

Methods: We performed a meta-analysis following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines with the intent to provide hand surgeons a better understanding of the diagnosis and treatment of the disease.

Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.

Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.

Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.

Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.

Plasma Cardiac Troponin-I Concentration in Normal Horses and in Horses with Cardiac Abnormalities.

Cardiac troponin-I (cTnI) is a highly sensitive and specific marker of myocardial injury detectable in plasma by immunoassay techniques. Inclusion criteria over a 3-year period required a diagnosis of cardiac disease accompanied by electrocardiographic (ECG) and cardiac ultrasound examinations (n = 23) in adult horses (≥2 years of age). A second group of normal adult ponies (n = 12) was studied as a reference group.

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

Cycle Effects Are Not Universal: A Case Study of Urinary C-Reactive Protein Concentrations in Rural Polish and Polish American Samples.

Objectives: We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent.

Chronic rhinosinusitis with nasal polyps: Key considerations in the multidisciplinary team approach.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent inflammatory disease associated with several comorbidities and a significant disease burden for patients. Treatments include corticosteroids and sinonasal surgery, but these can be associated with the risk of adverse events and nasal polyp recurrence. Biologic treatments such as mepolizumab can be used as an add-on treatment and are effective at reducing surgery and corticosteroid use.

Forging new paths in the development of community mental health interventions for people with mental illness at risk of criminal legal system contact.

Background: Individuals with serious mental illness (SMI) have disproportionately high rates of criminal legal system involvement. For many, this becomes a repeated cycle of arrest and incarceration. Treatments that address symptoms of mental illness are a critical component of the continuum of services for people with SMI in the legal system; yet on their own, psychiatric treatments have not been successful at reducing criminal legal system involvement for this population.

Ethnic enclaves, neighborhood socioeconomic status, and obesity among Hispanic women in Chicago: a latent profile analysis approach.

Purpose: The prevalence of obesity, a crucial risk factor for breast cancer, is markedly higher among Hispanic women. The interaction between ethnic enclaves and neighborhood socioeconomic status (SES) as a determinant of this disparity warrants further research. We aimed to identify neighborhood profiles based on ethnic enclaves and socioeconomic status to evaluate the association with obesity among Hispanic women in the metropolitan Chicago region.

Five principles to prioritise in small-scale surgical quality improvement: a qualitative study of the views of surgical improvement leaders.

Objective: Variations in the quality and safety of surgical care remain persistent. Efforts to improve are needed, but are themselves variably effective, with often disappointing impacts. When compared with large-scale, multisite and better resourced improvement efforts, the evidence base for small-scale quality improvement (QI) has remained under-developed and lacking in clarity on good practice.

Efficacy of Amniotic Suspension Allografts in the Treatment of Knee Osteoarthritis: A Systematic Review.

Knee osteoarthritis significantly impacts mobility and quality of life. This condition is a leading cause of disability in aging populations, with total knee replacement commonly sought in advanced cases. Traditional nonoperative management strategies, including anti-inflammatories, corticosteroid injections, and hyaluronic acid, often provide limited relief, especially in severe cases.

Relationships between activity monitoring device data and ovarian, uterine, hormonal, and pregnancy variables in beef cows.

Implementing accelerometer technologies in beef operations is an alternative to increase precision in estrous detection. We hypothesized that (1) the accelerometer algorithm has similar accuracy in detecting behavioral estrus as does visual observation of pressure-sensitive sensors (estrus patches) in grazing beef cows; (2) variables measured by the accelerometer, such as estrus intensity, are associated with hormonal, ovarian, and uterine variables monitored before, during, and after estrus; and (3) the accelerometer variables are associated with the probability of pregnancy in grazing beef cows submitted to embryo transfer (ET). Fifty cows were fitted with accelerometer and patches to detect estrus after a synchronization protocol in eight subsequent rounds.

Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

Objective: To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment.

Methods: A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC.

Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase.

Fatty acids (FAs) are essential building blocks for all the domains of life, of which bacterial de novo synthesis, called type II FA synthesis (FAS II), is energetically expensive. The recycling of exogenous FAs (eFAs) partially relieves the FAS II demand and, therefore, compromises the efficacy of FAS II-directed antimicrobials. The versatile acyl-acyl carrier protein (ACP) synthetase, AasS, enables bacterial channeling of diverse eFA nutrients through holo-ACP, an activated form of ACP.

ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.

Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA () to facilitate polyploidization, maturation, and functional competence of hepatocytes.

Alcohol dehydrogenase 1 acts as a scaffold protein in mitophagy essential for fungal pathogen adaptation to hypoxic niches within hosts.

Fungi have evolved diverse physiological adaptations to hypoxic environments. However, the mechanisms mediating such adaptations remain obscure for many filamentous pathogenic fungi. Here, we show that autophagy mediated mitophagy occurs in the insect pathogenic fungus Beauveria bassiana under hypoxic conditions induced by host cellular immune responses.

Point-of-care ultrasound in Gastroenterology and Hepatology.

Point-of-care ultrasound (POCUS) is changing the practice of nearly all specialties and is increasingly being incorporated as a bedside tool by more gastroenterologists and hepatologists. POCUS is most often used to answer focused clinical questions, supplement the traditional physical examination, and guide performance of invasive bedside procedures. This review describes several common POCUS applications used in gastroenterology and hepatology, as well as some novel applications that warrant further investigation.