Aspiration of Right Atrial Tumor Metastasis.

A 72-year-old man with cirrhosis had undiagnosed hepatocellular carcinoma with distant metastasis occupying nearly the entire right atrium. He was a poor surgical candidate because of his bleeding risks and advanced liver cirrhosis. He successfully underwent urgent large-bore aspiration thrombectomy under simultaneous echocardiography and fluoroscopy, thus leading to a diagnosis of metastatic malignant disease.

Etiological Spectrum of Lymphadenopathy Among Children on Lymph Node Biopsy.

Background Pediatric peripheral lymphadenopathy is commonly a benign condition and most cases resolve spontaneously; however, it can be a manifestation of a serious underlying disease. This study aimed to determine the etiological spectrum of persistent pediatric lymphadenopathy on excisional biopsy in a tertiary care children's hospital in a low-middle-income country and to make recommendations regarding evaluation, diagnostic testing, and surgical interventions best suited to the population. Methodology A prospective cross-sectional study was conducted on 243 pediatric patients between the ages of one to 12 years undergoing excisional biopsy for persistent lymphadenopathy (more than four weeks duration) from April 1, 2021, to March 31, 2024. Patient demographic data along with signs, symptoms, and results of investigations including histopathological diagnosis were documented on a structured proforma. Results Patients' age range was two to 12 years (mean = 7.29 ± 2.30 years). The male-to-female ratio was 1:53. The Mean duration of lymphadenopathy was 35.89 ± 6.95 days (range = 25 to 57 days). The average size of lymph nodes ranged from 1 cm to a complex nodal mass of 7 cm. Histopathology showed reactive hyperplasia (40.32%, n = 98), tuberculosis (TB) (33.7%, n = 82), lymphoma (10.3%, n = 25), atypical mycobacterial adenitis (6.99%, n = 17), chronic granulomatous inflammation-histiocytosis (6.2%, n = 15), and Langerhans cell histiocytosis (2.5%, n = 6). The most common site was cervical. Sputum GeneXpert for TB had a true-positive rate of 78.84% while PPD was positive in only 13 TB patients. Atypical mycobacterial adenitis was successfully treated with excision and antibiotics. Supraclavicular nodes were strongly associated with lymphoma (p = 0.008). Conclusions Persistent pediatric lymphadenopathy is most commonly caused by TB followed by lymphoma. Positive sputum GeneXpert for TB with a suggestive clinical picture in endemic regions may be sufficient to start empiric therapy without the need for excisional biopsy in mycobacterial TB adenitis with negative PPD results and normal chest X-ray. In all other cases, excisional biopsy remains the gold standard for diagnosis. However, further studies should be conducted to formulate less invasive management algorithms.

Protocol for Diagnostic Test Accuracy Study: Evaluation of Cone Beam Computed Tomography (CBCT) in Prediction of Inferior Alveolar Nerve Injury as Compared to Orthopantomography (OPG) Secondary to Surgical Removal of Impacted Mandibular Third Molars.

Introduction Impairment of the inferior alveolar/dental nerve (IAN) is a relatively uncommon complication after lower wisdom tooth removal. Studies report varying incidences of IAN injury, with dysesthesia being noted as particularly distressing and 0-0.9% cases extending for a long duration. Neurosensory disruptions can severely impact speech, chewing, swallowing, and social interactions, leading to chronic pain and a lower quality of life. It also poses a risk of inadvertent injuries during meals. Although orthopantomogram (OPG) is primarily used for diagnosis, but when the lower wisdom tooth and nerve are in close approximation, cone beam computed tomography (CBCT) is recommended, despite its higher cost and radiation exposure. A white paper on third molar management necessitates further research on CBCT's role, citing conflicting evidence. Further in a multicentric trial, the difference between the OPG versus CBCT group was not statistically significant due to the low incidence of IAN injuries. They have emphasized the need for more well-designed studies to reach a statistically significant conclusion by meta-analyses. Hence, this study aims to provide additional evidence. Methods It is a two-arm, parallel, diagnostic study design involving individuals between the ages of 18 and 50 years, requiring lower wisdom tooth removal that is closely approximated with the nerve. Eligible adults, based on the specified inclusion/exclusion criteria, will be recruited into the study; informed consent will be obtained; then assigned randomly to the OPG or CBCT group using a random computer-generated sequence. Extractions will be done under local anesthesia using a standard surgical protocol with odontectomy. Surgical variables will include the experience of the surgeon, amongst others. The outcome variables will be recorded using patient interviews (subjective) and objective examinations from day one up to six months after surgery. The primary outcome will comprise the number of patients reporting abnormal sensations post-surgery. Secondary outcomes will include objectively confirmed IAN injuries and permanent IAN injuries (>6 months). Results will be analyzed statistically to look for significance and possible risk factors associated with it. Results If a statistically significant result is obtained, then we can deliberately reduce CBCT referrals and reserve them only for high-risk cases, wherein the risk of IAN injury cannot be predicted by OPG alone. If the experience of the surgeon proves to be an important risk factor, then it can also help refer high-risk patients to surgeons with more experience. Conclusion If CBCT proves to be statistically superior to OPG in the prediction of nerve injury, then we will be able to avoid significant morbidity and improve the quality of life of such patients by either modifying the surgical steps or by choosing other conservative treatment modalities. Further, this may reduce unnecessary CBCT referrals, thus reducing radiation exposure, the cost to patients, and, in turn, national healthcare expenditure. Besides, CBCT is not available at all centers, so a lot of low-risk patients can be managed safely at primary health centers, thus reducing the urban patient load.

The effect of video-assisted learning on pre-operative knowledge and satisfaction for total knee arthroplasty surgery: a randomised-controlled study.

INTRODUCTION: Traditionally, surgical procedures are explained through consultations between the surgeon and the patient to ensure informed consent. Patient education enhances engagement and knowledge, aiding informed decision-making. This study aimed to assess the effect of an educational video on preoperative patient knowledge and satisfaction in the context of total knee arthroplasty (TKA) as an adjunct to the consent process. METHODS: A prospective randomized controlled study involving 100 patients in dedicated elective orthopedic units in UK-based hospitals was conducted. After consultation with a dedicated knee surgeon and a preoperative education day for TKA run by dedicated orthopedic nurse specialists, patients were randomized into one of two limbs (video vs no video) at a 1:1 ratio. The treatment group (video group) was shown a video about the principles and steps of the procedure, including the recovery time. Following this, a 10-point knowledge test was completed, and patients rated their satisfaction with the preoperative education on a scale of 0-10. RESULTS: Patients in the video limb group had a significantly greater mean knowledge score and greater satisfaction with preoperative education than patients who did not view the video. The video group (n = 49) had a mean knowledge score of 8.73 +/- 0.159 compared to 7.68 +/- 0.281 for the nonvideo limb (n = 50) (p < 0.05). The video group had a mean satisfaction score of 9.00 +/- 0.123 compared to 8.40 +/- 0.121 for the nonvideo limb group (p < 0.05). CONCLUSION: Video-assisted consent in total knee arthroplasty improves preoperative knowledge and patient satisfaction when used as an adjunct in the consent process. A simple, standardized video, either pre- or post-consultation could reinforce information that the patient receives in a simple effective manner, allowing for true informed consent.

Bilateral femoral shaft fractures in osteomalacia: A case report and literature review.

INTRODUCTION AND IMPORTANCE: When two non-traumatic femoral shaft fractures happen at the same time, they are usually not caused by high-energy trauma or medical conditions like osteomalacia caused by poor nutrition, long-term bisphosphonate medication use, or steroid use. Because this phenomenon is connected to inadequate bone mineralization and bone metabolism, it occurs when a bone is consistently under high stress. CASE PRESENTATION: A 40-year-old lady with a medical history of osteomalacia, including continuous vitamin D replacement therapy, showed up at the emergency room complaining of discomfort and swelling in her right thigh caused by a fall. During the emergency examination, X-rays showed a subtrochanteric fracture with a short oblique fracture line and a displaced oblique fracture in the right femoral shaft, but no fragmentation in the left femoral shaft. Osteomalacia caused the bilateral femoral shaft fracture in which the patient was identified as being displaced. We planned a surgical correction that included a closed reduction with intramedullary nailing and distal static screws on the right side, as well as intramedullary nailing followed by locking screw insertion on the left. Following the operation, the avoidance of bisphosphonate medications gained precedence. CLINICAL DISCUSSION: Patients of any age who come with bone pain, non-traumatic fractures, and muscle weakness should have their blood vitamin D, ALP levels, and BMD evaluated for osteomalacia. If a conventional X-ray shows normal, an MRI or bone scan of both hips is recommended to rule out any underlying fatigue fractures. Finding and treating the underlying cause of osteomalacia can help improve the prediction. CONCLUSION: Intramedullary nailing with screws is the most effective treatment for femoral shaft fractures. Improving patient outcomes relies on identifying and treating the underlying cause of osteomalacia. Given the patient's history and condition, avoiding bisphosphonate medicines following surgery was a primary priority in this case.

The Role of Nanomaterials in Diagnosis and Targeted Drug Delivery.

Nanomaterials owing to their small size imparts them with unique properties and they can also be designed and engineered according to the specific need. The use of nanoparticles (NPs) in medicine is particularly  revolutionary as it has opened new therapeutic avenues to diagnose, treat and manage diseases in an efficient and timely manner. The review article presents the biomedical applications of nanomaterials including bioimaging, magnetic hypothermia and photoablation therapy, with a particular focus on disease diagnosis and targeted drug delivery. Nanobiosensors are highly specific and can be delivered into cells to investigate important biomarkers. They are also used for targeted drug delivery and deliver theranostic agents to specific sites of interest. The review also explores the role of nano-based drug delivery systems for the management and treatment of nervous system disorders, tuberculosis and orthopaedics. The nano-capsulated drugs can be transported by blood to the targeted site for a sustained release over a prolonged period. Some other applications like their role in invasive surgery, photodynamic therapy and quantum dot imaging have also been explored. Despite that, the safety concerns related to nanomedicine should be comprehended as well as the biodistribution of NPs in the body and the mechanistic insight.

Complications and Revision Surgery in Orthopedics Focusing on Traumatology.

BACKGROUND: Orthopedic traumatology, a vital component of orthopedic surgery, poses significant challenges in managing complications and necessitating revision surgeries. These challenges impact clinical outcomes, healthcare economics, and patient well-being. OBJECTIVE: This study aimed to provide insights that informed clinical decision-making and improved patient outcomes by thoroughly examining the range of complications encountered in orthopedic traumatology. Specifically, the research focused on the indications, techniques, and outcomes of revision surgeries. METHODOLOGY: This retrospective cohort research looked at orthopedic traumatology complications and revision procedures over a thorough two-year period from March 2021 to March 2023 at Hayatabad Medical Complex in Peshawar, Pakistan. The following information was gathered from 316 patients receiving orthopedic surgery for traumatic injuries: demographics, kinds of trauma, surgical methods, complications, indications, methods, and results of revision surgery. For data analysis, chi-square tests and descriptive statistics were used, with the goal of finding patterns and correlations within the research population. RESULTS: The average age of the 316 patients was 42.5 years, and 64.76% of them were male (n = 192). The most frequent kind of trauma (n = 218; 69.01%) was fractures, which were mostly brought on by falls (n = 147; 46.52%). The most common surgical method (n = 138; 43.67%) was found to be internal fixation, which was followed by external fixation (n = 67; 21.20%). The most common complication (n = 78; 24.68%) was surgical site infection, which resulted in revision procedures mostly for infection (n = 68; 21.52%) and implant failure (n = 56; 17.72%). Debridement was the most often used revision approach (n = 95; 30.10%), and it was substantially correlated with surgical outcomes, such as increased function (31%) and full resolution (36%). CONCLUSION: This research emphasizes the need to maximize patient outcomes for improved well-being and highlights the crucial role that careful care plays in managing complications and revision operations in orthopedic traumatology.

Epidemiology of Colorectal Cancer in Saudi Arabia: A Review.

Colorectal cancer (CRC) is the second leading cause of cancer death in the world, originating from the glandular epithelial cells of the large intestine and the rectum. This article aims to review the epidemiology of CRC in Saudi Arabia, focusing on prevalence, incidence, risk factors, preventive measures, and outcomes. This narrative review utilized the PubMed database for data extraction, including freely accessible studies published in the last 15 years. Sixteen articles from different study designs were included, while awareness and non-English language studies were excluded. In 2020, the incidence and mortality rate of CRC in Saudi Arabia were 14.6% and 1.48% among all cancers, respectively. From 2006 to 2016, the number of colon cancer and rectal cancer cases increased by 8% and 7%, respectively. Risk factors for CRC in Saudi Arabia include low education level, unemployment, physical inactivity, excess weight, poor knowledge of foods rich in fiber, cigarette smoking, reduced serum vitamin D and calcium levels, and certain gene mutations. National guidelines in Saudi Arabia recommend CRC screening for all individuals above 45 years using colonoscopy, flexible sigmoidoscopy, or fecal occult blood test. The 10-year survival rate for CRC in Saudi Arabia is 44.6%. The overall 5-year survival rate for the Ministry of National Guard-Health Affairs is 52.0%. To lower the incidence and mortality of CRC, primary, secondary, and tertiary prevention are all very important. The most crucial aspect is to concentrate on primary prevention, which may involve raising public awareness of CRC risk factors and strategies for reducing or eliminating them.

Computation of differential and integral operators using M -polynomials of gold crystal.

Gold is generally considered a noble metal since it is inherently inert in its bulk state. However, gold demonstrates reactivity when it is in its ionic state. The inherent inertness of bulk gold has resulted in its widespread recognition as a vital raw material in various biomedical processes. The applications of these technologies include drug delivery microchips, dental prostheses, reconstructive surgery, culinary additives, and cardiovascular stents. Gold can also exist in molecules or ions, particularly gold ions, which facilitates the production of gold nanomaterials. In this paper, we have computed differential and integral operators by using the M -Polynomial of gold crystals and by utilizing this polynomial, we have also computed eleven topological indices like 1 s t Zagreb, 2 n d Zagreb, Hyper, Sigma, Second Modified, General Randic, General Reciprocal Randic, 3 r d Redefined Zagreb, Symmetric Division Degree, Harmonic, Inverse Sum indices for the structure of Gold crystal.

Left Atrial Strain as a Predictor of Early Anthracycline-Induced Chemotherapy-Related Cardiac Dysfunction: A Pilot Systematic Review and Meta-Analysis.

Background: Chemotherapy-related cardiac dysfunction (CTRCD) significantly affects patients undergoing anthracycline (AC) therapy, with a prevalence ranging from 2% to 20%. Reduced left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS) are prognostic parameters for CTRCD detection. Our study aimed to investigate the role of emerging parameters such as left atrial strain (LAS). Methods: We searched multiple databases for studies comparing LAS changes post-AC versus pre-AC therapy in patients with cancer. Primary outcomes included left atrial reservoir strain (LASr), left atrial conduit strain (LAScd), and left atrial contractile strain (LASct). RevMan (v5.4) was used to pool the standardized mean difference (SMD) under a random effects model, with p < 0.05 as the threshold for statistical significance. Results: In an analysis of 297 patients across five studies, AC therapy significantly lowered LASr (SMD = -0.34, 95% CI:-0.55, -0.14, I2 = 0%, p = 0.0009) and LAScd (SMD = -0.41, 95% CI: -0.59, -0.23, I2 = 0%, p < 0.00001) levels. Conversely, LASct demonstrated no significant change (SMD = 0.01, 95% CI: -0.21, 0.23, I2 = 9%, p = 0.95). AC therapy also significantly reduced LV GLS (SMD = -0.31, 95% CI: -0.51, -0.11, I2 = 0%, p = 0.003). While not statistically significant, LVEF decreased (SMD = -0.20, 95% CI: -0.42, 0.03, I2 = 0%, p = 0.09), and left atrial volume index trended higher (SMD = 0.07, 95% CI: -0.14, 0.27, I2 = 0%, p = 0.52) after AC therapy. Conclusions: AC treatment led to reduced LAS and LV GLS values, indicating its potential as an early CTRCD indicator. Larger trials are required to fully explore their clinical significance.

After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence.

BACKGROUND & AIMS: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS: Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSIONS: Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

A targetable secreted neural protein drives pancreatic cancer metastatic colonization and HIF1a nuclear retention.

Pancreatic ductal adenocarcinoma (PDAC) is an increasingly diagnosed cancer that kills 90% of afflicted patients, with most patients receiving palliative chemotherapy. We identified neuronal pentraxin 1 (NPTX1) as a cancer secreted protein that becomes over-expressed in human and murine PDAC cells during metastatic progression and identified adhesion molecule with Ig like domain 2 (AMIGO2) as its receptor. Molecular, genetic, biochemical and pharmacologic experiments revealed that secreted NPTX1 acts cell-autonomously on the AMIGO2 receptor to drive PDAC metastatic colonization of the liver-the primary site of PDAC metastasis. NPTX1-AMIGO2 signaling enhanced hypoxic growth and was critically required for hypoxia induced factor-1a (HIF1a) nuclear retention and function. NPTX1 is over-expressed in human PDAC tumors and upregulated in liver metastases. Therapeutic targeting of NPTX1 with a high-affinity monoclonal antibody substantially reduced PDAC liver metastatic colonization. We thus identify NPTX1-AMIGO2 as druggable critical upstream regulators of the HIF1a hypoxic response in PDAC.

89Zr-immunoPET-guided selection of a CD33xIL15 fusion protein optimized for antitumor immune cell activation and in vivo tumour retention in acute myeloid leukaemia.

PURPOSE: Immune cells are capable of eliminating leukemic cells, as evidenced by outcomes in hematopoietic cell transplantation (HCT). However, patients who fail induction therapy will not benefit from HCT due to their minimal residual disease (MRD) status. Thus, we aimed to develop an immunomodulatory agent to reduce MRD by activating immune effector cells in the presence of leukaemia cells via a novel fusion protein that chimerises two clinically tolerated biologics: a CD33 antibody and the IL15Ra/IL15 complex (CD33xIL15). METHODS: We generated a set of CD33xIL15 fusion protein constructs with varying configurations and identified those with the best in vitro AML-binding, T cell activation, and NK cell potentiation. Using 89Zr-immunoPET imaging we then evaluated the biodistribution and in vivo tumour retention of the most favourable CD33xIL15 constructs in an AML xenograft model. Ex vivo biodistribution studies were used to confirm the pharmacokinetics of the constructs. RESULTS: Two of the generated fusion proteins, CD33xIL15 (N72D) and CD33xIL15wt, demonstrated optimal in vitro behaviour and were further evaluated in vivo. These studies revealed that the CD33xIL15wt candidate was capable of being retained in the tumour for as long as its parental CD33 antibody, Lintuzumab (13.9 ± 3.1%ID/g vs 18.6 ± 1.1%ID/g at 120 h). CONCLUSION: This work demonstrates that CD33xIL15 fusion proteins are capable of targeting leukemic cells and stimulating local T cells in vitro and of concentrating in the tumour in AML xenografts. It also highlights the importance of 89Zr-immunoPET to guide the development and selection of tumour-targeted antibody-cytokine fusion proteins.

Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin.

Cutaneous T-cell lymphomas (CTC) are a heterogeneous group of T-cell lymphoproliferative malignancies of the skin with limited treatment options, increased resistance and remission. Metabolic reprogramming is vital in orchestrating the uncontrolled growth and proliferation of cancer cells. Importantly, deregulated signalling plays a significant role in metabolic reprogramming. Considering the crucial role of metabolic reprogramming in cancer-cell growth and proliferation, target identification and the development of novel and multi-targeting agents are imperative. The present study explores the underlying mechanisms and metabolic signalling pathways associated with Glabridin mediated anti-cancer actions in CTCL. Our results show that Glabridin significantly inhibits the growth of CTCL cells through induction of programmed cell death (PCD) such as apoptosis, autophagy and necrosis. Interestingly, results further show that Glabridin induces PCD in CTCL cells by targeting MAPK signalling pathways, particularly the activation of ERK. Further, Glabridin also sensitized CTCL cells to the anti-cancer drug, bortezomib. Importantly, LC-MS-based metabolomics analyses further showed that Glabridin targeted multiple metabolites and metabolic pathways intricately involved in cancer cell growth and proliferation in an ERK-dependent fashion. Overall, our findings revealed that Glabridin induces PCD and attenuates the expression of regulatory proteins and metabolites involved in orchestrating the uncontrolled proliferation of CTCL cells through ERK activation. Therefore, Glabridin possesses important features of an ideal anti-cancer agent.

Prevalence and Factor Associated with Anti-N-Methyl-D-Aspartate Receptor Encephalitis Among Patients with Medical Conditions: A Systematic Review and Meta-Analysis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune encephalitis due to immune production of anti-NMDAR antibodies against the NR1 subunit of the NMDA receptor which is present throughout the central nervous system. This condition had been reported to be prevalent in patients with certain medical conditions; however so far, there have been limited systematic reviews and meta-analyses on the prevalence and factors associated. OBJECTIVE: This study was to determine the prevalence and factors associated with anti-NMDAR encephalitis among affected patients. MATERIAL AND METHODS: The protocol of this study has been registered (2019: CRD42019142002) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary outcome was the incidence or prevalence of anti-NMDAR encephalitis and secondary outcomes were factors associated with anti-NMDAR encephalitis. RESULTS: There were 11 studies and a total of 873 million patients taken from high-risk populations across 11 countries that were included in the primary analysis. The overall pooled prevalence of anti-NMDAR encephalitis among patients with medical conditions was 7.0% (95% CI = 4.4, 9.6). Those with first episode of psychosis or schizophrenia were at a higher risk of developing anti-NMDAR encephalitis with an odds ratio of 5.976 (95% CI = 1.122, 31.825). CONCLUSION: We found that almost one-tenth of patients with medical conditions had anti-NMDAR encephalitis; particularly those with first episode of psychosis or schizophrenia were among the high-risk medical conditions.

Targeting of S-phase kinase associated protein 2 stabilized tumor suppressors leading to apoptotic cell death in squamous skin cancer cells.

S-phase kinase-associated protein 2 (Skp2) is an F-box protein overexpressed in human cancers and linked with poor prognosis. It triggers cancer pathogenesis, including stemness and drug resistance. In this study, we have explored the potential role of Skp2 targeting in restoring the expression of tumor suppressors in human cutaneous squamous cell carcinoma (cSCC) cells. Our results showed that genetic and pharmacological Skp2 targeting markedly suppressed cSCC cell proliferation, colony growth, spheroid formation, and enhanced sensitization to chemotherapeutic drugs. Further, western blot results demonstrated restoration of tumor suppressor (KLF4) and CDKI (p21) and suppression of vimentin and survivin in Skp2-knocked-down cSCC cells. Importantly, we also explored that Skp2 targeting potentiates apoptosis of cSCC cells through MAPK signaling. Moreover, co-targeting of Skp2 and PI3K/AKT resulted in increased cancer cell death. Interestingly, curcumin, a well-known naturally derived anticancer agent, also inhibits Skp2 expression with concomitant CDKI upregulation. In line, curcumin suppressed cSCC cell growth through ROS-mediated apoptosis, while the use of N-acetyl cysteine (NAC) reversed curcumin-induced cell death. Curcumin treatment also sensitized cSCC cells to conventional anticancer drugs, such as cisplatin and doxorubicin. Altogether, these data suggest that Skp2 targeting restores the functioning of tumor suppressors, inhibits the expression of genes associated with cell proliferation and stemness, and sensitizes cancer cells to anticancer drugs. Thus, genetic, and pharmacological ablation of Skp2 can be an important strategy for attenuating cancer pathogenesis and associated complications in skin squamous cell carcinoma.

A Novel Coated Suture Displays Antimicrobial Activity Without Compromising Structural Properties.

BACKGROUND: Treated or coated sutures promise to prevent contamination of wounds. PURPOSE: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties. STUDY DESIGN, SETTING, SAMPLE: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded. PREDICTOR VARIABLE: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures. MAIN OUTCOME VARIABLE(S): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells. COVARIATES: Not applicable. ANALYSES: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05). RESULTS: Fourier transform infrared spectroscopy peak at 1490 cm-1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers. CONCLUSION AND RELEVANCE: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture.

Non-Invasive Multi-Gas Detection Enabled by Cu-CuO/PEDOT Microneedle Sensor.

Metal-oxide-based gas sensors are extensively utilized across various domains due to their cost-effectiveness, facile fabrication, and compatibility with microelectronic technologies. The copper (Cu)-based multifunctional polymer-enhanced sensor (CuMPES) represents a notably tailored design for non-invasive environmental monitoring, particularly for detecting diverse gases with a low concentration. In this investigation, the Cu-CuO/PEDOT nanocomposite was synthesized via a straightforward chemical oxidation and vapor-phase polymerization. Comprehensive characterizations employing X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro Raman elucidated the composition, morphology, and crystal structure of this nanocomposite. Gas-sensing assessments of this CuMPES based on Cu-CuO/PEDOT revealed that the response current of the microneedle-type CuMPES surpassed that of the pure Cu microsensor by nearly threefold. The electrical conductivity and surface reactivity are enhanced by poly (3,4-ethylenedioxythiophene) (PEDOT) polymerized on the CuO-coated surface, resulting in an enhanced sensor performance with an ultra-fast response/recovery of 0.3/0.5 s.