The crosstalk between neuropilin-1 and tumor necrosis factor-α in endothelial cells.

Tumor necrosis factor-α (TNFα) is a master cytokine which induces expression of chemokines and adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in endothelial cells to initiate the vascular inflammatory response. In this study, we identified neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, as a modulator of TNFα-induced inflammatory response of endothelial cells. NRP1 shRNA expression suppressed TNFα-stimulated leukocyte adhesion and expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVECs). Likewise, it reduced TNFα-induced phosphorylation of MAPK p38 but did not significantly affect other TNF-induced signaling pathways, such as the classical NFκB and the AKT pathway. Immunofluorescent staining demonstrated co-localization of NRP1 with the two receptors of TNF, TNFR1 and TNFR2. Co-immunoprecipitation further confirmed that NRP1 was in the same protein complex or membrane compartment as TNFR1 and TNFR2, respectively. Modulation of NRP1 expression, however, neither affected TNFR levels in the cell membrane nor the receptor binding affinities of TNFα. Although a direct interface between NRP1 and TNFα/TNFR1 appeared possible from a protein docking model, a direct interaction was not supported by binding assays in cell-free microplates and cultured cells. Furthermore, TNFα was shown to downregulate NRP1 in a time-dependent manner through TNFR1-NFκB pathway in HUVECs. Taken together, our study reveals a novel reciprocal crosstalk between NRP1 and TNFα in vascular endothelial cells.

Cysts of the ligamentum flavum are often linked to ischemic conditions: A morphological study.

"Cysts of the ligamentum flavum (cysts-LF)" is the term for non-neoplastic cystic lesion involving LF. The aim of the present study was to elucidate the histopathological characteristics and pathogenesis of "cysts-LF". Herein, we defined cysts-LF as spinal cysts containing degenerative LF components. From archival cases, we investigated 18 symptomatic cysts-LF surgically removed from 18 patients (13 males and five females; median age 68.5 years [range, 42-86 years]). The elastic fibers of LF components in the wall were separated and/or torn, and cyst walls were accompanied by chondroid metaplasia (17 cases), myxoid changes (13 cases), ossification (11 cases), amyloid deposits (14 cases), hemosiderosis (six cases), granular/smudgy calcification (four cases), synovial cell linings (three cases), and severe inflammatory infiltrates (one case). These histologic features of our cysts-LF were shared by previously reported "cysts-LF." Fourteen cysts-LF demonstrated vascular stenosis/occlusion, and eight showed thick hyalinized vessels, suggesting local circulatory insufficiency. Eight cases (44%) exhibited lipomembranous fat necrosis, accompanied by hyalinized vascular changes (p = 0.003). Ischemic conditions were observed in nearly half of the present cysts-LF, and may be one of the main contributing factors for the formation of cysts-LF, via degeneration and cystic changes in the LF.

Mid-term survivorship and clinical results of cementless total hip arthroplasty for steroid-induced avascular necrosis.

OBJECTIVE: The purpose of the present study was to evaluate the mid-term implant survivorship, modes of failure, radiographic results, and clinical outcomes of current cementless total hip arthroplasty (THA) treatment designs for steroid-induced avascular necrosis (AVN). METHODS: A time span of 5 years between January 2012 and November 2017 was scanned to accommodate 5 years of follow-up and a total of 15 patients (18 hips), who had undergone implantation of ultra-high molecular weight polyethylene (UHMWPE) and newly designed other head and liner components, were included in the study. Only patients operated for steroid-induced AVN were included in the study. Patients with alcohol-induced, idiopathic, and traumatic AVN were excluded from the study. The primary outcomes were the assessments of Harris Hip Score (HHS) and the presence of loosening, osteolysis, polyethylene wear or a reoperation (with or without revision of components). The fixation of cementless femoral components was assessed according to Engh criteria. RESULTS: The study group consisted of 18 hips from 15 patients. The mean age was 47.6±8.1 (29-55) years. A cementless femoral stem and acetabular cup were used for all patients. Septic loosening was detected in all components of one patient (5.6%). The mean HHS score was 83.3±7.2 (60-92) for all patients. Of the 18 hips, 83% (15 hips), 5.6% (1 hip), 5.6% (1 hip), and 5.6% (1 hip) had good, poor, fair, and excellent HHS scores. Ceramic or polyethylene liner wear was not detected in any of the patients. The Engh Grading Scale revealed a "bone ingrowth" in 16 (89%) hips, "suspected in-growth" in 1 (5.6%) hip and "suboptimum but stable" femoral fixation in a patient with septic loosening (5.6%) just before revision surgery. There was no significant correlation between femoral stem design and Engh score (p=0.842). CONCLUSION: Modern total hip arthroplasty systems, including ceramic on ceramic or ceramic on polyethylene headliner options with cementless femoral stem, offer promising mid-term survivorship and positive clinical outcomes for steroid-induced AVN treatment. However, studies including long-term follow-ups with larger sample size are needed to obtain more precise data.

Rare Extrapulmonary Tuberculosis: Covert symptoms and Diagnostic Dilemma.

Background: Pulmonary tuberculosis may result in haematogenous and lymphatic extension in case of failure of early detection, or immunocompromised status, leading to extrapulmonary tuberculosis. Rare sites of extrapulmonary tuberculosis include the gastrointestinal tract, musculoskeletal system, genital tract, middle ear and pericardium. Histopathological findings of macro-confluent granuloma with or without caseous necrosis, along with detection of acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining, and GeneXpert for detection of Mycobacterium tuberculosis DNA, are key in establishing a diagnosis of tuberculosis. Methodology: Biopsy-proven extrapulmonary granulomatous lesions were included in this study. Histopathological evaluation of all extrapulmonary biopsy specimens sent to the Department of Pathology were done for the presence of granuloma and necrosis, and ZN staining for AFB was done in all the cases of granulomatous lesions with or without the presence of necrosis. The same cases, with biopsy specimens sent in normal saline, were re-evaluated in a molecular laboratory with the help of GeneXpert MTB to detect the DNA of Mycobacterium tuberculosis. All biopsy specimens from extrapulmonary sites which were sent to the Department of Pathology were used for DNA extraction. Results: Out of the 10 cases of extrapulmonary granulomatous lesions, 8 showed caseous necrosis on microscopy, and 7 showed the presence of acid-fast bacilli on Ziehl-Neelsen staining. GeneXpert detected DNA of Mycobacterium tuberculosis in 9 cases. Conclusion: Extrapulmonary tuberculosis rarely occurs as primary, and mostly spreads from lung parenchyma via a haematogenous route. Tuberculosis of the gastrointestinal tract, peritoneum, lymph nodes, and solid viscera are together termed abdominal tuberculosis. Entities like tuberculosis of the pericardium and ear are extremely rare. Extrapulmonary tuberculosis should be a differential in cases of chronic non-responding cases with diagnostic dilemmas. To avoid diagnostic delay, in cases of high suspicion, one should go for biopsy along with ZN staining for diagnostic confirmation as this is cost-effective, followed by GeneXpert for Mycobacterium tuberculosis in highly suspected cases with absent caseous necrosis and negative ZN staining.

Comparison of Intraoperative and Postoperative Outcomes With Skin Flaps Raised Using Either Harmonic Scalpels or Electrocautery During Modified Radical Mastectomy.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Hence, its treatment has become our utmost priority in developing countries like India. Modified radical mastectomy (MRM) has traditionally been used as the standard of care for early-stage invasive breast carcinoma and still is the most commonly used surgical treatment for carcinoma breast. AIM: The study compared the incidence of intraoperative and postoperative outcomes with skin flaps raised using a harmonic scalpel versus those raised using electrocautery. METHODS: Sixty women with biopsy-proven breast cancer who had to undergo MRM were randomly assigned to undergo skin flap raising during mastectomy by using electrocautery or harmonic scalpel. Thirty patients had surgery with electrocautery (Group 1) and 30 with a harmonic scalpel (Group 2) by the same surgical team. RESULTS: The mean operative time was significantly longer with harmonic scalpel when compared to that with electrocautery (140.67 ± 28.55 vs. 122.00 ± 19.16 mins, P =0.004). The amount of intraoperative blood loss (178.33 ± 21.06 vs 138.50 ± 28.53 mL P = 0.001) was less in the group operated with the harmonic scalpel, which was statistically significant. There was no significant difference between the groups regarding total drainage content (310.83 ± 88.93 vs 298.20 ± 127.87 mL, P = 0.659), drain duration (6.83 ± 0.75 vs 7.43 ± 2.27 days, p=0.174), seroma (3.3% vs. 0%) wound infection (3.3% vs 0%), flap necrosis (16.7% vs. 3.3%, P = 0.195), duration of hospital stays (8.57 ± 0.77 vs 8.43 ± 1.61 days, p=0.684). CONCLUSION: Harmonic scalpels have a few advantages over electrocautery, but are not cost-effective.

A nationwide study of Stevens-Johnson syndrome and toxic epidermal necrolysis in hospitalized pregnant women in the United States, 2009-2020.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rarely described in the pregnant population, and knowledge of their impact on the mother/fetus is limited. Objective: To describe SJS/TEN in pregnant women and to investigate the risk factors for developing SJS/TEN in pregnancy. Methods: We utilized hospitalization data from the 2009-2020 National Inpatient Sample. Pregnancy hospitalizations and SJS/TEN involvement were identified by ICD-9/10 codes and analyzed by chi-square and logistic regression. Results: We identified 650 pregnancies complicated by SJS/TEN requiring hospitalization. The median age was 28 years, and most were non-Hispanic White (55.2%). There were ≤10 cases associated with mortality. Most SJS/TEN cases (73.9%) occurred during the third trimester. HIV infection (OR = 9.49; P = .030), herpes simplex virus infection (OR = 2.49; P = .021), genitourinary tract infections (OR = 3.80; P < .001), malignant neoplasm (OR = 8.67; P = .031), and lupus erythematosus (OR = 41.94; P < .001) were associated with increased odds of developing SJS/TEN in pregnancy. Rates of preterm births were higher in the SJS/TEN cohort, 16.9% versus 8.2% (P < .001). Rates of pre-eclampsia, stillbirths, and post-term births were similar between the SJS/TEN versus non-SJS/TEN pregnancy cohorts. Limitations: Limited cohort size. Conclusions: SJS/TEN in pregnancy appears to be mild and is associated with favorable maternal-fetal outcomes, except for increased preterm birth.

The role of TNF-α and il-6 SNP in polycystic ovary syndrome susceptibility.

OBJECTIVE: Aim: To shed the light on the impact of TNF-α 1031 T/C (rs-1800629) and IL-6 174 G/C (rs1800795) polymorphism with disease susceptibility and development. PATIENTS AND METHODS: Materials and Methods: A case-control study has been established based on 50 women with confirmed diagnosed polycystic ovarian syndrome, and 50 healthy controls. Allele specific PCR have been done in order to study SNP of TNF-alpha and IL-6 in both groups. RESULTS: Result: The findings of the present investigation indicated that there was a signif i cant dif f erence in the frequency distribution of TNF-alpha 1031 T/C SNP according to genotype between patients and controls group p = 0.02. In addition, there is a high significant difference in the frequencies of distribution of alleles (T/C) between patients and control group p = 0.001. There was a signif i cant dif f erence in the frequency distribution of IL-6 174 G/C between patients and controls group p = 0.026. In addition, there is a signif i cant dif f erence in the frequencies of distribution of participants according to allele (G/C) between patients and control group p = 0.047. Genotype GC was significantly lower in patients' group and genotype GG was high significant in patients' group in comparison with a control group and the differences were significant, p = 0.024 and 0.006, respectively. CONCLUSION: Conclusions: The present study concluded that IL-6 174 G/C, (rs:1800795) single nucleotide polymorphism (SNP) and TNF-alpha 1031 T/C (rs-1800629) were associated with PCOS susceptibility, and GG genotype in IL-6 and C allele in TNF are considered as risk factor.

Early detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis.

OBJECTIVES: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. METHODS: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. RESULTS: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. CONCLUSIONS: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

Epiploic Appendagitis Unveiled: A Case of Misleading Abdominal Pain With Omental Fat Necrosis.

Epiploic appendagitis is a benign inflammatory condition of the epiploic appendages, small fat-filled structures attached to the colon. Misdiagnosed frequently as more serious conditions like appendicitis or diverticulitis, it usually resolves with minimal treatment. This case report aims to emphasize the importance of recognizing epiploic appendagitis in differential diagnoses, highlighting the role of accurate imaging and surgical intervention in managing unusual presentations. We report a case involving a 27-year-old male who presented with acute, severe pain in the left iliac fossa. Initial assessments showed stable vital signs and negative virology screenings. Ultrasound imaging did not reveal any abnormalities in the abdominal organs but noted multiple gas-filled bowel loops and a 48 x 22 mm collection in the left iliac region. A CT scan with IV contrast further identified a 35 x 26 mm area of fat stranding in the left iliac fossa, indicative of epiploic appendagitis, and a 1 cm area of omental fat necrosis near the hepatic flexure. Persistent symptoms led to a diagnostic laparoscopy, which confirmed and treated gangrenous appendices epiploica. The patient's postoperative recovery was uneventful, highlighting the effectiveness of surgical management. This case underscores the necessity for heightened awareness and diagnostic precision when encountering patients with acute abdominal pain that does not match common ailments. Early and accurate imaging, followed by timely surgical intervention if needed, can significantly improve outcomes by preventing complications from misdiagnosis or delayed treatment.

Investigating the Roles of Coat Protein and Triple Gene Block Proteins of Potato Mop-Top Virus Using a Heterologous Expression System.

Potato mop-top virus (PMTV) is an emerging viral pathogen that causes tuber necrosis in potatoes. PMTV is composed of three single-stranded RNA segments: RNA1 encodes RNA-dependent RNA polymerase, RNA2 contains the coat protein (CP), and RNA3 harbors a triple gene block (TGB 1, TGB2, and TGB3). CP plays a role in viral transmission, while TGB is known to facilitate cell-to-cell and long-distance systemic movement. The role of CP in symptom development, specifically in the presence of TGB genes, was investigated using potato virus X (PVX) as a delivery vehicle to express PMTV genes in the model plant Nicotiana benthamiana. Plants expressing individual genes showed mild symptoms that included leaf curling and crumpling. Interestingly, symptom severity varied among plants infected with three different combinations: CP with TGB1, CP with TGB2, and CP with TGB3. Notably, the combination of CP and TGB3 induced a hypersensitive response, accompanied by stunted growth and downward curling and crumpling. These results suggest the potential role of TGB co-expressed with CP in symptom development during PMTV infection. Additionally, this study demonstrates the use of the PVX-based expression system as a valuable platform for assessing the role of unknown genes in viral pathogenicity.

Paradoxical Psoriasis in Patients Receiving Therapy with Tumor Necrosis Factor Inhibitors: Potential Pathogenic Mechanisms and the Role of Genetic Factors.

TNF inhibitors (TNFi) have revolutionized the therapeutic management of various chronic immune-mediated inflammatory diseases. Despite their known benefits, these therapies are related to paradoxical adverse effects (PAEs), including paradoxical psoriasis (PP). Although the underlying mechanism remains somewhat unclear, some theories suggest that genetic factors, particularly certain single-nucleotide polymorphisms (SNPs), may play an important role. The present review aimed to research and analyze recent findings regarding the pathomechanisms involved in the appearance of PP and the association between various genetic factors and PP in individuals treated with TNFi. We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.

Antioxidant and antiproliferative activity of enzymatic hydrolysates from red tilapia (Oreochromis spp.) viscera.

The antioxidant and antiproliferative activity of red tilapia (Oreochromis spp.) viscera hydrolysates (RTVH) was evaluated. For that, the hydrolysates was applied to three cancer cell lines (HepG2, Huh7 and SW480) and the control (CCD-18Co). Finally, the line on which the hydrolysate had the greatest effect (SW480) and the control (CCD-18Co) were subjected to the ApoTox-Glo Triplex Assay to determine apoptosis, toxicity, and cell viability. The result showed that hydrolysate had a dose-dependent cytotoxic effect selective on the three cancer cell lines, compared to the control cells. There is a relationship between the antioxidant capacity of RTVHs and their antiproliferative capacity on cancer cells evaluated, which achieved cell viability by action of RTVH of 34.68 and 41.58 and 25.41 %, to HepG2, Huh7 and SW480, respectively. The action of RTVH on cancer cell line SW480 is not due to the induction of apoptosis but to the rupture of the cell membrane.

Analysis of influential factors on surgical outcomes in pediatric femur neck fractures: a single-institution retrospective study.

AIM: This retrospective study aimed to evaluate surgical outcomes and identify influential factors in pediatric femoral neck fractures. MATERIALS AND METHODS: A total of 25 hips from 23 pediatric patients who underwent surgical intervention for femoral neck fractures were included. Data encompassing patient demographics, fracture types, surgical techniques, complications, and follow-up outcomes were analyzed retrospectively. Factors such as fracture displacement, timing of surgery, fixation methods, and reduction quality were assessed concerning postoperative complications. RESULTS: Falling from a height accounted for 48% of the trauma mechanisms, and avascular necrosis (AVN) was the most prevalent complication (4 hips). Although fracture displacement, bad reduction quality, and delayed surgery were more common among complicated cases, statistical significance was not attained. The study noted an association between presence of avascular necrosis and worse clinical results(rho: 0.428, p: 0.05, CI: 95%). CONCLUSION: Surgical treatment yielded favorable clinical outcomes; however, limitations due to the study's retrospective design, limited sample size, and single-center approach underscore the necessity for larger multicenter studies. Our findings emphasize the need for comprehensive investigations to better understand and manage pediatric femoral neck fractures, especially regarding factors influencing AVN and long-term outcomes.

The role of TNF-α as a potential marker for acute cutaneous lupus erythematosus in patients with systemic lupus erythematosus.

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE-diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor-alpha (TNF-α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF-α. Additionally, both TNF-α and ACLE are positively correlated with disease activity. TNF-α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate-to-severe disease activity.

Paracetamol overdose causing acute kidney injury without hepatotoxicity: a case report.

BACKGROUND: Paracetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen. CASE PRESENTATION: We present a case of acute kidney injury without hepatotoxicity in paracetamol overdose. A 15-year-old girl was admitted 48 h after she had taken 10 g of paracetamol. She was complaining of abdominal pain and vomiting. Her blood level of creatinine was 1.20 mg/dL on admission, with a peak at 3.67 mg/dL 3 days later. The liver blood tests and blood paracetamol level were negative. She did not receive N-acetyl cysteine and was treated with intravenous fluid (crystalloid). The ultrasonography of the kidneys was normal. Her renal function returned almost to baseline 7 days after admission. It was concluded that the diagnosis was an acute kidney injury caused by acute tubular necrosis due to paracetamol overdose. CONCLUSION: This case shows that nephrotoxicity can occur without hepatotoxicity in paracetamol overdose.

Comparative evaluation of thermal impact of 980nm diode laser on soft tissue using irrigation and non-irrigation systems: A histomorphometric study.

Background: Diode laser is one of the most captivating technologies in dental practice. In periodontics, when used at appropriate settings, it possesses the best properties for selective surgical and nonsurgical procedures such as subgingival calculus removal without a thermal change of the root surface, and also provides tissue surface sterilization. However, lasers always produce a certain amount of thermal damage to the soft tissues. Therefore, this study aimed to comparatively evaluate the thermal impact of 980-nm diode laser incisions, when used with irrigation versus nonirrigation systems. Materials and Methods: The study was conducted on 24 gingival tissue samples obtained from the goat's mandible and maxilla. The samples were divided into two groups of 12 samples each, and laser incisions were given in 4 power settings, using 980-nm diode laser in super short pulse mode, with and without saline irrigation. Martius Scarlet Blue staining technique was used to prepare the histological slides. Then, slides were examined under a research microscope (Olympus CX 21), and the pictures of the slides were taken by mounting the camera onto the microscope mobile mount. The microscopic images hence obtained were analyzed for the depth and width of the incisions, area of carbonization, necrosis, and reversible damage, using the Digimizer image analysis software. Results: The results of this study demonstrated that the mean incision depth was higher (592.49 ± 180.97, P < 0.05), with less carbonization (25.52 ± 29.21, P = 0.00) and less necrosis (311.63 ± 156.441, P < 0.05) in the laser incisions with irrigation, as compared to the laser incisions given without irrigation system. Conclusion: Within the limitations of this study, it can be concluded that using an irrigation system causes less collateral damage while maintaining the incising efficiency of the diode laser. Further studies with a higher sample size, controlled irrigation systems, and incision techniques are needed to evaluate the efficiency of diode lasers for the clinical explanation of the results.

Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period.

Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system's role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.

The Use of Apparent Diffusion Coefficient Values for Differentiating Bevacizumab-Related Cytotoxicity from Tumor Recurrence and Radiation Necrosis in Glioblastoma.

OBJECTIVES: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response. METHODS: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance. RESULTS: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups (p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis. CONCLUSION: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.

The role of TNF-α in osteoporosis, bone repair and inflammatory bone diseases: A review.

Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine synthesised primarily by mononuclear cells; it has a potent pro-inflammatory effect, playing a crucial role in metabolic, immune, and inflammatory diseases. This cytokine has been studied in various biological systems. In bone tissue, TNF-α plays an integral role in skeletal disorders such as osteoporosis, fracture repair and rheumatoid arthritis through its involvement in regulating the balance between osteoblasts and osteoclasts, mediating inflammatory responses, promoting angiogenesis and exacerbating synovial proliferation. The biological effect TNF-α exerts in this context is determined by a combination of the signalling pathway it activates, the type of receptor it binds, and the concentration and duration of exposure. This review summarises the participation and pathophysiological role of TNF-α in osteoporosis, bone damage repair, chronic immunoinflammatory bone disease and spinal cord injury, and discusses its main mechanisms.

Development of a hepatic cryoinjury model to study liver regeneration.

The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. Following this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma with an individual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.