Complications following surgical treatment of ankle fractures in the elderly: can they be avoided?

Background Following surgical treatment of ankle fractures, geriatric patients face high complication rates (CR) in literature. Commonly used diagnostic and treatment algorithms fail to consider requirements of ageing patients which increases the risk of postoperative complications. Objective Present study critically evaluated surgical management of ankle fractures in patients over 65 years old, with focus on identifying modifiable risk factors and effective comorbidity management strategies. Methods We conducted a retrospective single-center study on patients who underwent surgical treatment of an ankle fracture. Based on their age, participants were divided into non-geriatric patients (NGP<65y) and geriatric patients (GP≥65y). We analyzed overall CR and number of minor and major complications in relation to timing of surgery, biological sex, injury pattern, osteosynthesis, pre-existing medical conditions, and postoperative care. Results 402 patients were included. GP encountered significantly higher overall (p<0.001), minor (p<0.001) and major (p=0.003) complications. They presented more complex, displaced and open fractures. Predominant factor contributing to higher CR in NGP and markedly in GP was concomitant diseases, presenting a strong OR of 19,290 (p<0.001) and 17,022 (p<0.001). Delaying surgery and managing comorbidities preoperatively had a favorable impact. Conclusion We revealed a high significant correlation between pre-existing medical conditions and postoperative results. To ascertain viability of delayed surgery in facilitating additional diagnostics and treatment of comorbidities, further comparative trials with a larger cohort are imperative.

Pure mucinous adenocarcinoma of the breast with the rare lymphoplasmacytic infiltration: A case report with review of literature.

Key Clinical Message: A unique ER/PR-positive mucinous adenocarcinoma of breast but CK7/CK20 negativity. A rare finding of Lymphoplasmacytic Infiltration is noted. Successful treatment included modified radical mastectomy and tamoxifen-based therapy, leads to remission. Abstract: Mucinous carcinoma, which is characterized by the presence of abundant extracellular mucin, is a rare and distinctive subtype of invasive breast cancer. This subtype accounts for less than 5% of all invasive breast cancers, with pure mucinous carcinoma representing only around 2%. It is most commonly found in older patients, typically in the sixth to early eighth decade of life. We present the case of a 55-year-old female with a 15-year history of a painless, gradually enlarging palpable lump on her left breast. Upon examination, a 5 × 5 cm lump with well-defined margins and a hard consistency was found in the lower outer quadrant of the left breast. Histopathological examination confirmed a diagnosis of Mucinous Adenocarcinoma of the Left Breast. The patient underwent modified radical mastectomy and received adjuvant endocrine therapy with tamoxifen due to hormone receptor-positive status. Mucinous carcinoma of the breast is a unique entity with specific histological features including the presence of extracellular mucin pools. Immunohistochemical staining is crucial for determining hormone receptor status, which can guide treatment decisions. Although surgical intervention is the primary approach, the extent of surgery may vary, ranging from lumpectomy to mastectomy. Adjuvant therapies such as chemotherapy and radiotherapy may also be considered based on individual cases. This case underscores the importance of a multidisciplinary approach in managing rare subtypes of breast cancer, such as mucinous carcinoma. Accurate diagnosis, appropriate surgical intervention, adjuvant therapy, and long-term follow-up are critical components of treatment.

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images.

IMPLICATIONS: Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.

Distinct mesenchymal cell states mediate prostate cancer progression.

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.

Anticoagulant Prescribing Patterns in New-Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. METHODS: Administrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. RESULTS: A total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. CONCLUSIONS: A minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient's risk of stroke with the increased risk of bleeding, particularly in the postoperative period.

Synthesis and molecular docking simulation of new benzimidazole-thiazole hybrids as cholinesterase inhibitors.

Dementia is a cognitive disturbance that is generally correlated with central nervous system diseases, especially Alzheimer's disease. The limited number of medications available is insufficient to improve the lifestyle of the patients suffering from this disease. Thus, new benzimidazole-thiazole hybrids (3-10) were designed and synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory agents. The in vitro evaluation displayed that the derivatives 4b, 4d, 5b, 6a, 7a, and 8b demonstrated dual inhibitory efficiency against both AChE with IC50 ranging from 4.55 to 8.62 µM and BChE with IC50 ranging from 3.50 to 8.32 µM. By analyzing the Lineweaver-Burk plot, an uncompetitive form of inhibition was determined for the highly active compound 4d, revealing its inhibition type. The human telomerase reverse transcriptase-immortalized retinal pigment epithelial cell line was used to ensure the safety of the most potent cholinesterase inhibitors. Furthermore, compounds 4b, 4d, 5b, 6a, 7a, and 8b were evaluated for their neuroprotective and antioxidant properties, as well as their ability to suppress COX-2. The results demonstrated that compounds 4d, 5b, and 8b presented significant neuroprotection efficiency against H2 O2 -induced damage in SH-SY5Y cells with % cell viability of 67.42 ± 7.90%, 62.51 ± 6.71%, and 72.61 ± 8.10%, respectively, while the tested candidates did not reveal significant antioxidant activity. Otherwise, compounds 4b, 6a, 7a, and 8b displayed outstanding COX-2 inhibition effects with IC50 ranging from 0.050 to 0.080 µM relative to celecoxib (IC50 = 0.050 µM). In addition, molecular docking was carried out for the potent benzimidazole-thiazole hybrids with the active sites of both AChE (PDB ID: 4EY7) and BChE (PDB code: 1P0P). The tested candidates fit well in the active sites of both portions, with docking scores ranging from -8.65 to -6.64 kcal/mol (for AChE) and -8.71 to -7.73 kcal/mol (for BChE). In silico results show that the synthesized benzimidazole-thiazole hybrids have good physicochemical and pharmacokinetic properties with no Lipinski rule violations. The preceding results exhibited that compound 4d could be used as a new template for developing more significant cholinesterase inhibitors in the future.

Can Perioperative Antibiotic Choice Impact Rates of Infectious Complications After Percutaneous Nephrolithotomy? A Single-Blind, Prospective Randomized Trial.

Objective: National guidelines recommend periprocedural antibiotics before percutaneous nephrolithotomy (PCNL), yet it is not clear which is superior. We conducted a randomized trial to compare two guideline-recommended antibiotics: ciprofloxacin (cipro) vs cefazolin, on PCNL outcomes, focusing on the development of systemic inflammatory response syndrome (SIRS) criteria. Methods: Adult patients who were not considered high risk for surgical or infectious complications and undergoing PCNL were randomized to receive either cipro or cefazolin perioperatively. All had negative preoperative urine cultures. Demographic and perioperative data were collected, including SIRS criteria, intraoperative urine culture, duration of hospitalization, and need for intensive care. SIRS is defined by ≥2 of the following: body temperature <96.8°F or >100.4°F, heart rate >90 bpm, respiratory rate >20 per minute, and white blood cell count <4000 or >12,000 cells/mm3. Results: One hundred forty-seven patients were enrolled and randomized (79 cefazolin and 68 cipro). All preoperative characteristics were similar (p > 0.05), except for mean age, which was higher in the cipro group (64 vs 57 years, p = 0.03). Intra- and postoperative findings were similar, with no difference between groups (p > 0.05), except a longer mean hospital stay in the cefazolin group (2 hours longer, p = 0.02). There was no difference between SIRS episodes in both univariate and multivariate analyses. Conclusions: Despite the relatively broader coverage for urinary tract pathogens with ciprofloxacin, this prospective randomized trial did not show superiority over cefazolin. Our findings therefore support two appropriate options for perioperative antibiotic prophylaxis in patients undergoing PCNL who are nonhigh risk for infectious complications.

Notch-based gene signature for predicting the response to neoadjuvant chemotherapy in triple-negative breast cancer.

BACKGROUND: While the efficacy of neoadjuvant chemotherapy (NACT) in treating triple-negative breast cancer (TNBC) is generally accepted, not all patients derive benefit from this preoperative treatment. Presently, there are no validated biomarkers to predict the NACT response, and previous attempts to develop predictive classifiers based on gene expression data have not demonstrated clinical utility. However, predictive models incorporating biological constraints have shown increased robustness and improved performance compared to agnostic classifiers. METHODS: We used the preoperative transcriptomic profiles from 298 patients with TNBC to train and test a rank-based classifier, k-top scoring pairs, to predict whether the patient will have pathological complete response (pCR) or residual disease (RD) following NACT. To reduce overfitting and enhance the signature's interpretability, we constrained the training process to genes involved in the Notch signaling pathway. Subsequently, we evaluated the signature performance on two independent cohorts with 75 and 71 patients. Finally, we assessed the prognostic value of the signature by examining its association with relapse-free survival (RFS) using Kaplan‒Meier (KM) survival estimates and a multivariate Cox proportional hazards model. RESULTS: The final signature consists of five gene pairs, whose relative ordering can be predictive of the NACT response. The signature has a robust performance at predicting pCR in TNBC patients with an area under the ROC curve (AUC) of 0.76 and 0.85 in the first and second testing cohorts, respectively, outperforming other gene signatures developed for the same purpose. Additionally, the signature was significantly associated with RFS in an independent TNBC patient cohort even after adjusting for T stage, patient age at the time of diagnosis, type of breast surgery, and menopausal status. CONCLUSION: We introduce a robust gene signature to predict pathological complete response (pCR) in patients with TNBC. This signature applies easily interpretable, rank-based decision rules to genes regulated by the Notch signaling pathway, a known determinant in breast cancer chemoresistance. The robust predictive and prognostic performance of the signature make it a strong candidate for clinical implementation, aiding in the stratification of TNBC patients undergoing NACT.

In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

The prognostic significance of surgical resection margins for local recurrence, distant metastasis, and overall survival in sarcoma.

BACKGROUND AND OBJECTIVES: Surgical resection with microscopically negative margins constitutes one of the key elements of a curative therapeutic approach for localized sarcomas. However, the prognostic value of quantitative margin width remains controversial. We sought to determine the prognostic significance of margin status and margin width for local recurrence (LR), distant recurrence (DR), and overall survival. METHODS: Retrospective analysis of 210 patients undergoing resection of localized sarcoma between 1997 and 2018 at a national sarcoma reference center. RESULTS: Logistic regression did not reveal an effect of metric margin width as a prognostic factor for LR (odds ratio [OR] = 0.98, p = 0.574), DR (OR = 1, p = 0.908), or overall survival (hazard ratio = 0.98, 95% confidence interval = 0.73-1.20, p = 0.609). Subgroup analysis revealed no differences between complete first resections (R0) and re-resections (re-R0) following unplanned R1-resections for LR (p = 0.727) and overall survival (p = 0.125), but a significantly higher DR-rate in re-R0 cases (p = 0.022). CONCLUSIONS: Achieving a negative margin is essential in sarcoma surgery, however, metric margin width was not associated with disease-specific outcomes. Re-resection of unplanned R1-resections should be performed to control for LR and overall survival rates. As re-R0 cases were at significantly higher risk of DR, these patients should be followed up closely in standardized surveillance protocols.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Assessing environmental and radiological impacts and lithological mapping of beryl-bearing rocks in Egypt using high-resolution sentinel-2 remote sensing images.

Emerald and other beryls represent a family of the most valuable gemstone around the world and particularly in Egypt. Beryllium (Be) contents in beryl-bearing bedrocks in south Sinai (Wadi Ghazala and Wadi Sedri), and in central and south Eastern Desert of Egypt (Igla area, Zabara-Um Addebaa belt, Homret Akarem, and Homret Mukpid) were investigated in this study. The environmental risk levels of Be, associated major ions, and heavy metals in groundwater nearby to beryl-bearing mineralization were also evaluated. Results showed that Be contents ranged from 1 to 374 ppm in beryl-bearing bedrocks, while in nearby groundwater, Be content has a range of 0.0001-0.00044 mg/L with an average of 0.00032 mg/L, which is within the permissible levels and below (0.004) the U.S. EPA maximum contaminant level (MCL). Most levels of heavy metals (e.g., Be, B, Ni, V, Fe, and Al) in the investigated groundwater of central and south Eastern Desert and south Sinai are within the permissible levels and below their corresponding U.S. EPA MCLs. This study also investigated the radiological risk of natural radionuclides distributed in beryl-bearing bedrocks in the study area using gamma spectrometry; Sodium Iodide [NaI(Tl)] scintillation detector. Among the estimated mean 238U, 232Th, and 226Ra activity concentrations of the studied beryl-bearing rocks, Homret Mukpid (79, 87.15, 60.26 Bq kg-1) and Homret Akarem (111.6, 51.17, 85.1 Bq kg-1) contain the highest values. This may be attributed to their highly fractionated granitic rocks that host uranium and thorium reservoir minerals such as zircon, allanite, and monazite. The estimated data of multi-radiological parameters such as absorbed gamma dose, outdoor and indoor annual effective dose, radium equivalent activity, internal and external indices, index of excess cancer, and effective dose to human organs reflecting no significant impacts from the emitted natural gamma radiation.

[Limb-sparing resection of axillary soft tissue sarcomas]. / Extremitätenerhaltende Resektion von Weichteilsarkomen in der Regio axillaris.

OBJECTIVE: For patients with soft tissue sarcoma, surgical resection is a key element of curative therapy. Surgery is performed as a wide resection with microscopically negative margins (R0 resection) and as limb-sparing procedure whenever possible to preserve maximum function. INDICATIONS: Soft tissue sarcoma, metastases. CONTRAINDICATIONS: Extensive disease with major neurovascular involvement, placement of biopsy tract necessitates extensive resection, palliative care. SURGICAL TECHNIQUE: Extended deltopectoral approach. Release of pectoralis major and minor tendons. Vascular and neurologic exploration, identification of the axillary vessels and brachial plexus, placing of loops around major structures. Mobilization of these structures to achieve adequate exposure. Clipping of vessels entering the tumor. Tumor resection, suture marking for histological analysis. Soft tissue reconstruction by transosseous reinsertion of the pectoralis minor to the coracoid process. Drill channel placement, transosseous refixation of the pectoralis major to the humerus. POSTOPERATIVE MANAGEMENT: Shoulder abduction brace for 6 weeks, passive mobilization for 6-12 weeks followed by active mobilization. Compression sleeve. Oncological follow-up. RESULTS: Between 2017 and 2022, wide resection was performed in 6 consecutive cases including 4 primary soft tissue sarcomas and 2 metastases. Primary R0 resection was achieved in 100%. Mean follow-up was 22.5 months (3-60 months). There were no local recurrences. Mean active shoulder abduction was 135.0 ± 41.4° (90-180°). Neurological deficits were not observed. Mean subjective shoulder function was 80.0 ± 21.0% (50-100%). The mean Musculoskeletal Tumor Society (MSTS) score was 89.5% (32-100%), indicating good functional outcome in the study cohort.

Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction.

Introduction: Cadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats. Methods: In total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days. Results: Exposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats. Conclusion: Thus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Anti-inflammatory activity of novel derivatives of pyrazolo [3,4d] pyridazine against digestive system inflammation.

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation.

DNA methylation changes underlie the long-term association between periodontitis and atherosclerotic cardiovascular disease.

Periodontitis, the leading cause of adult tooth loss, has been identified as an independent risk factor for cardiovascular disease (CVD). Studies suggest that periodontitis, like other CVD risk factors, shows the persistence of increased CVD risk even after mitigation. We hypothesized that periodontitis induces epigenetic changes in hematopoietic stem cells in the bone marrow (BM), and such changes persist after the clinical elimination of the disease and underlie the increased CVD risk. We used a BM transplant approach to simulate the clinical elimination of periodontitis and the persistence of the hypothesized epigenetic reprogramming. Using the low-density lipoprotein receptor knockout (LDLRo ) atherosclerosis mouse model, BM donor mice were fed a high-fat diet to induce atherosclerosis and orally inoculated with Porphyromonas gingivalis (Pg), a keystone periodontal pathogen; the second group was sham-inoculated. Naïve LDLR o mice were irradiated and transplanted with BM from one of the two donor groups. Recipients of BM from Pg-inoculated donors developed significantly more atherosclerosis, accompanied by cytokine/chemokines that suggested BM progenitor cell mobilization and were associated with atherosclerosis and/or PD. Using whole-genome bisulfite sequencing, 375 differentially methylated regions (DMRs) and global hypomethylation in recipients of BM from Pg-inoculated donors were observed. Some DMRs pointed to the involvement of enzymes with major roles in DNA methylation and demethylation. In validation assays, we found a significant increase in the activity of ten-eleven translocase-2 and a decrease in the activity of DNA methyltransferases. Plasma S-adenosylhomocysteine levels were significantly higher, and the S-adenosylmethionine to S-adenosylhomocysteine ratio was decreased, both of which have been associated with CVD. These changes may be related to increased oxidative stress as a result of Pg infection. These data suggest a novel and paradigm-shifting mechanism in the long-term association between periodontitis and atherosclerotic CVD.

HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HIV.

BACKGROUND: The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. MATERIAL AND METHODS: This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. RESULTS: The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with Treponema pallidum (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)). CONCLUSIONS: The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.