Solvent/detergent treated pooled human plasma can decrease the recurrence of allergic transfusion reactions in pediatric, adolescent, and young adult patients.

BACKGROUND: Octaplas is a solvent/detergent (S/D)-treated pooled human plasma indicated for the treatment of thrombotic thrombocytopenic purpura (TTP) as well as multiple coagulation factor deficiency in patients with liver disease or undergoing liver transplantation or cardiac surgery. We aimed at providing pediatric, adolescent, and young adult evidence for the decrease in allergic transfusion reactions (ATRs) with S/D-treated plasma. STUDY DESIGN/METHODS: A single-center retrospective review of patient records was performed from January 2018 through July 2022 for patients who received S/D treated plasma (Octaplas™; Octapharma). RESULTS/FINDINGS: A total of 1415 units of S/D-treated plasma were transfused to nine patients at our institution. Patient ages ranged from 13 months to 25 years old. The reason to initiate transfusion with S/D treated plasma in six patients was mild to severe ATR to plasma-containing products and the need for therapeutic plasma exchange (TPE) or plasma transfusions (PTs). TPE or PT was performed for various clinical indications. Average S/D treated plasma volume per TPE or PT ranged from 200 to 1800 mL per event. During the study period, since initiating transfusions with S/D treated plasma, there have been no allergic or other transfusion reactions reported among these patients. CONCLUSION: We have successfully utilized S/D treated plasma over the last 4.5 years for pediatric, adolescent, and young adult patients who otherwise would have suffered ATR due to necessary TPE or PT. S/D treated plasma is an additional tool that can be utilized by transfusion services, including pediatrics, to safely transfuse their patients.

Informational video impact before caesarean delivery on anxiety and satisfaction: a systematic review and meta-analysis.

BACKGROUND: Anxiety prior to caesarean section can lead to a negative birth experience, which may affect different aspects of woman's life in the long term. Improving preoperative information may result in lower anxiety leading to a more positive birth experience. Thus, we aimed to evaluate the impact of informational video before planned caesarean delivery on maternal anxiety and satisfaction. METHODS: Four different databases were searched from inception till March 2023. We selected randomised controlled trials (RCTs) that compared educational or informative videos about the aspects of the expected caesarean delivery process versus no preoperative information in the control group. No language restrictions were imposed. We used Revman software during performing our meta-analysis. Our main outcomes were preoperative and postoperative anxiety as well as maternal satisfaction post-procedure. RESULTS: Six RCTs were retrieved with a total number of 702 patients. Informative video significantly reduced the anxiety level before caesarean delivery in comparison with the control group (MD = -4.21, 95% CI [-5.46, -2.95], p<0001). Moreover, the postoperative anxiety level was significantly improved in the informational video group (MD = -4.71, 95% CI [-7.06, -2.36], p<0001). In addition, there was a significant improvement in maternal satisfaction score after caesarean delivery among the informational video group (p = 0.001). CONCLUSIONS: Informational video prior to caesarean delivery decreases preoperative and postoperative anxiety levels with improvement in maternal post-procedure satisfaction. However, the existing evidence is limited by several shortcomings, chiefly small sample size. More trials with larger sample size are required to confirm our findings.

Neurological manifestations in coronavirus disease 2019 (COVID-19) patients: a systematic review of literature.

BACKGROUND: The exact incidence of neurological complications from coronavirus disease 2019 (COVID-19) infection remains unknown. Neurological symptoms are more common with severe form of the disease. Through neuro-invasion, the virus can affect both neurons and glial cells and induce wide range of neurological pathologies. OBJECTIVES: To systematically assess the neurological manifestations in patients diagnosed with COVID-19. METHODS: A systematic literature search of the PubMed, Scopus, and Cochrane databases was performed. Randomized controlled trials, nonrandomized controlled trials, observational studies of neurological manifestations in patients diagnosed with COVID-19. RESULTS: All three-database search identified 89 publications. A total of 22 full-text articles assessed for eligibility with 12 articles excluded. Altogether, the included studies reported 290 patients with neurological manifestations. Neurological manifestations were subdivided into central causes (CNS) and peripheral causes (PNS). CNS symptoms is commoner representing 91% of all neurological patients with 9% only with PNS. Headache represented the commonest neurological symptoms in regard to number of patients, meanwhile dizziness has the highest incidence with 11.9%. Neurological manifestations were divided according to COVID-19 severity into: (1) nonsevere and (2) severe; with all CNS manifestations were more in severe patients except headache were more in nonsevere patients. All included studies were on adult patients except one study in pediatric patients with limited number of participants. CONCLUSIONS: From the descriptive analyses and available data of relatively small sample-sized studies, it can be concluded that in spite of the aforementioned limitations, that a wide spectrum of neurological manifestations including CNS and PNS can occur in COVID-19 patients.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of ß-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the ß-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in ß-arrestin2 and its downstream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (AKT) activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased ß-arrestin2, PIP2, and AKT activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of ß-arrestin2 pathway.

Pornography Use Prevalence and Associated Factors in Arab Countries: A Multinational Cross-Sectional Study of 15,027 Individuals.

BACKGROUND: There has been a tangible increase in pornography consumption during the past decade, with the absence of a large-scale study of Arab countries. AIM: The present study aimed to assess the prevalence of pornography viewing and its associated risk factors in Arab countries. METHODS: A large cross-sectional online survey was carried out recruiting participants without restrictions on the age, socioeconomic level, job, or educational level. Multivariable logistic regression analysis was performed to identify possible risk factors for viewing porn and results were expressed as odds ratios (ORs) and 95% confidence interval (95% CI). OUTCOMES: Main outcomes were pornography viewing (first exposure and frequency), the perceptions of this act, use of spare time, physical activity (exercising), and frequency of psychiatrist visits. RESULTS: The final number of participants included in the study was 15027 participants with a mean age ± standard deviation of 23.82 years ± 24.99. Most of the participants were men (84.56%), living with parents (81.71%), and 60.51% university graduates. There were statistically significant differences (P < .001) in the attitude and practice of men compared with women throughout all tested variables. Frequent pornography viewing was associated with male gender (OR [95% CI] = 7.08 [6.43 to 7.81]; P < .001) and age group ≤15 years (OR [95% CI] = 1.33 [1.01 to 1.75]; P = .044). By contrast, higher education was inversely associated with viewing rates reaching the lowest level in PhD awardees (OR [95% CI] = 0.36 [0.26 to 0.51]; P = .003). It was also noted that regular exercising (OR [95% CI] = 0.66 [0.58 to 0.74]; P < .001) was associated with a reduction in pornography viewing rates. CLINICAL IMPLICATIONS: Young age, male gender, and lower educational level are all predictors for higher pornography viewing and should be considered when designing public health intervention in a related context. STRENGTHS AND LIMITATIONS: This is the first large-scale multi-national survey to be conducted in Arab countries to investigate pornography viewing. The main limitations were the cross-sectional design (cannot indicate causality) and the self-report nature (liable to social desirability and recall bias). CONCLUSION: Pornography viewing is common in Arab countries and associated with some personal and behavioral factors. Eljawad MA, Se'eda H, Ghozy S, et al. Pornography Use Prevalence and Associated Factors in Arab Countries: A Multinational Cross-Sectional Study of 15,027 Individuals. J Sex Med 2021;18:539-548.

Nitrosative Stress Is Associated with Dopaminergic Dysfunction in the HIV-1 Transgenic Rat.

Advances in antiretroviral therapy have resulted in significantly decreased HIV-related mortality. HIV-associated neurocognitive disorders, however, continue to be a major problem in infected patients. The neuropathology underlying HIV-associated neurocognitive disorders has not been well characterized, and evidence suggests different contributing mechanisms. One potential mechanism is the induction of oxidative stress. Using the HIV-1 transgenic (Tg) rat model of HIV, we found increased striatal NADPH oxidase-4 and neuronal nitric oxide synthase expression in the adult (7- to 9-month-old) Tg rat compared with control rats but not in the young (1-month-old) Tg rats. This was accompanied by increased 3-nitrotyrosine (3-NT) immunostaining in the adult Tg rats, which worsened significantly in the old Tg rats (18 to 20 months old). There was, however, no concurrent induction of the antioxidant systems because there was no change in the expression of the nuclear factor-erythroid 2-related factor 2 and its downstream targets (thioredoxin and glutathione antioxidant systems). Colocalization of 3-NT staining with neurofilament proteins and evidence of decreased tyrosine hydroxylase and dopamine transporter expression in the old rats support dopaminergic involvement. We conclude that the HIV-1 Tg rat brain shows evidence of nitrosative stress without appropriate oxidation-reduction adaptation, whereas 3-NT modification of striatal neurofilament proteins likely points to the ensuing dopaminergic neuronal loss and dysfunction in the aging HIV-1 Tg rat.

Safety of Combination Immune Checkpoint Inhibitors Compared to Monotherapy; A Systematic Review and Meta-Analysis.

Combination immune checkpoint inhibitors (ICIs) achieved higher efficacy than monotherapy in many types of cancers. We searched PubMed, Scopus, and Cochrane databases for randomized phase II/III trials in cancer patients receiving combination ICIs vs. Monotherapy. Our search retrieved 934 records. Eight studies were found to be eligible for meta-analysis recruiting 2544 patients. Combined immunotherapy nivolumab plus ipilimumab was associated with statistically significant higher risk of all grade adverse events (AE), and discontinuation due to all grade AEs as compared to both ipilimumab or nivolumab. Although combination ICIs showed better oncological activity, it carried a higher risk of all grade irAEs.

Dietary supplementation of brown seaweed (Sargassum latifolium) alleviates the environmental heat stress-induced toxicity in male Barki sheep (Ovis aries).

Heat stress (HS) is the most potent environmental stressors for livestock in tropical and subtropical regions. HS induced splanchnic tissue hypoxia and intestinal oxidative damage, leading to endotoxemia and systemic inflammation. The present study evaluated and compared the modulatory effects of feeding Barki male sheep (Ovis aries) on a standard concentrated diet containing 2% or 4% of the brown seaweed (Sargassum latifolium) followed by roughage for 40 consecutive days on the toxicity-induced by exposure to severe environmental HS (temperature-humidity index = 28.55 ± 1.62). The present study showed that the diet containing Sargassum latifolium (especially 4%) modulated significantly (P < 0.05-0.001) almost all changes shown in the HS-exposed sheep including the increase in the thermo-respiratory responses (skin and rectal temperatures, and respiration rate) and the resulted dyslipidemia, anemia, and systemic inflammation (blood leukocytosis, the elevation in the erythrocyte sedimentation rate, and the increase in serum proinflammatory cytokines and heat shock protein-70 concentrations). In addition, Sargassum latifolium improved significantly (P < 0.05-0.001) the body-weight gain, kidney functions (especially at the high dose), and blood antioxidant defense system (total antioxidant capacity, and the activities of catalase and superoxide dismutase) in the HS-exposed sheep, as well as protected the animals from oxidative tissue damage and the risk of atherosclerosis. In conclusion, feeding sheep with the diet containing 4% of Sargassum latifolium was safe and suitable for animal nutrition, as well as efficiently alleviated the harmful effects of the environmental HS in Barki sheep through improving the animal antioxidant defense system, and regulating the thermo-respiratory and inflammatory responses.

The Promise of JAK Inhibitors for Treatment of Sarcoidosis and Other Inflammatory Disorders with Macrophage Activation: A Review of the Literature.

Certain inflammatory disorders are characterized by macrophage activation and accumulation in tissue; sometimes leading to the formation of granulomas, as in sarcoidosis. These disorders are often difficult to treat and more effective, molecularly targeted therapies are needed. Recent work has shown that overproduction of inflammatory cytokines, such as interferon gamma (IFN-γ) leading to constitutive activation of the JAK-STAT pathway may be a conserved feature of these disorders. Use of JAK inhibitors, which can block these signals, has resulted in dramatic improvement in several patients with sarcoidosis. JAK inhibitors also appear to have activity in other inflammatory disorders with macrophage activation including hemophagocytic lymphohistiocystosis, Crohn's disease, granuloma annulare, and necrobiosis lipoidica. Here, we review the role of JAK dependent cytokines in macrophage activation and granuloma formation and the clinical evidence supporting the use of JAK inhibition in these disorders. Ongoing efforts to evaluate role of JAK inhibitors in these disorders is also discussed.

Monitoring and removal of cyanobacterial toxins from drinking water by algal-activated carbon.

Microcystins (MCs) are the most potent toxins that can be produced by cyanobacteria in drinking water supplies. This study investigated the abundance of toxin-producing algae in 11 drinking water treatment plants (DWTPs). A total of 26 different algal taxa were identified in treated water, from which 12% were blue green, 29% were green, and 59% were diatoms. MC levels maintained strong positive correlations with number of cyanophycean cells in raw and treated water of different DWTPs. Furthermore, the efficiency of various algal-based adsorbent columns used for the removal of these toxins was evaluated. The MCs was adsorbed in the following order: mixed algal-activated carbon (AAC) ≥ individual AAC > mixed algal powder > individual algal powder. The results showed that the AAC had the highest efficient columns capable of removing 100% dissolved MCs from drinking water samples, thereby offering an economically feasible technology for efficient removal and recovery of MCs in DWTPs.

Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study.

BACKGROUND: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. METHODS: Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. RESULTS: [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. CONCLUSION: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.

Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV.

The dopaminergic system is especially vulnerable to the effects of human immunodeficiency virus (HIV) infection, rendering dopaminergic deficits early surrogate markers of HIV-associated neuropathology. We quantified dopamine D2/3 receptors in young HIV-1 transgenic (Tg) (n  =  6) and age-matched control rats (n  =  7) and adult Tg (n  =  5) and age-matched control rats (n  =  5) using [18F]fallypride positron emission tomography (PET). Regional uptake was quantified as binding potential (BPND) using the two-tissue reference model with the cerebellum as the reference. Time-activity curves were generated for the ventral striatum, dorsal striatum, thalamus, and cerebellum. Whereas BPND values were significantly lower in the ventral striatum (p < .001) and dorsal striatum (p  =  .001) in the adult Tg rats compared to controls rats, they were significantly lower only in the dorsal striatum (p < .05) in the young rats. Tg rats had smaller striatal volumes on magnetic resonance imaging. We also found lower expression levels of tyrosine hydroxylase on immunohistochemistry in the Tg animals. Our findings suggest that progressive striatal D2/3 receptor deficits occur in Tg rats as they age and can be detected using small-animal PET imaging. The effectiveness of various approaches in preventing or halting this dopaminergic loss in the Tg rat can thus be measured preclinically using [18F]fallypride PET as a molecular imaging biomarker of HIV-associated neuropathology.

Optimization of free-breathing whole-heart 3-dimensional cardiac magnetic resonance imaging at 3 tesla to identify coronary vein anatomy and to compare with multidetector computed tomography.

OBJECTIVE: This study optimizes use of 3-T magnetic resonance imaging (MRI) to delineate coronary venous anatomy and compares 3-T MRI with multidetector computed tomography (MDCT) measurements. METHODS: The study population included 37 consecutive subjects (22 men, 19-71 years old). Whole-heart contrast-enhanced MRI images at 3 T were acquired using segmented k-space gradient echo with inversion recovery prepared technique. The MDCT images were obtained using nonionic iodinated contrast. RESULTS: The coronary sinus and great cardiac, posterior interventricular, and anterior interventricular veins were visualized in 100% of cases by both MRI and MDCT. Detection of the posterior vein of the left ventricle and the left marginal vein by MRI was 97% and 81%, respectively. Bland-Altman plots showed agreement in ostial diameter measured by both modalities with correlation coefficients ranging from 0.5 to 0.76. Vein length and distances also agreed closely. CONCLUSIONS: Free-breathing whole-heart 3-dimensional MRI at 3 T provides high-spatial-resolution images and could offer an alternative imaging technique instead of MDCT scans.

Role of Ulva lactuca extract in alleviation of salinity stress on wheat seedlings.

Seaweeds are potentially excellent sources of highly bioactive materials that could represent useful leads in the alleviation of salinity stress. The effects of presoaking wheat grains in water extract of Ulva lactuca on growth, some enzymatic activities, and protein pattern of salinized plants were investigated in this study. Algal presoaking of grains demonstrated a highly significant enhancement in the percentage of seed germination and growth parameters. The activity of superoxide dismutase (SOD) and catalase (CAT) increased with increasing the algal extract concentration while activity of ascorbate peroxidase (APX) and glutathione reductase (GR) was decreased with increasing concentration of algal extract more than 1% (w/v). The protein pattern of wheat seedling showed 12 newly formed bands as result of algal extract treatments compared with control. The bioactive components in U. lactuca extract such as ascorbic acid, betaine, glutathione, and proline could potentially participate in the alleviation of salinity stress. Therefore, algal presoaking is proved to be an effective technique to improve the growth of wheat seedlings under salt stress conditions.

Is Programmed Death-Ligand 1 of Prognostic Significance in Triple-Negative Female Mammary Carcinoma?

Introduction: The most widespread female malignancy is breast cancer (BC), considerable percentage of patients with triple-negative BC (TNBC) experience rapid progression, recurrence, and metastasis. BC has not historically been treated as an immunogenic cancer. Nonetheless, several researchers have started to concentrate on immunotherapy. Aim: The aim of the study is to investigate the immunohistochemical (IHC) expression of programmed death-ligand 1 (PD-L1) by stromal tumor-infiltrating lymphocytes (TILs) and tumor cells (TC) in female (TNBC) and to correlate with pathological features of such tumors, particularly those determine biologic behavior, such as the grade and stage the overall survival. Methodology: This is a retrospective study which includes 49 paraffin-embedded tumor tissue sections which were collected from breast surgery specimens either radical or conservative of female patients with TNBC. The samples were analyzed immunohistochemically for PD-L1 expression. Results: There were statistically significant relations among TC PD-L1 expression and TILs PD-L1 expression as well as relations among TILs PD-L1 expression with histologic grade, stromal TILs, and Ki-67 were statistically significant. Correlations between TC PD-L1 expression and N stage, histologic grade, and anatomic stage were statistically significant. Improved survival was detected within TILs PD-L1-positive cases; however, the correlation between the overall survival and PD-L1 expression in both TCs and stromal TIL was not statistically significant. Conclusion: PD-L1 expressed in tumors with poor prognostic features such as the high grade, advanced T stage, and high Ki-67 index, TILs PD-L1-positive cases experienced improved survival supporting its prognostic significance. However, the correlation with overall survival was not statistically significant.

Herbal Composite Preparation and Investigating its Efficiency to Inhibit Biofilm Formation and Virulence Factors of Prevotella Intermedia and Porphyromonas Gingivalis - Formulation of Mouthwash Using a Herbal Composite and Evaluating its Anti-microbial Activity.

Herbal composite preparation was studied with the aim of inhibiting the virulence factors of two dental pathogens: Prevotella intermedia and Porphyromonas gingivalis. A novel herbal composite was developed using the herbal extracts of Wrightia tinctoria and Bauhinia variegata. During the study, the following observations were noted. The minimal inhibitory concentration of Wrightia tinctoria and Bauhinia variegata composites (WBc) was obtained for the test concentration of 20 µg/ml (16 ± 0.57 mm and 15 ± 0.75 mm of inhibitory zones against Prevotella intermedia and Porphyromonas gingivalis, respectively). Biofilm inhibition assay results revealed about 0.51 ± 1.25 mg/ml and 0.53 ± 0.57 mg/ml of minimal biofilm eradication concentration (MBEC) against Prevotella intermedia and Porphyromonas gingivalis, respectively. The effect of WBc on lactic acid production showed that 200 µg/ml and 400 µg/ml concentrates reduced up to 80% and 70% in Prevotella intermedia and Porphyromonas gingivalis, respectively. Formulated herbal mouthwash showed good stability under all three different test conditions (5°C, 25°C, and 40°C) as the color, odor, phase separation, and homogeneity were not changed for the period of 3 months. The anti-bacterial activity of formulated mouthwash (30 µg/ml) exhibited maximum inhibitory zones of about 18 ± 0.75 mm and 19 ± 1.05 mm against the respective test bacteria - Prevotella intermedia and Porphyromonas gingivalis. Amplification of mfa1 and clpB genes showed 246 bp and 294 bp fragments of P. gingivalis and 238 bp and 280 bp fragments of P. intermedia during agarose electrophoretic analysis. The docking report revealed -5.84 Kcal/Mol binding energy and found three hydrogen bonding between the quercetin and target protein, mfa1 of Porphyromonas gingivalis. The target protein, clpB of Prevotella intermedia, and quercetin had -6.72 Kcal/Mol binding energy and found four hydrogen bonds between them. The developed composite could be optimized in future to develop a novel and biocompatible herbal mouthwash for the prevention of different dental caries and gingival inflammation associated with dental biofilm formation.

In-vitro Evaluation of Wild Bitter Melon (Momordica charantia) Extracts against Periodontopathic Bacteria (Prevotella intermedia and Porphyromonas gingivalis) using Antibacterial, Anti-Inflammatory and Molecular Docking Analysis.

Wild bitter melon (Momordica charantia) extracts were prepared and their antibacterial and anti-biofilm assay were investigated against two different periodontopathic bacteria (Prevotella intermedia and Porphyromonas gingivalis) for the first time to the best of our knowledge based on the presence of different phytochemical compounds. Momordica charantia solvent extracts were prepared and phytochemical analysis was performed. Minimal inhibitory and bactericidal concentrations were determined. Antibacterial activity was evaluated using the standard well diffusion method. Anti-inflammatory studies on periodontal ligament (PDL) cell viability and lipopolysaccharide (LPS)-induced inflammation were performed. Molecular docking was investigated between the bioactive compound (Charantadiol A) of plant extract and biofilm-expressing genes in each test organism. Phytochemicals from ethanol extract showed promising results; alkaloids, flavonoids, phenols, and tannins were found present at considerable levels. The minimum inhibitory concentration was found to be 400 µg/mL for Prevotella intermedia and Porphyromonas gingivalis. Antibacterial activity expressed in terms of zone of inhibition showed 14 mm to 18 mm zones against the test organisms. The molecular docking report revealed the maximum binding energy of about -6.54 Kcal/Mol of binding energy between Charantadiol A and fimA of Porphyromonas gingivalis. Anti-biofilm study showed that the minimum biofilm eradication concentration (MBEC) of Momordica charantia expressed significantly good results against the test organisms. The PDL cell viability values expressed in percentage indicated the anti-inflammatory properties of Momordica charantia extracts at three different known concentrations. The findings concluded that Momordica charantia extracts have promising prospects as an anti-periodontopathic and anti-inflammatory agent.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies. METHODS: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)). RESULTS: We observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival. CONCLUSIONS: Our proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.