Identification of Yeast and Yeast-Like Fungi at a Tertiary Care Center: A Retrospective Study.

Background Fungal infections pose a significant global health challenge. Despite their substantial impact, these ubiquitous fungi can become pathogenic but have not received adequate attention in public health, leading to infections that are often underestimated by the general public and healthcare professionals. Candida species and Cryptococcus species play a key role in these infections, with emerging multidrug resistance in Candida species posing considerable challenges. This study aimed to understand the prevalence of yeast and yeast-like infections, particularly in the COVID-19 era, and to assess the antifungal susceptibility pattern. Methodology A retrospective observational study was conducted at a rural tertiary care medical college in Maharashtra, India. Retrospective records of samples processed for fungal culture were analyzed in the microbiology department. Yeast identification and antifungal susceptibility were performed using the VITEK-2 automated system. Results Among 95 fungal isolates, 86 (90.52%) were yeast isolates, primarily non-albicans Candida (NAC) species. Candida albicans accounted for 41 (47.67%) yeast isolates. In 14 isolates, NAC species were not identified by the VITEK-2 system up to the species level. Isolates from urine samples contributed the highest percentage of 61% (58) of yeast isolates. C. albicans showed high sensitivity to most antifungal agents. Other Candida species, such as Candida famata, Candida parapsilosis, and Candida guilliermondii, were sensitive to all antifungal agents. Candida auris showed complete resistance to amphotericin B and fluconazole but sensitivity to other agents. Mixed sensitivity patterns were observed in Candida ciferri and Candida lusitaniae, with some resistance to voriconazole, caspofungin, and micafungin. Conclusions This study shows the increasing prevalence of yeast and yeast-like infections, particularly NAC, during the COVID-19 era. Improved yeast identification and susceptibility testing are crucial for guiding the appropriate treatment and mitigating the impact of these infections, emphasizing the need for comprehensive future studies in this area.

Microbial exopolysaccharides in the biomedical and pharmaceutical industries.

The most significant and renewable class of polymeric materials are extracellular exopolysaccharides (EPSs) produced by microorganisms. Because of their diverse chemical and structural makeup, EPSs play a variety of functions in a variety of industries, including the agricultural industry, dairy industry, biofilms, cosmetics, and others, demonstrating their biotechnological significance. EPSs are typically utilized in high-value applications, and current research has focused heavily on them because of their biocompatibility, biodegradability, and compatibility with both people and the environment. Due to their high production costs, only a few microbial EPSs have been commercially successful. The emergence of financial barriers and the growing significance of microbial EPSs in industrial and medical biotechnology has increased interest in exopolysaccharides. Since exopolysaccharides can be altered in a variety of ways, their use is expected to increase across a wide range of industries in the coming years. This review introduces some significant EPSs and their composites while concentrating on their biomedical uses.

The Impact of COVID-19-Related Psychological Stress on Fetoplacental Circulation: A Doppler Scan of Umbilical Vessels in Third-Trimester Antenatal Women.

INTRODUCTION: The placenta is an important organ of pregnancy. A multitude of physiological and pathological factors influence blood flow in the placenta during pregnancy. However, the fetal effects of maternal psychological stress were inconclusive. The recent COVID-19 pandemic had unprecedented economic, social, and psychological effects. The effect of COVID-19-induced psychological stress in antenatal women and its resultant fetal impact were studied by observing the Doppler waveforms of the uterine and umbilical arteries. METHODS: The cross-sectional study was conducted on 26 healthy third-trimester antenatal women who satisfied pre-set inclusion and exclusion criteria. A pandemic-related pregnancy stress scale (PREPS) was used to evaluate the stress in pregnant women and categorize it into mild, moderate, and severe levels. The Doppler ultrasound of the uterine and umbilical vessels was done along with a routine growth scan in the third trimester of pregnancy. The arterial waveforms, Pulsatility index (PI) of uterine and umbilical arteries, umbilical vein blood flow, and biometric parameters of the fetus were recorded and analyzed. RESULTS: Seventeen of the 26 participants were found to be moderately stressed. Among the three dimensions of the PREPS tool, the perinatal infection stress dimension was expressed predominantly. A strong expression of the positive affirmation dimension was seen in antenatal women. The mean Pulsatility index in the mild, moderate, and severe groups was 0.74, 0.93, and 0.63, respectively. The association between the PREPS score and the Pulsatility index of the umbilical artery alone was found to be significant at p=0.02. CONCLUSION: The COVID-19 pandemic caused moderate to severe levels of psychological stress in pregnant women. The statistically significant association between the PREPS score and the umbilical artery PI indicates possible fetoplacental compromise, suggesting the need for cognitive therapy to manage psychological stress in antenatal women.

Evaluation of anterior tooth-ridge angulation, root position and labial bone perforation using dental cone-beam computed tomography: An observational study.

Purpose: The objective of this study was to use cone-beam computed tomography (CBCT) scans to measure and correlate the maxillary and mandibular tooth-ridge angulation (TRA) and labial bone perforation (LBP) in anterior teeth. Materials and Methods: A standardized technique was used to orientate Planmeca CBCT images in 140 patients. On the sagittal section, TRA was defined as the angle between the long axis of the tooth and the alveolar housing of the corresponding tooth. The maxillary and mandibular anterior teeth's sagittal root locations were evaluated. Virtual implant software was used to analyze bone perforations using a predetermined taper implant system. Results: A total of 1680 teeth were scanned for this investigation, and 1338 teeth were selected for further analysis. In comparison to the mandible, the maxilla had a greater TRA. LBP was found to be 4.26% (57 teeth) more common in the mandibular arch (n = 39; 68.42 and) than in the maxillary arch (n = 18; 31.58%). When comparing both the sides, there was no significant difference in LBP. There was a significant relationship between TRA and LBP (P < 0.05). There was a significant association between all parameters. There was no statistically significant difference in TRA, sagittal root position (SRP), and LBP between the right and left teeth. Conclusions: The SRP type 1 is most typically present in the anterior teeth. The maxillary anterior teeth were placed at a 5°-10° angle, while the mandibular incisors were parallel to the alveolar ridge. The LBP was more characteristically present in the mandibular incisors. SRP and TRA were directly correlated with LBP. Clinically, bone perforations may be reduced using taper implants and abutments with a 5°-10° angle in maxillary anterior teeth, while straight implants are preferred in mandibular anterior teeth, which may be recommended.

Assessment of Urinary Biomarkers for Infectious Diseases Using Lateral Flow Assays: A Comprehensive Overview.

Screening of biomarkers is a powerful approach for providing a holistic view of the disease spectrum and facilitating the diagnosis and prognosis of the state of infectious diseases. Unaffected by the homeostasis mechanism in the human body, urine accommodates systemic changes and reflects the pathophysiological condition of an individual. Easy availability in large volumes and non-invasive sample collection have rendered urine an ideal source of biomarkers for various diseases. Infectious diseases may be communicable, and therefore early diagnosis and treatment are of immense importance. Current diagnostic approaches preclude the timely identification of clinical conditions and also lack portability. Point-of-care (POC) testing solutions have gained attention as alternative diagnostic measures due to their ability to provide rapid and on-site results. Lateral flow assays (LFAs) are the mainstay in POC device development and have attracted interest owing to their potential to provide instantaneous results in resource-limited settings. The discovery and optimization of a definitive biomarker can render POC testing an excellent platform, thus impacting unwarranted antibiotic administration and preventing the spread of infectious diseases. This Review summarizes the importance of urine as an emerging biological fluid in infectious disease research and diagnosis in clinical settings. We review the academic research related to LFAs. Further, we also describe commercial POC devices based on the identification of urinary biomarkers as diagnostic targets for infectious diseases. We also discuss the future use of LFAs in developing more effective POC tests for urinary biomarkers of various infections.

Surgical Residents' Awareness of the Costs of Common Operating Room Supplies.

BACKGROUND: The Accreditation Council for Graduate Medical Education mandates that residency programs incorporate cost awareness into patient care. This presents a challenge for surgical residents because they must understand operating room costs in addition to other expenses. Trainees' understanding of operating room supply costs is not well understood. METHODS: A survey was distributed to surgical residents (N = 73) at an urban, university-based residency program. Residents estimated the costs of 21 single-use operating room items. Descriptive statistics and a regression analysis were calculated. RESULTS: The response rate was 62%. Respondents accurately estimated costs for a median of 7/21 items, with error ranging from 26% to 5438%. They substantially underestimated the three highest-cost items. Increasing post-graduate year did not improve estimation accuracy (ß = .233, P = .138). DISCUSSION: Residents have a poor understanding of single-use item costs, and this does not improve with post-graduate training, suggesting inefficiencies. There is opportunity to educate residents and ultimately decrease surgical health care costs.

Emerging and Re-Emerging Viral Infections: An Indian Perspective.

Emerging and re-emerging viral infections pose a constant threat, especially in healthcare settings. Viral infections can be thought of as an ecological system, like a forest or a pond, with different species competing for resources. Pandemics tend to occur when there is a disruption to this ecosystem, such as introducing a strain of virus into humans or animals that they have no immunity against. Around 60% of human infectious diseases and 75% of emerging infections are zoonotic, with two-thirds originating in wildlife. There is an ongoing risk of viral diseases as the human population continues to grow and the rate of urbanization increases. The emergence and re-emergence of viral diseases are influenced by a variety of virologic and environmental factors. These factors can be roughly categorized as affecting humans, the environment and/or ecology, and viruses. The spread of zoonotic diseases among humans can be prevented by reducing the transmission risk associated with wildlife and exotic pets through education, legislation, and behavioral change programs that target individuals at risk for exposure.

Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study.

Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina's Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.

Sleep quality and sleep hygiene in preclinical medical students of tertiary care center amidst COVID-19 pandemic: a cross-sectional observational study.

Objectives: Due to the long-lasting pandemic measures, such as lockdown and stay-at-home orders, the COVID-19 pandemic has had a negative impact on higher education. In this study, we aimed to determine sleep quality, excessive daytime sleepiness, and sleep hygiene, and their association with anxiety, and their correlation in preclinical medical students during the COVID-19 pandemic. Materials and Methods: We included 101 medical students, aged between 17-20 years of both sex from a tertiary care medical institute. Standard questionnaires were used to assess sleep quality, sleep hygiene, daytime sleepiness, and anxiety among medical students. Results: Fifty-one percent of the medical students had good sleep quality, but 35% had borderline poor sleep quality, and 13% had poor sleep quality during the lockdown. Six percent of medical students had alarmingly high daytime sleepiness. The total Adolescent Sleep Hygiene Scale (ASHS) score was grouped into poor sleep hygiene (ASHS score ≤ 3.8) and good sleep hygiene (ASHS score ≥ 4.9). Overall, sleep hygiene of medical students was poor due to behavioral arousal and bedtime routine factors, and the scores for anxiety and sleep hygiene were significantly negatively correlated, whereas daytime sleepiness showed a significant positive correlation. Conclusion: Our study revealed a high prevalence of poor sleep quality among medical students during the lockdown. Poor sleep hygiene is an eye-opener for the mostly ignored aspect of altered sleep patterns.

Sequential modulation of the Wnt/ß-catenin signaling pathway enhances tumor-intrinsic MHC I expression and tumor clearance.

BACKGROUND: Progress in immunotherapy use for gynecologic malignancies is hampered by poor tumor antigenicity and weak T cell infiltration of the tumor microenvironment (TME). Wnt/ß-catenin pathway modulation demonstrated patient benefit in clinical trials as well as enhanced immune cell recruitment in preclinical studies. The purpose of this study was to characterize the pathways by which Wnt/ß-catenin modulation facilitates a more immunotherapy-favorable TME. METHODS: Human tumor samples and in vivo patient-derived xenograft and syngeneic murine models were administered Wnt/ß-catenin modulating agents DKN-01 and CGX-1321 individually or in sequence. Analytical methods included immunohistochemistry, flow cytometry, multiplex cytokine/chemokine array, and RNA sequencing. RESULTS: DKK1 blockade via DKN-01 increased HLA/MHC expression in human and murine tissues, correlating with heightened expression of known MHC I regulators: NFkB, IL-1, LPS, and IFNy. PORCN inhibition via CGX-1321 increased production of T cell chemoattractant CXCL10, providing a mechanism for observed increases in intra-tumoral T cells. Diverse leukocyte recruitment was noted with elevations in B cells and macrophages, with increased tumor expression of population-specific chemokines. Sequential DKK1 blockade and PORCN inhibition decreased tumor burden as evidenced by reduced omental weights. CONCLUSIONS: Wnt/ß-catenin pathway modulation increases MHC I expression and promotes tumor leukocytic infiltration, facilitating a pro-immune TME associated with decreased tumor burden. This intervention overcomes common tumor immune-evasion mechanisms and may render ovarian tumors susceptible to immunotherapy.

Relationship between Frailty, Glycemic Control, and Nutritional Status among the Elderly with Diabetes Mellitus Residing in an Urban Community of Mysuru.

Background: In India, the elderly (aged 60 and above) constitute 8.2% of the total population and are expected to increase to 10% by the year 2020. Globally, around 450 million people are suffering from diabetes mellitus. Frailty is regarded as a predisability state and, therefore, if identified early, may avert many adverse health outcomes in the elderly. Diabetes and frailty are found to be close associates. Materials and Methods: This community-based cross-sectional study was conducted among 104 elderlies with diabetes mellitus residing in an urban slum situated in Mysuru for a period of 6 months. Pretested structured questionnaire was used to collect the information on sociodemographic characteristics and details of diabetes. The Tilburg's Frailty Scale was used to assess frailty, and the Mini Nutritional Assessment Scale was used to assess the nutritional status. Results: The prevalence of frailty among the study population was 53.8%. 51% of the subjects were found to have their glycemic status under control, 16.3% were malnourished, and 70.2% were at risk of malnutrition (RMN). The majority of the subjects with malnourishment were frail (76.5%) followed by those at RMN, 36 (49.3%). Gender, marital status, engaging in occupation, socio economic status, poor glycemic control were found to be significantly associated with frailty. Conclusion: The prevalence of frailty is significantly higher among elderly diabetics. The poorer glycemic control is a significant factor associated with frailty, and malnourished elderlies are more at risk of developing frailty.

Sleep quality and sleep hygiene in preclinical medical students of tertiary care center amidst COVID-19 pandemic: a cross-sectional observational study / Journal of Rural Medicine

Objectives: Due to the long-lasting pandemic measures, such as lockdown and stay-at-home orders, the COVID-19 pandemic has had a negative impact on higher education. In this study, we aimed to determine sleep quality, excessive daytime sleepiness, and sleep hygiene, and their association with anxiety, and their correlation in preclinical medical students during the COVID-19 pandemic.Materials and Methods: We included 101 medical students, aged between 17–20 years of both sex from a tertiary care medical institute. Standard questionnaires were used to assess sleep quality, sleep hygiene, daytime sleepiness, and anxiety among medical students.Results: Fifty-one percent of the medical students had good sleep quality, but 35% had borderline poor sleep quality, and 13% had poor sleep quality during the lockdown. Six percent of medical students had alarmingly high daytime sleepiness. The total Adolescent Sleep Hygiene Scale (ASHS) score was grouped into poor sleep hygiene (ASHS score ≤ 3.8) and good sleep hygiene (ASHS score ≥ 4.9). Overall, sleep hygiene of medical students was poor due to behavioral arousal and bedtime routine factors, and the scores for anxiety and sleep hygiene were significantly negatively correlated, whereas daytime sleepiness showed a significant positive correlation.Conclusion: Our study revealed a high prevalence of poor sleep quality among medical students during the lockdown. Poor sleep hygiene is an eye-opener for the mostly ignored aspect of altered sleep patterns.

Utilization of a 3-D tissue engineered model to investigate the effects of perfusion on gynecologic cancer biology.

Among gynecologic malignancies, ovarian cancer (OC) has the poorest survival rate, and its clinical management remains challenging due to the high rate of recurrence and chemoresistance. Improving survival for these patients is critical, although this requires the ability to translate preclinical studies to actual patient care: bench to bedside and back. Our objective was to develop a preclinical model that accurately represents tumor biology and its microenvironment. We utilized SKOV-3, OVCAR-8, and CS-99 cell lines to show that this model was suitable for in vitro assessment of cell proliferation. We tested OC cells independently and in co-culture with cancer associated fibroblasts (CAFs) or immune cells. Additionally, we used patient-derived ovarian carcinoma and carcinosarcoma samples to show that the system maintains the histologic morphology of the primary tissue after 7 days. Moreover, we tested the response to chemotherapy using both cell lines and patient-derived tumor specimens and confirmed that cell death was significantly higher in the treated group compared to the vehicle group. Finally, we immune profiled the 3-D model containing patient tissue after several days in the bioreactor system and revealed that the immune populations are still present. Our data suggest that this model is a suitable preclinical model to aid in research that will ultimately impact the treatment of patients with gynecologic cancer.

Genetic association of anthropometric traits with type 2 diabetes in ethnically endogamous Sindhi families.

BACKGROUND: Ethnically endogamous populations can shed light on the genetics of type 2 diabetes. Such studies are lacking in India. We conducted this study to determine the genetic and environmental contributions of anthropometric traits to type 2 diabetes risk in the Sindhi families in central India. METHODS: We conducted a family study in Indian Sindhi families with at least one case of type 2 diabetes. Variance components methods were used to quantify the genetic association of 18 anthropometric traits with eight type 2 diabetes related traits. Univariate and bivariate polygenic models were used to determine the heritability, genetic and environmental correlation of anthropometric traits with type 2 diabetes related traits. RESULTS: We included 1,152 individuals from 112 phenotyped families. The ascertainment-bias corrected prevalence of type 2 diabetes was 35%. Waist circumference, hip circumference and the biceps, triceps, subscapular and medial calf skinfold thicknesses were polygenically and significantly associated with type 2 diabetes. The range of heritability of the anthropometric traits and type 2 diabetes related traits was 0.27-0.73 and 0.00-0.39, respectively. Heritability of type 2 diabetes as a discrete trait was 0.35. Heritability curves demonstrated a substantial local influence of type 2 diabetes related traits. Bivariate trait analyses showed that biceps and abdominal skinfold thickness and all waist-containing indexes were strongly genetically correlated with type 2 diabetes. CONCLUSIONS: In this first study of Sindhi families, we found evidence for genetic and environmental concordance of anthropometric traits with type 2 diabetes. Future studies need to probe into the genetics of type 2 diabetes in this population.

Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer.

OBJECTIVE: Patients with epithelial ovarian cancer (EOC) typically present with late-stage disease, posing a significant challenge to treatment. Although taxane and platinum-based chemotherapy plus surgical debulking are initially effective, EOC is marked by frequent recurrence with resistant disease. Immunotherapy represents an appealing treatment paradigm given the ability of immune cells to engage metastatic sites and impede recurrence; however, response rates to checkpoint blockade in ovarian cancer have been disappointing. Here, we tested whether class I HDAC inhibition can promote anti-tumor T cell responses in a spontaneous and nonspontaneous murine model of EOC. METHODS: We used the spontaneous Tg-MISIIR-Tag and nonspontaneous ID8 models of murine ovarian cancer to test this hypothesis. Whole tumor transcriptional changes were assessed using the nCounter PanCancer Mouse Immune Profiling Panel. Changes in select protein expression of regulatory and effector T cells were measured by flow cytometry. RESULTS: We found that treatment with the class I HDAC inhibitor entinostat upregulated pathways and genes associated with CD8 T cell cytotoxic function, while downregulating myeloid derived suppressor cell chemoattractants. Suppressive capacity of regulatory T cells within tumors and associated ascites was significantly reduced, reversing the CD8-Treg ratio. CONCLUSIONS: Our findings suggest class I HDAC inhibition can promote activation of intratumoral CD8 T cells, potentially by compromising suppressive networks within the EOC tumor microenvironment. In this manner, class I HDAC inhibition might render advanced-stage EOC susceptible to immunotherapeutic treatment modalities.

Neutralization of TGFß Improves Tumor Immunity and Reduces Tumor Progression in Ovarian Carcinoma.

The immunosuppressive effects of TGFß promotes tumor progression and diminishes response to therapy. In this study, we used ID8-p53-/- tumors as a murine model of high-grade serous ovarian cancer. An mAb targeting all three TGFß ligands was used to neutralize TGFß. Ascites and omentum were collected and changes in T-cell response were measured using flow. Treatment with anti-TGFß therapy every other day following injection of tumor cells resulted in decreased ascites volume (4.1 mL vs. 0.7 mL; P < 0.001) and improved the CD8:Treg ratio (0.37 vs. 2.5; P = 0.02) compared with untreated mice. A single dose of therapy prior to tumor challenge resulted in a similar reduction of ascites volume (2.7 vs. 0.67 mL; P = 0.002) and increased CD8:Tregs ratio (0.36 vs. 1.49; P = 0.007), while also significantly reducing omental weight (114.9 mg vs. 93.4 mg; P = 0.017). Beginning treatment before inoculation with tumor cells and continuing for 6 weeks, we observe similar changes and prolonged overall survival (median 70 days vs. 57.5 days). TGFß neutralization results in favorable changes to the T-cell response within the tumor microenvironment, leading to decreased tumor progression in ovarian cancer. The utilization of anti-TGFß therapy may be an option for management in patients with ovarian cancer to improve clinical outcomes and warrants further investigation.

Inhibition of the Wnt/ß-catenin pathway enhances antitumor immunity in ovarian cancer.

BACKGROUND: The Wnt/ß-catenin pathway is linked to tumorigenesis in a variety of tumors and promotes T cell exclusion and resistance to checkpoint inhibitors. We sought to determine whether a small molecule inhibitor of this pathway, WNT974, would impair tumor growth, affect gene expression patterns, and improve the immune response in human and murine ovarian cancer models. METHODS: Human ovarian cancer cells were treated with WNT974 in vitro. RNAseq libraries were constructed and differences in gene expression patterns between responders and nonresponders were compared to The Cancer Genome Atlas (TCGA). Mice with subcutaneous or intraperitoneal ID8 ovarian cancer tumors were treated with WNT974, paclitaxel, combination, or control. Tumor growth and survival were measured. Flow cytometry and ß-TCR repertoire analysis were used to determine the immune response. RESULTS: Gene expression profiling revealed distinct signatures in responders and nonresponders, which strongly correlated with T cell infiltration patterns in the TCGA analysis of ovarian cancer. WNT974 inhibited tumor growth, prevented ascites formation, and prolonged survival in mouse models. WNT974 increased the ratio of CD8+ T cells to T regulatory cells (Tregs) in tumors and enhanced the effector functions of infiltrating CD4+ and CD8+ T cells. Treatment also decreased the expression of inhibitory receptors on CD8+ T cells. Combining WNT974 with paclitaxel further reduced tumor growth, prolonged survival, and expanded the T cell repertoire. CONCLUSIONS: These findings suggest that inhibiting the Wnt/ß-catenin pathway may have a potent immunomodulatory effect in the treatment of ovarian cancer, particularly when combined with paclitaxel.

Inhibiting WNT Ligand Production for Improved Immune Recognition in the Ovarian Tumor Microenvironment.

In ovarian cancer, upregulation of the Wnt/ß-catenin pathway leads to chemoresistance and correlates with T cell exclusion from the tumor microenvironment (TME). Our objectives were to validate these findings in an independent cohort of ovarian cancer subjects and determine whether inhibiting the Wnt pathway in a syngeneic ovarian cancer murine model could create a more T-cell-inflamed TME, which would lead to decreased tumor growth and improved survival. We preformed RNA sequencing in a cohort of human high grade serous ovarian carcinoma subjects. We used CGX1321, an inhibitor to the porcupine (PORCN) enzyme that is necessary for secretion of WNT ligand, in mice with established ID8 tumors, a murine ovarian cancer cell line. In order to investigate the effect of decreased Wnt/ß-catenin pathway activity in the dendritic cells (DCs), we injected ID8 cells in mice that lacked ß-catenin specifically in DCs. Furthermore, to understand how much the effects of blocking the Wnt/ß-catenin pathway are dependent on CD8+ T cells, we injected ID8 cells into mice with CD8+ T cell depletion. We confirmed a negative correlation between Wnt activity and T cell signature in our cohort. Decreasing WNT ligand production resulted in increases in T cell, macrophage and dendritic cell functions, decreased tumor burden and improved survival. Reduced tumor growth was found in mice that lacked ß-catenin specifically in DCs. When CD8+ T cells were depleted, CGX1321 treatment did not have the same magnitude of effect on tumor growth. Our investigation confirmed an increase in Wnt activity correlated with a decreased T-cell-inflamed environment; a relationship that was further supported in our pre-clinical model that suggests inhibiting the Wnt/ß-catenin pathway was associated with decreased tumor growth and improved survival via a partial dependence on CD8+ T cells.

Reactive mechanism and the applications of bioactive prebiotics for human health: Review.

Prebiotics plays an important role in improving the growth of gut bacteria and it majorly found in various natural food sources such as fruits and vegetables. Nowadays, the prebiotic sources are added as a supplement in various food products such as dairy products, beverages, health drinks, infant formulae, and meat products. The presence of prebiotics provides various health benefits such as improveing calcium and magnesium absorption, increases bone density, reduces cancer risk, decreases cardiovascular diseases and also improves the immune system.

S,S-Chiral Linker Induced U Shape with a Syn-facial Sensitizer and Photocleavable Ethene Group.

There is a major need for light-activated materials for the release of sensitizers and drugs. Considering the success of chiral columns for the separation of enantiomer drugs, we synthesized an S,S-chiral linker system covalently attached to silica with a sensitizer ethene near the silica surface. First, the silica surface was modified to be aromatic rich, by replacing 70% of the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3-component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate to the (3-phenoxypropyl)silane-coated silica surface. We hypothesized that the chiral linker would increase exposure of the ethene site for enhanced 1 O2 -based sensitizer release. However, the chiral linker caused the sensitizer conjugate to adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in a reduced efficiency of surface loading. Further accentuating the U shape was π-π stacking between the (3-phenoxypropyl)silane and sensitizer. Semiempirical calculations and singlet oxygen luminescence data provided deeper insight into the sensitizer's orientation and release. This study has lead to insight on modifications of surfaces for drug photorelease and can help lead to the development of miniaturized photodynamic devices.