Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells.

Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC. SIGNIFICANCE: The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models. This article is featured in Selected Articles from This Issue, p. 5.

Use of allograft fat for aesthetic and functional restoration of soft tissue contour deformities.

The authors report a case series of five patients with Leneva grafted into the nose, hand, genitalia and below-the-knee stump. Leneva is an allograft adipose matrix derived from aseptically processed human adipose tissue with retained matrix proteins, growth factors, cytokines and collagens. It is manufactured hydrated and is available in pre-loaded syringes. Five patients (3F, 2 M) with a mean age of 50.7 (range 31-77 years) injected with a mean volume of 4.2 cc (range 3-6 cc) of Leneva in various anatomic locations with an average follow up time of 4.25 months (range 0.5-12 months) experienced no allergic reactions, infection, fat necrosis or oil cysts. All patients were pleased with the restoration of fullness to the injected site. The authors believe that Leneva is a promising multi-use filler for restoring soft tissue defects following resection of tumours, to rejuvenate age-related atrophy, aesthetically enhance the genitals and provide padding for transtibial prostheses.

Effect of Thermoelectric Warming Therapy for the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To evaluate the efficacy of thermoelectric warming therapy (MiBoFlo) in improving patient symptoms with standardized questionnaires and objective signs of meibomian gland dysfunction (MGD), which is an important underlying treatable factor in dry eye disease (DED), such as ocular surface staining, tear quality, and meibomian gland morphology. Multivariate analysis to identify predictors for the improvement in Ocular Surface Disease Index (OSDI) was also performed. DESIGN: Retrospective before-and-after study. METHODS: A total of 203 eyes of 102 patients with DED were treated with MiBoFlo at the dry eye center. The OSDI and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires, best-corrected visual acuity, tear osmolarity, tear film breakup time (TBUT), corneal and conjunctival staining, meibography, number of glands expressing liquid, and quality of the improved meibum were assessed before and 6 months after MiBoFlo. Exclusion criteria included active ocular inflammation. RESULTS: Dry eye symptoms improved in the population, with both SPEED and OSDI lowering of dry eye symptoms by approximately 35% (P < .001) at month 6. Significant improvements in lissamine green conjunctival staining, corneal fluorescein staining, TBUT, osmolarity, and secreting meibomian glands and meibum quality were also seen. Improvement was seen across all domains of the questionnaires and across all baseline parameters. Eyes with blepharitis and autoimmune disease improved less than average. No complications or adverse events occurred. CONCLUSIONS: MiBoFlo treatments produced clinical and statistically significant improvements in the signs and symptoms of MGD, irrespective of underlying ocular conditions. This improvement was sustained for the 6-month period of observation after initiating the treatment.

IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents 3% of all cancer cases and 7% of all cancer deaths in the United States. Late diagnosis and inadequate response to standard chemotherapies contribute to an unfavorable prognosis and an overall 5-year survival rate of less than 10% in PDAC. Despite recent advances in tumor immunology, tumor-induced immunosuppression attenuates the immunotherapy response in PDAC. To date, studies have focused on IgG-based therapeutic strategies in PDAC. With the recent interest in IgE-based therapies in multiple solid tumors, we explored the MUC1-targeted IgE potential against pancreatic cancer. Our study demonstrates the notable expression of FceRI (receptor for IgE antibody) in tumors from PDAC patients. Our study showed that administration of MUC1 targeted-IgE (mouse/human chimeric anti-MUC1.IgE) antibody at intermittent levels in combination with checkpoint inhibitor (anti-PD-L1) and TLR3 agonist (PolyICLC) induces a robust antitumor response that is dependent on NK and CD8 T cells in pancreatic tumor-bearing mice. Subsequently, our study showed that the antigen specificity of the IgE antibody plays a vital role in executing the antitumor response as nonspecific IgE, induced by ovalbumin (OVA), failed to restrict tumor growth in pancreatic tumor-bearing mice. Utilizing the OVA-induced allergic asthma-PDAC model, we demonstrate that allergic phenotype induced by OVA cannot restrain pancreatic tumor growth in orthotopic tumor-bearing mice. Together, our data demonstrate the novel tumor protective benefits of tumor antigen-specific IgE-based therapeutics in a preclinical model of pancreatic cancer, which can open new avenues for future clinical interventions.

Preclinical Models for Studying the Impact of Macrophages on Cancer Cachexia.

Cancer-associated cachexia is defined by loss of weight and muscle mass, and by the potential loss of adipose tissue accompanied by insulin resistance and increased resting energy expenditure. Cachexia is most prevalent in pancreatic cancer, the third leading cause of cancer-related deaths. While various factors interact to induce cachexia, the precise mechanisms underlying this clinical condition are not fully understood. Clinically relevant animal models of cachexia are needed given the lack of standard diagnostic methods or treatments for this condition. Described in this article are in vitro and in vivo models used to study the role of macrophages in the induction of cachexia in pancreatic cancer. Included are procedures for isolating and culturing bone marrow-derived macrophages, harvesting tumor- and macrophage-derived conditioned medium, and studying the effect of conditioned medium on C2C12 myotubes. Also described are procedures involving the use of an orthotopic model of pancreatic cancer, including a method for examining skeletal muscle atrophy in this model. © 2020 Wiley Periodicals LLC. Basic Protocol 1: In vitro model of pancreatic tumor-induced cachexia using C2C12 cell lines (myotube model) Support Protocol 1: Molecular evaluation of cachectic markers in C2C12 myotubes using real-time PCR and immunoblotting Basic Protocol 2: In vivo model to study cachectic phenotype in pancreatic tumor-bearing mice Support Protocol 2: Evaluation of cachectic markers in the skeletal muscle of tumor-bearing mice.

Age-related changes in diastolic function in children: Echocardiographic association with vortex formation time.

BACKGROUND: This study aims to understand the age-related changes in vortex formation time (VFT) index in children, and thus, describe the ranges of VFT in different pediatric age groups with the ultimate goal of assessment of diastolic function. METHODS AND RESULTS: Transthoracic echocardiograms in healthy (n = 84) subjects from birth to 20 years were analyzed to compute VFT and diastolic performance. LV apical and short-axis views were used. Three separate measurements were performed, and the mean was used to derive VFT and other indices. Statistical comparisons were made amongst the groups, stratified by age. RESULTS: Vortex formation times in neonates (median 1.79, interquartile range 1.31-1.92) and infants (1.38, 1.07-1.72) were found to be significantly lower (P < .05) than the older age groups (1-5 years 2.47, 1.87-2.94, 5-10 years 2.18, 1.89-2.53, 10-20 years 2.34, 1.84-2.96). The changes in VFT correlate to the changes in diastolic function in children. CONCLUSION: Our results show that unlike adults, VFT changes along with the growth-related myocardial adaptations in children, and its range may be used to evaluate diastolic function. The present study is the first to test the significance of the trans-mitral VFT in children by comparing different age groups of healthy subjects.

Combined General and Epidural Anesthesia is Associated With Decreased Opioid Consumption and Enhanced Pain Control After Penile Inversion Vaginoplasty in Transwomen.

BACKGROUND: Penile skin inversion vaginoplasty is a gender-affirming surgical procedure for transwomen with limited surgical analgesic protocol. This study compares the postoperative pain and opioid use in patients managed for surgery with general anesthesia (GA) with patients who were given combined epidural and general anesthesia (E/GA) with continuing postoperative epidural analgesia. METHODS: All patients who underwent penile inversion vaginoplasty between May of 2016 and May of 2018 under the care of single surgeon were identified retrospectively, 18 patients of which met the inclusion criteria. A retrospective chart review was conducted. Outcome measures were postoperative pain using visual analog scale, type and dosage of postoperatively administered intravenous or oral opioids (converted to morphine milligram equivalents, duration of inpatient admission, and time to ambulation. RESULTS: Patients who received combined E/GA reported significantly less pain and used less opioids during the first 4 postoperative days in comparison with patients who received GA alone. The reduction in mean pain associated with the use of an epidural was found to be statistically significant (P < 0.0005) as was the difference in opioid used in the 2 groups (P < 0.005) over the first 4 days postoperatively. Differences in day 5 pain suggest that postoperative pain is significantly lower even after the epidural has been removed (P < 0.005). There was no significant difference in length of hospital stay and time to ambulation (P > 0.05). CONCLUSIONS: Combined E/GA was associated with decreased inpatient opioid consumption after surgery and provided superior pain control than administration of GA alone. Based on these findings, combined E/GA should be strongly considered for patients undergoing penile inversion vaginoplasty.

Conocimiento de la técnica de utilización de los aerosoles en pacientes con asma bronquial / Knowledge of the use´s technique of aerosols in patients with bronchial asthma

Introducción: El principal inconveniente de la utilización de la vía inhalada para la administración de fármacos estriba en la dificultad que la mayoría de los pacientes tienen para utilizarlos correctamente. Un uso inapropiado de estos contribuye a un control deficiente del asma. Objetivo: Determinar el conocimiento del uso de los inhaladores en pacientes asmáticos. Métodos: Se realizó un estudio descriptivo de corte transversal con los 29 pacientes diagnosticados como asmáticos en el Consultorio 9, Área II, de Cienfuegos. Se utilizaron como variables: edad, sexo y los nueve pasos a evaluar en el uso de los nebulizadores. Los datos se expresaron en frecuencia absoluta y relativa para mejor comprensión. Resultados: Se demostró que el 72,4 por ciento de los enfermos recibieron calificación de mal. Predominaron los errores en realizar una espiración lenta y profunda, rectificar la curvatura de la tráquea, periodo de apnea y en retener la respiración, al menos, 10 segundos. Conclusiones: El mayor número de pacientes presentó un uso incorrecto de los aerosoles presurizados, a pesar de haber sido adiestrados por especialistas(AU)

Introduction: The main drawback of the inhaled pathway for drugs administration lies in the difficulty that most patients present to use them correctly. An inappropriate use of those contributes to an inadequate control of asthma. Objective: To determine the knowledge on the use of inhalers in asthmatic patients. Methods: A descriptive, cross-sectional study was conducted with the 29 patients diagnosed as asthmatics in the Family Doctor´s Office 9, Area II, Cienfuegos province. The variables used were: age, sex, as well as the nine steps to assess in the use of nebulizers. Data were expressed in absolute and relative frequency for a better understanding. Results: It was shown that 72.4 percent of the patients received bad scores predominating errors in the performance of a slow and deep exhalation, in rectifying the curvature of the trachea, in the apnea period and holding the breath for at least 10 seconds. Conclusions: The highest number of patients presented a misuse of pressurized aerosols despite being trained by specialists(AU)

Effect of an Educational Video to Increase Calls and Screening into an Anal Cancer Clinical Trial Among HIV+ Hispanics in PR: Results from a Randomized Controlled Behavioral Trial.

Anal cancer incidence is higher in persons living with HIV/AIDS (PLWHA) than in the general population. Participation of PLWHA in anal cancer clinical trials (CTs) is essential; Hispanic PLWHA are underrepresented in CTs. We conducted a behavioral CT among 305 PLWHA in Puerto Rico to measure the efficacy of an educational video in increasing calls and screening into an anal cancer CT. Participants received printed educational materials on anal cancer and CTs; the intervention group also received an educational video. Outcome assessment based on follow-up interviews showed that printed materials increased awareness about CTs and high-resolution anoscopy (HRA), and willingness to participate in an anal cancer CT in both groups. However, the addition of the video increased the likelihood of participants to call the CT for orientation (RRadjusted = 1.66, 95% CI 1.00-2.76; p = 0.05) and pre-screening evaluation (RRadjusted = 1.70, 95% CI 0.95-3.03; p = 0.07). This intervention could help increase participation of Hispanics into anal cancer-related CTs.

Removal of Cu2+ and Ni2+ from Aqueous Solution using SnO2 Nanomaterial effect of: pH, Time, Temperature, interfering cations.

Tin oxide, SnO2, nanomaterial was synthesized and tested for the removal of Cu2+ and Ni2+ ions from aqueous solutions. Various parameters for the binding were investigated in batch studied, which included pH, time, temperature, and interferences. In addition, isotherm studied were performed to determine the maximum binding capacity for both Cu2+ and Ni2+ ions. The optimal binding pH determined from the effects of pH were to be at pH 5 for both the Cu2+ and Ni2+ ions. The isotherm studies were performed at temperatures of 4°C, 25 °C, and 45 °C for both the Cu2+ and Ni2+ ions and were found to follow the Langmuir isotherm model. The binding capacities for the Cu2+ ions were 2.63 mg/g, 2.95 mg/g and 3.27 mg/g at the aforementioned temperatures, respectively. Whereas the binding capacities for Ni2+ were 0.79 mg/g, 1.07 mg/g, and 1.46 mg/g at the respective temperatures. The determined thermodynamic parameters for the binding showed that the binding processes for the reactions were endothermic, as the ΔG was observed to decrease with decreasing temperatures. As well the ΔH was 28.73 kJ/mol for Cu2+ (III) and 13.37 kJ/mol for Ni2+. The ΔS was observed to be 92.65 J/mol for Cu2+ and 54.53 J/mol for Ni2+. The free energy of adsorption for the Cu2+ was determined to be 13.99 kJ/mol and the activation energy for the binding of Ni2+ was determined to be 8.09 KJ/mol. The activation energy data indicate that the reaction was occurring through chemisorption.

Periodontitis and oral human papillomavirus infection among Hispanic adults.

INTRODUCTION: Research on the association between periodontitis and oral human papilloma virus (HPV) infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults. METHODS: Data from the 2014-2016 San Juan Overweight Adults Longitudinal Study (n = 740) was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: 5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0-8.4, p < 0.05) in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection. CONCLUSIONS: Severe periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammation's role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies.

Association of marijuana use with oral HPV infection and periodontitis among Hispanic adults: Implications for oral cancer prevention.

BACKGROUND: Despite limited data, research suggests that marijuana use is associated with oral HPV infection and periodontitis, two potential oropharyngeal cancer risk factors. We assessed these associations in a Hispanic adult population in Puerto Rico. METHODS: A cross-sectional study of 735 adults assessed marijuana use, determined through an audio computer-assisted self-interview, and periodontitis and self-collection of oral HPV samples following the National Health and Nutrition Examination Survey methodology. The Centers of Disease Control and Prevention/American Academy of Periodontology definition was used for periodontitis. HPV typing was performed using polymerase chain reaction with modified L1 consensus primers (MY09/MY11). RESULTS: 26.5% of adults reported lifetime use of marijuana, 2.7% were frequent users (lifetime use ≥ 26 times, past year use ≥ 6 times, and past 30-day use ≥2 times), 5.7% had oral HPV infection, and 20.1% had severe periodontitis. The multivariate logistic regression analysis showed that frequent marijuana users were more likely to have severe periodontitis (OR = (2.93, 95%: 1.08-7.96)) than never/once lifetime users after adjusting for age, sex, healthcare coverage, smoking, binge drinking, number of oral sex partners, and oral HPV infection. However, frequent marijuana use was not associated with oral HPV infection. CONCLUSION: Marijuana use was associated with periodontitis, but not with oral HPV infection. Further evaluation of the role of marijuana use in oral HPV infection and periodontitis may inform novel preventive public health strategies, as marijuana users could be at increased risk of oral cancer.

Community-Academic Partnership to Implement a Breast and Cervical Cancer Screening Education Program in Puerto Rico.

OBJECTIVE: To describe how a community-academic partnership between Taller Salud Inc., a community-based organization, and the Puerto Rico Community Cancer Control Outreach Program of the University of Puerto Rico was crucial in the adaptation and implementation of Cultivando La Salud (CLS), an evidencebased educational outreach program designed to increase breast and cervical cancer screening among Hispanic women living in Puerto Rico. This collaboration facilitated the review and adaptation of the CLS intervention to improve cultural appropriateness, relevance, and acceptability for Puerto Rican women. METHODS: A total of 25 interviewers and 12 Lay Health Workers (LHWs) were recruited and trained to deliver the program. The interviewers recruited women who were non-adherent to recommended screening guidelines for both breast and cervical cancer. LHWs then provided one-on-one education using the adapted CLS materials. RESULTS: A total of 444 women were recruited and 48% of them were educated through this collaborative effort. CONCLUSION: Our main accomplishment was establishing the academic-community partnership to implement the CLS program. Nevertheless, in order to promote better collaborations with our community partners, it is important to carefully delineate and establish clear roles and shared responsibilities for each partner for the successful execution of research activities, taking into consideration the community's needs.

Cervical Cancer Screening and Sexual Risky Behaviors among a Population of Hispanic Origin.

OBJECTIVE: To assess the prevalence of cervical cancer screening through Papanicolaou (Pap) test utilization and its association with sexual behaviors among a population-based sample of Hispanic women in Puerto Rico (PR). METHODS: This study was a secondary data analysis of the database of a cross-sectional study of HPV infection in PR (2010-2013; n = 554 women). Pap test utilization (past 3 years) was self-reported and sexual risky behavior was defined as an index that considered the following sexual behaviors: early age of sexual debut (≤16 years), 11 or more lifetime sexual partners, and 2 or more sexual partners in the last year. Multivariable logistic regression was used to estimate the magnitude of the association between sexual risk behavior and Pap test utilization, after adjusting for socioeconomic and lifestyles characteristics. RESULTS: The overall prevalence of Pap test utilization was 78.0%. Pap test screening varied with sexual behavior, with women with none or one risky sexual behavior having higher odds of Pap test utilization in the past 3 years (odds ratio [OR], 1.74; 95% CI, 1.03-2.93) compared with those with two or three risky sexual behaviors. This difference remained marginally significant (p < .10) after adjusting for age, educational attainment, smoking status and STI history (OR, 1.72; 95% CI, 0.96-3.08). CONCLUSIONS: The prevalence of cervical cancer screening in this population (78%) is still below Healthy People 2020 recommendations (93%). Also, women with risky sexual behaviors are less likely to have been screened. Efforts to promote cervical screening programs should focus on these high-risk women as a method for cervical cancer prevention and control.

Body dysmorphic disorder and psychological distress in orthognathic surgery patients.

PURPOSE: Body dysmorphic disorder (BDD) is a distressing condition involving preoccupation with an imagined or exaggerated deformity. The purpose of our study was to investigate the presence of BDD and its comorbidity with anxiety, depression, and obsessive-compulsive disorder (OCD) in patients undergoing orthognathic surgery (OS). MATERIALS AND METHODS: The present prospective study included 99 patients from the outpatient oral and maxillofacial surgery clinic at Stanford University who requested OS. The incidence of BDD, depression, anxiety, and OCD was assessed preoperatively using validated self-report measures. To determine the prevalence of Axis I psychological symptoms among patients, the descriptive and bivariate statistics were computed. P < .05 was considered significant. RESULTS: In our sample, 13 patients (13%) screened positive for BDD. We did not find any significant correlations between the presence of BDD and gender, race, age, or marital status. Depressive symptoms were reported by 42% of the patients, OCD symptoms by 29%, and mild, moderate, and severe anxiety by 14%, 5%, and 4%, respectively. Using Spearman correlations, we found significant correlations between BDD and anxiety, depression, and OCD (P < .01). CONCLUSIONS: The results of the present study suggest that the rates of BDD, depression, anxiety, and OCD are high in patients undergoing OS. Furthermore, we found a strong correlation between BDD and anxiety, OCD, and depression in these patients. Future studies are necessary to determine the postoperative changes in these psychological disorders and whether these changes are affected by having positive BDD screening results at baseline.