Evaluation of aspirin platelet inhibition in left ventricular assist device population.

INTRODUCTION: Aspirin therapy is recommended in durable left ventricular assist device (LVAD) patients to prevent thromboembolic complications. Up to 30% of patients treated with aspirin may demonstrate aspirin resistance, which has been related to thrombotic complications. However, it is unknown whether individual patients exhibit temporal alterations in aspirin sensitivity during LVAD support. We hypothesized that aspirin platelet inhibition would wane after the initial postimplant period. METHODS: This was a retrospective, observational, single center study conducted at an academic medical center. This study evaluated changes in aspirin platelet inhibition over the first 6 months of LVAD support. Patients who underwent placement of centrifugal LVAD with aspirin platelet sensitivity assays were included for analysis. Aspirin responsiveness was assessed postimplant after 5 days, 3 months, and 6 months. RESULTS: A total of 28 patients were included for analysis of which 7% of patients were aspirin resistant initially. At 3 months, 32% (odds ratio [OR], 6.1, p = .03) of patients were aspirin resistant and 28% (OR, 4.1, p = .1) at 6 months. Over the first 3 months postimplant, the odds of aspirin resistance increased sixfold and remained relatively constant at 6 months. Patients who were aspirin resistant and received an increase in aspirin dose at 3 months subsequently had a sensitive ARU at 6 months. CONCLUSION: Aspirin responsiveness not only varies between patients but can significantly wane within individual LVAD patients over time. Additional study is needed to determine if monitoring aspirin resistance may prevent thrombotic complications after LVAD implantation.

Improving enzyme production by solid-state cultivation in packed-bed bioreactors by changing bed porosity and airflow distribution.

Enzymes production by solid-state cultivation in packed-bed bioreactor needs to be improved by mathematical modeling and also by experimentation. In this work, a mixture of sugarcane bagasse and wheat bran was used for the growth of the fungus Myceliophthora thermophila I-1D3b, able to secrete endoglucanase and xylanase, enzymes of interest in the second-generation ethanol production. Bench and pilot-scale bioreactors were used for the experiments, while critical parameters as bed porosity and airflow distribution were evaluated. Results showed enzymes with higher activities for the most porous medium, even though the less substrate amount to be cultivated. For the pilot-scale bioreactor, only the most porous medium was evaluated using different airflow distribution techniques. Using an inner tube for air supply resulted in more homogeneous enzyme production, with higher activities. The results here presented will be helpful for the scale-up of this class of bioreactor into industrial apparatuses.

Impact of a multidisciplinary multimodal opioid minimization initiative in kidney transplant recipients.

Opioid use after kidney transplant has been shown to be a risk factor for chronic opioid use, which leads to an increased risk of mortality. The purpose of this study was to evaluate the early impact of a multimodal pain regimen and education quality improvement program on opioid use after kidney transplant 2 months after implementation. This was a retrospective, single-center analysis of post-operative opioid use, comparing the average daily Morphine milligram equivalents (MME) of the patients who received education on opioids and a multimodal pain regimen (preoperative TAP/QL block, scheduled APAP and gabapentin) compared to a historical control group. Despite having no differences in pre-transplant opioid exposure, daily and overall inpatient opioid utilization was significantly reduced in the multimodal pain protocol cohort (38.6 vs 8.0 MME/day; P < .001); 5% of patients in the multimodal pain protocol cohort were discharged with an opioid prescription, compared to 96% of controls (P < .001). Our early results demonstrate that a multimodal pain protocol can effectively and dramatically reduce short-term opioid utilization in kidney transplant recipients.

Among Adolescents, BDNF and Pro-BDNF Lasting Changes with Alcohol Use Are Stage Specific.

Adolescent alcohol use demonstrates distinct developmental trajectories with dissimilar times of onset and trajectories. Given the importance of brain-derived neurotrophic factor (mature BDNF) in this development stage, the current study investigated its relationship with alcohol use. It also extends the literature by assessing the role of its precursor (pro-BDNF). Therefore, over the span of 5 years, we enrolled and followed participants to define age-related changes in BDNF levels in healthy adolescents. Then, the onset and frequency of alcohol use from ages 11 to 18 were collected to determine how the relationship between alcohol, pro-BDNF, and m-BDNF unfolds over time. With respect to development, analyses demonstrated that BDNF concentration slowly increases throughout adolescence. However, despite having similar basal BDNF levels, compared to controls, adolescents that started drinking before 15 years of age always exhibited lower BDNF levels. They also had a significant decrease in pro-BDNF levels. On the other hand, levels of mature BDNF steadily increased (974.896 ± 275 pg/ml) in those starting alcohol use after the age of 15. Similar to the younger users, a significant drop in pro-BDNF levels was observed over the course of the study. Our results suggested that both pathways may participate in the complex processes of alcohol dependence. The findings highlight the relevance of assessing alcohol-associated changes across the different phases of this vulnerable developmental period. This is the first study evidencing that m-BDNF changes associated with drinking behaviors differed between young and older adolescents. It is also the first article, documenting that drinking during adolescence leads to long-term decreases in pro-BDNF. These results have important implications for policies and programs targeting alcohol use disorders.

Computer-assisted psychological assessment and psychotherapy for collegians.

OBJECTIVE: This article reviews research on computerized and computer-assisted psychological assessment and psychotherapy for college and university students. METHOD: Published reviews of outcome research on the topic are reviewed, along with individual clinical trials and other relevant studies not covered by reviews, as well as reviews of closely-related research. RESULTS: Computer-assisted assessment and psychotherapy have proven effective with collegians across samples, nations, and presenting concerns. CONCLUSIONS: Currently-available digital technologies can address these mental health service delivery challenges: cost, limited human resources, failure of students to seek help, stigmatization of collegians seeking help, premature termination, inadequate process and outcome data to assess and improve treatment effectiveness, and lack of real-time data-based treatment selection.

Safety and Efficacy of Perioperative Sublingual Tacrolimus in Pancreas Transplant Compared With Oral Tacrolimus.

OBJECTIVES: Early posttransplant, the administration of oral or enteral medications in pancreas transplant is challenging because of the management of postoperative ileus and gastroparesis. The use of sublingual tacrolimus may offer a promising alternative. The objective of this study was to compare the pharmacokinetics and perioperative outcomes between oral and sublingual tacrolimus in pancreas transplant. MATERIALS AND METHODS: This was a single-center, retrospective study of pancreas transplants between January 1, 2011, and July 1, 2018. We transitioned our tacrolimus protocol from oral to sublingual dosing in pancreas transplant patients beginning January 1, 2017. RESULTS: This analysis included 54 pancreas transplant recipients, with 17 patients on sublingual tacrolimus matched to 37 patients on oral tacrolimus. Within the sublingual group, it took a mean of 3.2 days to achieve a therapeutic tacrolimus trough level (≥8 ng/mL) compared with a mean of 3.8 days in the oral group (P = .175). There was no difference in the incidence of hyperkalemia and supratherapeutic tacrolimus levels between groups. The conversion factor from sublingual to oral in this patient population was 0.67, which was different than what has been reported in other populations. Clinical outcomes were similar between groups. CONCLUSIONS: Sublingual tacrolimus use in pancreas transplant patients appears to be a safe and effective strategy to avoid oral or intravenous therapy in the perioperative period and may reduce the time to achieve therapeutic levels.

Disparities in Sleep Health among Adolescents: The Role of Sex, Age, and Migration.

Background. Disparities in sleep disturbances have been described in adults; nevertheless, among adolescents, data have yielded conflicting results. Therefore, analyses of our cohort study of 500 urban, normally developed Hispanic adolescents (10-18 years), aim to determine if rates of sleep debt differ between: (a) male and female adolescents, (b) US-born Hispanics and first-generation immigrant ethnic counterparts, and (c) specific activities that these teens trade for sleep. Participants' weekday and weekend sleep patterns, along with the reasons for sleeping less than the recommended hours were recorded. Standardized surveys were used to gather information regarding sociodemographics, migration, acculturation, and medical history. Using the criteria set forth by the National Sleep Foundation, analyses indicated that sleep deprivation is a pervasive problem, with 75% in the preadolescents and 45% of the late adolescents exhibiting sleep problems. Females slept on average at least one hour less per day than their male counterparts (7 vs. 8 hours). The sleep problems were rooted in several overlapping causes, including use of technology, video games, studying, and employment. Nevertheless, reasons for sleep loss differed by gender and by immigrant status. Multivariable adjusted logistic regression analyses showed that females, US-born teens, and preadolescents had higher odds of being sleep deprived. Pediatricians and sleep experts should be aware of gender-specific causes and responses of sleep problems. Cultural ecological frameworks need to be considered, and clearly indicate that findings may not generalize to youth from other cultural backgrounds.

Cutaneous Drug Eruptions in Pediatrics-A Primer.

Cutaneous adverse drug reactions (ADRs) are commonly seen in the pediatric population in both inpatient and outpatient settings and are important to identify, evaluate, and appropriately manage. Early recognition and proper classification of a cutaneous drug reaction allows the clinician the ability to narrow in on a culprit drug and determine whether the medication is safe to continue. This review discusses the clinical presentation, categorization, and management of cutaneous ADRs in the pediatric population. [Pediatr Ann. 2020;49(3):e132-e139.].

Repeated batches as a strategy for high 2G ethanol production from undetoxified hemicellulose hydrolysate using immobilized cells of recombinant Saccharomyces cerevisiae in a fixed-bed reactor.

BACKGROUND: The search for sustainable energy sources has become a worldwide issue, making the development of efficient biofuel production processes a priority. Immobilization of second-generation (2G) xylose-fermenting Saccharomyces cerevisiae strains is a promising approach to achieve economic viability of 2G bioethanol production from undetoxified hydrolysates through operation at high cell load and mitigation of inhibitor toxicity. In addition, the use of a fixed-bed reactor can contribute to establish an efficient process because of its distinct advantages, such as high conversion rate per weight of biocatalyst and reuse of biocatalyst. RESULTS: This work assessed the influence of alginate entrapment on the tolerance of recombinant S. cerevisiae to acetic acid. Encapsulated GSE16-T18SI.1 (T18) yeast showed an outstanding performance in repeated batch fermentations with cell recycling in YPX medium supplemented with 8 g/L acetic acid (pH 5.2), achieving 10 cycles without significant loss of productivity. In the fixed-bed bioreactor, a high xylose fermentation rate with ethanol yield and productivity values of 0.38 gethanol/gsugars and 5.7 g/L/h, respectively were achieved in fermentations using undetoxified sugarcane bagasse hemicellulose hydrolysate, with and without medium recirculation. CONCLUSIONS: The performance of recombinant strains developed for 2G ethanol production can be boosted strongly by cell immobilization in alginate gels. Yeast encapsulation allows conducting fermentations in repeated batch mode in fixed-bed bioreactors with high xylose assimilation rate and high ethanol productivity using undetoxified hemicellulose hydrolysate.

Marijuana use among adolescents is associated with deleterious alterations in mature BDNF.

BACKGROUND: With increases in marijuana use and legalization efforts, it is imperative to establish its impact on the developing brain. Therefore, we investigated whether exposure to marijuana alters brain derived neurotropic-factor (BDNF), given its critical role in brain development and plasticity. We then examined whether onset age of cannabis use was associated with more severe changes. A single site, cohort study following 500 urban healthy American adolescents. Changes in plasma m-BDNF levels were longitudinally assessed, and a multi-method approach was implemented to ascertain marijuana use. Multivariate and general linear model (GLM) regression modeling were utilized to test the main hypothesis, controlling for confounders. RESULTS: Group-based trajectory modeling identified four distinct groups, characterized by naive (60% control), starters (14%), chronic users (20%), and experimenting/quitters (6%). Compared to controls, those initiating marijuana use had similar pre-existent m-BDNF (1939.2 ± 221 vs. 2640.7 ± 1309 ng/ml, p=0.4) After adjusting for confounding factors, GLM analyses revealed that, compared to controls, younger adolescents increased BDNF levels when experimenting and during moderate marijuana use. Older adolescents had a steeper increase in endogenous BDNF levels, particularly when escalating use. Multivariate analyses confirmed marijuana use as a predictor of m-BDNF (p = 0.001). CONCLUSIONS: This is the first study demonstrating BDNF alterations were not a precondition. Rather, BDNF alteration was secondary to marijuana use, serving as cautionary evidence of marijuana's deleterious effects. Findings suggest that when marijuana use escalates, the BDNF pathway becomes more deregulated. Analyses confirm that age of marijuana use onset influences the magnitude of these changes.

Belatacept in Solid Organ Transplant: Review of Current Literature Across Transplant Types.

Calcineurin inhibitors (CNIs) have been the backbone immunosuppressant for solid organ transplant recipients for decades. Long-term use of CNIs unfortunately is associated with multiple toxicities, with the biggest concern being CNI-induced nephrotoxicity. Belatacept is a novel agent approved for maintenance immunosuppression in renal transplant recipients. In the kidney transplant literature, it has shown promise as being an alternative agent by preserving renal function and having a minimal adverse effect profile. There are emerging studies of its use in other organ groups, particularly liver transplantation, as well as using with other alternative immunosuppressive strategies. The purpose of this review is to analyze the current literature of belatacept use in solid organ transplantation and discuss its use in current practice.

Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery.

The majority of penile carcinoma is squamous cell carcinoma. Although uncommon in the United States, it represents a larger proportion of cancers in the underdeveloped world. Invasive squamous cell carcinoma may arise from precursor lesions or de novo , and has been associated with lack of circumcision and HPV infection. Early diagnosis is imperative as lymphatic spread is associated with a poor prognosis. Radical surgical treatment is no longer the mainstay, and penile sparing treatments now are often used, including Mohs micrographic surgery. Therapeutic decisions should be made with regard to the size and location of the tumor, as well as the functional desires of the patient. It is critical for the dermatologist to be familiar with the evaluation, grading/staging, and treatment advances of penile squamous cell carcinoma. Herein, we present a review of the literature regarding penile squamous cell carcinoma, as well as a case report of invasive squamous cell carcinoma treated with Mohs micrographic surgery.

Mal de Meleda: A Focused Review.

Mal de Meleda is a rare autosomal recessive palmoplantar keratoderma (PPK) disease with an estimated prevalence of 1:100,000. Clinically, the onset of the disease is typically soon after birth and features a transgrediens (plantar surface progressing to dorsal surface) and progrediens (worsening with age) pattern of hyperkeratosis of the palms and soles. The disease can feature other potentially disfiguring effects on the hands and feet that can severely impact function. Histologically, the lesions show hyperkeratosis and acanthosis without epidermolysis in the epidermis, accompanied by perivascular lymphocytic infiltrate in the dermis. Secreted LY6/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP-1) genetic mutations are implicated in Mal de Meleda. SLURP-1 is involved in mediation of inflammation as well as keratinocyte apoptosis regulation. Because the disease is so rare, there are no set guidelines for management, but the accepted approach tends to include oral acitretin plus topical keratolytic therapy. Genetic counseling should also be offered. This focused review highlights the clinical and histological features, differential diagnoses, genetic background, and the current thoughts on management of Mal de Meleda.

Contact Dermatitis in Pediatrics.

Contact dermatitis is an umbrella term that describes the skin's reaction to contacted noxious or allergenic substances. The two main categories of contact dermatitis are irritant type and allergic type. This review discusses the signs, symptoms, causes, and complications of contact dermatitis. It addresses the testing, treatment, and prevention of contact dermatitis. Proper management of contact dermatitis includes avoidance measures for susceptible children. Implementation of a nickel directive (regulating the use of nickel in jewelry and other products that come into contact with the skin) could further reduce exposure to the most common allergens in the pediatric population. [Pediatr Ann. 2016;45(8):e287-e292.].

Exposure to Stress and Separation-induced BDNF impairments in adolescents.

BACKGROUND: Although the deleterious effects of separation during early childhood have been extensively studied, little is known regarding other stress-sensitive periods in development, such as adolescence. Also unknown are the biological mechanisms explaining its deleterious effects. This study was carried out to determine how different types of separation can impact neurotrophic factors during adolescence. METHODS: A community sample of 450 Hispanic adolescents was queried in 3 separate visits about regarding four indicators of stress exposure: migration, low closeness to parents, divorce, and growing up with individuals other than their biological parents. Chronological age at the time of exposure to the stressor were documented. BDNF and Pro-BDNF levels were obtained at three time points during the length of the study. RESULTS: The expression of pro-BDNF and m-BDNF was altered by separation, both divorce and death. Of concern, near half of the sample reported their parents to be divorce as a result the majority had mothers that work full time. Exposure to recent life events such as a parent divorce resulted in a time-point dependent, differential down-regulation of m-BDNF levels. Parent-child conflict positively related to BDNF. Specifically, BDNF was affected only in those the father/male adolescent relationship. CONCLUSION: Our data confirmed that separation triggers alterations in BDNF, even after the growth spurt of the brain during early childhood. The important implication of this study is the persistent abnormal levels of BDNF. The prolonged alteration is of concern when considering that BDNF plays a critical role in the pruning process occurring during adolescence. Additional studies are needed to assess whether these alterations can lead to neuropsychological disruptions.

Low HIV/AIDS Knowledge among Hispanic Adolescents.

INTRODUCTION: Hispanic adolescents domiciling in Florida rank second in the U.S. with respect to HIV/AIDS incidence and prevalence. Extending studies showing that risky sexual behavior is associated with limited access to information, this project surveyed knowledge about HIV etiology, prevention and treatment. METHODS: The sample consisted of 400 Hispanic youth between 11-18 years of age living in Miami, Florida. The sample is enrolled in an ongoing project Role of Brain Derived Neurotrophic Factor in Decision Making (ROBIM). The HIV Knowledge Questionnaire (HIV-KQ-18), an 18 item self-administered questionnaire was used to measure HIV knowledge, particularly transmission and prevention. RESULTS: Less than 10% of the sample had comprehensive knowledge about HIV/AIDS. Approximately 25% incorrectly answered all of the questions. Questions pertaining to transmission were incorrectly answered by more than half of the sample. The most frequent topics reflecting absence of knowledge are related to high-risk sexual behaviors (sex during the menses) and infection prevention methods (e.g. condoms). A majority of youth believed incorrectly that HIV could be cured (61%), an effective vaccine is available (61%), and antibiotics protect against HIV infection (76%). School (28%) and parents (26%) were the most frequent sources of knowledge about HIV/AIDS. However, youth receiving information from parents had significantly higher knowledge scores than peers receiving education in school (7.4 ± 4.15 vs. 6.1 ± 4.5 scores, p = 0.037). Yet, 68% of the sample had never discussed condom use with their parents. CONCLUSIONS: These findings indicate Hispanic youths, although at very high risk, are poorly informed about prevention of HIV/AIDS. Moreover, the most frequent source of information, namely schools, inculcates less knowledge than parents. Lastly, youths who discuss sex with parents do not typically dialog about condoms, the most readily available protection from HIV/AIDS. These findings identify gaps that need to be addressed for lowering the high rate of HIV infection in Hispanic youths.

Preservation of lysozyme structure and function upon encapsulation and release from poly(lactic-co-glycolic) acid microspheres prepared by the water-in-oil-in-water method.

When proteins are encapsulated in bioerodible polymers by water-in-oil-in-water (w/o/w) encapsulation techniques, inactivation and aggregation are serious drawbacks hampering their sustained delivery. Hen egg-white lysozyme was employed to investigate whether stabilizing it towards the major stress factors in the w/o/w encapsulation procedure would allow for the encapsulation and release of structurally unperturbed, non-aggregated, and active protein. When it was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres without stabilizing additives, lysozyme showed substantial loss in activity and aggregation. It has been shown that by co-dissolving various sugars and polyhydric alcohols with lysozyme in the first aqueous buffer, interface-induced lysozyme aggregation and inactivation can be minimized in the first emulsification step [J. Pharm. Pharmacol. 53 (2001) 1217]. Herein, it was found that those excipients, which were efficient in preventing interface-induced structural perturbations, were also efficient in minimizing lyophilization-induced structural perturbations (e.g. lactulose). The efficient excipients identified also reduced structural perturbations upon lysozyme encapsulation in PLGA microspheres and this led to reduced lysozyme inactivation and aggregation. However, the data obtained also show that later steps in the encapsulation procedure are detrimental to lysozyme activity. Lysozyme inactivation was completely prevented only by employing the efficient excipients in the second aqueous phase also. In summary, protein aggregation and inactivation were minimized by rationally selecting excipients efficient in stabilizing lysozyme against the major stress factors of w/o/w encapsulation.

Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers.

Sustained release of pharmaceutical proteins from biocompatible polymers offers new opportunities in the treatment and prevention of disease. The manufacturing of such sustained-release dosage forms, and also the release from them, can impose substantial stresses on the chemical integrity and native, three-dimensional structure of proteins. Recently, novel strategies have been developed towards elucidation and amelioration of these stresses. Non-invasive technologies have been implemented to investigate the complex destabilization pathways that can occur. Such insights allow for rational approaches to protect proteins upon encapsulation and release from bioerodible systems. Stabilization of proteins when utilizing the most commonly employed procedure, the water-in-oil-in-water (w/o/w) double emulsion technique, requires approaches that are based mainly on either increasing the thermodynamic stability of the protein or preventing contact of the protein with the destabilizing agent (e.g. the water/oil interface) by use of various additives. However, protein stability is still often problematic when using the w/o/w technique, and thus alternative methods have become increasingly popular. These methods, such as the solid-in-oil-in-oil (s/o/o) and solid-in-oil-in-water (s/o/w) techniques, are based on the suspension of dry protein powders in an anhydrous organic solvent. It has become apparent that protein structure in the organic phase is stabilized because the protein is "rigidified" and therefore unfolding and large protein structural perturbations are kinetically prohibited. This review focuses on strategies leading to the stabilization of protein structure when employing these different encapsulation procedures.