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The present psychobiography took up the three main psychoanalytic conceptions of love to illuminate the psychological development of famed experimental writer William Seward Burroughs (1914-1997). The study found evidence of all three concepts of love in the subject's life strategies: (1) Love as cathexis was present in Burroughs' fascination with centipedes and other vermin that appeared in his dreams and which symbolised, in part, his terror over early childhood traumas as well as his concomitant struggle to integrate sex with intimacy. (2) Love as eroto-philiac fusion was observed in Burroughs' unstable and even exploitative relationships with others. This tendency was most salient in Burroughs' abortive attempts to seduce straight men, as well as in his failed efforts to be a traditional husband and father. (3) Reparative love became the subject's primary mode of interaction late in life. The study showed that, in his declining years, Burroughs was able to overcome partially the maladaptive strategies of his early life through his numerous pet cats, upon whom he projected aspects of his past romantic partners and friends.

Background Transfusion-associated circulatory overload (TACO) is a largely preventable transfusion complication that results in significant morbidity and mortality. Cancers, related treatments, and comorbidities are among the factors that can predispose patients to TACO, but currently there are limited data on this topic in the literature. Methods We collected data retrospectively from the electronic health records of 93 adult patients with cancer who met Centers for Disease Control and Prevention (CDC) criteria for TACO from July 1, 2019, through October 31, 2020. The parameters we studied included demographics, comorbidities, treatment modalities, transfusion practices, and outcomes. We summarized data by means and ranges for continuous variables, and proportions for categorical variables. Results During the study period, the incidence of TACO among oncology patients was 0.84 per 1000 transfusions (95% CI, 0.68–1.02), representing 6.6% of all reactions. This percentage is high, compared with 1%–6% among other populations. Unique characteristics such as hematology malignancy (75.3%), receipt of cardiotoxic chemotherapy (87.1%), pneumonia (57.0%), preexisting oxygen use (59.1%), dyspnea (62.4%), hypertension (55.9%), renal insufficiency (46.2%), daily use of corticosteroids (43.0%), daily use of diuretics (40.9%), daily use of beta-blockers (36.6%), and elevated NT-proBNP (33.3%) were frequently observed in these group of oncology patients. Conclusions Our study indicates that oncology patients have unique factors that may lead to diagnosis of TACO. Developing appropriate guidelines that apply to oncology patients, in addition to those set forth by the CDC, should be considered. Implementation by ordering healthcare providers of a tools that can predict TACO can help in early recognition and mitigation of TACO.

Controversial reports of human-virus chimeric reads (HVCRs) suggested a possible integration of SARS-CoV-2 sequences into human DNA (1-3).….

The Branch Vein Occlusion Study is a multi-center, randomized, controlled clinical trial designed to answer several questions regarding the management of complications of branch vein occlusion. This report discusses the question, "Is argon laser photocoagulation useful in improving visual acuity in eyes with branch vein occlusion and macular edema reducing vision to 20/40 or worse?" One hundred thirty-nine eligible eyes were assigned randomly to either a treated or an untreated control group. Comparing treated patients to control patients (mean follow-up 3.1 years for all study eyes), the gain of at least two lines of visual acuity from baseline maintained for two consecutive visits was significantly greater in treated eyes (P = .00049, logrank test). Because of this improvement in visual acuity with argon laser photocoagulation of macular edema from branch vein occlusion, we recommend laser photocoagulation for patients with macular edema associated with branch vein occlusion who meet the eligibility criteria of this study.

Innovative musician, producer, and songwriter Walter Becker (1950–2017) wielded humor to distance himself from a traumatic childhood and to bind himself to a peer group that shared his skewed, wry worldview. Following years of struggle at the fringes of the music business, Becker achieved worldwide success as cofounder of the platinum-selling band Steely Dan. By the end of the 1970s, however, Steely Dan was defunct, and Becker retreated to the Polynesian-American subculture of Maui, Hawaii, where he continued to write and record songs that tackled the orientalist theme of ‘East meets West’ in his inimitable, droll style. The present chapter takes up Eysenck’s psychology of humor as well as various social theorists’ assessments of Romantic irony as lenses through which to view Walter Becker’s lifelong struggle to bend his potentially ego-diminishing sardonicism into positive relations with self and others. Positive Psychology 2.0 (PP2) will be called upon to frame the chapter’s discussion section, in which it is concluded that Becker was able to mitigate the self-other corrosion that emanated from his hipster-satirist persona by integrating into his art the more earnest, sincere sentiments that sprang from life on his Maui estate, where sustained interaction with family, friends, and artistic collaborators reflected his embrace of a slow-paced, pastoral culture that the Manhattan-born bohemian had earlier dismissed as shallow and vacuous.

Complex DNA mixtures are challenging to interpret and require computational tools that aid in that interpretation. Recently, several computational methods that estimate the number of contributors (NOC) to a sample have been developed. Unlike analogous tools that interpret profiles and report LRs, NOC tools vary widely in their operational principle where some are Bayesian and others are machine learning tools. Conjunctionally, NOC tools may return a single n estimate, or a distribution on n. This vast array of constructs, coupled with a gap in standardized methods by which to validate NOC systems, warrants an exploration into the measures by which differing NOC systems might be tested for operations. In the current paper, we use two exemplar NOC systems: a probabilistic system named NOCIt, which renders an a posteriori probability (APP) distribution on the number of contributors given an electropherogram and an artificial neural network (ANN). NOCIt is a continuous Bayesian inference system incorporating models of peak height, degradation, differential degradation, forward and reverse stutter, noise and allelic drop-out while considering allele frequencies in a reference population. The ANN is also a continuous method, taking all the same features (barring degradation) into account. Unlike its Bayesian counterpart, it demands substantively more data to parameterize, requiring synthetic data. We explore each system’s performance by conducting tests on 214 PROVEDIt mixtures where the limit of detection was 1-copy of DNA. We found that after a lengthy training period of approximately 24 h, the ANN’s evaluation process was very fast and perfectly repeatable. In contrast, NOCIt only took a few minutes to train but took tens of minutes to complete each sample and was less repeatable. In addition, it rendered a probability distribution that was more sensitive and specific, affording a reasonable method by which to report all reasonable n that explain the evidence for a given sample. Whatever the method, by acknowledging the inherent differences between NOC systems, we demonstrate that validation constructs will necessarily be guided by the needs of the forensic domain and be dependent upon whether the laboratory seeks to assign a single n or range of n.

Introduction: With the opioid epidemic escalating across the country, we sought to evaluate and characterize post-operative opioid prescribing habits and trends among urology residents in the United States. Methods: Urology residents were sent a 16-question survey regarding opioid prescribing patterns, influencing factors, opioid training experience, and amounts of opioids prescribed for common urologic procedures. Results: One hundred and four urology residents participated in the survey (75% male and 25% female). Common factors influencing opioid prescribing were standard prescribing practice for certain operations (80%), attending/senior resident preference (62.1%), and immediate post-operative pain (54.7%). Residents reported prescribing more opioids at discharge for open abdominal and robotic procedures (167.9 and 134.2 morphine milligram equivalents, MME, respectively) and lower amounts for outpatient surgeries (39.7 and 55.8 MME for vasectomy and transurethral resections). Only 15.5% of residents utilize any formal algorithm for post-operative opioid prescribing at their institution. Further, 51.6% of residents received no formal education on safe opioid prescribing during residency, and only 42.1% routinely assess patient risk for opioid abuse. Urology residents who received formal opioid training prescribed less opioids on average for common urologic procedures compared to those who had not trained. Conclusions: This study highlights the importance of increasing resident education on opioid prescribing during residency training, as well as an opportunity for the implementation of standardized post-operative opioid prescribing regimens to help improve trends in urology resident opioid prescribing.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a molecular target for the sensitization of cancer cells to the FDA-approved topoisomerase inhibitors topotecan and irinotecan. High-throughput screening of natural product extract and fraction libraries for inhibitors of TDP1 activity resulted in the discovery of a new class of knotted cyclic peptides from the marine sponge Axinella sp. Bioassay-guided fractionation of the source extract resulted in the isolation of the active component which was determined to be an unprecedented 42-residue cysteine-rich peptide named recifin A. The native NMR structure revealed a novel fold comprising a four strand antiparallel β-sheet and two helical turns stabilized by a complex disulfide bond network that creates an embedded ring around one of the strands. The resulting structure, which we have termed the Tyr-lock peptide family, is stabilized by a tyrosine residue locked into three-dimensional space. Recifin A inhibited the cleavage of phosphodiester bonds by TDP1 in a FRET assay with an IC(50) of 190 nM. Enzyme kinetics studies revealed that recifin A can specifically modulate the enzymatic activity of full-length TDP1 while not affecting the activity of a truncated catalytic domain of TDP1 lacking the N-terminal regulatory domain (Δ1–147), suggesting an allosteric binding site for recifin A on the regulatory domain of TDP1. Recifin A represents both the first of a unique structural class of knotted disulfide-rich peptides and defines a previously unseen mechanism of TDP1 inhibition that could be productively exploited for potential anticancer applications.

Background Active surveillance for transfusion reactions is critically important among pediatric patients undergoing chemotherapy. Among pediatric-adolescent-young-adult (AYA) hematology/oncology patients, who have been typically excluded from transfusion reaction studies, this profile remains poorly characterized. Methods We assessed the incidence and clinical characteristics of transfusion reactions (n = 3246 transfusions) in this population (n = 201 patients) at our center. Findings The incidence of adjudicated transfusion reactions was 2·04%. The incidence was higher for platelet (2·78%) compared to packed red blood cell transfusions (1·49%) (p = 0·0149). The majority (61·4%) of all reactions were classified as febrile non-haemolytic transfusion, while 35·7% were considered allergic, and 2·9% were classified as transfusion-associated circulatory overload. The incidence of transfusion reactions in patients who were pre-medicated was higher (2·51%) than in patients who were not (1·52%) (p = 0·0406). Sub-set analysis revealed a 3·95% incidence of adjudicated transfusion reactions among recipients of immune effector cells (IECs) (n = 3), all of which occurred during the potential window for cytokine release syndrome; two-thirds of these reactions were severe/potentially life-threatening. Interpretation The incidence of transfusion reactions among pediatric-AYA hematology/oncology patients may be lower than the general pediatric population. Patients with a prior history of transfusion reactions and those receiving platelet transfusions may be at higher risk for reaction. From our limited sample, IEC recipients may be at risk for severe transfusion reactions. Large multi-center prospective studies are needed to characterize transfusion reactions in this population. Appropriate characterization of reactions in this population may inform risk stratification and mitigate missed opportunities for prompt recognition and appropriate management. Funding None.

Background In recent months, multiple efforts have sought to characterize COVID-19 social distancing policy responses. These efforts have used various coding frameworks, but many have relied on coding methodologies that may not adequately describe the gradient in social distancing policies as states “re-open.” Methods We developed a COVID-19 social distancing intensity framework that is sufficiently specific and sensitive to capture this gradient. Based on a review of policies from a 12 U.S. state sample, we developed a social distancing intensity framework consisting of 16 domains and intensity scales of 0–5 for each domain. Results We found that the states with the highest average daily intensity from our sample were Pennsylvania, Washington, Colorado, California, and New Jersey, with Georgia, Florida, Massachusetts, and Texas having the lowest. While some domains (such as restaurants and movie theaters) showed bimodal policy intensity distributions compatible with binary (yes/no) coding, others (such as childcare and religious gatherings) showed broader variability that would be missed without more granular coding. Conclusion This detailed intensity framework reveals the granularity and nuance between social distancing policy responses. Developing standardized approaches for constructing policy taxonomies and coding processes may facilitate more rigorous policy analysis and improve disease modeling efforts.

Author(s): Vinh, Daniel B; Zhao, Xiao; Kiong, Kimberley L; Guo, Theresa; Jozaghi, Yelda; Yao, Chris; Kelley, James M; Hanna, Ehab Y | Abstract: BackgroundTesting for SARS-CoV-2 is important for decision making prior to surgery in otolaryngology. An understanding of current and developing testing methods is important for interpreting test results.MethodsWe performed a literature review of current evidence surrounding SARS-CoV-2 diagnostic testing highlighting its utility, limitations, and implications for otolaryngologists.ResultsThe currently accepted RT-PCR test for SARS-CoV-2 has varying sensitivity according to which subsite of the aerodigestive tract is sampled. Nasal swab sensitivities appear to be about 70%. Chest CT imaging for screening purposes is not currently recommended.ConclusionDue to the current sensitivity of RT-PCR based testing for SARS-CoV-2, a negative test cannot rule out COVID-19. Full PPE should be worn during high-risk procedures such as aerosol generating procedures even if testing is negative. Patients who test positive during screening should have their surgeries postponed if possible until asymptomatic and have tested negative for SARS-CoV-2.

Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a non-interacting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear-thinning self-assembled fibrillar peptide hydrogel network. The resulting Microcrystalline Tofacitinib Hydrogel (MTH) can be syringe-injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4-Ig, a co-stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.

The now-dominant medical model of psychiatry has recently been challenged by the post-psychiatry movement. However, the former discounts the agential or subjective aspect of the human being; the latter misses the axiological aspect. A new model is proposed-the Transcendent Meaning Model (TMM)-that nests the individual person within the social (the interperson), and the social within the transcendent or ideological. The study concludes that TMM, with its integration of the personal, the social and the religious-ideological with the material, is a viable blueprint for a future psychiatry that can address some of the current model's vulnerabilities.

Throughout Donald Fagen’s life, he used the concept of bohemianism to position himself vis-a-vis his family, peers, and the mainstream culture as a whole. A psychobiographical examination of the subject with an object relations emphasis found that Fagen used his role as a successful musician to confer on himself a sense of legitimacy and to distance himself from the strictures of conventional, “bourgeois” existence. However, by the end of the first phase of his band Steely Dan’s recording career, Fagen found himself in a musical, romantic, and social dead end, his bohemianism’s promise of self-contained aesthetic completion being revealed as a mistaking of the ideal for the real. This chapter shows that Fagen recovered meaning in life, and thus a multilayered positivity, through psychotherapy, which led to the singer’s reentry into the worlds of music, family, and friendship by tempering the perfectionism and isolationism concealed within his bohemian self-image. Ironically, Fagen’s reality principle gained in strength as he loosened his grip on his mistaken self-identification as a bohemian; Fagen’s self-reformulation late in life allowed him to turn a category error about the artist’s role in modernity into a positive adaptation to a society that requires an adult to play multiple, often contradictory, roles.

Background With the increasing safety of allogeneic blood supply and declining need for transfusion due to patient blood management, the practice of preoperative autologous donation (PAD) continues to decline. The practice gained popularity during the 1980s and 1990s with the emergence of transfusion-transmitted human immunodeficiency virus and hepatitis C. At the peak of this public concern, the National Marrow Donor Program recommended that marrow donors have 1 to 3 autologous units of blood collected before their marrow harvest to minimize the likelihood of allogeneic transfusion. After three decades, the practice remains prevalent in marrow donors. We aimed to study the efficacy of PAD in healthy marrow donors. Study design and methods PADs performed before marrow harvest in healthy donors at our center between January 2013 and July 2015 were reviewed. The utilization of autologous units and decrease in hemoglobin levels due to PAD and marrow harvest were studied. Similar practices were assessed in the rest of the United States through a brief survey. Results Of a total of 262 autologous units collected from 136 donors, 25.2% were wasted. Ninety-nine percent of the marrow donors received at least 1 unit of blood irrespective of the need. PAD contributed to preoperative anemia, exposing three donors to allogeneic blood transfusion. The survey results showed a mixed response with some institutions continuing and others not practicing PAD. Conclusion PADs are not justified in healthy marrow donors as they expose them to a risk of preoperative anemia and hence a greater risk of transfusion.

C1 domain-containing proteins, such as protein kinase C (PKC), have a central role in cellular signal transduction. Their involvement in many diseases, including cancer, cardiovascular disease, and immunological and neurological disorders has been extensively demonstrated and has prompted a search for small molecules to modulate their activity. By employing a diacylglycerol (DAG)-lactone template, we have been able to develop ultra potent analogs of diacylglycerol with nanomolar binding affinities approaching those of complex natural products such as phorbol esters and bryostatins. One current challenge is the development of selective ligands capable of discriminating between different protein family members. Recently, structure-activity relationship studies have shown that the introduction of an indole ring as a DAG-lactone substituent yielded selective Ras guanine nucleotide-releasing protein (RasGRP1) activators when compared to PKCα and PKCε. In the present work, we examine the effects of ligand selectivity relative to the orientation of the indole ring and the nature of the DAG-lactone template itself. Our results show that the indole ring must be attached to the lactone moiety through the sn-2 position in order to achieve RasGRP1 selectivity. Fil: Elhalem, Eleonora. Instituto Nacional de Tecnología Industrial; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gandolfi Donadío, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial; Argentina Fil: Zhou, Xiaoling. National Cancer Institute; Estados Unidos Fil: Lewin, Nancy E.. National Cancer Institute; Estados Unidos Fil: Garcia, Lia Cynthia. Instituto Nacional de Tecnología Industrial; Argentina Fil: Lai, Christopher C.. National Institutes of Health; Estados Unidos Fil: Kelley, James A.. National Institutes of Health; Estados Unidos Fil: Peach, Megan L.. National Institutes of Health; Estados Unidos Fil: Blumberg, Peter M.. National Cancer Institute; Estados Unidos Fil: Comin, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial; Argentina

BACKGROUND Immunosuppressed, RhD-negative oncology patients tend to have lower rates of sensitization to the D antigen when they receive transfusion with RhD-positive blood components. Clinical factors associated with alloimmunization to the D antigen in RhD-negative oncology patients when they receive transfusion with RhD-positive red blood cells (RBCs) have not been well defined. STUDY DESIGN AND METHODS This was a 4-year, retrospective analysis identifying RhD-negative oncology patients who received RhD-positive RBCs and were not previously alloimmunized to the D antigen. Age, sex, race, ABO group, primary oncology diagnosis, and numbers of RhD-incompatible RBC transfusions were recorded. The association between antibody formation and clinical factors was studied. The incidence of alloanti-D was calculated from a subsequent antibody-detection test performed at least 28 days after receipt of the first transfusion of RhD-positive RBCs. RESULTS In total, 545 RhD-negative oncology patients received 4295 RhD-positive RBC transfusions. Of these, 76 (14%) became alloimmunized to the D antigen. Diagnosis type was the only factor significantly associated with responder status. The logistic regression model indicated that patients who had myelodysplastic syndrome or solid malignancies were more likely to be responders than those who had acute leukemia. CONCLUSION We measured a 14% sensitization rate to the D antigen in our RhD-negative oncology population. The rate of alloimmunization was higher in patients who had solid cancers (22.6%) or myelodysplastic syndrome (23%) compared with those who had other hematologic malignancies (7%). Knowledge of diagnoses that predispose to RhD alloimmunization enables better utilization of RhD-negative RBCs during times of shortage.

In 1978, Jim Jones and over 900 of his followers perished in what has been called “The Jonestown Massacre”. This study uses methods of psychobiography and objection relations theory to account for Jones’ lifelong ambivalence toward those to whom he acted as caregiver. The author proposes a psychological schema he names “nurture failure” to account for Jim Jones’ style of leadership, which mixed solicitude with violence in the context of a religious organization that promised to right all of society’s wrongs. The means by which this utopia was to be brought about became more and more extreme until the infamous murder/suicide shattered the dream for good. The study’s findings expand our understanding of the motivational dynamics that undergird religious leaders’ often Januslike relations to their followers.

We investigated how many cases of the same chemical sold as different products (at possibly different prices) occurred in a prototypical large aggregated database and simultaneously tested the tautomerism definitions in the chemoinformatics toolkit CACTVS. We applied the standard CACTVS tautomeric transforms plus a set of recently developed ring–chain transforms to the Aldrich Market Select (AMS) database of 6 million screening samples and building blocks. In 30 000 cases, two or more AMS products were found to be just different tautomeric forms of the same compound. We purchased and analyzed 166 such tautomer pairs and triplets by 1H and 13C NMR to determine whether the CACTVS transforms accurately predicted what is the same “stuff in the bottle”. Essentially all prototropic transforms with examples in the AMS were confirmed. Some of the ring–chain transforms were found to be too “aggressive”, i.e. to equate structures with one another that were different compounds.

In a review posted to NPR a day before Harper Lee's novel went on sale, Maureen Corrigan wrote: “Go Set a Watchman is a troubling confusion of a novel, politically and artistically, beginning with ...

Purpose – The purpose of this paper to use Self-Determination Theory (SDT) to explain the online brand community (OBC) identity internalization process through brand website interactivity. Secondary purpose of the research is to explore the role of several individual difference factors and brand-specific constructs in predicting brand website interactivity. Design/methodology/approach – This study proposes the OBC motivation development continuum of brand website interactivity. Thus, a national panel was collected by a reputable online survey firm and a structural equation model was used to test the proposed model. Findings – The authors examined four brand-related antecedents and mediators (brand engagement in self-concept, susceptibility of normative influence, opinion leadership, and consumer innovativeness) and found evidence of the differing roles that brand engagement in self-concept and purposive motives play as mediators to brand website interactivity. Practical implications – Marketing managers can use the proposed model as a useful tool for understanding ways to target and motivate segment specific consumers in ways that will increase the effectiveness of managers’ OBC building strategies. Originality/value – This study utilized SDT to explain the internalization process of brand website interactivity. Further, several individual difference factors were explored as antecedents and mediators of brand website interactivity.

This study introduces and examines a simulated attention-tracking methodology as an emerging technique to improve the study of in-store shopper behavior and decision making. To assess the viability of this new methodology, we examine its efficacy in producing consumer behavior data consistent with results predicted by the marketing literature. Empirical data across five grocery categories are used to examine the influence of personal, product, and situational differences on external information search. Findings show that the attention-tracking methodology is able to demonstrate expected results in almost all cases. The methodology is also able to provide a more complete view of external information search through tracing the observed search behavior preceding decision making. This proof of methodology responds directly to calls in the marketing and retailing literature to test new and emerging methodologies in support of research on in-store marketing and shopper behavior. Findings also provide ma...

Dengue virus infections are mostly asymptomatic but can produce a mild, self-limiting acute febrile illness, dengue fever, or a life threatening severe illness, dengue hemorrhagic fever. Dengue hemorrhagic fever is associated with increased vascular permeability partly as a result of elevated levels of matrix metalloproteinases (MMPs). We characterized MMP-2 and MMP-9 production in mosquito and mammalian cells after infection with three strains of dengue virus type-2 (D2-) ranging in virulence: 16681, the prototype New Guinea C (NGC), and PDK-53 vaccine strain. These strains were used to test variations in viral properties in vaccine candidates and confirm the production of MMP as a possible marker for virulence. A zymogram gelatinolytic activity assay was used to assess MMP-2 and MMP-9 production. We found that dengue-infected mosquito and mammalian cell lines had unique MMP-2 and MMP-9 production patterns depending on the virulence of the infecting dengue strain and the duration infection. MMP levels were highest after infection with the most virulent strain D2-16681, followed by the prototype NGC strain, in both cell lines. The MMP levels appeared to correspond with the relative amounts of infectious virions produced later in infection. Our findings improve our understanding of dengue pathogenesis and may facilitate the selection of markers to further the development of dengue vaccines.

Background Patients undergoing chemotherapy and especially hematopoietic stem cell transplantation (HSCT) require frequent transfusions, and thus, transfusion reaction (TR) vigilance is critical in this population. The reported incidence of TRs across all patients is 2%, and pediatric patients may experience 2-2.6 times more reactions than adults. However, the TR profile may differ in the immunocompromised population. There is a paucity of data in this area, as pediatric oncology and HSCT patients are often excluded from TR studies. Our goals were to assess the prevalence and describe TRs among immunocompromised pediatric patients and to improve recognition of TRs across this population. Methods Pediatric clinical providers completed a TR training module in May – June, 2019. A single-institution retrospective review was conducted. All TRs in patients aged less than 25 years were reviewed over a 3-month period from July 1, 2019 to October 1, 2019. Results Over a 3-month period, 1,786 transfusions were administered in our designated population. Of those, 50.4% were platelets, 44.0% were red blood cells (RBC), 3.4% were cryoprecipitate, 1.4% were thawed plasma, and 0.8% were granulocytes. Those undergoing HSCT consumed 27.7% of total transfusions. Of all transfusions, there were 48 (2.7%) reported as possible TRs by nursing. Of those, 30 (1.7% of all transfusions) were adjudicated as true TRs. Fourteen (46.7%) of these true TRs were in patients with leukemia, 9 (30.0%) with HSCT, 5 (16.7%) with solid tumors, and 2 (6.7%) with aplastic anemia. Of the 9 reactions in HSCT patients, 4 occurred in allogeneic transplant recipients (3 umbilical cord blood and one matched unrelated donor) and 5 were in those receiving autologous HSCT. In HSCT patients, 1.8% of transfusions resulted in TRs compared to 1.6% in non-HSCT patients. Of the products triggering reactions, platelets accounted for 22 TRs (73.3%) and RBCs accounted for 8 TRs (26.7%). Of all 30 TRs, 15 (50%) were classified as febrile non-hemolytic transfusion reactions (FNHTR), 14 (46.7%) were considered allergic reactions, and 1 (3.3%) was diagnosed as transfusion-associated circulatory overload. Pre-medication was given in 22 (76.7%) of transfusions causing reactions. Of the 18 reports that were not adjudicated as true TRs, most (n=15) were generated for fever, but deemed unrelated to transfusion. Conclusions Our baseline analysis revealed a higher prevalence than our historical institutional prevalence (1.7% vs. 1.3%), consistent with higher rates of TRs in the pediatric population, but lower than the 2% quoted in the literature, suggesting either underreporting or a different TR phenotype in this population. This population had a higher prevalence of FNHTR than the general pediatric population (50.0% vs. 31.5%). High rates of pre-medication and comorbidities (resulting in fevers) may influence TR presentation in this population.

Many high-reliability organizations in industries outside of health care have sustained high levels of excellence and prevention of harm while managing complex systems and risk. To date, no health care organizations has organized its efforts to achieve highly reliable results despite several decades of improvement science. Laboratorians were early adopters of quality initiatives and process improvements. In the late 1990s, the Division of Pathology and Laboratory Medicine at The University of Texas MD Anderson Cancer Center embarked on a major effort to improve quality and patient safety and to reduce waste. This article describes the institution’s journey toward approaching high reliability with the intent to share not only the tools and best practices, but also the ongoing reassessment of the problems detected on the journey. The authors hope that their experience will help the reader develop interventions to adapt in their own environment to facilitate more optimal patient care.

Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

Background Human papillomavirus (HPV) infections in Thailand are a public health concern but information on HPV infection in sex workers and men who have sex with men (MSM) is limited. The aim of this study was to measure the prevalence and genotype distribution of HPV among low- and high-risk, HIV-negative populations.

Heptamethine cyanines are important near-IR fluorophores used in many fluorescence applications. Despite this utility, these molecules are susceptible to light-promoted reactions (photobleaching) involving photochemically generated reactive oxygen species (ROS). Here, we have sought to define key chemical aspects of this nearly inescapable process. Near-IR photolysis of a model heptamethine cyanine leads to the regioselective oxidative cleavage of the characteristic polyene. We report the first quantitative analysis of the major reaction pathway following either photolysis or exposure to candidate ROS. These studies clearly indicate that only singlet oxygen (1O2), and not other feasible ROS, recapitulates the direct photolysis pathway. Computational studies were employed to investigate the regioselectivity of the oxidative cleavage process, and the theoretical ratio is comparable to observed experimental values. These results provide a more complete picture of heptamethine cyanine photooxidation, and provide insight for the design of improved compounds for future applications.

Cell-free DNA testing is a recently introduced method for screening pregnant women for fetal trisomy, which is associated with some common significant genetic diseases, as well as the sex of the fetus. The case described here demonstrates the connection between the ultrasound "vanishing twin" phenomenon and the misdiagnosis of prenatal sex using cell-free DNA testing.

Newly described NMR experimental approaches can provide valuable structural details and a complementary means of structure verification., Ambiguities and errors in the structural assignment of organic molecules hinder both drug discovery and total synthesis efforts. Newly described NMR experimental approaches can provide valuable structural details and a complementary means of structure verification. The caulamidines are trihalogenated alkaloids from a marine bryozoan with an unprecedented structural scaffold. Their unique carbon and nitrogen framework was deduced by conventional NMR methods supplemented by new experiments that define 2-bond heteronuclear connectivities, reveal very long-range connectivity data, or visualize the 35,37Cl isotopic effect on chlorinated carbons. Computer-assisted structural elucidation (CASE) analysis of the spectroscopic data for caulamidine A provided only one viable structural alternative. Anisotropic NMR parameters, specifically residual dipolar coupling and residual chemical shift anisotropy data, were measured for caulamidine A and compared to DFT-calculated values for the proposed structure, the CASE-derived alternative structure, and two energetically feasible stereoisomers. Anisotropy-based NMR experiments provide a global, orthogonal means to verify complex structures free from investigator bias. The anisotropic NMR data were fully consistent with the assigned structure and configuration of caulamidine A. Caulamidine B has the same heterocyclic scaffold as A but a different composition and pattern of halogen substitution. Caulamidines A and B inhibited both wild-type and drug-resistant strains of the malaria parasite Plasmodium falciparum at low micromolar concentrations, yet were nontoxic to human cells.

Advancements in immunotherapy have opened a new era in oncology, to include genetic modification of human T-cells to express a chimeric antigen receptor (CAR) that enables targeted tumor recognition (Kochenderfer et al., 2015; Lee et al., 2015; Maus and Levine 2016; Rosenberg et al., 2008). Herein, we report a false-positive HIV testing in a patient who had undergone CAR T-cell therapy created with a lentiviral vector.

Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.

Therapies to prevent or reverse endothelial dysfunction and vascular leak found in dengue hemorrhagic fever (DHF) have not been identified. In this review we summarize dengue viruses and the spectrum of human disease and highlight evidence of endothelial cell dysfunction in DHF based on studies in patients and mouse and tissue culture models. Evidence suggests that both virus antigen and host immune response, can cause endothelial cell dysfunction and weaken endothelial barrier integrity. We suggest possible therapeutic interventions and highlight how therapies targeting altered endothelial function might be evaluated in animal models and in patients with DHF.