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There is increasing narrowing of the genetic base of exotic species introduced in many parts of the world. This is causing a restricted genetic diversity and consequential loss of biotic and abiotic tolerance of these species. Hence, there is need to establish the genetic stability of such species for future genetic broadening. One such plant is Moringa oleifera Lam. which belongs to the family moringaceae; a monogeneric family of shrubs and trees consisting of 13 species and is native to India. M. oleifera is the most economically useful species in the genus and is widely cultivated and naturalized in tropical and subtropical areas and in over 60 countries worldwide. In Kenya, M. oleifera is widely cultivated in coast and some parts of Eastern Kenya. A provenance trial was set up at South Eastern Kenya University (SEKU), located at Kwa Vonza location, lower Yatta Sub-County, Kitui County. The aim of the provenance trial was i) to determine whether the collected Moringa exhibited different growth and fruiting habits and ii) if so, select the best performing provenances for large-scale propagation of the species in Kenya. The trial involved fifteen provenances selected from a wide geographical region in Eastern and Coastal regions of Kenya. Each provenance consisted of 200 seedlings at a spacing of 2m by 2m and was replicated three times. The experiment was laid in a randomized complete block design (RCBD). Growth data (diameter and height), fruiting and fruit maturation were measured for a period of 12 months. Monthly growth data were used to generate horizontal and vertical growth curves. Duncan Multiple Range Test (DMRT) and test of homogeneity of variances were used to detect existence of statistically significant differences in the fifteen provenances. The results indicated statistically significant differences (p

Background Oral health plays a role in overall health, indicating the need to identify barriers to accessing oral care. The objective of this study was to identify barriers to accessing oral health care and examine the association between socioeconomic, psychosocial, and physical measures with access to oral health care among older Canadians. Methods A cross-sectional study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) follow-up 1 survey to analyze dental insurance and last oral health care visit. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between socioeconomic, psychosocial, and physical measures with access to oral care, measured by dental insurance and last oral health visit. Results Among the 44,011 adults included in the study, 40% reported not having dental insurance while 15% had not visited an oral health professional in the previous 12 months. Several factors were identified as barriers to accessing oral health care including, no dental insurance, low household income, rural residence, and having no natural teeth. People with an annual income of Conclusions Identifying barriers to oral health care is important when developing public health strategies to improve access, however, further research is needed to identify the mechanisms as to why these barriers exist.

What better way is there to learn psychiatry and psychology than to have exciting examples of personality disorders, depression, and psychosis from playwrights? Every time a person goes to the theater, an experience of “psychiatry on the stage” can occur. If a professor returns to the clinic after such theater presentations, examples are available to present to psychiatry residents. In addition, new brain pathways are formed that will be invaluable. Greek playwrights, Shakespeare, and modern playwrights have given us invaluable gifts with their plays. Great playwrights like Tom Stoppard stimulate our brains with their brilliant works. I look forward to viewing many more plays to maintain my brain functions.

In Eugene O’Neill’s Long Day’s Journey Into Night, Mary, who is addicted to morphine, is the center of a dysfunctional family where drinking is also a problem. In The Iceman Cometh by O’Neill, a group of alcoholics try to deal with life and their longing for oblivion. Many other plays show us the outcome of alcoholism or drug addiction. Halfway Bitches Go Straight to Heaven, Stephen Adly Guirgis’s play is set in a women’s shelter that is filled with people who are addicted and mentally ill people. The playwright takes us into their psyches and steers us toward new pathways of thinking.

In Shakespeare’s world, we have Othello, the tale of a jealous king who believes his innocent queen, Desdemona, has betrayed him sexually. In psychiatry, this type of paranoia is called the Othello complex. Hamlet is a Shakespearean character who illustrates the Oedipus complex at work. Hamlet is indecisive and passive, rather than active in avenging his father’s death because unconsciously he wished for his father’s death. His “to be or not to be” monologue is a brilliant display of his passivity. King Lear is an example of a narcissistic personality who needs his three daughters to prove their love for him. Two do so insincerely, and the third, Cordelia, speaks truthfully and simply. King Lear, stuck in a rigid personality, winds up forfeiting everything, including his kingdom, his life, and his children due to his foolishness and narcissism. Richard III is a portrait of a sociopathic personality who kills everyone on his path to the throne.

Alfred Adler was another doctor who had studied with Freud but decided to break away from him. Adler’s innovations of individual psychology emphasized aggression and the inferiority complex. He wrote about the aggression drive, the neurotic disposition, and masculine protest. According to Adler, the neurotic person lacks confidence, is oversensitive, is guilty, and inhibits aggression. His concentration on other factors besides the Freudian libido led to the work of Karen Horney, Harry Stack Sullivan, and Erich Fromm. In Mamet’s Glengarry Glen Ross, characters aggressively struggle for power. New neural networks can be induced according to Adler, although he did not know of or use these modern terms, by watching theater like that of Mamet.

This chapter considers modern plays. In modern plays, like The Cherry Orchard and The Seagull, Chekhov shows us characters denying reality and suffering as a result. August Strindberg gives us sadomasochistic behaviors in Miss Julie. In Tennessee Williams’ The Glass Menagerie, Laura, who may be schizophrenic or on the autistic spectrum, regresses as she tries to deal with the “gentleman caller.” Eugene O’Neill shows us numerous examples of complexes, unconscious impulses, and ego and superego struggles in his play Long Day’s Journey Into Night. The chapter examines how plays reveal various perspectives, prejudices, individual and group psychology, and, of course, various psychiatric principles of psychoanalysis.

How the patient sees him or herself is essential to understand when doing any kind of therapy. The identity of a character includes who the person is in terms of what values they hold, how they see themselves, their roles in society, their memories, experiences, relationships. There is identification with someone, like identification with the aggressors in Mamet’s Glengarry Glen Ross. Introjection is a way of establishing identity as well. In introjections people may have identification with a victim, as Willy Loman does in Arthur Miller’s Death of a Salesman. In the play Transnormal, there is understanding of how identity changes with gender. Through these identifications neural networks are formed that would never have considered.

Starting from the ancient Greeks, plays have demonstrated basic psychiatric principles. For example, Sophocles’ Oedipus Rex shows Oedipus’s journey from marrying his mother to killing his father. Psychological studies revealed that boys of about three years old desire to be with their mothers and want to eliminate their fathers. We call this principle the Oedipus complex after Sophocles’s play. Similarly, girls at three yearn to be with their fathers and rid themselves of their mothers. Sophocles’s play Electra illustrates this psychiatric concept. Many other Greek plays portray fundamental truths in psychology. In Euripides’s Medea the extreme emotions of revenge of a woman betrayed by her husband are witnessed.

Sigmund Freud is considered the first psychiatrist. The oedipal complex (see Chapter 1) is a central tenet of his psychoanalytical theory. Many plays illustrate this complex, as it is an essential feature of family dynamics. Freud, aware of the basic themes of childhood sexuality, named the “Oedipus complex” after Sophocles’s play, Oedipus Rex. Freud also called the childhood aspect of female sexuality, in which the girl wants to eliminate her mother and marry her father, the Oedipus complex. It took Jung to consider another Sophocles play, Electra, and name the female oedipal complex the “Electra complex,” although now we use the Oedipus complex to include females and males alike.

Carl Gustav Jung broke away from Freudian concepts and went deeper into the unconscious with his “collective unconscious,” archetypes, and the anima and animus. Jung was fascinated by mythology, and not just Greek mythology. Myth revealed the collective unconscious to the conscious mind; second, dreams for him were analogues of myth. Myth was also a way of thinking, which was the opposite of directed and logical thinking. He also introduced the ideas of extraversion and introversion of character. Two extraverted characters are Strindberg’s Miss Julie or Judge Brack in Hedda Gabler. More introverted characters include Chekhov’s Ivanov and Laura in The Glass Menagerie.

Why theater is important for our brains and lives may not be immediately clear to people. I have found it essential in my life. First I studied medicine and became a psychiatrist. Then I had the opportunity to learn playwriting, which I did at the Neighborhood Playhouse. Many of my plays have been produced here in New York City. New neural networks are developed in the brain when we watch plays. It is not a dying media as some critics claim. It is alive and well. Shakespeare is understandable, especially when his plays are seen live on the stage. Transference occurs when people project their early emotions on to people in their present lives. Meisner technique stresses that actors must focus on each other and interact with them, whereas Stanislavski requires the actor to focus on inner feelings.

Melanie Klein is famous for her work in object relations theory. Klein’s object relations theory is a variation of psychoanalytic theory. It places less emphasis on biological-based drives and more importance on interpersonal relationships. People are always dealing with relationships to objects (which can also be people). Her concepts of the “good breast” (mother providing nourishment) versus the “bad breast” (no nourishment from mother) established paranoid or depressed positions that patients could take. In Romeo and Juliet, the lovers become good and bad “breasts” to each other at different times and ultimately commit suicide when they feel the loss of each other as “objects.”

Depressed patients have problems eating and sleeping, and their moods are blue. They may have anhedonia and hopelessness. Many are irritable and guilty. The danger is they may commit suicide if their depressions are not treated. Depression is common and strikes fifteen to thirty percent of the population. It is not simply a down mood as many people believe. Chekhov’s Uncle Vanya provides a good example of a depressed character to whom the audience can relate because of his humor and humanity. Many times defenses like humor or sarcasm are used by depressed patients to hide their depressed moods. Bipolar patients can alternate from bouncing around in hypomania, like Chekhov’s Ivanov, or be depressed like Vanya. If a person swings back and forth between a down mood and an up mood, the person may very well have bipolar disorder.

A personality disorder is an inflexible, lasting pattern of thinking, feeling, and behavior. Patients with personality disorders are stuck. They may be acting against themselves and others, but they cannot change. Many examples are seen in plays. Shakespeare presented Richard III, Iago, Macbeth, and Lady Macbeth, who were all antisocial personalities. Chekhov showed us Lomov in The Marriage Proposal as a passive-aggressive personality who cannot propose to his prospective bride. The categorizing of personality disorders does not help with predicting clinical outcomes or in treatment planning. There is also the problem of diagnostic reliability, co-occurrence, and inconsistent and arbitrary boundaries.

Psychology and theater have often intersected in the most interesting ways to describe characters, situations, and interactions. This book presents an overview of basic psychiatric principles applied to plays from the Greeks to Shakespeare to modern times. Included are illustrative vignettes. Technical terms are fully explained so that everyone may enjoy this book. Neuroscience is in the process of discovering how the brain longs for patterns that are found in theater and other art forms. Theatergoers may be enhancing their brains while they enjoy themselves. Practitioners in psychiatry are always referring to literature and drama to understand patients better. For instance, the Oedipal complex, a basic building block of psychoanalysis, was first illustrated in Sophocles’s Oedipus Rex. Sigmund Freud derived his understanding of psychiatric complexes from his familiarity with Greek mythology.

Brucella ceti infection is associated with a variety of disease outcomes in cetaceans globally. Multiple genotypes of B. ceti have been identified. This retrospective aimed to determine if specific lesions were associated with different B. ceti DNA sequence types (STs). Characterization of ST was performed on 163 samples from 88 free-ranging cetaceans, including common bottlenose dolphin Tursiops truncatus (T.t.; n = 73), common short-beaked dolphin Delphinus delphis (D.d.; n = 7), striped dolphin Stenella coeruleoalba (n = 3), Pacific white-sided dolphin Lagenorhynchus obliquidens (n = 2), sperm whale Physeter macrocephalus (n = 2), and harbour porpoise Phocoena phocoena (n = 1), that stranded along the coast of the US mainland and Hawaii. ST was determined using a previously described insertion sequence 711 quantitative PCR. Concordance with 9-locus multi-locus sequence typing was assessed in a subset of samples (n = 18). ST 26 was most commonly identified in adult dolphins along the US east coast with non-suppurative meningoencephalitis (p = 0.009). Animals infected with ST 27 were predominately perinates that were aborted or died shortly after birth with evidence of in utero pneumonia (p = 0.035). Reproductive tract inflammation and meningoencephalitis were also observed in adult T.t. and D.d. with ST 27, though low sample size limited interpretation. ST 23 infections can cause disease in cetacean families other than porpoises (Phocoenidae), including neurobrucellosis in D.d. In total, 11 animals were potentially infected with multiple STs. These data indicate differences in pathogenesis among B. ceti STs in free-ranging cetaceans, and infection with multiple STs is possible.

This study was designed to investigate the effects of chlorhexidine 0.12%, TrisEDTA (tromethamine ethylenediamintetraacetic acid), and a combination of chlorhexidine 0.12% and TrisEDTA on an in vitro plaque biofilm model comprised of three bacterial species commonly found in canine subgingival plaque. Porphyromonas gulae, Actinomyces canis, and Neisseria canis were grown in a biofilm on polished hydroxyapatite coated titanium alloy pucks for 72 h prior to exposure to one of four test solutions: TrisEDTA, chlorhexidine 0.12%, a combination of TrisEDTA and chlorhexidine 0.12%, or sterile deionized water as a control. Following exposure to the test solution, a sample was collected of the biofilm either immediately or following 24 h of additional incubation in a broth medium. Lower numbers of CFU/mL of Porphyromonas gulae resulted when the biofilm was treated with a solution of chlorhexidine 0.12% and TrisEDTA compared to with chlorhexidine 0.12% alone, TrisEDTA alone, or the control and so this solution can be said to be synergistic against Porphyromonas gulae in this controlled in vitro model. Greater reductions in the numbers of CFU/mL of Actinomyces canis and Neisseria canis resulted from treatment with chlorhexidine 0.12% alone than if treated with the combination of TrisEDTA and chlorhexidine 0.12%. When treated biofilm samples were allowed 24 h of additional growth in fresh media, greater variance resulted and this variance highlights the complex dynamics involved in bacterial growth within a biofilm.

Telomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1∆ and bur2∆ set2∆ were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2∆ set2∆ mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation.

Supplementary Material 1

Overcoming replicative senescence is an essential step during oncogenesis, and the reactivation of TERT through promoter mutations is a common mechanism. TERT promoter mutations are acquired in about 75% of melanomas but are not sufficient to maintain telomeres, suggesting that additional mutations are required. We identified a cluster of variants in the promoter of ACD encoding the shelterin component TPP1. ACD promoter variants are present in about 5% of cutaneous melanoma and co-occur with TERT promoter mutations. The two most common somatic variants create or modify binding sites for E-twenty-six (ETS) transcription factors, similar to mutations in the TERT promoter. The variants increase the expression of TPP1 and function together with TERT to synergistically lengthen telomeres. Our findings suggest that TPP1 promoter variants collaborate with TERT activation to enhance telomere maintenance and immortalization in melanoma.

Parenting strategies such as communicating clear expectations, providing calm directions, and teaching specific skills can strengthen young children’s social-emotional development. Parenting programs for children with disruptive behavior often emphasize gaining compliance via effective directives, and less on how to facilitate child skill acquisition or on effective parenting for differing situations and task demands. We aimed to study how parenting strategies and associated child behavior vary by situational contexts. Specifically, we focused on the differential use of directives and guidance during different tasks. This observation study utilized a microsocial coding system, the Parent–Child Play Task Observation System (PCPTOS), to closely examine parent and child interactions in multiple analogue task situations. The study drew on pre-intervention data for 224 parent–child dyads who participated in a parenting-focused intervention trial for children ages 3–7 who presented elevated levels of disruptive behaviors. Interrater reliabilities were very good to excellent. Parents used directives more frequently during the clean-up task and guidance more frequently during the teaching task compared to the other tasks. Associations of parent use of directives and guidance with child behavior and affect differed by task. Observed parent directives were associated with child disruptive behavior during each task, whereas parent guidance was negatively associated with child disruptive behavior and positively associated with child positive affect during the teaching task. Parenting strategies that are well matched to the situational context and proactively consider task demands are more likely to facilitate children’s social-emotional development.

Background The aim of this study was to determine the relative and absolute reliabilities of 5 key performance-based measures of physical function in the Canadian Longitudinal Study on Aging (CLSA). Methods An age-stratified subsample of 147 participants from the CLSA who were undergoing their 3-year data collection visit participated in 2 repeat visits (within 1 week). Participants underwent tests of grip strength, 4-m gait speed, Timed Up and Go (TUG), chair rise, and single-leg stance (left, right, mean, maximum). Intraclass correlation coefficients (ICCs), standard error of measurement, and minimal detectable change (MDC) values were calculated. Results The relative reliability for grip strength was excellent (ICC = 0.95); the TUG and single-leg stance tests had good reliability (ICC = 0.80 or 0.78–0.82, respectively); gait speed and the chair-rise test had moderate reliability (ICC = 0.64 for both) for participants overall. For participants between 50 and 64 years, TUG and gait speed had poor reliabilities (ICC = 0.38 or 0.33, respectively). For participants aged 75 years and older, the single-leg stance had poor reliability (ICC = 0.30–0.39). The MDC90 was about 6 kg for grip strength, 2.3 seconds for TUG, 0.2 m/second for gait speed, 5.2 seconds for chair rise, and ranged from 22.8 to 26.2 seconds for the single-leg stance. Conclusions Among community-dwelling Canadians older than 50 years, the reliabilities of the CLSA measures were moderate to excellent. The TUG and gait speed in the youngest age group, and the single-leg stance in the oldest age group, showed poor reliability. MDC values can be used to interpret changes over time.

Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate “off-the-shelf” delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction. In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at −80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells. Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.

In budding yeast, Rif1 negatively regulates telomere length, but the mechanism of this regulation has remained elusive. Previous work identified several functional domains of Rif1, but none of these has been shown to mediate telomere length. To define Rif1 domains responsible for telomere regulation, we localized truncations of Rif1 to a single specific telomere and measured telomere length of that telomere compared to bulk telomeres. We found that a domain in the N-terminus containing HEAT repeats, Rif1177–996, was sufficient for length regulation when tethered to the telomere. Charged residues in this region were previously proposed to mediate DNA binding. We found that mutation of these residues disrupted telomere length regulation even when Rif1 was tethered to the telomere. Mutation of other conserved residues in this region, which were not predicted to interact with DNA, also disrupted telomere length maintenance, while mutation of conserved residues distal to this region did not. Our data suggest that conserved amino acids in the region from 436 to 577 play a functional role in telomere length regulation, which is separate from their proposed DNA binding function. We propose that the Rif1 HEAT repeats region represents a protein-protein binding interface that mediates telomere length regulation.

Background Heart transplant volume varies significantly among centers. We hypothesized that centers where the transplant team routinely accepts organs previously declined by other centers and where operating room availability is unrestricted have higher transplant volumes. Methods and Results We used the potential transplant recipient sequence number in the United Network for Organ Sharing database as a surrogate for graft acceptance threshold and the number of transplantations occurring on weekends and 8 major holidays as a marker of center resource availability. Centers were classified as low-, medium-, or high-volume if the average annual number of transplants were, respectively, 30 over a 10-year period. From July 12, 2006, to December 31, 2015, 19,054 transplants were performed by 142 centers. There were 59 low-volume centers, 69 medium-volume centers, and 14 high-volume centers with median potential transplant recipient sequence numbers for transplanted candidates of 7 (interquartile range 3–11), 7 (5–10), and 15 (7–40), respectively (P = .002). The median proportion of off-hours transplantations performed by medium-volume centers was 28% (25%–31%) compared with 32% (29%–33%) by high-volume centers (P = .009). Five-year survival was equivalent among all centers (P = .053). Conclusions Transplants for candidates with high sequence numbers and unrestricted operating room availability are associated with increased center volume without sacrificing post-transplantation survival.

Objectives Poor diet due to poor oral health was proposed as a potential mediator of the association between poor oral health and frailty. This study explores the cross-sectional associations between poor oral health, poor diet, and frailty in Canadian adults, aged 45 to 85 years, and then tests whether the expected oral health-frailty association is changed by taking into account the pathway through poor diet. Design Cross-sectional study. Setting The baseline wave of the Canadian Longitudinal Study on Aging, a nationally representative population study. Participants Data from 28 738 community-dwelling participants, aged 45 to 85 years. Measurements We characterized poor oral health (cumulative count of 24 items of oral health problems), poor diet (scale of poor food consumption from 7 healthy foods groups), and frailty (cumulative frailty index of 76 items). Regression-based path analyses were used to investigate associations between poor oral health, poor diet, and frailty, adjusted for age group, sex, income, smoking, living alone, education, physical activity, social support, and dental visit. Results Poorer oral health was associated with low income, smoking, low physical activity, low social support, and no dental visit. There were associations between poorer oral health and poorer diet (effect size β adjusted = .40; 95% confidence interval [CI] = .20-.61) and between poorer oral health and increased frailty (β adjusted = .85; 95% CI = .68-1.02). The indirect effect through the path of poor diet was approximately 0.01 (95% CI = 0.01-0.02) (ie, explaining ∼1% of the effect of poor oral health on frailty). Conclusions Poor oral health was associated with poor diet and frailty. Each additional oral health problem was associated with an increase of approximately 1 frailty index point, even after full adjustment for poor diet. The indirect effect of poor oral health through poor diet was modest. Though poor oral health was associated with poorer diet quality, a more direct effect of poor oral health on increasing frailty may be indicated. J Am Geriatr Soc 68:959-966, 2020.

Telomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1∆ and bur2∆ set2∆ were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2∆ set2∆ mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation.

The emergence of antimicrobial resistance (AMR) in dogs constitutes a threat to animal and human health. There is a lack of studies in Illinois that evaluated the prevalence of AMR among urinary bacterial pathogens. In the study, we included 803 isolates (299 Gram-positive and 504 Gram-negative) that were isolated from 2,583 canine urine samples submitted to the Veterinary Diagnostic Laboratory, the University of Illinois between 2019 and 2020 from dogs suspected of urinary tract infections (UTI). The most common Gram-positive isolates included Staphylococcus pseudintermedius (17.93%), Enterococcus faecalis (9.46%), Streptococcus canis (6.10%), and Enterococcus faecium (3.74%), while Gram-negative isolates included Escherichia coli (45.58%), Proteus mirabilis (11.08%), Klebsiella pneumoniae (3.11%), and Pseudomonas aeruginosa (2.99%). Among the Gram-positive isolates, Staphylococcus pseudintermedius isolates showed a very high prevalence of resistance to penicillin (56.94%), a high prevalence of resistance to trimethoprim-sulfamethoxazole (31.94%), enrofloxacin (29.17%), and oxacillin (27.08%). Among Gram-negative bacteria, Escherichia coli isolates showed a high prevalence of resistance to ampicillin (31.42%). Considering the high prevalence of resistance to antimicrobials commonly used to treat UTI in dogs, urine samples should be collected for bacterial culture and susceptibility testing before treatment initiation to prevent treatment failures and the development of multidrug resistance. Given the possibility of zoonotic transmission of antimicrobial-resistant bacteria, veterinarians when treating UTI cases, should inform dog owners of the potential transmission risk.

The goal of this project was to determine whether screening youth and parents for firearm presence and imbedding those results in the electronic medical record (EMR) increased health care provider (HCP) documentation of firearms and subsequent delivery of a safe storage message. The study took place in a large adolescent medicine practice. Fifty-six dyads (40% of eligible) were randomized to usual care or the intervention, in which screening results for firearms were imbedded in the EMR. Health care providers delivered a safe storage message to 20% of controls and 51.2% in the intervention ( P = .04). When HCPs documented the delivery of a safe storage message, 64% of parents recalled hearing it, compared with only 36% when there was no documentation ( P = .012). Therefore, we found that incorporating firearm screening into the EMR increases the attention HCPs give to delivering a firearm safe storage message and correlates with parents recalling having heard a safe storage message.

Purpose of Review We describe the impact of COVID-19 on PEPFAR programs in Africa and how PEPFAR adapted and leveraged its interventions to the changing landscape of the COVID-19 pandemic. Recent Findings To mitigate the potential impact of COVID-19 on the HIV response and protect the gains, continuity of treatment was the guiding principle regarding the provision of services in PEPFAR-supported countries. As the COVID-19 pandemic matured, PEPFAR’s approach evolved from a strictly “protect and salvage” approach to a “restore and accelerate” approach that embraced innovative adaptations in service and “person-centered” care. Summary The impact of service delivery interruptions caused by COVID-19 on progress towards HIV epidemic control in PEPFAR-supported African countries remains undetermined. With COVID vaccine coverage many months away and more transmissible variants being reported, Africa may experience more pandemic surges. HIV programs will depend on nimble and innovative adaptations in prevention and treatment services in order to advance epidemic control objectives.

Salmonellosis is an important zoonotic infection, and exposure to pet reptiles has been implicated in several human outbreaks. Although several studies report a low prevalence of salmonellae in free-ranging chelonians, they may serve as a reservoir. In spring and summer of 2013 and 2019, free-ranging eastern box turtles (Terrapene carolina carolina) from populations in Illinois (rural) and Tennessee (urban) were collected through canine and visual search. Cloacal swab samples were collected from each turtle, selectively enriched with tetrathionate broth, then plated on selective and differential media to isolate Salmonella spp. Genus was confirmed via MALDI-TOF MS and antibiotic sensitivities were performed. Isolates were serotyped by the National Veterinary Services Laboratory. Of the 341 turtles sampled, Salmonella spp. were detected in nine individuals (2.64%; 95% CI: 1.2–5.0%). The isolates included five different serovars: Anatum (n = 2), Newport (n = 2), Thompson (n = 1), Bareilly (n = 2), and Hartford (n = 2). Salmonella spp. were detected from six animals in 2013 (3.19%, 95% CI: 1.2–6.8%) and three in 2019 (1.96%, 95% CI: 0.4–5.6%). There was no significant difference in prevalence between state, (P = 0.115), Illinois locations (P = 0.224), season (P = 0.525), year (P = 0.297), sex (P = 0.435), or age class (P = 0.549). The health of Salmonella-positive and -negative turtles was not significantly different, as assessed through hematology and plasma biochemistry (P > 0.05), indicating asymptomatic carrier status. The low prevalence detected in this study likely concludes that free-ranging eastern box turtles play a minimal role in the spread of salmonellae. However, the identified serotypes are potentially human- and animal-pathogenic. Documenting the prevalence of Salmonella serotypes in animal indicators furthers our understanding of their spread between humans, animal agriculture, and the environment.

Objectives To compare the prevalence of poor self-reported oral health (SROH) and dental service-use in a representative sample of Canadian residents, and to identify associations between SROH and psychosocial determinants of health at baseline of the Canadian Longitudinal Study on Aging. Methods Data from baseline interviews from 2010 to 2015 involving 93% of 51 388 adults (n = 47 761) were weighted to compare the prevalence of oral health characteristics adjusted for age, sex, socioeconomics, general health and residence. SROH was assessed as 'excellent', 'very good', 'good', 'fair' or 'poor', and dichotomized as 'fair/poor' and 'good/very good/excellent'. Multivariable logistic regression was used to assess the association of fair/poor oral health with psychosocial determinants of health. Results Most participants reported 'good/very good/excellent' oral health (92.5%), natural teeth (92.0%) and dental service-use in the previous year (79.6%), yet over 10% had discomfort when eating. Reports of 'fair/poor' oral health were significantly more frequent among participants who had dental concerns, had low socioeconomic status, smoked tobacco or reported poor general health. Dental service-use and tooth loss differed by province. The odds of poor/fair SROH were high (odds ratio ≥1.5) among participants who avoided foods, did not use dental services frequently, had low incomes, smoked tobacco, were depressed, felt unhealthy or had multiple chronic conditions, but by neither sex or age. There were no interprovincial differences. Conclusions Most Canadian residents feel in good oral health and use dental services. Oral health inequality is evident between different socioeconomic groups and between healthy and unhealthy people. SROH is strongly associated with socioeconomic and general health status but not with place of residence. However, there were substantial differences in reports of tooth loss and dental service-use across provinces.

Methicillin-resistant Staphylococcus aureus (MRSA) carriage and infection are well documented in the human and veterinary literature; however only limited information is available regarding MRSA carriage and infection in laboratory NHP populations. The objective of this study was to characterize MRSA carriage in a representative research colony of rhesus and cynomolgus macaques through a cross-sectional analysis of 300 animals. MRSA carriage was determined by using nasal culture. Demographic characteristics of carriers and noncarriers were compared to determine factors linked to increased risk of carriage, and MRSA isolates were analyzed to determine antimicrobial susceptibility patterns, staphylococcal chromosome cassette mec (SCCmec) type, and multilocus sequence type (ST). Culture results demonstrated MRSA carriage in 6.3% of the study population. Animals with greater numbers of veterinary or experimental interventions including antibiotic administration, steroid administration, dental procedures, and surgery were more likely to carry MRSA. Susceptibility results indicated that MRSA isolates were resistant to β-lactams, and all isolates were resistant to between 1 and 4 non β-lactam antibiotics. In addition, 73.7% of MRSA isolates were identified as ST188-SCCmec IV, an isolate previously observed in an unrelated population of macaques and 15.8% were ST3268-SCCmec V, which has only been described in macaques. A single isolate had a novel sequence type, ST3478, and carried SCCmec V. These results suggest that NHP-adapted strains of MRSA exist and highlight the emergence of antimicrobial resistance in laboratory NHP populations.

Freedom to Choose: Two Systems of Self-Regulation represents the culmination and distillation of fifty years of clinical work and research by two prominent child, adolescent, and adult psychoanalys...

We present a theoretical analysis of the elastic stresses in a composite reinforced with beaded fibers by extending the classic Cox shear lag theory. The motivation for reinforcing a composite with beaded fibers is to improve both strength and toughness, two often conflicting properties. It is found that owing to their geometry beads intermittently placed on a fiber enhance fiber anchoring in the matrix, and can potentially dissipate energy by deforming the matrix during failure. The composite stiffness is shown to improve compared to a composite with beadless fibers, particularly when the beads are large and stiffer than the surrounding matrix. The stress profiles in the fiber, bead, matrix and along their respective interfaces incur periodic perturbations induced by the beads, modeled by Hill equation. For given elastic constants and bead geometry, these profiles reveal the weakest link loci in the structure, and consequently determine the composite strength and failure mode. A finite element analysis is presented that confirms our results. The bead-fiber and bead-matrix interfaces may be tuned by choice of materials and coatings to achieve desired mechanical properties.

Reflectance imaging spectroscopy (RIS) in the visible and near infrared is revolutionizing the way cultural heritage investigators may analyze paintings nondestructively. In an ongoing, highly coll...

The most severe outcome of intimate partner violence (IPV) is IPV-related homicide. Access to affordable housing may both facilitate exit from abusive relationships and reduce financial stress in intimate relationships, potentially preventing IPV-related homicide. We examined the association of the availability of rental housing through the Low-Income Housing Tax Credit (LIHTC) program, a federal program providing tax incentives to support the development of affordable housing, with IPV-related homicide and assessed whether this association differed by eviction rates at the state-level. We used 2005-2016 National Violent Death Reporting System, LIHTC Property, and Eviction Lab data for 13 states and compared the rate of IPV-related homicide in state-years with ≥30 to state-years with30 LIHTC units per 100,000 population, overall and stratified by eviction rates. We conducted analyses in fall 2020. Adjusting for potential state-level confounders, the rate of IPV-related homicide in state-years with ≥30 LIHTC units per 100,000 population was lower than in state-years with30 LIHTC units per 100,000 population (RR = 0.89, 95% CI 0.81, 0.98). The reduction in the rate of IPV-related homicide was slightly larger in state-years with higher eviction rates (≥3500 evictions per 100,000 renter population; RR = 0.83, 95% CI 0.74, 0.93) compared to state-years with lower eviction rates (3500 evictions per 100,000 renter population; RR = 0.91, 95% CI 0.81, 1.03). Overall, at the state-level, increased availability of affordable housing through the LIHTC program was associated with lower rates of IPV-related homicide. Increasing the availability of affordable housing may be one tool for preventing IPV-related homicide.

Poverty broadly and financial stress owing to housing insecurity specifically are associated with an increased risk of child maltreatment. Therefore, it is possible that a program designed to increase access to affordable housing such as the Low-Income Housing Tax Credit program could reduce child maltreatment. The purpose of this study is to examine the association of the availability of housing units through the Low-Income Housing Tax Credit Program with the rates of child maltreatment reports, including reports for physical abuse and neglect, at the state and county levels.Data were from the 2005‒2015 National Child Abuse and Neglect Data System and the Low-Income Housing Tax Credit Program database. Generalized estimating equations were conducted in 2021 to calculate rate ratios and 95% CIs, adjusting for relevant confounders.At the state level, ≥25 compared with25 Low-Income Housing Tax Credit Program units per 100,000 population was associated with a lower rate of overall child maltreatment (i.e., neglect and physical abuse; rate ratio=0.96, 95% CI=0.93, 0.99), neglect (rate ratio=0.96, 95% CI=0.94, 0.99), and physical abuse (rate ratio=0.96, 95% CI=0.93, 1.00) reports. Similarly, at the county level, ≥1 compared with 0 Low-Income Housing Tax Credit Program units per 100,000 population was associated with a lower rate of overall child maltreatment (rate ratio=0.94, 95% CI=0.92, 0.97), neglect (rate ratio=0.96, 95% CI=0.93, 0.98), and physical abuse (rate ratio=0.94, 95% CI=0.91, 0.98) reports.Increasing access to affordable housing may be an effective strategy to reduce child maltreatment at both the state and county levels.

ObjectivesSystemic sclerosis (SSc) is an autoimmune fibrotic disease affecting multiple tissues including the lung. A subset of patients with SSc with lung disease exhibit short telomeres in circulating lymphocytes, but the mechanisms underlying this observation are unclear.MethodsSera from the Johns Hopkins and University of California, San Francisco (UCSF) Scleroderma Centers were screened for autoantibodies targeting telomerase and the shelterin proteins using immunoprecipitation and ELISA. We determined the relationship between autoantibodies targeting the shelterin protein TERF1 and telomere length in peripheral leucocytes measured by qPCR and flow cytometry and fluorescent in situ hybridisation (Flow-FISH). We also explored clinical associations of these autoantibodies.ResultsIn a subset of patients with SSc, we identified autoantibodies targeting telomerase and the shelterin proteins that were rarely present in rheumatoid arthritis, myositis and healthy controls. TERF1 autoantibodies were present in 40/442 (9.0%) patients with SSc and were associated with severe lung disease (OR 2.4, p=0.04, Fisher’s exact test) and short lymphocyte telomere length. 6/6 (100%) patients with TERF1 autoantibodies in the Hopkins cohort and 14/18 (78%) patients in the UCSF cohort had a shorter telomere length in lymphocytes or leukocytes, respectively, relative to the expected age-adjusted telomere length. TERF1 autoantibodies were present in 11/152 (7.2%) patients with idiopathic pulmonary fibrosis (IPF), a fibrotic lung disease believed to be mediated by telomere dysfunction.ConclusionsAutoantibodies targeting telomere-associated proteins in a subset of patients with SSc are associated with short lymphocyte telomere length and lung disease. The specificity of these autoantibodies for SSc and IPF suggests that telomere dysfunction may have a distinct role in the pathogenesis of SSc and pulmonary fibrosis.

We developed a method to tag telomeres and measure telomere length by nanopore sequencing in the yeast S. cerevisiae. Nanopore allows long read sequencing through the telomere, subtelomere and into unique chromosomal sequence, enabling assignment of telomere length to a specific chromosome end. We observed chromosome end specific telomere lengths that were stable over 120 cell divisions. These stable chromosome specific telomere lengths may be explained by stochastic clonal variation or may represent a new biological mechanism that maintains equilibrium unique to each chromosomes end. We examined the role of RIF1 and TEL1 in telomere length regulation and found that TEL1 is epistatic to RIF1 at most telomeres, consistent with the literature. However, at telomeres that lack subtelomeric Y’ sequences, tel1Δ rif1Δ double mutants had a very small, but significant, increase in telomere length compared to the tel1Δ single mutant, suggesting an influence of Y’ elements on telomere length regulation. We sequenced telomeres in a telomerase-null mutant (est2Δ) and found the minimal telomere length to be around 75bp. In these est2Δ mutants there were many apparent telomere recombination events at individual telomeres before the generation of survivors, and these events were significantly reduced in est2Δ rad52Δ double mutants. The rate of telomere shortening in the absence of telomerase was similar across all chromosome ends at about 5 bp per generation. This new method gives quantitative, high resolution telomere length measurement at each individual chromosome end, suggests possible new biological mechanisms regulating telomere length, and provides capability to test new hypotheses.

Background High-prevalence childhood mental health problems like early-onset disruptive behavior problems (DBPs) pose a significant public health challenge and necessitate interventions with adequate population reach. The treatment approach of choice for childhood DBPs, namely evidence-based parenting intervention, has not been sufficiently disseminated when relying solely on staff-delivered services. Online-delivered parenting intervention is a promising strategy, but the cost minimization of this delivery model for reducing child DBPs is unknown compared with the more traditional staff-delivered modality. Objective This study aimed to examine the cost-minimization of an online parenting intervention for childhood disruptive behavior problems compared with the staff-delivered version of the same content. This objective, pursued in the context of a randomized trial, made use of cost data collected from parents and service providers. Methods A cost-minimization analysis (CMA) was conducted comparing the online and staff-delivered parenting interventions. Families (N=334) with children 3-7 years old, who exhibited clinically elevated disruptive behavior problems, were randomly assigned to the two parenting interventions. Participants, delivery staff, and administrators provided data for the CMA concerning family participation time and expenses, program delivery time (direct and nondirect), and nonpersonnel resources (eg, space, materials, and access fee). The CMA was conducted using both intent-to-treat and per-protocol analytic approaches. Results For the intent-to-treat analyses, the online parenting intervention reflected significantly lower program costs (t168=23.2; P Conclusions The online-delivered parenting intervention in this randomized study produced substantial cost minimization compared with the staff-delivered intervention providing the same content. Cost minimization was driven primarily by personnel time and, to a lesser extent, by facilities costs and family travel time. The CMA was accomplished with three critical conditions in place: (1) the two intervention delivery modalities (ie, online and staff) held intervention content constant; (2) families were randomized to the two parenting interventions; and (3) the online-delivered intervention was previously confirmed to be non-inferior to the staff-delivered intervention in significantly reducing the primary outcome, child disruptive behavior problems. Given those conditions, cost minimization for the online parenting intervention was unequivocal. Trial Registration ClinicalTrials.gov NCT02121431; https://clinicaltrials.gov/ct2/show/NCT02121431

BACKGROUND High-prevalence childhood mental health problems like early-onset disruptive behavior problems (DBPs) pose a significant public health challenge and necessitate interventions with adequate population reach. The treatment approach of choice for childhood DBPs, namely evidence-based parenting intervention, has not been sufficiently disseminated when relying solely on staff-delivered services. Online-delivered parenting intervention is a promising strategy, but the cost minimization of this delivery model for reducing child DBPs is unknown compared with the more traditional staff-delivered modality. OBJECTIVE This study aimed to examine the cost-minimization of an online parenting intervention for childhood disruptive behavior problems compared with the staff-delivered version of the same content. This objective, pursued in the context of a randomized trial, made use of cost data collected from parents and service providers. METHODS A cost-minimization analysis (CMA) was conducted comparing the online and staff-delivered parenting interventions. Families (N=334) with children 3-7 years old, who exhibited clinically elevated disruptive behavior problems, were randomly assigned to the two parenting interventions. Participants, delivery staff, and administrators provided data for the CMA concerning family participation time and expenses, program delivery time (direct and nondirect), and nonpersonnel resources (eg, space, materials, and access fee). The CMA was conducted using both intent-to-treat and per-protocol analytic approaches. RESULTS For the intent-to-treat analyses, the online parenting intervention reflected significantly lower program costs (t168=23.2; P<.001), family costs (t185=9.2; P<.001), and total costs (t171=19.1; P<.001) compared to the staff-delivered intervention. The mean incremental cost difference between the interventions was $1164 total costs per case. The same pattern of significant differences was confirmed in the per-protocol analysis based on the families who completed their respective intervention, with a mean incremental cost difference of $1483 per case. All costs were valued or adjusted in 2017 US dollars. CONCLUSIONS The online-delivered parenting intervention in this randomized study produced substantial cost minimization compared with the staff-delivered intervention providing the same content. Cost minimization was driven primarily by personnel time and, to a lesser extent, by facilities costs and family travel time. The CMA was accomplished with three critical conditions in place: (1) the two intervention delivery modalities (ie, online and staff) held intervention content constant; (2) families were randomized to the two parenting interventions; and (3) the online-delivered intervention was previously confirmed to be non-inferior to the staff-delivered intervention in significantly reducing the primary outcome, child disruptive behavior problems. Given those conditions, cost minimization for the online parenting intervention was unequivocal. CLINICALTRIAL ClinicalTrials.gov NCT02121431; https://clinicaltrials.gov/ct2/show/NCT02121431