Horizontal gene transfer of a functional cki homolog in the human pathogen Schistosoma mansoni.

Schistosomes are parasitic flatworms responsible for the neglected tropical disease schistosomiasis, causing devastating morbidity and mortality in the developing world. The parasites are protected by a skin-like tegument, and maintenance of this tegument is controlled by a schistosome ortholog of the tumor suppressor TP53. To understand mechanistically how p53-1 controls tegument production, we identified a cyclin dependent kinase inhibitor homolog (cki) that was co-expressed with p53-1. RNA interference of cki resulted in a hyperproliferation phenotype, that, in combination with p53-1 RNA interference yielded abundant tumor-like growths, indicating that cki and p53-1 are bona fide tumor suppressors in Schistosoma mansoni. Interestingly, cki homologs are widely present throughout parasitic flatworms but evidently absent from their free-living ancestors, suggesting this cki homolog came from an ancient horizontal gene transfer event. This in turn implies that the evolution of parasitism in flatworms may have been aided by a highly unusual means of metazoan genetic inheritance.

A niche-derived nonribosomal peptide triggers planarian sexual development.

Germ cells are regulated by local microenvironments (niches), which secrete instructive cues. Conserved developmental signaling molecules act as niche-derived regulatory factors, yet other types of niche signals remain to be identified. Single-cell RNA-sequencing of sexual planarians revealed niche cells expressing a nonribosomal peptide synthetase (nrps). Inhibiting nrps led to loss of female reproductive organs and testis hyperplasia. Mass spectrometry detected the dipeptide ß-alanyl-tryptamine (BATT), which is associated with reproductive system development and requires nrps and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after nrps or aadc inhibition, restoring fertility. Thus, a nonribosomal, monoamine-derived peptide provided by niche cells acts as a critical signal to trigger planarian reproductive development. These findings reveal an unexpected function for monoamines in niche-germ cell signaling. Furthermore, given the recently reported role for BATT as a male-derived factor required for reproductive maturation of female schistosomes, these results have important implications for the evolution of parasitic flatworms and suggest a potential role for nonribosomal peptides as signaling molecules in other organisms.

Chemotherapy safe handling practices in Ethiopia: A comprehensive multi-center evaluation.

INTRODUCTION: The increasing incidence of cancer and capacity for cancer care in Ethiopia has led to an upsurge in chemotherapy use in the country; however, studies indicate that there is a gap in the safe handling of chemotherapy by healthcare workers. There exists a need to understand if such unsafe practices occur in Ethiopia and, if so, which areas along the chemotherapy life cycle need the most improvement. METHODS: This study utilized a multi-method design through an online survey administered to health care professionals and evaluative site visits of eight cancer units in Addis Ababa, Ethiopia to understand the current conditions of chemotherapy handling. In addition, a survey was conducted among Ethiopian health care professionals from across the country. RESULTS: Fifty-five percent of survey participants disagreed or strongly disagreed that there are systems in place to identify, prevent, and address chemotherapy hazards in their workplace, and 71% of respondents denied having an active and effective health and safety committee and/or worker health and safety representative where they work. At evaluative site visits, only 30% of health care workers met the minimum guidelines for proper hand hygiene, and 20% of health care workers used adequate Personal Protective Equipment according to guidelines across the chemotherapy lifecycle. CONCLUSIONS: Results of this study indicate an urgent need for implementation of evidence-based interventions to improve chemotherapy handling in Ethiopia so that all patients and health care workers are protected from the hazardous toxicities of these drugs.

A novel animal model for understanding secondary traumatic stress and visceral pain in male rats.

Empathetic relationships and the social transference of behaviours have been shown to occur in humans, and more recently through the development of rodent models, where both fear and pain phenotypes develop in observer animals. Clinically, observing traumatic events can induce 'trauma and stressor-related disorders' as defined in the DSM 5. These disorders are often comorbid with pain and gastrointestinal disturbances; however, our understanding of how gastrointestinal - or visceral - pain can be vicariously transmitted is lacking. Visceral pain originates from the internal organs, and despite its widespread prevalence, remains poorly understood. We established an observation paradigm to assess the impact of witnessing visceral pain. We utilised colorectal distension (CRD) to induce visceral pain behaviours in a stimulus rodent while the observer rodent observed. Twenty four hours post-observation, the observer rodent's visceral sensitivity was assessed using CRD. The observer rodents were found to have significant hyperalgesia as determined by lower visceral pain threshold and higher number of total pain behaviours compared with controls. The behaviours of the observer animals during the observation were found to be correlated with the behaviours of the stimulus animal employed. We found that observer animals had hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis, highlighted by reduced corticosterone at 90 minutes post-CRD. Using c-Fos immunohistochemistry we showed that observer animals also had increased activation of the anterior cingulate cortex, and decreased activation of the paraventricular nucleus, compared with controls. These results suggest that witnessing another animal in pain produces a behavioural phenotype and impacts the brain-gut axis.

The gut microbiota in persistent post-operative pain following breast cancer surgery.

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind the role of the gut microbiota in the development of PPSP and could inform future treatment strategies.

Key Performance Indicators and Metrics for the Implementation of an Oral Chemotherapy Adherence Program.

BACKGROUND: Oral anticancer agents (OAAs) transformed cancer care for patients, extending survival and delaying progression in certain cases. There are multiple pharmacy-driven models to improve patient knowledge and adherence to OAAs. However, a lack of measurable key performance indicators (KPIs) has limited the adoption, implementation, and maintenance of these models. The objective of this study was to identify a set of KPIs, their metrics, and the target values that indicated improved patient care through an OAA adherence program. METHODS: A literature review was conducted to identify an initial list of defined KPIs, metrics of the KPIs, and targets for success. We assembled an advisory panel of clinicians (n=9), administrators (n=7), and patients (n=2) from across an academic and affiliated community cancer center to gauge agreement on identified KPIs for use within a structured adherence intervention. We used a Qualtrics survey consisting of questions measured using a 5-point Likert scale response that ranged from 1 (strongly disagree) to 5 (strongly agree) and a subsequent consensus-building discussion with the advisory panel to identify agreeability with the definitions, metrics, and targets of identified KPIs. RESULTS: Eleven KPIs were identified: (1) time to intended OAA initiation; (2) adherence rate during active treatment; (3) adverse events; (4) medication-related financial toxicity; (5) patient satisfaction; (6) treatment-related emergency department visits; (7) treatment-related hospital admissions; (8) proportion of patients with adherence, toxicity, and financial barriers assessed; (9) proportion of patients referred to social work; (10) time spent by patient in each phase of care as defined by the intervention's standard operating procedure; and (11) revenue generated by billing for service. CONCLUSIONS: This study identified 11 KPIs that can be used in evaluating the success of an OAA adherence program. Use of these KPIs will be piloted after formal implementation of the program in both academic and community cancer centers.

Iron homeostasis in older adults: balancing nutritional requirements and health risks.

Iron plays a crucial role in many physiological processes, including oxygen transport, bioenergetics, and immune function. Iron is assimilated from food and also recycled from senescent red blood cells. Iron exists in two dietary forms: heme (animal based) and non-heme (mostly plant based). The body uses iron for metabolic purposes, and stores the excess mainly in splenic and hepatic macrophages. Physiologically, iron excretion in humans is inefficient and not highly regulated, so regulation of intestinal absorption maintains iron homeostasis. Iron losses occur at a steady rate via turnover of the intestinal epithelium, blood loss, and exfoliation of dead skin cells, but overall iron homeostasis is tightly controlled at cellular and systemic levels. Aging can have a profound impact on iron homeostasis and induce a dyshomeostasis where iron deficiency or overload (sometimes both simultaneously) can occur, potentially leading to several disorders and pathologies. To maintain physiologically balanced iron levels, reduce risk of disease, and promote healthy aging, it is advisable for older adults to follow recommended daily intake guidelines and periodically assess iron levels. Clinicians can evaluate body iron status using different techniques but selecting an assessment method primarily depends on the condition being examined. This review provides a comprehensive overview of the forms, sources, and metabolism of dietary iron, associated disorders of iron dyshomeostasis, assessment of iron levels in older adults, and nutritional guidelines and strategies to maintain iron balance in older adults.

Lifetime Upward Economic Mobility and US-Born Latina Women's Preterm Birth Rates.

OBJECTIVES: To determine whether Latina women's upward economic mobility from early-life residence in impoverished urban neighborhoods is associated with preterm birth (< 37 weeks, PTB) . METHODS: Multivariate logistic regression analyses were performed on the Illinois transgenerational birth-file with appended US census income information for Hispanic infants (born 1989-1991) and their mothers (born 1956-1976). RESULTS: In Chicago, modestly impoverished-born Latina women (n = 1,674) who experienced upward economic mobility had a PTB rate of 8.5% versus 13.1% for those (n = 3,760) with a lifelong residence in modestly impoverished neighborhoods; the unadjusted and adjusted (controlling for age, marital status, adequacy of prenatal care, and cigarette smoking) RR equaled 0.65 (0.47, 0.90) and 0.66 (0.47, 0.93), respectively. Extremely impoverished-born Latina women (n = 2,507) who experienced upward economic mobility across their life-course had a PTB rate of 12.7% versus 15.9% for those (n = 3,849) who had a lifelong residence in extremely impoverished neighborhoods, the unadjusted and adjusted RR equaled 0.8 (0.63. 1.01) and 0.95 (0.75, 1.22), respectively. CONCLUSIONS FOR PRACTICE: Latina women's upward economic mobility from early-life residence in modestly impoverished urban neighborhoods is associated with a decreased risk of PTB. A similar trend is absent among their peers with an early-life residence in extremely impoverished areas.

Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.

Iron deficiency (ID) and iron-deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4 ); however, dosing at several-fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron-regulatory hormone hepcidin.

Schistosome Infection Impacts Hematopoiesis.

Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. In this article, we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm that causes schistosomiasis. We analyzed the frequency or number of hematopoietic cell types in the bone marrow, spleen, liver, thymus, and blood and observed multiple hematopoietic changes caused by infection. Schistosome infection impaired bone marrow HSC function after serial transplantation. Functional HSCs were present in the infected liver. Infection blocked bone marrow erythropoiesis and augmented spleen erythropoiesis, observations consistent with the anemia and splenomegaly prevalent in schistosomiasis patients. This work defines the hematopoietic response to schistosomiasis, a debilitating disease afflicting more than 200 million people, and identifies impairments in HSC function and erythropoiesis.

The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage.

Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacterium responsible for antibiotic-associated pseudomembranous colitis. Clostridioides difficile infection (CDI) symptoms can range from diarrhea to life-threatening colon damage. Toxins produced by C. difficile (TcdA and TcdB) cause intestinal epithelial injury and lead to severe gut barrier dysfunction, stem cell damage, and impaired regeneration of the gut epithelium. Current treatment options for intestinal repair are limited. In this study, we demonstrate that treatment with the microbial metabolite urolithin A (UroA) attenuates CDI-induced adverse effects on the colon epithelium in a preclinical model of CDI-induced colitis. Moreover, our analysis suggests that UroA treatment protects against C. difficile-induced inflammation, disruption of gut barrier integrity, and intestinal tight junction proteins in the colon of CDI mice. Importantly, UroA treatment significantly reduced the expression and release of toxins from C. difficile without inducing bacterial cell death. These results indicate the direct regulatory effects of UroA on bacterial gene regulation. Overall, our findings reveal a novel aspect of UroA activity, as it appears to act at both the bacterial and host levels to protect against CDI-induced colitis pathogenesis. This research sheds light on a promising avenue for the development of novel treatments for C. difficile infection.IMPORTANCETherapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.

Evaluation of real-world versus clinical trial outcomes of tyrosine kinase inhibitor therapy for chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for chronic myeloid leukemia (CML). Patients enrolled in clinical trials investigating the safety and efficacy of TKIs in CML are generally younger, have fewer comorbidities, and are monitored differently than patients treated in the real world. This narrative literature review summarizes efficacy outcomes (complete cytogenetic response, major molecular response, and disease progression) and safety outcomes (duration of TKI therapy, TKI discontinuation rates, dosage changes, and frequently reported adverse events) from landmark clinical trials as well as real-world studies. Patients with CML treated with TKIs in a real-world setting may achieve different rates of specific response milestones than those treated on clinical trials. While real-world studies reported similar overall incidences of adverse events as clinical trials, real-world patients with CML were more likely to discontinue TKIs due to adverse events.

Prevalence of oral mucosal lesions in an adult population from eight communities in Santo Domingo, Dominican Republic / Prevalencia de lesiones de mucosa oral en una población adulta de ocho comunidades en Santo Domingo, República Dominicana

ABSTRACT The purpose of the study was to evaluate the prevalence of Oral Mucosal Lesions (OMLs) in an adult population from Santo Domingo, Dominican Republic. 751 subjects from eight communities from Santo Domingo accepted the invitation to participate in an oral screening from October 2016 to January 2017. 248 subjects were evaluated and clinically examined, age range 18-86 years. A validated instrument was designed to record demographic factors, age group, gender, anatomical location, presence or absence of OMLs, risk factors such as tobacco consumption and its frequency, and different forms of tobacco and alcohol use. A systematic oral clinical examination was conducted by a specialist. The presence or absence, and anatomic location of OMLs were recorded. The sample consisted of 44.4% males and 55.6 % females. 228 subjects had 1 or more lesions (91.9%), the median was 3 lesions per patient. In relation to risk factors, tobacco use in general was reported by 26.2 % of the subjects, with cigarette smoking reported by 75.4%, followed by other forms as "hookah" 9.2 %, marihuana 9.2%, cigars ("puros")4.6% and pipe smoking 1.5%. Among the oral lesions detected by screening, the nonpathological group was prevalent, and included physiologic melanin pigmentation as the most frequent (25.0%) followed by palatal/mandibular tori (20.2%), Fordyce granules (7.9%), and Exostosis (5.6%). Potentially malignant disorders (Oral Leukoplakia, Oral Lichen Planus and Actinic Cheilitis) corresponded to 2.2%, 0.3 %, and 0.3%, respectively. No malignancy was observed clinically. This study contributes to determining the prevalence of OMLs in Dominican Republic and to identifying risk factors. This is the first study reporting the prevalence of oral mucosal lesions among the Dominican adult population. This information is vital for establishing a public health program targeting the high-risk group to improve the oral health status in this population.

RESUMEN El objetivo del presente estudio fue evaluar la prevalencia de lesiones de la mucosa oral (LMO) en una población adulta proveniente de Santo Domingo, República Dominicana. 751 individuos procedentes de ocho comunidades de la provincia de Santo Domingo, respondieron a la invitación para participar en el examen bucal, desde Octubre 2016 a Enero 2017. 248 sujetos con un rango de edad de 18-86 años, fueron evaluados y examinados clínicamente. Se diseñó y validó un instrumento para obtener datos de factores demográficos, grupos de edad, género, localización anatómica, presencia o ausencia de lesiones de la mucosa oral, factores de riesgo tales como: consumo de tabaco, frecuencia, diferentes formas de uso de tabaco y alcohol. Un especialista en el área, realizó un examen clínico bucal sistematizado en el cual se evaluó y registró la presencia o ausencia de lesiones y su localización anatómica. De acuerdo a la distribución por género, 44.4% correspondió a masculino y 55.6 % femenino. 228/248 sujetos presentaron 1 o más lesiones (91.9%), siendo la media de 3 lesiones por paciente. En relación a los factores de riesgo, el tabaco se reportó en 26.2%, siendo el fumar cigarrillos el 75.4%, seguido de otras formas como "hookah" 9.2%, marihuana 9.2%, cigarros ("puros") 4.6% y pipa fumada 1.5 %. En cuanto a las lesiones bucales detectadas en el examen, el grupo de condiciones no patológicas fue el más frecuente e incluía a pigmentaciones fisiológicas melánicas (25.0%), seguida de torus palatino/mandibulares (20.2 %), gránulos de Fordyce (7.9%) y exostosis (5.6%),respectivamente. Las lesiones potencialmente malignas detectadas (Leucoplasia oral, Liquen plano oral y Queilitis actínica) correspondieron al 2.2%, 0.3 % y 0.3%, respectivamente. Clínicamente, no se observó malignidad. Este estudio contribuye a determinar la prevalencia de LMO en República Dominicana e identificar factores de riesgo. Los hallazgos representan el primer estudio que muestra la prevalencia de las lesiones de mucosa oral en la población adulta dominicana. Se recomienda la creación de un programa de salud pública orientado a grupos de alto riesgo para mejorar el estatus de salud oral en esta población.

Subgingival microbiological profile of periodontitis patients in Dominican Republic

The aim of this study was to evaluate the deproteinization of primary enamel by analyzing etching pattern types, with and without the application of 5% NaOCl before acid etching with 37% H3PO4. Fifteen extracted human primary molars were randomly selected for the present in vitro study; 1mm x 1mm blocks were prepared and divided into two groups (n = 21). These groups were treated as follows: Group AAcid Etching with 37% H3PO4 gel for 15 s; Group B5% NaOCl for 60 s + Acid Etching with 37% H3PO4for 15 s. The specimens were prepared for scanning electron microscopy analysis. The images were evaluated for quality types I and II etching of the enamel surface using ImageJ software. Datasets were checked for normality by KolgomorvSmirnov test and the nonparametric unpaired MannWhitney test was applied. The mean surface area of type I and II etching pattern values was 1922.314 µm2for Group A and 3840.473 µm2Group B. We conclude that deproteinization with 5% NaOCl prior to acid etching can be used to increase the area of adhesion and the quality of the etching pattern (AU)

El objetivo del estudio fue evaluar la desproteinización del esmalte primario a través de los tipos de patrones de grabado, con y sin NaOCl 5% utilizado antes del grabado ácido con H3PO4 37%. Quince dientes primarios humanos extraídos se seleccionaron al azar para el presente estudio in vitro, se prepararon bloques de 1mm x 1 mm y se dividieron en dos grupos (n = 21). Estos grupos se trataron de la siguiente manera: Grupo A: Grabado ácido con H3PO4 37% en gel durante 15 segundos; Grupo B: NaOCl 5% durante 60 segundos + Grabado ácido con H3PO4 37% durante 15 segundos. Las muestras se prepararon para el análisis de microscopía electrónica de barrido. Las imágenes obtenidas se evaluaron principalmente por la calidad de los grabados tipo I y II de la superficie del esmalte primario, utilizando el software Image J. Los datos se analizaron en cuanto a su normalidad mediante la prueba de KolgomorvSmirnov, se utilizó pruebas no paramétricas: Prueba de MannWhitney no pareada. Como resultado, se encontró que el área de superficie media de los valores de patrón de grabado de tipo I y II para el Grupo A era 1922,314 µm2 y el Grupo B era 3840,473 µm2. Finalmente, llegamos a la conclusión de que se puede usar la desproteinización con NaOCl 5% antes del grabado ácido para aumentar el área de adhesión y la calidad del patrón de grabado (AU)

Producción científica en periodoncia e implantes a nivel de Iberoamérica / Scientific production in periodontics and implants in Latin America

Objetivo Analizar la producción científica y la evidencia científica en periodoncia y terapéutica de implantes de las revistas a nivel de Iberoamérica. Materiales y métodos Perfil bibliométrico que analizó los artículos científicos publicados en las revistas odontológicas de los países que conforman la Federación Iberopanamericana de Periodoncia en el intervalo de los años 2012 hasta el 2014. La búsqueda de los artículos se realizó a través de un análisis manual vía el portal web de cada revista, así como a través de las bases de datos SciELO, RedALyC y LiLACS. Se analizaron la productividad científica por año, el tipo, el diseño y el nivel de evidencia de cada artículo, así como la temática de periodoncia y/o implantes dentales. Resultados Fueron analizados 505 artículos publicados en un periodo de 3 años, el 47,7% de estudios fueron publicados en Brasil, el 14,7% en México y el 8,1% en Chile. El 23,9% de los estudios fueron artículos de revisión y el 43,76% pertenecieron a un nivel de evidencia científica de nivel IV. Conclusión La mayor productividad de publicaciones se concentra en las revistas de los países de Brasil, México, Chile y España; la principal temática de las publicaciones científicas son las referidas a los implantes dentales. La calidad de las publicaciones a nivel de Iberoamérica es baja, con un predominio de los reportes de caso y artículos de revisión (nivel IV) y en menor medida las revisiones sistemáticas y los ensayos clínicos.

Aim To analyse the scientific production in therapeutic implants and periodontology in Latin American journals. Materials and methods A literature review that analysed scientific articles published in dental journals in the countries of the Ibero-Pan-American Federation of Periodontology during the years 2012-2014. The search for articles was made through a manual analysis via the web portal in each journal and through SciELO, RedALyC, and LiLACS data bases. The scientific productivity was determined by year, type, design, and level of evidence for each article, as well as the subject of Periodontology and/or dental implants. Results The analysis was performed on 505 articles over a period of 3 years, and most of them were published in three countries: 47.7% from Brazil, 14.7% in Mexico, and 8.1% in Chile. Of these, 23.9% were review articles and 43.76% had an evidence level of IV. Conclusion The highest productivity of publications is concentrated in journals from Brazil, Mexico, Chile, and Spain. The main theme of scientific publications referred to dental implants. The quality of publications at Latin American level is low, with a predominance of case reports and review articles (level IV), and less systematic reviews and clinical trials.